Study of Male Denisovan from Taiwan in Science

A groundbreaking study published in Science confirmed that a fossil discovered in Taiwan belonged to a male Denisovan, marking the first molecular evidence of this ancient human lineage in low-latitude regions. The research was led by an international team of 15 scientists, including Associate Professor Cheng-Hsiu Tsai from National Taiwan University and collaborators from Taiwan, Japan, and Denmark. Using ancient protein analysis (paleoproteomics), the team identified Denisovan traits in the fossil and further determined the individual’s sex by detecting the male-specific amelogenin Y protein.

The discovery is significant because Denisovan fossils with molecular confirmation have so far been limited to Siberia and Tibet, even though genetic studies suggest their presence across East Asia, Southeast Asia, and Oceania. Until now, warmer regions lacked direct fossil evidence. This Taiwanese specimen therefore fills a critical gap, expanding our understanding of Denisovan distribution and the complexity of human evolution.

While ancient DNA could not be retrieved, the successful extraction of proteins offered crucial molecular insights. The fossil, curated at the National Museum of Natural Science in Taiwan, was recovered from the seabed between Taiwan and the Penghu Islands, where other prehistoric animal remains such as Stegodon have also been found. The findings highlight the scientific importance of Taiwan’s fossil record for studying ancient humans and evolutionary history.

This is not the first time fossils from Taiwan have drawn global attention. In 2023, Tsai’s lab contributed to another Science paper on island extinctions, demonstrating the international impact of Taiwan’s paleontological research. Together, these discoveries reaffirm Taiwan’s role in uncovering key chapters of life’s evolutionary journey.

NTU Launches Global Research Center

The Max Planck-IAS-NTU Center (MPC) for Particle Physics, Cosmology, and Geometry has been founded through cooperation between the Max Planck Society in Germany, the Institute for Advanced Study (IAS) in Princeton, and National Taiwan University (NTU). The Center will begin operations in July 2025 with five years of initial funding. An opening symposium will be held at NTU in September 2025, followed by a kick-off conference at IAS in March 2026.

Led by co-directors Johannes Henn (Max Planck Institute for Physics), Nima Arkani-Hamed (IAS), and Daniel Baumann (NTU), the Center unites leading scholars in particle physics, cosmology, and geometry. Their goal is to develop new frameworks for quantum field theory, study particle interactions, and explore the origins of the Universe.

The initiative will act as a global hub for collaboration, engaging faculty, postdoctoral scholars, and students from around the world. Planned activities include international workshops, summer schools, and research exchanges across institutions and disciplines.

Funded by NTU and Taiwan’s National Science and Technology Council, the Center is part of the broader Max Planck Centers program. NTU President Wen-Chang Chen emphasized that this collaboration strengthens Taiwan’s role in global science and will spark exciting new discoveries in fundamental physics.

NTU Achieves Beating Heart Transplant

National Taiwan University Hospital (NTUH) has successfully completed the world’s first beating heart transplant with zero ischemic time, with the patient recovering smoothly and being discharged. This groundbreaking surgery was recently featured in the Journal of Thoracic and Cardiovascular Surgery Techniques, marking a major advancement in global heart transplantation.

Since performing Taiwan’s first heart transplant in 1990, National Taiwan University Hospital has completed over 700 transplants, establishing itself as a national leader in the field. This extensive experience laid the foundation for the innovative surgery, which represents a paradigm shift in organ transplantation.

Unlike traditional heart transplants that require cold storage and inevitably involve ischemic time, the new method maintains continuous perfusion, keeping the donor heart beating throughout the procedure. This approach eliminates ischemic injury, minimizes reperfusion damage, and is expected to significantly improve both heart function and patient survival rates.

As a leading force in cardiac transplantation in Asia, National Taiwan University Hospital’s achievement opens new possibilities for organ preservation and transplant success worldwide. Moving forward, the hospital will continue advancing its techniques and technologies, enabling more patients to benefit from zero-ischemic-time transplantation.

NTU–Japan Study Uncovers Adzuki Bean Origins

A multinational team led by Prof. Cheng-Ruei Lee of National Taiwan University (NTU) has revealed that domesticated adzuki beans originated in Japan. Their findings, published in Science, show that agriculture in Japan began thousands of years earlier than previously believed, offering new insights into the history of farming in East Asia.

