Plants, like all living organisms, must respond quickly when their environment becomes stressful, such as during extreme heat. One way they do this is by changing how their DNA is packaged, which helps turn important genes on or off. In this study, we found that a transcription factor called HSFA1 plays a central role in helping plants respond to heat stress. Using both a simple land plant and a flowering plant, we showed that HSFA1 controls which parts of the DNA become accessible during heat stress. This mechanism is highly conserved and is also found in animals, including humans. We also discovered that some plant hormones, such as ABA, influence heat-responsive genes without changing DNA structure. By combining these data with machine learning, we were able to predict how genes respond to stress across species. Our findings reveal a shared and ancient strategy that living organisms use to survive in hot environments.

Agroinfiltration is a widely used technique in plant gene research. It involves using bacteria to temporarily introduce foreign genes into plant leaves, allowing scientists to observe how these genes function within the plant quickly. Traditionally, the most commonly used bacterium for this purpose has been Agrobacterium tumefaciens. However, our recent research has revealed that a strain of Rhizobium rhizogenes, a relative of A. tumefaciens, performs even better. This study was published on April 9, 2025, in Plant Biotechnology Journal.\\n\\nR. rhizogenes has mainly been studied for its ability to induce “hairy roots” in plants, but its potential to deliver genes into leaves has not been well explored. In this study, we tested several bacterial strains on Nicotiana benthamiana, a widely used model plant in laboratories. We found that strain A4 of R. rhizogenes triggered stronger and faster gene expression than any other tested strain. Building on the genomic information of A4, we developed a series of modified, disarmed strains with no pathogenic effects. These new strains demonstrated outstanding performance in experiments: they could efficiently introduce genes into older plant leaves, something many standard strains struggle with, and outperformed widely used laboratory strains like GV3101 and C58C1. Moreover, in crops such as tomato, pepper, and eggplant that are typically difficult to use for transient gene expression, these A4-derived strains also delivered excellent results.\\n\\nThis breakthrough provides plant scientists with a more flexible and efficient tool for gene function studies. It holds particular promise for research and breeding in solanaceous crops, accelerating crop improvement, and promoting sustainable agriculture.

A research team led by Drs. Hsiu-An Chu and Chih-Horng Kuo from the Institute of Plant and Microbial Biology, Academia Sinica, and Dr. Ching-Neng Chen from the Department of Oceanography, National Sun Yat-sen University, has successfully decoded the complete genome of Cyanobacterium sp. DS4—a newly discovered marine cyanobacterial strain isolated from a high-temperature lagoon on Dongsha Island in the South China Sea. Through whole-genome sequencing and comparative genomic analysis, the team found that DS4 is closely related to the thermophilic species Cyanobacterium aponinum, yet exhibits unique genetic traits. These include a complete nitrogen fixation gene cluster, specialized metabolic pathways, and biosynthetic genes for novel secondary metabolites. The findings provide new insights into the molecular mechanisms underlying thermal and salinity tolerance in cyanobacteria and open up new avenues for biotechnological applications of heat-tolerant and euryhaline marine cyanobacteria in extreme environments. The study has been published in the international journal BMC Microbiology.

Agrobacterium-mediated transformation via floral inoculation (AMT-FI) enables genetic engineering without tissue culture. It is widely used in the model plant Arabidopsis thaliana, yet its efficiency, underlying mechanisms and broader applicability remain limited. To provide conceptual and practical advances in AMT-FI, the team developed dual-reporter systems to simultaneously track Agrobacterium infection, transformation events and ovule viability in real time. The team identified that flowers opened at 5 to 9 days post-inoculation (DPI) are optimal for high transformation efficiency, with a peak at 6 DPI, achieving nearly 100% of siliques harboring transformants and the ~26% stable transformation efficiency. However, Agrobacterium infection induced ovule abortion, whereas efr mutants lacking the EF-Tu receptor (EFR) showed reduced ovule abortion and exhibited significantly higher genome editing efficiency. The research group further engineered stealth Agrobacterium strains (AS201 and AS202) for evading recognition by EFR to enhance both transient expression and genome editing efficiency. By integrating floral-stage selection, immune evasion, and Agrobacterium engineering, the team provides a practical platform to advance plant genome engineering and demonstrate that genome-edited T1 plants can be recovered without selection.

Viruses pose major threats to human health and food security, and they are key regulators of organism abundance in the environment. However, we know little about how long different viruses have been around on Earth and generally lack the knowledge of their origins and ancient evolution. Unlike animals and plants, where fossil ages can be used as calibration points in molecular dating analyses, a major limiting factor for estimating viral divergence times is the absence of fossil records. Here, we developed a host-calibrated dating method for viruses and inferred the evolutionary timescale of giant viruses (i.e., the whole phylum of Nucleocytoviricota), which have large genomes and infect various eukaryotes (vertebrate and invertebrate animals, fungi, algae, amoebae, flagellates, and many others). The evolutionary time tree of this entire phylum provides the estimated times of virus lineage origins, such as two major transitions from amoebozoan hosts to animal hosts that eventually led to the emergence of iridoviruses and African swine fever viruses, respectively. Consistent with the high demand of giant virus replication for energy generated by mitochondria, the last Nucleocytoviricota common ancestor dates back to an era with significantly higher oxygen levels on Earth than before. Although giant viruses are much younger than eukaryotes, they spread across all major lineages of eukaryotes through extensive host shifts within the last hundreds of millions of years and have become one of the virus groups with the widest host range.

Monoclonal antibodies (mAbs) represent a major class of therapeutics with widespread clinical applications in oncology, immunology, hematology, neurology and infectious disease. Since the introduction of hybridoma technology in 1975, the field has been advanced by a succession of innovations including chimeric and humanized antibody engineering, phage display, transgenic mouse platforms and high-throughput single B cell isolation. These technological developments have enhanced the specificity, potency and safety of mAbs, resulting in 144 FDA-approved antibody drugs on the market and 1,516 worldwide candidates in clinical development as of August 2025. Engineering breakthroughs have led to new modalities of antibody-based therapeutics, such as antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor T (CAR-T) cell therapies. Each of these modalities has therapeutic utility across multiple disease domains. Recent advances in delivery strategies, notably mRNA-lipid nanoparticles (LNPs) and antibody-directed in vivo CAR-T cell reprogramming, can enable precision therapies while reducing off-target effects and manufacturing complexity. The integration of artificial intelligence (AI) and machine learning (ML), next-generation sequencing (NGS), and structural modeling tools has further accelerated antibody discovery, affinity maturation and immunogenicity prediction, allowing for more efficient and rational antibody design. The advances in antibody technology are reflected in the rapid market growth of antibody-based therapeutics, which had global sales exceeding USD 267 billion in 2024. This review provides a comprehensive update on recent developments in antibody discovery platforms, therapeutic formats and market trends, highlighting emerging strategies that are reshaping the landscape of antibody-based medicine. Furthermore, we discuss clinical translation, regulatory landscapes, and the integration of engineering, biology and informatics. Together, these aspects shape a dynamic and multidisciplinary future for the therapeutic antibody field, which is poised to address unmet clinical needs and global healthcare priorities.

