Effects of Acute and Developmental Exposure to Bisphenol S on Chinese Medaka (Oryzias sinensis).

Bisphenol S (BPS), one of the substitutes for bisphenol A (BPA), is widely used in various commodities. The BPS concentrations in surface water have gradually increased in recent years, making it a predominant bisphenol analogue in the aquatic environment and raising concerns about its health and ecological effects on aquatic organisms. For this study, we conducted a 96 h acute toxicity test and a 15-day developmental exposure test to assess the adverse effects of BPS exposure in Chinese medaka (Oryzias sinensis), a new local aquatic animal model. The results indicate that the acute exposure of Chinese medaka embryos to BPS led to relatively low toxicity. However, developmental exposure to BPS was found to cause developmental abnormalities, such as decreased hatching rate and body length, at 15 dpf. A transcriptome analysis showed that exposure to different concentrations of bisphenol S often induced different reactions. In summary, environmental concentrations of BPS can have adverse effects on the hatching and physical development of Chinese medaka, and further attention needs to be paid to the potential toxicity of environmental BPS.

Synchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders.

Highly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.

Marginal effects of public health measures and COVID-19 disease burden in China: A large-scale modelling study.

China had conducted some of the most stringent public health measures to control the spread of successive SARS-CoV-2 variants. However, the effectiveness of these measures and their impacts on the associated disease burden have rarely been quantitatively assessed at the national level. To address this gap, we developed a stochastic age-stratified metapopulation model that incorporates testing, contact tracing and isolation, based on 419 million travel movements among 366 Chinese cities. The study period for this model began from September 2022. The COVID-19 disease burden was evaluated, considering 8 types of underlying health conditions in the Chinese population. We identified the marginal effects between the testing speed and reduction in the epidemic duration. The findings suggest that assuming a vaccine coverage of 89%, the Omicron-like wave could be suppressed by 3-day interval population-level testing (PLT), while it would become endemic with 4-day interval PLT, and without testing, it would result in an epidemic. PLT conducted every 3 days would not only eliminate infections but also keep hospital bed occupancy at less than 29.46% (95% CI, 22.73-38.68%) of capacity for respiratory illness and ICU bed occupancy at less than 58.94% (95% CI, 45.70-76.90%) during an outbreak. Furthermore, the underlying health conditions would lead to an extra 2.35 (95% CI, 1.89-2.92) million hospital admissions and 0.16 (95% CI, 0.13-0.2) million ICU admissions. Our study provides insights into health preparedness to balance the disease burden and sustainability for a country with a population of billions.

Quartet RNA reference materials improve the quality of transcriptomic data through ratio-based profiling.

Certified RNA reference materials are indispensable for assessing the reliability of RNA sequencing to detect intrinsically small biological differences in clinical settings, such as molecular subtyping of diseases. As part of the Quartet Project for quality control and data integration of multi-omics profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets between two samples, providing cross-platform and cross-laboratory 'ground truth'. Investigation of the intrinsically subtle biological differences among the Quartet samples enables sensitive assessment of cross-batch integration of transcriptomic measurements at the ratio level. The Quartet RNA reference materials, combined with the ratio-based reference datasets, can serve as unique resources for assessing and improving the quality of transcriptomic data in clinical and biological settings.

Multi-omics data integration using ratio-based quantitative profiling with Quartet reference materials.

Characterization and integration of the genome, epigenome, transcriptome, proteome and metabolome of different datasets is difficult owing to a lack of ground truth. Here we develop and characterize suites of publicly available multi-omics reference materials of matched DNA, RNA, protein and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters. These references provide built-in truth defined by relationships among the family members and the information flow from DNA to RNA to protein. We demonstrate how using a ratio-based profiling approach that scales the absolute feature values of a study sample relative to those of a concurrently measured common reference sample produces reproducible and comparable data suitable for integration across batches, labs, platforms and omics types. Our study identifies reference-free 'absolute' feature quantification as the root cause of irreproducibility in multi-omics measurement and data integration and establishes the advantages of ratio-based multi-omics profiling with common reference materials.