Working with Dr. Ken Naito of Japan’s National Agriculture and Food Research Organization (NARO), the team analyzed genetic material from adzuki beans preserved in Japan’s national germplasm collections. The results provide the first genomic evidence that the Jōmon people, long thought to be solely foragers, practiced early crop selection between 3,000 and 5,000 years ago.

The researchers also identified genes responsible for seed color and domestication traits, finding mutations that date back nearly 10,000 years. This suggests that adzuki bean trait selection began far earlier than previously assumed and demonstrates how genomics can complement archaeological research.

This study, supported by Taiwan’s National Science and Technology Council, Academia Sinica, and NTU, not only reshapes our understanding of Japanese agriculture but also opens new directions for crop breeding and plant domestication research.

Link to the article in Science: https://www.science.org/doi/10.1126/science.ads2871

NTU Hospital links metabolism to mortality

Liver disease remains a major health issue in Taiwan, driven by the high prevalence of chronic hepatitis B (HBV) and hepatitis C (HCV). A research team at National Taiwan University (NTU) Hospital, led by Vice Superintendent Jia-Horng Kao, has been investigating the interaction between hepatitis viruses and metabolic abnormalities. Their latest findings, published in the Journal of Hepatology, have drawn global attention.

Prof. Tung-Hung Su and Dr. Shang-Chin Huang reported that HBV patients with metabolic syndrome face a significantly higher risk of death. In contrast, those with only simple fatty liver but no other metabolic issues have a 50% lower long-term mortality rate. For HCV, Prof. Chen-Hua Liu showed that even after patients are cured with direct-acting antiviral (DAA) therapy, those with metabolic-associated fatty liver disease (e.g., diabetes, hypertension, obesity) remain at a substantially higher risk of developing hepatocellular carcinoma (HCC). These findings stress the importance of early intervention for metabolic abnormalities alongside antiviral treatment.

Prof. Jun-Ren Liu, Director of National Taiwan University (NTU) Hospital’s Hepatitis Research Center, emphasized that in addition to controlling hepatitis viruses, patients must also manage metabolic health through weight control, diet, and regular monitoring. Timely screening for blood pressure, blood sugar, and lipid abnormalities, combined with regular liver ultrasound, can help reduce risks of cirrhosis and liver cancer and improve long-term prognosis.

Full articles:

https://www.journal-of-hepatology.eu/article/S0168-8278(24)02763-6/fulltext
https://www.journal-of-hepatology.eu/article/S0168-8278(24)02578-9/fulltext

Study: Sucralose Harms Sperm and Hormones

Further context

This article is a repost from News-Medical, covering a recent study led the research team of Professor Shih-Min Hsia at Taipei Medical University (TMU)’s College of Nutrition. The study investigates the potential effects of sucralose on male reproductive health. The research has also been featured by New York Post and MSN, highlighting the growing international attention to TMU’s contributions to preventive and translational medicine.

Male infertility is a global health concern, impacting 8% to 12% of couples and contributing to nearly half of infertility cases worldwide. Male infertility is affected by hormonal, environmental, and genetic factors that impede spermatogenesis and reproductive function. Dietary and lifestyle changes, including the elevated intake of non-nutritive sweeteners (NNSs) and sugar-sweetened beverages, are among these factors implicated in the growing prevalence of infertility.

Sucralose, an NNS, constitutes 30% of the sweetener market in the United States. Although sucralose has antibacterial properties and lower calories, there are emerging concerns about potential health risks and environmental persistence. It is also a persistent contaminant in aquatic systems, with studies revealing its consistent presence throughout the urban water cycle. Notably, the study highlights concerns about sucralose-6-acetate, a genotoxic byproduct of sucralose manufacturing and metabolism, which may exacerbate health and environmental risks. Despite research on NNSs, data on potential links between sucralose and male infertility are limited.