The hippocampus is a key brain region for learning and memory that can be divided into multiple compartments, including the dorsal and ventral hippocampi. Each compartment has unique functions, connectivity, and molecular properties. However, the molecular mechanisms underlying the specification of these subregions remain unclear. In this study, we investigated the role of COUP-TFI, a patterning transcription factor expressed in a high-caudal-to-low-rostral gradient in hippocampal progenitors, in establishing the dorsal-ventral axis of the hippocampus in mice. The highest COUP-TFI expression in the hippocampal progenitors was observed in the caudal medial pallium that gives rise to the ventral hippocampus, and the lowest expression was found in rostral medial pallium that develops into the dorsal hippocampus. We generated mice with different levels of COUP-TFI expression in the cortex and performed a comprehensive analysis of subregion-specific gene expression across the entire hippocampus in these mice. The deletion of COUP-TFI resulted in an expansion of the dorsal hippocampus at the expense of the ventral hippocampus. Conversely, increased COUP-TFI expression led to the generation of ectopic ventral hippocampus in the dorsal compartments. We further demonstrated that COUP-TFI dose-dependently regulates Wnt signaling pathway, a crucial player in regulating hippocampus development. Together, our findings reveal a novel mechanism governing hippocampal development, in which COUP-TFI determines the fate of hippocampal subregions and balances the hippocampus into dorsal and ventral compartments.

The notochord is a defining feature of chordates, yet its evolutionary origin remains mysterious. Our group has identified a regulatory syntax that controls the notochordal expression of brachyury, which encodes a transcription factor essential for notochord development. This syntax is composed of binding sites of four transcription factors in a specific arrangement and is deeply conserved in diverse animals and even in a unicellular relative to animals. In chordates, it has been rewired to respond to different upstream signals, facilitating the origin of the notochord. This study reveals that during animal evolution, regulatory elements can be preserved in a specific code and repurposed for novel functions. This study was published on July 25, 2025, in Science Advances. The first author is Tzu-Pei Fan from ICOB, with Yi-Hsien Su as the corresponding author. The research team includes Jr-Kai Yu, Che-Yi Lin, Yi-Chih Chen, Jun-Ru Lee, and collaborators Ann Cutting and Andy Cameron from California Institute of Technology. This research was supported by Academia Sinica and NSTC.

Reproduction is tightly coupled to nutrient availability and metabolic homeostasis, yet how specific metabolic pathways interface with cellular signaling to regulate oogenesis remains unclear. Using a targeted RNAi screen in the Drosophila germline, we identify Acetyl-CoA Carboxylase (Acc), the rate-limiting enzyme in fatty acid synthesis, as an essential regulator of germline stem cell (GSC) maintenance and oocyte development. Loss of Acc shifts cellular metabolism toward fatty acid oxidation, increasing mitochondrial ATP production and hyperactivating TOR signaling. Elevated TOR activity drives excessive protein synthesis, leading to defects in endosomal trafficking and fusome branching, a germline-specific structure required for coordinated cyst divisions and oocyte specification. These phenotypes are rescued by inhibiting fatty acid oxidation, suppressing TOR signaling, reducing protein synthesis, or restricting dietary protein intake, indicating that Acc functions as a metabolic checkpoint maintaining germline homeostasis. Importantly, this Acc–FAO–TOR axis is highly conserved, providing mechanistic insight into how metabolic imbalance can disrupt stem cell function. Our findings have translational relevance for understanding metabolic infertility and suggest that dietary or metabolic interventions may offer therapeutic avenues to preserve reproductive capacity in metabolic disease and aging.

Clinical studies have shown that multidrug-resistant mycobacterium infections can be effectively treated using naturally-occurring mycobacteriophages. The mycobacterial outer membrane, enriched in mycolic acids and complex glycolipids, is a highly hydrophobic barrier central to drug resistance and pathogenicity, and serves as a critical interface for phage recognition and infection. By integrating cryo-electron microscopy, cryo-electron tomography, we resolved the first high-resolution three-dimensional structure of a mycobacteriophage, established a complete 3D model, and visualized the phage infection process from host membrane recognition to genome injection. Furthermore, glycan microarray and protein chemistry analyses revealed the specificity of interactions between mycobacteriophage surface proteins and mycobacterial glycolipids.

The Min system in Escherichia coli mediates positioning of the cell division through continuous interpolar oscillation over the cell cycle. This oscillation behavior is driven by only two proteins, MinD and MinE in the Min system. During interpolar oscillation, the spatial distribution of MinD forms a concentration gradient that is highest at the poles and decreases toward midcell. Because the division inhibitor MinC binds to MinD, it adopts a similar spatial profile, thereby reducing division-inhibitory activity at the cell center, thereby directing division to occur at the midcell. In this study, we investigated the oscillatory dynamics of the Min system in live bacteria and show that the coupling between MinD–MinE molecular interactions and diffusion confers plasticity to the MinD concentration gradient throughout the growth cycle. By combining livecell time-lapse imaging with quantitative analysis, we observed that as cells elongate, the MinD concentration gradient gradually steepens toward the cell center, the concentration at midcell progressively decreases, and the regularity of the oscillation period becomes increasingly stabilized. Through simulations using a one-dimensional mathematical model incorporating kinetic rate constants that represent distinct molecular interactions in the Min system, we captured the nonlinear dynamics of the system and identified dynamic equilibrium states among these rate constants. This equilibrium underlies the emergence of variable concentration gradients during cell growth. Overall, this work not only provides a quantitative understanding of MinD oscillatory dynamics in the cellular environment, but also highlights the broad significance of concentration gradients in cell biology.

