Suitable fermentation temperature of forage sorghum silage increases greenhouse gas production: Exploring the relationship between temperature, microbial community, and gas production.

Silage is an excellent method of feed preservation; however, carbon dioxide, methane and nitrous oxide produced during fermentation are significant sources of agricultural greenhouse gases. Therefore, determining a specific production method is crucial for reducing global warming. The effects of four temperatures (10 °C, 20 °C, 30 °C, and 40 °C) on silage quality, greenhouse gas yield and microbial community composition of forage sorghum were investigated. At 20 °C and 30 °C, the silage has a lower pH value and a higher lactic acid content, resulting in higher silage quality and higher total gas production. In the first five days of ensiling, there was a significant increase in the production of carbon dioxide, methane, and nitrous oxide. After that, the output remained relatively stable, and their production at 20 °C and 30 °C was significantly higher than that at 10 °C and 40 °C. Firmicutes and Proteobacteria were the predominant silage microorganisms at the phylum level. Under the treatment of 20 °C, 30 °C, and 40 °C, Lactobacillus had already dominated on the second day of silage. However, low temperatures under 10 °C slowed down the microbial community succession, allowing, bad microorganisms such as Chryseobacterium, Pantoea and Pseudomonas dominate the fermentation, in the early stage of ensiling, which also resulted in the highest bacterial network complexity. According to random forest and structural equation model analysis, the production of carbon dioxide, methane and nitrous oxide is mainly affected by microorganisms such as Lactobacillus, Klebsiella and Enterobacter, and temperature influences the activity of these microorganisms to mediate gas production in silage. This study helps reveal the relationship between temperature, microbial community and greenhouse gas production during silage fermentation, providing a reference for clean silage fermentation.

Role of pyruvate kinase M2 in regulating sepsis (Review).

Glycolysis occurs in all living organisms as a form of energy supply. Pyruvate kinase M2 (PKM2) is one of the rate­limiting enzymes in the glycolytic process. PKM2 is considered to serve an important role in several terminal diseases, including sepsis. However, to the best of our knowledge, the specific mechanistic role of PKM2 in sepsis remains to be systematically summarised. Therefore, the present review aims to summarise the roles of PKM2 in sepsis progression. In addition, potential treatment strategies for patients with sepsis are discussed. The present review hopes to lay the groundwork for studying the role of PKM2 and developing therapeutic strategies against metabolic disorders that occur during sepsis.

Metabolically healthy obesity and left ventricular geometric remodelling in Chinese children.

AIM: To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children. MATERIALS AND METHODS: This cross-sectional study used data from two population-based samples in China, including 2871 children aged 6-11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus-based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476-1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling. RESULTS: Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23-3.28) for concentric remodelling, 6.36 (4.03-10.04) for eccentric hypertrophy, and 17.07 (7.97-36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47-3.75), 10.85 (7.11-16.55), and 18.56 (8.63-39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling. CONCLUSIONS: Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children.

National age-specific mortality trends for cervical and breast cancers in urban-rural areas of China from 2009 to 2021: a population-based analysis.

BACKGROUND: Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. METHODS: Age-specific mortality data for cervical and breast cancers among Chinese women aged 20-84 years were obtained from China's National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban-rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. RESULTS: From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35-64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5-7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: - 0.7%, 95% CI - 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI - 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: - 2.7%, 95% CI - 4.6 to - 0.7%, P = 0.007) in urban areas. Urban-rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35-54 age group across urban and rural areas, periods, and regions in China. CONCLUSIONS: Special attention should be given to women aged 35-54 years due to mortality trends and rural-urban disparities. Focusing on vulnerable age groups and addressing rural-urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.

High levels of high-density lipoprotein cholesterol may increase the risk of diabetic kidney disease in patients with type 2 diabetes.

Studies have indicated that low high-density lipoprotein cholesterol (HDL-C) level is an important risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). However, whether higher HDL-C levels decrease the risk of developing DKD remains unclear. This study aimed to clarify the relationship between HDL-C levels and DKD risk in individuals with T2D in China. In total, 936 patients with T2D were divided into DKD and non-DKD groups. The association between HDL-C levels and DKD risk was evaluated using logistic regression analysis and restricted cubic spline curves adjusted for potential confounders. Threshold effect analysis of HDL-C for DKD risk was also performed. Higher HDL-C levels did not consistently decrease the DKD risk. Furthermore, a nonlinear association with threshold interval effects between HDL-C levels and the incidence of DKD was observed. Patients with HDL-C ≤ 0.94 mmol/L or HDL-C > 1.54 mmol/L had significantly higher DKD risk after adjusting for confounding factors. Interestingly, the association between high HDL-C levels and increased DKD risk was more significant in women. A U-shaped association between HDL-C levels and DKD risk was observed; therefore, low and high HDL-C levels may increase the DKD risk in patients with T2D.