About the study

In the present study, researchers evaluated the effects of sucralose on male reproductive health. Male Sprague-Dawley (SD) rats, aged six weeks, were acclimated for a week under controlled conditions and subsequently randomized to one of four experimental groups. Sucralose was administered at 1.5 mg/kg, 15 mg/kg, 45 mg/kg, or 90 mg/kg for two months.

The controls received deionized water. Body weight was monitored weekly for eight weeks. At the end of the study, animals were euthanized, and blood samples were collected for biochemical analyses. Organs such as the liver, spleen, heart, testes, epididymis, and kidneys were harvested for histopathological evaluation.

The cauda epididymis was cut into pieces and briefly maintained in culture medium, and the supernatant was used for sperm motility analysis. Sperm samples were subject to a Western blot analysis to evaluate DNA damage markers. Besides, enzyme-linked immunosorbent assay was used to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and Kisspeptin1 (KISS1).

Chemiluminescence immunoassays were performed to measure serum testosterone, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Further, mouse Sertoli cells (TM4) and Leydig cells (TM3) were treated with varying concentrations of sucralose for 24–72 hours. These cells were subject to intracellular reactive oxygen species (ROS), cell viability, and Western blot analyses. To assess autophagy-lysosome dysfunction, researchers used Bafilomycin A1, a compound that blocks lysosomal acidification, revealing impaired fusion of autophagosomes and lysosomes.

The Kolmogorov-Smirnov test assessed data normality. Non-parametric tests were applied for data violating normality assumptions. A two-way analysis of variance was performed to evaluate the effects of sucralose and exposure duration. Group differences were compared using the Mann-Whitney U test or the Student’s t-test.

Findings

TM3 and TM4 cells exposed to varying sucralose concentrations (1 μM, 10 μM, 100 μM, 1000 μM, and 10,000 μM) had significantly lower cell viability. Cells also showed higher levels of microtubule-associated protein 1A/1B light chain 3B, form II (LC3B-II) at 1000 or 10,000 μM and slightly lower p62 levels. These changes, combined with reduced cathepsin B (a lysosomal enzyme), suggest impaired autophagic degradation. Following sucralose treatment, there was a significantly lower expression of cathepsin B, indicative of impaired lysosomal function.

ROS levels in TM3 and TM4 cells after sucralose exposure at 1 mM, 2.5 mM, 5 mM, 7.5 mM, or 10 mM were significantly higher; sucralose-treated cells also had elevated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and heme-oxygenase 1 (HO-1) levels, suggesting an increase in oxidative stress. Notably, exposed cells had a reduction in taste receptor type 1 member 3 (T1R3) protein expression.

Moreover, co-treatment with a known T1R3 antagonist (lactisole) repressed T1R3 expression more than sucralose treatment alone. To further examine the relevance of T1R3 modulation, rat pituitary adenoma cells (RC-4B/C) were treated with sucralose, with or without lactisole co-treatment. This revealed a significant reduction in LH levels dose-dependently. Lactisole co-treatment exacerbated this suppression, especially at lower sucralose levels.

SD rats exposed to sucralose showed no differences in body weight, AST or ALT levels, and heart and liver indices between groups. Although the appearance of reproductive organs was not remarkably different, exposed animals had significantly lower epididymis and testis indices. Further, rats showed significant reductions in serum testosterone and LH levels and serum and testicular KISS1 levels. KISS1, a key regulator of the hypothalamic-pituitary-gonadal (HPG) axis, is critical for initiating puberty and maintaining reproductive hormone balance; its suppression may directly contribute to impaired fertility.

Sucralose exposure also reduced protein levels of T1R3 in the testes. Exposed animals had abnormal sperm morphology (with coiled and bent tails) and lower sperm viability. Histological examination of the testes showed changes in the seminiferous epithelium, including severe vacuolization, disrupted germ cell organization, and nuclear condensation.

DNA damage was also observed in sperm, indicative of cellular impairment. The testes of sucralose-exposed animals had higher levels of LC3B and lower levels of p62, suggesting changes in autophagy. Moreover, exposed animals had higher serum and testicular levels of malondialdehyde, indicating increased lipid peroxidation.