This study elucidates the complete biosynthetic pathway of the epoxyquinoid natural product (−)-asperpentyn and uncovers how epoxide stereochemistry dictates downstream, regioselective ketoreduction. Through heterologous reconstitution of the intron-free aty gene set in Aspergillus oryzae, combined with chemical synthesis, chiral analysis, and in vitro biochemical assays, the authors confirm that the aty pathway produces (−)-asperpentyn (distinct from the previously reported (+) enantiomer). The FAD-dependent monooxygenase AtyG catalyzes an NADPH-driven oxidative decarboxylation step to furnish the key precursor for epoxyquinoid formation. AtyE, a cupin-domain enzyme, performs hydroquinone oxidation followed by stereospecific (2R,3S)-β-epoxidation (via a quinone intermediate), generating a β-epoxyquinone that sets the stage for selective reductions. Two ketoreductases then impose complementary stereochemical outcomes: AtyD is S-selective and, critically, exhibits strong regioselectivity on β-epoxide substrates by reducing only the C-4 ketone to a harveynone intermediate, while AtyC is R-selective and reduces the C-1 ketone to deliver (−)-asperpentyn. Strikingly, altering the epoxide configuration to an α-epoxyquinone redirects AtyD to reduce both C-1 and C-4, demonstrating that epoxide stereochemistry functions as a switch controlling reduction regiochemistry. Steady-state kinetics support a preferred sequence of β-epoxyquinone → harveynone (AtyD) → (−)-asperpentyn (AtyC). Structure-guided mutagenesis identifies key residues (notably F97, as well as L137 and Q246) that govern AtyD regioselectivity. Beyond mechanism, the work expands biocatalytic space by generating multiple new epoxyquinol and epoxyhydroquinone derivatives and enabling one-pot, stereodivergent routes to (−)- and (+)-asperpentyn using engineered AtyD variants with AtyC.

單樣本學習（One-shot learning）是一種關鍵性的學習範式，在智慧模型中具有廣泛的應用價值；在真實世界情境中因為可用樣本或訓練數據相當有限，其適用性特別重要。我們從小鼠在虛擬實境（VR）中的研究中發現了一種單樣本學習演算法，其靈感來自海馬體（哺乳動物大腦中對記憶與空間編碼至關重要的區域）中單神經元運算的概念。

Polygenic risk scores (PRS) are increasingly used to stratify disease risk, but most existing models are derived from European-ancestry cohorts and perform suboptimally in other populations. To address this gap for people of Han Chinese ancestry, we analysed genetic and longitudinal electronic medical record data from 463,447 participants of the Taiwan Precision Medicine Initiative (TPMI), a hospital-based cohort in which the great majority of individuals cluster with Han Chinese reference populations. We constructed 695 dichotomous disease phenotypes and 24 quantitative traits from coded diagnoses and laboratory measurements, and performed phenome-wide genome-wide association studies (GWAS), heritability estimation and fine mapping. These analyses yielded 2,656 independent variant–trait associations, including 95 loci not previously reported and 217 additional independent signals in known regions, thereby revealing population-specific genetic architecture and extensive pleiotropy across multiple disease categories. Using these results, we trained PRS for 265 diseases and 24 quantitative traits with several state-of-the-art methods, selecting the best-performing models for downstream analyses. Many scores showed robust discrimination for clinically important conditions, including cardiometabolic, autoimmune, infectious and kidney diseases; for example, area under the receiver operating characteristic curve (AUC) values approached or exceeded 0.70 for traits such as ankylosing spondylitis, psoriasis, atrial fibrillation, viral hepatitis B and prostate cancer. For highly heritable traits, the variance explained by PRS captured more than half of the SNP-based heritability. Leveraging patterns of genetic correlation, we further applied a multitrait training framework that combined information across clustered phenotypes, which significantly improved predictive performance relative to single-trait models. We evaluated these Han Chinese–specific scores in independent datasets from the Taiwan Biobank, and among East Asian ancestry participants in the UK Biobank and the All of Us Research Program. Across several traits, TPMI-derived scores outperformed leading European-derived PRS when applied to East Asian individuals. Aggregating top-performing scores across diseases, we showed that inherited risk profiles account for up to 10.3% of the variation in hospitalization duration, indicating a measurable contribution of genetics to overall health burden. Our work demonstrates that large, ancestry-matched cohorts enable discovery of population-specific risk variants and the development of well-calibrated PRS, providing a template for reducing disparities in genomic risk prediction and advancing precision medicine for under-represented populations.

The Taiwan Precision Medicine Initiative (TPMI), led by Academia Sinica, has published two landmark papers in Nature, representing major advances in precision medicine and biomedical big-data research. Th first paper describes the establishment of the largest non-European precision medicine cohort in the world, recruiting over 565,000 participants through partnering with 16 healthcare systems and 33 hospitals across Taiwan. This cohort systematically integrates genomic profiles with longitudinal electronic medical records (EMRs), forming an unprecedented resource that supports genome-wide association studies (GWAS), phenome-wide association studies (PheWAS), and polygenic risk score (PRS) analyses, addressing the historical underrepresentation of non-European populations in genomic resources. TPMI has five features: (1) With high efficient and lost cost study design, this project quickly established cohort, data collection and data analysis with the shortest recorded time; (2) This project used arrays specifically designed for Han Chinese, (3) The participant give consent for the project to access thrir EMR retrospectively and prospectively, (4) The participants could select for participating of future clinical validation and clinical trial, (5) The participants could select to receive their genetic results and subsequent gnenetic-tailored medical guideline. Importantly, TPMI offers a replicable blueprint for other populations around the world, contributing to greater equity in global healthcare.

In living cells, reactive oxygen species (ROS) play a dual role — they are important molecules that regulate cellular metabolism and signaling, but excessive ROS can lead to oxidative damage and chronic inflammation. For years, it has been widely recognized that oxidative stress is closely associated with immune imbalance, aging, cancer, and metabolic diseases. However, due to the lack of high-resolution tools to dynamically analyze redox signaling, the fundamental question of “how redox signals drive immune cell fate” has remained unresolved.\nTo address this, the research team developed an innovative technique called Single-cell Redox Signaling Network Profiling (SN-ROP). This method leverages mass cytometry (CyTOF) with metal-labeled antibodies to simultaneously quantify multiple redox indicators and signaling activities at the single-cell level. This allows researchers to track immune cell responses and fate transitions under oxidative stress.\nThe SN-ROP approach was applied to both mouse and human samples. The team discovered that early redox balance is closely linked to protein folding and cellular stress signaling. Disruption of this balance can push immune cells into distinct fate trajectories. Further analysis revealed coordinated redox signaling in CD8⁺ T cells upon antigen stimulation. The method also successfully identified oxidative signatures associated with CAR-T cell persistence and immune dysfunction in dialysis patients. These findings demonstrate that SN-ROP is a powerful tool for exploring redox regulatory networks in the immune system and may have broad applications in chronic diseases, cancer, and immunotherapy development.