Association of vaccination, international travel, public health and social measures with lineage dynamics of SARS-CoV-2.

Continually emerging SARS-CoV-2 variants of concern that can evade immune defenses are driving recurrent epidemic waves of COVID-19 globally. However, the impact of measures to contain the virus and their effect on lineage diversity dynamics are poorly understood. Here, we jointly analyzed international travel, public health and social measures (PHSM), COVID-19 vaccine rollout, SARS-CoV-2 lineage diversity, and the case growth rate (GR) from March 2020 to September 2022 across 63 countries. We showed that despite worldwide vaccine rollout, PHSM are effective in mitigating epidemic waves and lineage diversity. An increase of 10,000 monthly travelers in a single country-to-country route between endemic countries corresponds to a 5.5% (95% CI: 2.9 to 8.2%) rise in local lineage diversity. After accounting for PHSM, natural immunity from previous infections, and waning immunity, we discovered a negative association between the GR of cases and adjusted vaccine coverage (AVC). We also observed a complex relationship between lineage diversity and vaccine rollout. Specifically, we found a significant negative association between lineage diversity and AVC at both low and high levels but not significant at the medium level. Our study deepens the understanding of population immunity and lineage dynamics for future pandemic preparedness and responsiveness.

Transcriptome Analysis of the Developmental Effects of Bisphenol F Exposure in Chinese Medaka (Oryzias sinensis).

Bisphenol F (BPF) has been used in the syntheses of polymers, which are widely used in coatings, varnishes, adhesives, and other plastics. During the past decades, BPF contamination in the aquatic environment has dramatically increased due to its release from manmade products. Concerns have driven much attention to whether it may adversely impact aquatic lives or human beings. The present study performed an acute toxic exposure experiment and a 15 d developmental exposure of BPF at environmental concentrations (20, 200, and 2000 ng/L) using Chinese medaka (Oryzias sinensis). In the acute toxic exposure, the LC50 of BPF to Chinese medaka is 87.90 mg/L at 96 h. Developmental exposure induced a significant increase in the frequency of larvae with abnormalities in the 2000 ng/L BPF group compared to the control group. Transcriptomic analysis of the whole larvae revealed 565 up-regulated and 493 down-regulated genes in the 2000 ng/L BPF exposure group. Analysis of gene ontology and KEGG pathways enrichments indicated endocrine disorders to be associated with BPF-induced developmental toxicity. The present results suggest that BPF is developmentally toxic at 2000 ng/L concentration in Chinese medaka and causes endocrine-related aberrations in the transcriptional network of genes.

Optimization of Population-Level Testing, Contact Tracing, and Isolation in Emerging COVID-19 Outbreaks: a Mathematical Modeling Study - Tonghua City and Beijing Municipality, China, 2021-2022.

Introduction: The transmissibility of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant poses challenges for the existing measures containing the virus in China. In response, this study investigates the effectiveness of population-level testing (PLT) and contact tracing (CT) to help curb coronavirus disease 2019 (COVID-19) resurgences in China. Methods: Two transmission dynamic models (i.e. with and without age structure) were developed to evaluate the effectiveness of PLT and CT. Extensive simulations were conducted to optimize PLT and CT strategies for COVID-19 control and surveillance. Results: Urban Omicron resurgences can be controlled by multiple rounds of PLT, supplemented by CT - as long as testing is frequent. This study also evaluated the time needed to detect COVID-19 cases for surveillance under different routine testing rates. The results show that there is a 90% probability of detecting COVID-19 cases within 3 days through daily testing. Otherwise, it takes around 7 days to detect COVID-19 cases at a 90% probability level if biweekly testing is used. Routine testing applied to the age group 21-60 for COVID-19 surveillance would achieve similar performance to that applied to all populations. Discussion: Our analysis evaluates potential PLT and CT strategies for COVID-19 control and surveillance.