Conclusions

Taken together, sucralose exposure adversely affects male reproductive outcomes in rats by inducing oxidative stress, causing DNA damage, and disrupting autophagy. The study notes that in vitro doses (up to 10 mM) likely exceed typical human dietary exposure, warranting caution in extrapolating results to real-world intake levels.

The findings underscore the need for careful evaluation of dietary NNSs and call for better food safety regulations to alleviate potential risks. Additionally, the environmental persistence of sucralose and its byproduct, sucralose-6-acetate, highlights broader ecological concerns.

Further studies are required to examine dose-response relationships, long-term effects, and underlying molecular mechanisms to comprehensively delineate the adverse effects of sucralose.

Look for More Information

Original Study: Exposure to Sucralose and Its Effects on Testicular Damage and Male Infertility: Insights into Oxidative Stress and Autophagy

News: Sucralose disrupts male fertility by damaging sperm and altering hormones in animal study

Sucralose Harms Sperm and Hormones: Study

Male infertility is a global health concern, impacting 8% to 12% of couples and contributing to nearly half of infertility cases worldwide. Male infertility is affected by hormonal, environmental, and genetic factors that impede spermatogenesis and reproductive function. Dietary and lifestyle changes, including the elevated intake of non-nutritive sweeteners (NNSs) and sugar-sweetened beverages, are among these factors implicated in the growing prevalence of infertility.

Sucralose, an NNS, constitutes 30% of the sweetener market in the United States. Although sucralose has antibacterial properties and lower calories, there are emerging concerns about potential health risks and environmental persistence. It is also a persistent contaminant in aquatic systems, with studies revealing its consistent presence throughout the urban water cycle. Notably, the study highlights concerns about sucralose-6-acetate, a genotoxic byproduct of sucralose manufacturing and metabolism, which may exacerbate health and environmental risks. Despite research on NNSs, data on potential links between sucralose and male infertility are limited.

About the study

In the present study, researchers evaluated the effects of sucralose on male reproductive health. Male Sprague-Dawley (SD) rats, aged six weeks, were acclimated for a week under controlled conditions and subsequently randomized to one of four experimental groups. Sucralose was administered at 1.5 mg/kg, 15 mg/kg, 45 mg/kg, or 90 mg/kg for two months.

The controls received deionized water. Body weight was monitored weekly for eight weeks. At the end of the study, animals were euthanized, and blood samples were collected for biochemical analyses. Organs such as the liver, spleen, heart, testes, epididymis, and kidneys were harvested for histopathological evaluation.

The cauda epididymis was cut into pieces and briefly maintained in culture medium, and the supernatant was used for sperm motility analysis. Sperm samples were subject to a Western blot analysis to evaluate DNA damage markers. Besides, enzyme-linked immunosorbent assay was used to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and Kisspeptin1 (KISS1).

Chemiluminescence immunoassays were performed to measure serum testosterone, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Further, mouse Sertoli cells (TM4) and Leydig cells (TM3) were treated with varying concentrations of sucralose for 24–72 hours. These cells were subject to intracellular reactive oxygen species (ROS), cell viability, and Western blot analyses. To assess autophagy-lysosome dysfunction, researchers used Bafilomycin A1, a compound that blocks lysosomal acidification, revealing impaired fusion of autophagosomes and lysosomes.

The Kolmogorov-Smirnov test assessed data normality. Non-parametric tests were applied for data violating normality assumptions. A two-way analysis of variance was performed to evaluate the effects of sucralose and exposure duration. Group differences were compared using the Mann-Whitney U test or the Student’s t-test.

Findings

TM3 and TM4 cells exposed to varying sucralose concentrations (1 μM, 10 μM, 100 μM, 1000 μM, and 10,000 μM) had significantly lower cell viability. Cells also showed higher levels of microtubule-associated protein 1A/1B light chain 3B, form II (LC3B-II) at 1000 or 10,000 μM and slightly lower p62 levels. These changes, combined with reduced cathepsin B (a lysosomal enzyme), suggest impaired autophagic degradation. Following sucralose treatment, there was a significantly lower expression of cathepsin B, indicative of impaired lysosomal function.