“Sng” is a Taiwanese term that denotes an acid-like discomfort, which is one of the top complaints distinguishable from pain in clinics, especially for fibromyalgia patients suffering from both chronic widespread sng and pain. However, such chronic sng is often difficult to treat effectively and mis-diagnosed as pain. In order to solve the unmet medical need of intractable sng, it is essential for understanding the etiology of that type of “pain” and its subtypes. Dr. Chih-Cheng Chen and his international research team from IBMS, Academia Sinica have found sng and pain are 2 different somatosensory functions (and symptoms), with proprioceptors which are the sng-sensing neurons (sngceptors) to sense tissue acidosis and to trigger the acid-induced priming and “pain” chronicity in mouse models of fibromyalgia. These breakthrough findings have been recently published in the prestigious international journal \"Science Advances.\" To demonstrate the difference between sng-sensing neurons and pain-sensing neurons (nociceptors), Dr. Chen’s team tested effects of acidosis on “pain”-like responses in a mouse of fibromyalgia combined with interdisciplinary approaches, including mouse genetics, chemo-optogenetics, neuropharmacology, cellular electrophysiology. Unexpectedly, acidosis activated acid-sensing ion channel 3 (ASIC3) of proprioceptors, but not nociceptors, to induce hyperalgesic priming and the development of chronic mechanical hyperalgesia. Furthermore, experimental acidosis induced sng but not pain in a group of health Taiwanese volunteer. This discovery has overturned medical concepts that have prevailed for the past 50 years. The research team has established a novel theory of “sngception”, in which “sng” is the Romanization form of the Taiwanese word “痠”. Of note, sng is derived from a linguistic phenomenon where both “sour taste” and muscle soreness are encoded in the same word in the Taiwanese language, which is unique to Sino-Tibetan language family, but not in other languages. Revealing a role for proprioceptors in sngception is a paradigm-shifting discovery that will facilitate the precision medicine in sng and pain management, prevent not-evidence-based pain management for sng, and kick off a new era of sng medicine.

Plastids in plant cells differentiate into distinct types according to functional demands. In addition to the well-known chloroplasts that develop in leaves and carry out photosynthesis, plastids in seeds and roots differentiate into leucoplasts, which primarily function in nutrient storage. Because most human food is derived from plant seeds and roots, leucoplasts represent the plastid type most directly related to human food production. However, the long-standing lack of effective tools for efficiently delivering proteins into leucoplasts has limited precise regulation of their biosynthetic pathways. In this study, we established an in vitro leucoplast import system and identified six highly efficient protein targeting signals (transit peptides) that function as “address labels” to direct proteins accurately into leucoplasts. Compared with commonly used chloroplast transit peptides, these targeting signals exhibit comparable import efficiency in leaf chloroplasts, while achieving approximately 2- to 7-fold higher efficiency in leucoplasts of roots and petals. Further applications demonstrated that delivery of carotenoid biosynthetic enzymes into rice callus tissue, or herbicide-resistance–related enzymes into Arabidopsis thaliana using these targeting signals, significantly increased carotenoid accumulation and herbicide resistance, respectively. These results indicate that the targeting signals function with consistent and robust efficiency across different plant species and cargo proteins. Overall, this study establishes an efficient plastid protein-targeting strategy and demonstrates that the selection of appropriate targeting signals is an effective approach for modulating protein abundance within plastids, with potential applications in enhancing nutritional value, disease resistance, and sustainable agricultural practices.

Bacteria inhabit complex environments where they face constant threats from viral predators (phages) and neighboring microbes. However, how defenses against phages influence bacterial interactions remains poorly understood. In this study, we used Salmonella enterica to investigate the evolutionary tradeoffs between phage resistance and interbacterial competition. We found that Salmonella avoids phage infection by altering lipopolysaccharide (LPS) structures on its cell surface, which serve as primary receptors for phage attachment. However, the resulting phage-resistant strains become dramatically susceptible against competing bacteria, revealing a critical evolutionary tradeoff. Our results demonstrate that LPS plays a dual role: acting as both a target for phage attachment and a vital protective barrier against close-range attacks from bacterial competitors, such as the type VI secretion system (T6SS). Importantly, the LPS deficiency is not limited to genetic mutations; certain phages deploy tail-spike proteins (TSPs) to enzymatically degrade LPS on the bacterial surface, thereby compromising their competitiveness against antagonistic bacteria. Together, our findings reveal fundamental evolutionary tradeoffs between phage resistance and interbacterial antagonism, providing new insight into how phage pressure indirectly shapes bacterial interactions and community dynamics in mixed microbial populations.

During social interactions, individuals interpret others\' behaviors differently depending on their distance - too close or too far can alter perception. How animals integrate social cues (such as behavior) with spatial distance (via depth vision) to guide their responses is a frontier in neuroscience research. Dr. Kuo-Hua Huang’s team at the Institute of Molecular Biology used zebrafish, known for their innate social tendencies, to investigate how the body movements and proximity of the same species shape social affiliation. They created lifelike virtual zebrafish with realistic tail bends, turns, and displacements, and simulated motion parallax through a game engine. They discovered that depth sensation can either enhance or suppress social affiliation, depending on the context, offering insights into how the brain integrates social and depth information.

Converting cellulosic biomass into biofuels or biochemicals remains challenging because of the recalcitrant structure of cellulose. Natural cellulosomes offer a blueprint for overcoming this challenge through enzyme assembly, but creating enzyme complexes in yeast has been limited by scaffoldin size and lack of enzyme positioning control on the scaffoldin. We constructed the largest designer cellulosome scaffoldin to date in Kluyveromyces marxianus, am yeast commonly used in industry. It includes nine distinct cohesins, allowing the precise positioning of nine enzymes on the scaffoldin to achieve high enzyme proximity-effect and synergy. Our new system increased ethanol yield by fourfold or more compared to previously constructed yeast cellulosomes. Our approach opens new possibilities for assembling enzyme complexes to degrade lignin, hemicellulose and cellulose in a single consolidated process.

Mesopelagic fishes constitute the largest vertebrate biomass on Earth, yet their long-term ecological responses to climate change and environmental stressors remain poorly understood due to the lack of continuous biological records. This study provides the first quantitative, long-term reconstruction of mesopelagic fish community structure and productivity based on fossil otoliths preserved in deep-sea sediments, integrated with paleoceanographic reconstructions. Our results demonstrate that past episodes of intensified ocean stratification and deoxygenation were consistently associated with pronounced declines in mesopelagic fish diversity and production, revealing a high sensitivity of midwater ecosystems to oxygen availability. These findings offer a unique deep-time perspective on how mesopelagic communities respond to extreme environmental stress and provide a critical natural analogue for ongoing and future ocean deoxygenation driven by climate change. In this work, I led the taxonomic identification and ecological interpretation of fossil otolith assemblages and played a key role in integrating paleobiological data into an Earth system science framework. This study represents a major conceptual advance by establishing fossil otoliths as robust archives for reconstructing mesopelagic ecosystem dynamics, thereby expanding the scope of paleontology toward addressing globally relevant questions in marine biodiversity and climate change.