Bidirectional Movement of Emerging H5N8 Avian Influenza Viruses Between Europe and Asia via Migratory Birds Since Early 2020.

Migratory birds play a critical role in the rapid spread of highly pathogenic avian influenza (HPAI) H5N8 virus clade 2.3.4.4 across Eurasia. Elucidating the timing and pattern of virus transmission is essential therefore for understanding the spatial dissemination of these viruses. In this study, we surveyed >27,000 wild birds in China, tracked the year-round migration patterns of 20 bird species across China since 2006, and generated new HPAI H5N8 virus genomic data. Using this new data set, we investigated the seasonal transmission dynamics of HPAI H5N8 viruses across Eurasia. We found that introductions of HPAI H5N8 viruses to different Eurasian regions were associated with the seasonal migration of wild birds. Moreover, we report a backflow of HPAI H5N8 virus lineages from Europe to Asia, suggesting that Europe acts as both a source and a sink in the global HPAI virus transmission network.

Measuring the effects of COVID-19-related disruption on dengue transmission in southeast Asia and Latin America: a statistical modelling study.

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented disruption to society, which indirectly affects infectious disease dynamics. We aimed to assess the effects of COVID-19-related disruption on dengue, a major expanding acute public health threat, in southeast Asia and Latin America. METHODS: We assembled data on monthly dengue incidence from WHO weekly reports, climatic data from ERA5, and population variables from WorldPop for 23 countries between January, 2014 and December, 2019 and fit a Bayesian regression model to explain and predict seasonal and multi-year dengue cycles. We compared model predictions with reported dengue data January to December, 2020, and assessed if deviations from projected incidence since March, 2020 are associated with specific public health and social measures (from the Oxford Coronavirus Government Response Tracer database) or human movement behaviours (as measured by Google mobility reports). FINDINGS: We found a consistent, prolonged decline in dengue incidence across many dengue-endemic regions that began in March, 2020 (2·28 million cases in 2020 vs 4·08 million cases in 2019; a 44·1% decrease). We found a strong association between COVID-19-related disruption (as measured independently by public health and social measures and human movement behaviours) and reduced dengue risk, even after taking into account other drivers of dengue cycles including climatic and host immunity (relative risk 0·01-0·17, p<0·01). Measures related to the closure of schools and reduced time spent in non-residential areas had the strongest evidence of association with reduced dengue risk, but high collinearity between covariates made specific attribution challenging. Overall, we estimate that 0·72 million (95% CI 0·12-1·47) fewer dengue cases occurred in 2020 potentially attributable to COVID-19-related disruption. INTERPRETATION: In most countries, COVID-19-related disruption led to historically low dengue incidence in 2020. Continuous monitoring of dengue incidence as COVID-19-related restrictions are relaxed will be important and could give new insights into transmission processes and intervention options. FUNDING: National Key Research and Development Program of China and the Medical Research Council.

Generation of an induced pluripotent stem cell line ATCi001-A from a three-year-old Chinese girl with Brown-Vialetto-Van Laere syndrome-2.

Brown-Vialetto-Van Laere syndrome-2 is a rare neurological disorder characterized by sensory neuronopathy and pontobulbar palsy, caused by variations in SLC52A2 and SLC52A3 genes, encoding the riboflavin transporters. By reprogramming with SOX2, KLF4, c-MYC and OCT3/4, we generated an iPSC cell line from peripheral blood mononuclear cells (PBMCs) collected from a three-year-old Chinese female individual to be used as a disease model. By fully examination, the resulting iPSCs expressed pluripotency-associated stem cell markers, maintained the normal karyotype and proliferative potential for three-germ layer differentiation.

Collection on reports of molecules linked to epithelial-mesenchymal transition in the process of treating metastasizing cancer: a narrative review.