ROS levels in TM3 and TM4 cells after sucralose exposure at 1 mM, 2.5 mM, 5 mM, 7.5 mM, or 10 mM were significantly higher; sucralose-treated cells also had elevated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and heme-oxygenase 1 (HO-1) levels, suggesting an increase in oxidative stress. Notably, exposed cells had a reduction in taste receptor type 1 member 3 (T1R3) protein expression.

Moreover, co-treatment with a known T1R3 antagonist (lactisole) repressed T1R3 expression more than sucralose treatment alone. To further examine the relevance of T1R3 modulation, rat pituitary adenoma cells (RC-4B/C) were treated with sucralose, with or without lactisole co-treatment. This revealed a significant reduction in LH levels dose-dependently. Lactisole co-treatment exacerbated this suppression, especially at lower sucralose levels.

SD rats exposed to sucralose showed no differences in body weight, AST or ALT levels, and heart and liver indices between groups. Although the appearance of reproductive organs was not remarkably different, exposed animals had significantly lower epididymis and testis indices. Further, rats showed significant reductions in serum testosterone and LH levels and serum and testicular KISS1 levels. KISS1, a key regulator of the hypothalamic-pituitary-gonadal (HPG) axis, is critical for initiating puberty and maintaining reproductive hormone balance; its suppression may directly contribute to impaired fertility.

Sucralose exposure also reduced protein levels of T1R3 in the testes. Exposed animals had abnormal sperm morphology (with coiled and bent tails) and lower sperm viability. Histological examination of the testes showed changes in the seminiferous epithelium, including severe vacuolization, disrupted germ cell organization, and nuclear condensation.

DNA damage was also observed in sperm, indicative of cellular impairment. The testes of sucralose-exposed animals had higher levels of LC3B and lower levels of p62, suggesting changes in autophagy. Moreover, exposed animals had higher serum and testicular levels of malondialdehyde, indicating increased lipid peroxidation.

Conclusions

Taken together, sucralose exposure adversely affects male reproductive outcomes in rats by inducing oxidative stress, causing DNA damage, and disrupting autophagy. The study notes that in vitro doses (up to 10 mM) likely exceed typical human dietary exposure, warranting caution in extrapolating results to real-world intake levels.

The findings underscore the need for careful evaluation of dietary NNSs and call for better food safety regulations to alleviate potential risks. Additionally, the environmental persistence of sucralose and its byproduct, sucralose-6-acetate, highlights broader ecological concerns.

Further studies are required to examine dose-response relationships, long-term effects, and underlying molecular mechanisms to comprehensively delineate the adverse effects of sucralose.

Look for More Information

Original Study: Exposure to Sucralose and Its Effects on Testicular Damage and Male Infertility: Insights into Oxidative Stress and Autophagy

News: Sucralose disrupts male fertility by damaging sperm and altering hormones in animal study

Further context

This article is a repost from News-Medical, covering a recent study led the research team of Professor Shih-Min Hsia at Taipei Medical University (TMU)’s College of Nutrition. The study investigates the potential effects of sucralose on male reproductive health. The research has also been featured by New York Post and MSN, highlighting the growing international attention to TMU’s contributions to preventive and translational medicine.

National Taiwan University Public Health Department Professor Guo Baihsu and International Research Team Identify Bipolar Disorder Susceptibility Genes in Landmark Global Study Published in Nature

Professor Guo Baihsu of NTU’s Department of Public Health and the Institute of Epidemiology and Preventive Medicine has contributed to a study under the Psychiatric Genomics Consortium, collaborating with researchers worldwide. The groundbreaking research was published in Nature on January 2025.

Bipolar disorder is a severe psychiatric condition that not only diminishes quality of life and functionality but also significantly increases suicide risk. Clinically, bipolar disorder is categorized into Bipolar Disorder I (BD-I), marked by episodes of mania and depression, and Bipolar Disorder II (BD-II), characterized by hypomania and depression. Despite its relatively high prevalence, the diagnosis of bipolar disorder typically takes an average of eight years, and its biological mechanisms remain poorly understood.