Coral reefs around the world are degrading due to climate change and human activities, which threatens the long-term sustainability of fish communities. In the past, coral reef conservation has mainly relied on passive protection measures, such as marine protected areas. However, these measures alone are often not enough to help fish communities recover. One major reason is that we still do not fully understand how habitat conditions affect fish recruitment—the process by which young fish settle into reefs. This study conducted field surveys at Lyudao and Xiaoliuqiu to examine how reef substrate type, habitat structural complexity, adult fish communities, and underwater soundscapes influence the number and diversity of fish recruits. Our results show that habitat structural complexity is the most important and consistent positive factor for fish recruitment. In contrast, reefs dominated by algae or soft corals have fewer fish recruits. We also found that on less degraded reefs, louder nighttime fish choruses were strongly linked to higher diversity of fish recruits. These findings suggest that coral reef management should not rely on a single ecological indicator. Instead, effective conservation should use a multi-dimensional approach that considers both habitat structure and ecoacoustic signals. Such strategies can better support the recovery of coral reef ecosystems after degradation.

A research team led by Dr. Yin-Ru Chiang from the Biodiversity Research Center, Academia Sinica has isolated and characterized a novel anaerobic bacterium from the intestine of the giant mudskipper. This bacterium can convert testosterone (the primary male hormone in humans) into estrogen in an oxygen-free environment. This discovery challenges the traditional scientific understanding that estrogen production requires oxygen and aromatase (a monooxygenase unique to vertebrates). Genomic analysis reveals that this bacterium possesses a special gene cluster that produces a novel methyltransferase, generating estrogen by removing the methyl group between the A/B rings of testosterone. This anaerobic bacterium uses one of the Earth's earliest metabolic pathways (namely Wood-Ljungdahl pathway) to utilize the obtained methyl groups for energy production and cell construction. This new discovery in microbial metabolism suggests that anaerobic bacteria may have possessed the ability to produce estrogen early in Earth's evolutionary history. The research also partially explains why some invertebrates have estrogen in their bodies despite lacking aromatase. Furthermore, the identification of estrogen-producing bacteria in animal guts opens new avenues for potential microbiome-based hypoestrogenism therapies to supplement estrogen in menopausal or ovariectomized females, offering an innovative alternative to current hormone replacement strategies. Future research will prioritize investigating whether anaerobic estrogenesis and corresponding bacteria occur in the intestines of humans and other mammals. The research findings were published in the Proceedings of the National Academy of Sciences (PNAS) on March 08, 2025.

Global environmental change is reshaping thermal environments by increasing mean temperatures and altering diurnal temperature range (DTR) in complex, region-specific ways. Climate change, deforestation, and urbanization influence DTR with varying effects. How species with different daily temporal niches respond to such changes remains largely unexplored, particularly regarding interspecific interactions. We synthesize emerging evidence and develop a theoretical framework integrating thermal performance curves with temporal niche theory to address this critical knowledge gap. Our analysis shows that larger DTRs decrease the optimal mean temperatures for diurnal species, while increasing them for nocturnal species. Contrary to conventional views that temporal partitioning reduces competition, we show that DTR changes alter exploitative competition between temporally segregated species sharing common resources. This mechanism operates in diverse systems, from carrion competition between necrophagous insects to growth competition between plants with different photosynthetic pathways. Our framework provides mechanistic insights into how DTR changes affect biodiversity through altered competitive interactions and highlights the need to incorporate these dynamics into vulnerability assessments and conservation planning in the Anthropocene.

Assessing the physiological costs of sociality remains challenging due to complex interactions between environmental and social factors. To overcome this challenge, we integrated game theory with empirical research to examine how interspecific competition affects energy expenditure in the cooperatively breeding Asian burying beetle Nicrophorus nepalensis. Our nested tug-of-war model made two predictions: beetles facing interspecific competition would experience (1) lower physiological costs due to reduced investment in intragroup conflict, despite increased cooperative effort; and (2) decreasing physiological cost differences between dominance ranks. Using thermal imaging, we analysed body temperature as a proximal indicator of thermogenic effort during carcass work. Results supported our model's two key predictions: beetles competing with blowflies exhibited lower body temperatures, with less pronounced temperature differences between social ranks. Thus, reduced social conflict outweighs the energetic costs of increased cooperation in the face of external threats, providing insights into how environmental conditions shape energy allocation in social species.

Thermal trait diversity is critical for understanding species’ responses to climate change, yet its ecological drivers remain unclear. Using eco-evolutionary simulations and empirical data from 653 moth species across three Asian elevational gradients, we examine how temperature regimes shape thermal strategies in assemblages. Warmer environments support larger hypervolumes of moth assemblages, reflecting a broader array of coexisting thermal strategies. Contrary to the climatic variability hypothesis, which predicts generalized traits under stable climates, we find that warmer sites foster assemblage-level diversity even while individual species retain narrow thermal tolerance ranges. Short-term temperature fluctuations exert minimal influence, while seasonal variability promotes generalists but reduces overall hypervolume. These results demonstrate that mean temperature, not variability, is the dominant force structuring thermal trait diversity. By revealing how thermal strategies assemble under different climates, our study provides a mechanistic basis for predicting biodiversity responses to warming and emphasizes the conservation value of low-elevation ecosystems.

Although most birds build nests, not all of them build nest walls, and the evolutionary advantage conferring this architectural feature remains inconclusive. By integrating macro-evolutionary patterns with individual fitness consequences, we investigated the function of nest walls in protecting eggs and the evolutionary driver behind this construction. We examined two novel hypotheses relating to egg rolling-off risk: (i) heavy- bird hypothesis: heavier birds generate greater nest vibrations during attendance, increasing egg rolling-off risk; and (ii) light-egg hypothesis: lighter eggs are more susceptible to displacement from nest vibrations due to lower friction against the substrate. Phylogenetic comparative analyses across 4030 species revealed that birds with lower body and egg mass were more likely to construct nest walls, suggesting higher rolling-off risk for lighter eggs. Experiments combining behavioural observations and controlled trials with three-dimensional-printed eggs confirmed that lighter eggs were more prone to falling from nests without walls. The evidence across phylogeny and individual-level experiments consistently supports the light-egg hypothesis, suggesting the adaptive function of nest walls in preventing eggs from falling during external disturbance, particularly for lighter eggs. This study demonstrates how integrating macro- and micro- evolutionary approaches can reveal the functional mechanisms underlying correlated evolution between phenotypic traits.