Epithelial-mesenchymal transition (EMT) is a morphological process in which epithelial cells transform into mesenchymal cells via a specific procedure. EMT plays an important role in the cancer invasion-metastasis cascade and the current treatment of metastatic cancer, influences the migration, polarity, and adhesion of tumor cells, promotes their migration, invasiveness, anti-apoptotic ability. It contributes to the changes of the tumor microenvironment and suppresses the sensitivity of tumor cells to chemotherapy, causing cancer metastasis and worse, hindering the control and therapy of it. This paper reviews the mechanisms, detection, and treatments of cancer metastasis that have been identified and applied to date, summarizes the EMT-related biological molecules, providing a reference for EMT-targeted research and therapy. As EMT is significant in the progress of tumor metastasis, it is meaningful for the therapy and control of metastatic cancer to understand the mechanism of EMT at the molecular level. We summarized the mechanisms, detection and therapeutic implications of EMT, listed the research progress of molecules like genes, miRNAs, signaling pathways in EMT. We also discussed the prospects of EMT-targeted treatment in cancer metastasis interventions and the challenges the treatment and researches are facing. The summary is conducive to the treatment and further research of EMT and metastatic cancer.

Associations between changes in population mobility in response to the COVID-19 pandemic and socioeconomic factors at the city level in China and country level worldwide: a retrospective, observational study.

BACKGROUND: Until broad vaccination coverage is reached and effective therapeutics are available, controlling population mobility (ie, changes in the spatial location of a population that affect the spread and distribution of pathogens) is one of the major interventions used to reduce transmission of SARS-CoV-2. However, population mobility differs across locations, which could reduce the effectiveness of pandemic control measures. Here we assess the extent to which socioeconomic factors are associated with reductions in population mobility during the COVID-19 pandemic, at both the city level in China and at the country level worldwide. METHODS: In this retrospective, observational study, we obtained anonymised daily mobile phone location data for 358 Chinese cities from Baidu, and for 121 countries from Google COVID-19 Community Mobility Reports. We assessed the intra-city movement intensity, inflow intensity, and outflow intensity of each Chinese city between Jan 25 (when the national emergency response was implemented) and Feb 18, 2020 (when population mobility was lowest) and compared these data to the corresponding lunar calendar period from the previous year (Feb 5 to March 1, 2019). Chinese cities were classified into four socioeconomic index (SEI) groups (high SEI, high-middle SEI, middle SEI, and low SEI) and the association between socioeconomic factors and changes in population mobility were assessed using univariate and multivariable linear regression. At the country level, we compared six types of mobility (residential, transit stations, workplaces, retail and recreation, parks, and groceries and pharmacies) 35 days after the implementation of the national emergency response in each country and compared these to data from the same day of the week in the baseline period (Jan 3 to Feb 6, 2020). We assessed associations between changes in the six types of mobility and the country's sociodemographic index using univariate and multivariable linear regression. FINDINGS: The reduction in intra-city movement intensity in China was stronger in cities with a higher SEI than in those with a lower SEI (r=-0·47, p<0·0001). However, reductions in inter-city movement flow (both inflow and outflow intensity) were not associated with SEI and were only associated with government control measures. In the country-level analysis, countries with higher sociodemographic and Universal Health Coverage indexes had greater reductions in population mobility (ie, in transit stations, workplaces, and retail and recreation) following national emergency declarations than those with lower sociodemographic and Universal Health Coverage indexes. A higher sociodemographic index showed a greater reduction in mobility in transit stations (r=-0·27, p=0·0028), workplaces (r=-0·34, p=0·0002), and areas retail and recreation (rxs=-0·30, p=0·0012) than those with a lower sociodemographic index. INTERPRETATION: Although COVID-19 outbreaks are more frequently reported in larger cities, our analysis shows that future policies should prioritise the reduction of risks in areas with a low socioeconomic level-eg, by providing financial assistance and improving public health messaging. However, our study design only allows us to assess associations, and a long-term study is needed to decipher causality. FUNDING: Chinese Ministry of Science and Technology, Research Council of Norway, Beijing Municipal Science & Technology Commission, Beijing Natural Science Foundation, Beijing Advanced Innovation Program for Land Surface Science, National Natural Science Foundation of China, China Association for Science and Technology.

Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient.

We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.

Association between coronavirus disease 2019 (COVID-19) and long-term exposure to air pollution: Evidence from the first epidemic wave in China.

People with chronic obstructive pulmonary disease, cardiovascular disease, or hypertension have a high risk of developing severe coronavirus disease 2019 (COVID-19) and of COVID-19 mortality. However, the association between long-term exposure to air pollutants, which increases cardiopulmonary damage, and vulnerability to COVID-19 has not yet been fully established. We collected data of confirmed COVID-19 cases during the first wave of the epidemic in mainland China. We fitted a generalized linear model using city-level COVID-19 cases and severe cases as the outcome, and long-term average air pollutant levels as the exposure. Our analysis was adjusted using several variables, including a mobile phone dataset, covering human movement from Wuhan before the travel ban and movements within each city during the period of the emergency response. Other variables included smoking prevalence, climate data, socioeconomic data, education level, and number of hospital beds for 324 cities in China. After adjusting for human mobility and socioeconomic factors, we found an increase of 37.8% (95% confidence interval [CI]: 23.8%-52.0%), 32.3% (95% CI: 22.5%-42.4%), and 14.2% (7.9%-20.5%) in the number of COVID-19 cases for every 10-µg/m3 increase in long-term exposure to NO2, PM2.5, and PM10, respectively. However, when stratifying the data according to population size, the association became non-significant. The present results are derived from a large, newly compiled and geocoded repository of population and epidemiological data relevant to COVID-19. The findings suggested that air pollution may be related to population vulnerability to COVID-19 infection, although the extent to which this relationship is confounded by city population density needs further exploration.

Rising challenge of multidrug-resistant tuberculosis in China: a predictive study using Markov modeling.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is on the rise in China. This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures. METHODS: Eight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100 000 people. The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis (DS-TB+) were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not. RESULTS: Without any intervention changes to current conditions, the prevalence of DS-TB+ was projected to decline 67.7% by 2050, decreasing to 20 per 100 000 people, whereas that of MDR-TB was expected to triple to 58/100 000. Furthermore, 86.2% of the MDR-TB cases would be left untreated by the year of 2050. In the case where MDR-TB detection rate reaches 50% or 70% at 5% per year, the decline in prevalence of MDR-TB would be 25.9 and 36.2% respectively. In the case where treatment coverage was improved to 70% or 100% at 5% per year, MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%, respectively. If both detection rate and treatment coverage reach 70%, the prevalence of MDR-TB by 2050 would be reduced to 28/100 000 by a 51.7% reduction. CONCLUSIONS: MDR-TB, especially untreated MDR-TB, would rise rapidly under China's current MDR-TB control strategies. Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.

An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China.

Responding to an outbreak of a novel coronavirus [agent of coronavirus disease 2019 (COVID-19)] in December 2019, China banned travel to and from Wuhan city on 23 January 2020 and implemented a national emergency response. We investigated the spread and control of COVID-19 using a data set that included case reports, human movement, and public health interventions. The Wuhan shutdown was associated with the delayed arrival of COVID-19 in other cities by 2.91 days. Cities that implemented control measures preemptively reported fewer cases on average (13.0) in the first week of their outbreaks compared with cities that started control later (20.6). Suspending intracity public transport, closing entertainment venues, and banning public gatherings were associated with reductions in case incidence. The national emergency response appears to have delayed the growth and limited the size of the COVID-19 epidemic in China, averting hundreds of thousands of cases by 19 February (day 50).

Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies.

We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.