Body composition characteristics and influencing factors of different parts of sarcopenia in elderly people: A community-based cross-sectional survey.

Objectives: This study aims to describe the differences in body composition among different body parts of the elderly in the community and its relationship with sarcopenia. Methods: Elderly people aged ≥65 underwent bioelectric impedance analysis testing and were categorized into a sarcopenia group, possible sarcopenia group, and control group. The characteristics of body composition indicators in different parts and their relationship with different stages of sarcopenia were analyzed. Results: The sarcopenia group illustrated the lowest values of FFM, FFM%, BFM, BFM%, ICW, and limb PhA, along with higher ECW/TBW in the trunk and left leg compared to the control group. The possible sarcopenia group showed lower FFM% in limbs and trunk, and higher BFM% compared to the control group. Gender differences in elderly body composition were observed, with an increase in BFM% in various body parts posing a risk factor for possible sarcopenia in elderly males, whereas an increase in BFM% except in the left arm was a protective factor for sarcopenia in elderly females. Conclusion: The body composition of the elderly in the community varied significantly in different stages of sarcopenia and genders, which correlated with sarcopenia.

Longitudinal mass loads of phthalate esters in sewage sludge and their association with public health and social measures for COVID-19 control in Beijing.

This study examines the concentrations and population-normalized mass loads (PNML) of five phthalate esters (PAEs) and four metabolites (mPAEs) in 390 sewage sludge samples collected from two municipal wastewater treatment plants in Beijing between July 2020 and June 2023, amidst the COVID-19 pandemic. Through GC/MS analysis, the compounds were simultaneously quantified, with peak concentrations in 2020. Bis(2-ethylhexyl) phthalate (DEHP) and mono(2-ethyl-5-oxohexyl) phthalate emerged as predominant PAE and mPAE congeners with concentrations of 78.7 µg/g dw and 259 µg/g dw, respectively. DEHP and monobenzyl phthalate had the highest median PNML among PAEs and mPAEs, respectively, at 128 µg/inhabitant/day and 798 µg/inhabitant/day. Linear regression models revealed a positive association between PNML of PAEs and five public health and social measures aimed at mitigating the COVID-19 pandemic. This research contributes to the expanding body of literature by emphasizing the role of wastewater-based epidemiology as a vital tool for monitoring community-level exposure to environmental contaminants.

Real-World Survival Comparisons Between Radiotherapy and Surgery for Metachronous Second Primary Lung Cancer and Predictions of Lung Cancer-Specific Outcomes Using Machine Learning: Population-Based Study.

BACKGROUND: Metachronous second primary lung cancer (MSPLC) is not that rare but is seldom studied. OBJECTIVE: We aim to compare real-world survival outcomes between different surgery strategies and radiotherapy for MSPLC. METHODS: This retrospective study analyzed data collected from patients with MSPLC between 1988 and 2012 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) analyses and machine learning were performed to compare variables between patients with MSPLC. Survival curves were plotted using the Kaplan-Meier method and were compared using log-rank tests. RESULTS: A total of 2451 MSPLC patients were categorized into the following treatment groups: 864 (35.3%) received radiotherapy, 759 (31%) underwent surgery, 89 (3.6%) had surgery plus radiotherapy, and 739 (30.2%) had neither treatment. After PSM, 470 pairs each for radiotherapy and surgery were generated. The surgery group had significantly better survival than the radiotherapy group (P<.001) and the untreated group (563 pairs; P<.001). Further analysis revealed that both wedge resection (85 pairs; P=.004) and lobectomy (71 pairs; P=.002) outperformed radiotherapy in overall survival for MSPLC patients. Machine learning models (extreme gradient boosting, random forest classifier, adaptive boosting) demonstrated high predictive performance based on area under the curve (AUC) values. Least absolute shrinkage and selection operator (LASSO) regression analysis identified 9 significant variables impacting cancer-specific survival, emphasizing surgery's consistent influence across 1 year to 10 years. These variables encompassed age at diagnosis, sex, year of diagnosis, radiotherapy of initial primary lung cancer (IPLC), primary site, histology, surgery, chemotherapy, and radiotherapy of MPSLC. Competing risk analysis highlighted lower mortality for female MPSLC patients (hazard ratio [HR]=0.79, 95% CI 0.71-0.87) and recent IPLC diagnoses (HR=0.79, 95% CI 0.73-0.85), while radiotherapy for IPLC increased mortality (HR=1.31, 95% CI 1.16-1.50). Surgery alone had the lowest cancer-specific mortality (HR=0.83, 95% CI 0.81-0.85), with sublevel resection having the lowest mortality rate among the surgical approaches (HR=0.26, 95% CI 0.21-0.31). The findings provide valuable insights into the factors that influence cumulative cancer-specific mortality. CONCLUSIONS: Surgical resections such as wedge resection and lobectomy confer better survival than radiation therapy for MSPLC, but radiation can be a valid alternative for the treatment of MSPLC.