Endozoicomonas is a dominant symbiotic bacterial genus widely distributed in corals, sponges, and a broad range of marine invertebrates. It has long been associated with host health and ecosystem stability, yet its evolutionary history and functional potential have remained poorly resolved due to the scarcity of high-quality genomes. In this study, we employed third-generation HiFi long-read sequencing to generate high-completeness genomes for five newly isolated strains and one representative reference strain, and integrated these with 31 previously published high-quality genomes to conduct the most comprehensive comparative and pan-genomic analysis of Endozoicomonas to date. Our results show that Endozoicomonas can be divided into three major evolutionary lineages with distinct genomic architectures, orthologous gene compositions, and host associations, highlighting pronounced diversity in evolutionary trajectories and ecological strategies. In addition, we found that Endozoicomonas generally lacks the capacity to synthesize and transport vitamin B12, indicating a reliance on cross-species metabolic complementation within the symbiotic community. Notably, Endozoicomonas genomes are highly enriched in giant proteins, including a protein of approximately 65 kbp, the largest known protein reported in Proteobacteria, which is predicted to be involved in cell adhesion, host interactions, and antimicrobial functions. Together, this study reconstructs the ecofunctional landscape and evolutionary relationships of Endozoicomonas, providing deeper insights into how marine symbiotic microbes adapt to and influence their hosts.

Although most birds build nests, not all of them build nest walls, and the evolutionary advantage conferring this architectural feature remains inconclusive. By integrating macro-evolutionary patterns with individual fitness consequences, we investigated the function of nest walls in protecting eggs and the evolutionary driver behind this construction. We examined two novel hypotheses relating to egg rolling-off risk: (i) heavy-bird hypothesis: heavier birds generate greater nest vibrations during attendance, increasing egg rolling-off risk; and (ii) light-egg hypothesis: lighter eggs are more susceptible to displacement from nest vibrations due to lower friction against the substrate. Phylogenetic comparative analyses across 4030 species revealed that birds with lower body and egg mass were more likely to construct nest walls, suggesting higher rolling-off risk for lighter eggs. Experiments combining behavioural observations and controlled trials with three-dimensional-printed eggs confirmed that lighter eggs were more prone to falling from nests without walls. The evidence across phylogeny and individual-level experiments consistently supports the light-egg hypothesis, suggesting the adaptive function of nest walls in preventing eggs from falling during external disturbance, particularly for lighter eggs. This study demonstrates how integrating macro- and micro-evolutionary approaches can reveal the functional mechanisms underlying correlated evolution between phenotypic traits.

When we look at a forest, we tend to see a tree as a single unit. This study reveals a very different picture: leaves, twigs, litter, and soil on the same tree host distinct fungal worlds, even when separated by only a few meters. By examining fungal communities across these closely connected habitats in tropical forests of Taiwan, we found strikingly high turnover in fungal composition at extremely small spatial scales, challenging the assumption that microbial communities change gradually across space. Our analyses further show that different ecological “rules” govern different habitats. Fungal communities on leaves and twigs are shaped mainly by environmental filtering and biological interactions, whereas soil communities are more strongly influenced by chance. Rainfall and spatial distance together determine how fungi disperse and establish across forest habitats, and a small number of widespread fungi play a disproportionate role in stabilizing these hidden networks. These findings highlight forests as mosaics of interconnected micro-ecosystems and emphasize why understanding invisible microbial life is essential for appreciating how forest ecosystems function.

This study describes Primulina cucphuongensis, a newly recognized lithophilous species of Gesneriaceae discovered in Cuc Phuong National Park, northern Vietnam. The genus Primulina is largely restricted to limestone karst ecosystems of southern China and northern Vietnam and has experienced rapid taxonomic expansion over the past decade. Despite this growth, the limestone flora of northern Vietnam remains comparatively underexplored. Cuc Phuong National Park, Vietnam’s oldest protected area, is situated at a biogeographic crossroads and is known for its high biodiversity, yet its flora continues to face threats from tourism pressure and illegal exploitation.\n\nThe new species was first collected in August 2023 from shaded limestone rocks near the summit of May Bac Mountain (Silver Cloud Peak) at approximately 640 m elevation. Plants were cultivated until flowering in 2024, enabling detailed morphological study. Primulina cucphuongensis is distinguished by a unique combination of characters, including dark green elliptic leaves with densely white puberulous margins, violet corollas with yellow stripes on the ventral tube, and peduncles and pedicels densely covered with deep red hairs. Comparative analyses demonstrate clear differences from morphologically similar species such as P. swinglei, P. balansae, and P. minutimaculata, particularly in bract size, corolla coloration, stigma shape, and capsule length.\n\nPhylogenetic analyses based on nuclear ITS and plastid trnL–trnF sequences place P. cucphuongensis in a distinct position within Primulina. Although its exact placement is weakly supported, both molecular evidence and morphological distinctiveness support its recognition as a new species. The species is currently known only from its type locality, with fewer than 250 mature individuals observed in the wild and an estimated area of occupancy under 500 km². Given the limited data and the likelihood of undiscovered populations within intact forest, the authors propose a preliminary conservation status of Data Deficient (DD) following IUCN guidelines. This discovery highlights the continued importance of botanical exploration and taxonomic research in Southeast Asian limestone ecosystems.

Fungi engage in diverse symbiotic relationships with phototrophs. Lichens, symbiotic complexes involving fungi and either cyanobacteria, green algae, or both, have fungi forming the external layer and much of the interior. We discovered an erect thallus resembling a lichen, yet with a surprising thallus structure composed of interwoven cyanobacterial filaments with numerous fungal hyphae inserted within individual cyanobacterial sheaths, contrasting with typical lichen structure. Phylogenetics identified the fungus as a previously undescribed species, Serendipita cyanobacteriicola, closely related to endophytes, and the cyanobacterium belongs to the family Coleofasciculaceae, representing a genus and species not yet classified, Symbiothallus taiwanensis. These thalli exhibit N-fixing activity similar to mosses but lower than cyanolichens. Both symbiotic partners are distinct from known lichen-forming symbionts, uncovering a phylogenetically and morphologically unprecedented thallus-forming fungus-cyanobacterium symbiosis. We propose the name “phyllosymbia” for these thalli, to underscore their unique symbiotic nature and leaf-like appearance. This discovery marks the first instance of fungi solely residing within structures generated by cyanobacteria.