This study represents the largest multi-ethnic genomic investigation of bipolar disorder to date, analyzing data from 2.9 million individuals—including over 150,000 patients—from European, East Asian, African American, and Latino populations. By scanning 6.7 million common genetic variants, researchers identified 298 loci associated with increased risk for bipolar disorder—four times the number previously known. Advanced gene-mapping methods further pinpointed 36 genes with strong links to bipolar disorder. Additionally, the team discovered differences in genetic features among clinical, community, and self-report samples, which appear to correlate with the prevalence of BD-I and BD-II, highlighting the influence of data collection methods on research outcomes.

The research team also found that bipolar disorder-associated genetic signals are related to specific brain cells, including mid-GABAergic interneurons and medium spiny neurons in the prefrontal cortex and hippocampus, and unexpectedly, cells in the gut and pancreas may also be involved. Further studies are needed to elucidate the biological mechanisms underlying mood episodes in bipolar disorder. These findings promise to advance new therapies, early intervention strategies, and precision medicine, ultimately aiding clinicians in devising more effective treatment plans for patients.

National Taiwan University Identifies N-Cadherin as a Key Regulator of Cardiac Regeneration, Published in Nature Communications

Heart failure affects 23 million people globally, with limited treatment options. Unlike adult human hearts, which lack regenerative capacity, neonatal hearts retain the ability to repair damage. A research team led by Professor Kai-Jen Yang at NTU’s Institute of Pharmacology discovered that N-Cadherin, a neural cadherin protein, plays a crucial role in cardiomyocyte proliferation and heart regeneration.

Their study found that N-Cadherin levels are 2–3 times higher in neonatal cardiomyocytes than in adults and decline with age. Following heart injury, N-Cadherin expression increased, promoting cardiomyocyte proliferation. Loss of N-Cadherin reduced regeneration, while its overexpression reactivated cell cycling in adult mouse hearts, improving cardiac function post-myocardial infarction.

Mechanistically, N-Cadherin binds to β-Catenin, stabilizing its protein levels and activating Wnt signaling, which regulates genes essential for cardiac repair. These findings suggest that modulating N-Cadherin could serve as a novel heart failure therapy.

Truth About Dengue: How Accurate Are Global Disease Estimates?

As dengue fever continues to rise globally, accurate data on disease burden is essential for informed public health planning and resource allocation. A recent study led by Professor Wei-Cheng Lo of Taipei Medical University examines discrepancies between the Global Burden of Disease (GBD) estimates and reported dengue case data in 30 high-burden countries, calling attention to the need for improved methodologies in disease modeling.

Understanding the Gaps in Global Estimates

The study compared GBD’s model-generated dengue estimates with official surveillance data from countries including Brazil, India, Indonesia, China, and Taiwan. The findings revealed substantial differences: in some instances, GBD estimates were several hundred times higher than reported cases. For instance, in China and India, the GBD estimated 570 and 303 times more cases, respectively, than national health data indicated.

In countries like Taiwan and Argentina, where dengue outbreaks vary dramatically by year, GBD figures showed relatively steady trends, potentially overlooking the episodic nature of epidemic spikes.

Modeling Assumptions and Their Limitations

The observed discrepancies are linked to how the GBD constructs its estimates. These models account for underreporting by adjusting data based on known limitations in surveillance systems. However, many of these adjustments rely on data collected before 2010. In locations where diagnostic tools and case reporting have significantly improved in recent years—such as Taiwan—current estimates may not reflect these advancements.

Additionally, the smoothing algorithms used to illustrate long-term trends may downplay sharp increases in case numbers during outbreak years, especially in regions with cyclic epidemic patterns.

Implications for Public Health Policy

Reliable disease estimates are a crnerstone of health policy and planning. When estimates deviate significantly from local data, they can influence policy decisions and funding allocation. This study emphasizes the importance of aligning global modeling with recent,country-specific data to better support public health decision-making.

Recommendations for Improved Disease Burden Modeling

The authors advocate for more frequent updates to global health models and greater integration of real-time surveillance and diagnostic advancements. They also suggest that future models incorporate the cyclical behavior of diseases like dengue to better capture the reality of epidemic patterns.

Broader Considerations

While this research focuses on dengue, it raises important considerations for global disease burden estimation more broadly. Refining modeling approaches across disease areas will support more effective global health strategies and ensure resources are targeted where they are most needed.