The subclass Facetotecta are planktonic larval form “Y-larvae”, which could not be directly linked to adult stages, was first named by the Danish scientist Hansen in 1887. Previously, only morphological studies have been conducted on their larval developmental stages. The final larval stage is called ypsigon and is tentatively regarded as an early instar/juvenile of a hypothetical endoparasitic adult stage. I initiated and supervised a doctoral investigation involving collaboration with an international research team from Denmark, Spain, Russia, Japan, and Germany, to break through the present morphological-based study in the enigmatic Facetotecta and developed a successful molecular method for elucidating their diversity and molecular phylogeny. We demonstrated that Facetotecta has two feeding modes and comprises at least 5 monophyletic groups. Using NGS sequencing techniques, we documented the first genome-scale phylogenetic backbone for Facetotecta, and our phylogenomic analysis revealed parasitism has multiple origins in Thecostracan barnacles. This work was just published in Current Biology in July 2025 (Dreyer et al. 2025). We are the pioneering group of the Facetotecta and published a series of papers on the molecular phylogeny and ecology of Facetotecta. We were invited to contribute a review article to the prestigious book Oceanography and Marine Biology: An Annual Review, to summarize the past 100 years of study on Y-larvae and our recent molecular and ecological findings. This article currently serves as the foundational publication for studying this group of organisms. However, the full life cycle of which remains a mystery. Our next step is to uncover the hosts and adults of Y-larvae using meta-transcriptomic techniques.

In the Anthropocene, scleractinian corals face unprecedented threats from synergistic stressors that lead to global coral reef degradation. With over 1,698 coral species in the order Scleractinia, their conservation is increasingly complex due to their morphological plasticity and the challenge of accurate species identification. The genus Acropora, with approximately 400 nominal species, exemplifies these challenges, as morphological traits often vary within and among species, complicating taxonomic efforts. Traditional methods based on skeletal characteristics are insufficient for delineating Acropora species, prompting the use of integrative approaches combining morphology, reproduction, and molecular data. In this study, we employ multi-locus phylogenetic analyses and morphometric measurements to distinguish different growth forms of Acropora cf. solitaryensis as distinct species and delineate the species range boundaries of A. aff. divaricata and A. cf. solitaryensis in East Asian coral ecosystems. We identify arborescent and intermediate morphotypes belonging to A. aff. divaricata, which is distributed from tropical reefs in southeastern Taiwan to temperate non-reefal communities in Shikoku, Japan. Conversely, the solid-plate morphotype aligns with A. cf. solitaryensis, found primarily in non-reefal regions in northern Taiwan and Japan. The distinct distribution patterns underscore the necessity for biogeographic sampling in Acropora taxonomy, considering the Kuroshio Current’s impact on coral distributions, and a re-evaluation of poleward coral migration or expansion due to climate change. This has significant implications for coral conservation strategies, as accurate species identification is crucial for understanding coral responses to environmental changes and informing conservation efforts in the face of climate change.

Resolving the deep branches of the animal tree of life has long been a major challenge in evolutionary biology. One of the most enduring debates concerns the classification of Lophophorata, a group that includes brachiopods, phoronids, and bryozoans, all characterized by a ciliated feeding structure known as the lophophore. While some genomic studies have supported their monophyly, others have suggested that bryozoans should be grouped with different lineages, and the controversy has persisted for more than a century. A team led by Assistant Research Fellow Yi-Jyun Luo at the Biodiversity Research Center, in collaboration with researchers in Japan and the United Kingdom, has now generated the first chromosome-level genome of a phoronid and compared it with those of bryozoans and brachiopods. The study uncovered seven irreversible chromosome fusion events shared between phoronids and bryozoans, one of which is also shared with brachiopods. These fusions are absent in other lophotrochozoans such as molluscs, annelids, and nemerteans, providing sequence-independent evidence for the monophyly of lophophorates and demonstrating that these three phyla indeed share a recent common ancestor.

Bilaterally symmetrical animals are those with body structures exhibiting left–right symmetry, including species such as fruit flies, nematodes, and zebrafish. Despite this symmetry, their body plans vary significantly, with around 30 different animal phyla identified. A team led by Assistant Research Fellow Yi-Jyun Luo at the Biodiversity Research Center has analyzed chromosome-level genomes from 15 animal phyla, covering 54 classes. The study used a "rearrangement index" to quantify the extent of genomic structural rearrangements, finding that most bilaterally symmetrical animal genomes show significant rearrangement. In contrast, marine invertebrates such as sea urchins, amphioxus, and scallops exhibit relatively conserved genome structures, with little change over the past 500 million years. Further analysis revealed that the degree of genomic rearrangement is not significantly correlated with genome size, transposable element content, or GC content, but is strongly associated with rapid protein sequence evolution, indicating a synchronized evolution between genome structure and gene evolution. This research helps to understand the relationship between genome rearrangements and evolutionary adaptations in animals, and sheds light on the molecular mechanisms underlying the stability of chromosomal structures. The study was published in Genome Biology in August 2025 and supported by the Academia Sinica Career Development Award and the National Science and Technology Council Research Project Grant.

Genetic information from DNA is very important for protecting wildlife, and new DNA sequencing technologies have made it much easier for scientists to study the genetics of wild species. One powerful tool is a reference genome. Reference genomes can help researchers more accurately measure genetic diversity, detect inbreeding, and find DNA regions linked to adaptation. However, many wild species still lack reference genomes, and scientists do not yet fully understand how much these genomes can improve conservation decisions. In this study, we tested whether having a reference genome could reveal important information that earlier genetic studies had missed. We focused on a stag beetle found only in Taiwan and asked whether a reference genome could improve our understanding of recent population declines and local adaptation, both of which are critical for conservation planning. We built a draft reference genome for this beetle using Oxford Nanopore DNA sequencing and then reanalyzed existing genetic data collected in a previous study. Using the newly assembled genome, we discovered that beetle populations from different regions of Taiwan show clear genetic differences. The population living in the area with the most severe recent habitat destruction had long stretches of nearly identical DNA, which is a sign of inbreeding and a sharp drop in population size. We also found that the timing of this population decline matches historical records of recent habitat loss. In addition, we identified parts of the genome that appear to be evolving differently in different regions, which implies that these regional populations are adapting to local environments and should be protected as separate conservation units. As a result, our study shows that the genetic legacy of human-caused habitat disturbance can be detected when a reference genome is available, and that reference genomes are essential tools for understanding how species respond to environmental change and for making more effective conservation plans.

Photosynthesis is known as a major reaction to capture most of atmospheric CO2 on Earth. Its primary metabolite is C3 carbohydrates, which is used to produce carbohydrates for supporting growth and development. While acetyl-coA, a key C2 metabolite, is produced via decarboxylation of C3 in which 1/3 of CO2 is released. In addition, rubisco oxygenation causes 25% carbon loss via recycling glycolate (C2) to glycerate (C3) pathway. The synthetic McG cycle with native Calvin-cycle form a dual-cycle carbon fixation system, which is able to convert a PEP (C3) and a CO2 (C1) to produce two acetyl-coA or transform a glycolate to an acetyl-coA without net carbon loss. Introduction of McG cycle into Arabidopsis plants targeted to the chloroplasts remarkably increases their carbon fixation rates, biomasses, seed production, and oil contents in leaves and seeds. Moreover, Arabidopsis McG plants showed higher quantum use efficiency (phiPSII), higher protein abundance in photosystems, and more thylakoid grana numbers per chloroplast compared to the WT. This work has been accepted by Science recently. Next, to study the effects of McG in crop plants, we introduced the McG cycle into rice (Oryza sativa L. ssp Japonica TNG67 and Kitaake). Multiple T0 transgenic rice plants showed higher tiller numbers and contained more lipids in their leaves. Consequently, they produced more grains.

A research team led by Dr. Kuo-Chen Yeh identified ENA1, a plasma membrane-localized transporter that mediates the root secretion of nicotianamine (NA) — a key metal chelator. This discovery uncovers a novel mechanism by which plants regulate zinc (Zn) detoxification and tolerance, recently published in New Phytologist. The study shows that the Zn hyperaccumulator Arabidopsis halleri expresses significantly higher levels of ENA1 than A. thaliana, and under excess Zn conditions, ENA1 promotes NA secretion into the rhizosphere. This reduces Zn uptake and alleviates toxicity via Zn–NA complex formation. The findings open up new avenues for developing plants with enhanced phytoremediation capacity and improved nutritional value through targeted manipulation of NA transport.

Fusarium wilt has long threatened the global banana industry. Because most edible banana cultivars are sterile triploids, conventional breeding is difficult and often fails to deliver new cultivars acceptable to farmers and consumers. Through mutation induction via tissue culture combined with field selection, the Taiwan Banana Research Institute (TBRI) has successfully developed several commercial cultivars with resistance to Fusarium wilt, including ‘Tai-Chiao No. 5’, ‘Tai-Chiao No. 7’, and ‘Formosana’. These resistant cultivars have become critical resources for disease management in Taiwan and other banana-producing countries，but the genetic basis of their resistance has remained unclear. We employed genomic, transcriptomic, and functional analyses to comprehensively dissect the key differences between resistant lines and their susceptible progenitor, ‘Pei-Chiao’. The study found that resistant lines harbor large deletions on chromosome 4 or chromosome 5, resulting in reduced copy numbers of two autoinhibited Ca2+ ATPase genes. These calcium pumps function as negative regulators in salicylic acid–mediated immune responses. Using a virus-induced gene silencing system developed by Dr. Yeh’s team, suppression of these genes in the susceptible line enhanced salicylic acid–mediated immunity and significantly mitigated disease symptoms, confirming that the two genes act as critical susceptibility genes in banana. This work highlights the important role of chromosomal structural variation in banana mutation breeding and provides actionable genomic targets for precision breeding of disease-resistant cultivars.

Systemic acquired resistance (SAR) is an induced immune response in plants that is triggered by pathogen infection to protect uninfected tissues against subsequent threats. N-hydroxypipecolic acid (NHP) is a key small molecule required for the establishment of SAR in plants; however, the critical regulators involved in this pathway remain incompletely understood. Through a reverse genetic screen, we identified the Arabidopsis DAWDLE as being required for NHP-induced systemic resistance. Our findings show that loss of DAWDLE compromises NHP-induced SAR-associated gene expression, as well as the enhanced expression of PATHOGENESIS-RELATED GENE 1(PR1) following bacterial pathogen challenge. This study reports a previously unrecognized component involved in systemic acquired resistance beyond its established roles in plant development and small RNA biogenesis, and expands our understanding of plant defense priming.

Type 2 innate lymphoid cells (ILC2s) regulate the proliferation of preadipocytes that give rise to beige adipocytes. Whether and how ILC2 downstream Th2 cytokines control beige adipogenesis remain unclear. We used cell systems and genetic models to examine the mechanism through which IL-13, an ILC2-derived Th2 cytokine, controls beige adipocyte differentiation. IL-13 priming in preadipocytes drove beige adipogenesis by upregulating beige-promoting metabolic programs, including mitochondrial oxidative metabolism and PPARγ-related pathways. The latter was mediated by increased expression and activity of PPARγ through the IL-13 receptor 1 (IL-13R1) downstream effectors STAT6 and p38 MAPK, respectively. Il13-KO or preadipocyte Il13ra1-KO mice were refractory to cold- or β3-adrenergic agonist-induced beiging in inguinal white adipose tissue, whereas Il4-KO mice showed no defects in beige adipogenesis. Il13-KO and Il13ra1-KO mouse models exhibited increased body weight and fat mass and dysregulated glucose metabolism but had a mild cold-intolerant phenotype, likely due to their intact brown adipocyte recruitment. We also found that genetic variants of human IL13RA1 were associated with BMI and type 2 diabetes. These results suggest that IL-13 signaling-regulated beige adipocyte function may play a predominant role in modulating metabolic homeostasis rather than in thermoregulation.

Using long-term data from large population-based cohorts, this study demonstrates that serum hepatitis B surface antigen (HBsAg) levels can effectively identify patients with inactive chronic hepatitis B who have a negligible risk of hepatocellular carcinoma. Patients with HBsAg levels below 100 IU/mL showed an annual HCC incidence well below the surveillance threshold and comparable to that of the general population, even among older individuals traditionally recommended for surveillance. These findings provide strong evidence for using HBsAg as a practical marker to optimise HCC surveillance strategies and to support the clinical definition of partial HBV cure.

Green algae, commonly used as a source of food nutrients, contain ulvan, which is a water-soluble sulfated heteropolysaccharide isolated from Ulva. Ulvan exhibits a range of biological properties, including antitumor, antiviral, anticoagulant, and immunomodulatory activities. Its sugar backbone consists of 1→4-linked disaccharide repeating units, which are categorized as ulvanobiuronic acids (types A3′S and B3′S) and ulvanobioses (types U3′S and U2S3′S). Despite its promising therapeutic potential, the detailed structure–activity relationship of ulvan remains unclear. In this study, an efficient strategy was developed, utilizing orthogonally protected α1→4-linked l-Rha-d-Glc, l-Rha-l-Ido, and l-Rha-d-Xyl derivatives as disaccharide building blocks to synthesize di-, tetra-, hexa-, and octasaccharides of types A3′S, B3′S, and U3′S. The immunomodulatory effects of these compounds were evaluated through cytokine induction experiments. The results revealed that only the B3′S and U3′S octasaccharides had a significant influence on the gene expression of IL-1β, IL-6, IL-10, GM-CSF, and G-CSF. This chemical glycobiology approach offers valuable insights into the biomedical applications of marine ulvan oligosaccharides.