Reversing Metabolic Dysfunction-Associated Steatotic Liver Disease Promotes Healthy Pediatric Cardiovascular Structures: The PROC Study.

INTRODUCTION: We investigated the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on cardiovascular structure development in children. METHODS: We followed 1,356 children with the mean age of 6.6 years for 4.5 years in Beijing, China. We assessed the association of MASLD with cardiovascular structure (carotid intima-media thickness and left ventricular mass) outcomes at baseline and follow-up. RESULTS: Over follow-up, 59 children had persistent MASLD, 109 had incident MASLD (progression), and 35 had normalization of liver health. Children with MASLD normalization showed a significantly lower mean development in carotid intima-media thickness (0.161 vs 0.188 mm) and left ventricular mass (4.5 vs 12.4 g) than children with persistent MASLD. DISCUSSION: The control of MASLD was associated with improved cardiovascular structure development.

Constructing artificial gap junctions to mediate intercellular signal and mass transport.

Natural gap junctions are a type of channel protein responsible for intercellular signalling and mass communication. However, the scope of applications for these proteins is limited as they cannot be prepared at a large scale and are unable to spontaneously insert into cell membranes in vitro. The construction of artificial gap junctions may provide an alternative strategy for preparing analogues of the natural proteins and bottom-up building blocks necessary for the synthesis of artificial cells. Here we show the construction of artificial gap junction channels from unimolecular tubular molecules consisting of alternately arranged positively and negatively charged pillar[5]arene motifs. These molecules feature a hydrophobic-hydrophilic-hydrophobic triblock structure that allows them to efficiently insert into two adjacent plasma membranes and stretch across the gap between the two membranes to form gap junctions. Similar to natural gap junction channels, the synthetic channels could mediate intercellular signal coupling and reactive oxygen species transmission, leading to cellular activity.

Multimodal probing of T-cell recognition with hexapod heterostructures.

Studies using antigen-presenting systems at the single-cell and ensemble levels can provide complementary insights into T-cell signaling and activation. Although crucial for advancing basic immunology and immunotherapy, there is a notable absence of synthetic material toolkits that examine T cells at both levels, and especially those capable of single-molecule-level manipulation. Here we devise a biomimetic antigen-presenting system (bAPS) for single-cell stimulation and ensemble modulation of T-cell recognition. Our bAPS uses hexapod heterostructures composed of a submicrometer cubic hematite core (α-Fe2O3) and nanostructured silica branches with diverse surface modifications. At single-molecule resolution, we show T-cell activation by a single agonist peptide-loaded major histocompatibility complex; distinct T-cell receptor (TCR) responses to structurally similar peptides that differ by only one amino acid; and the superior antigen recognition sensitivity of TCRs compared with that of chimeric antigen receptors (CARs). We also demonstrate how the magnetic field-induced rotation of hexapods amplifies the immune responses in suspended T and CAR-T cells. In addition, we establish our bAPS as a precise and scalable method for identifying stimulatory antigen-specific TCRs at the single-cell level. Thus, our multimodal bAPS represents a unique biointerface tool for investigating T-cell recognition, signaling and function.

Prevalence of Lying Flat behaviors and its association with depressive symptoms among college students from three provinces and cities in China / 中国学校卫生

Objective@#To understand the prevalence of Lying Flat behaviors and its association with depressive symptoms among Chinese college students, so as to provide a scientific basis for promoting the physical and mental health development of adolescents.@*Methods@#From July to October 2023, three universities were selected through convenient sampling from Jiangxi Province, Liaoning Province and Beijing City, respectively. Selfdesigned questionnaire links were distributed on campus to collect basic information and Lying Flat behaviors among college students, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for students with depressive symptoms. Finally, a total of 4 225 valid questionnaires were obtained. Chisquare was used to compare of report rates of Lying Flat behaviors across different demographic characteristics. Ordered Logistic regression analysis was used to explore the association between Lying Flat behaviors and depressive symptoms, with Z test used to assess variations in the strength of associations.@*Results@#The reporting rates of academic, life, and social Lying Flat were 32.7%, 17.8% and 17.5%, respectively. And 6.7% of the participants were found of all three Lying Flat behaviors simultaneously.Among college students with three Lying Flat behaviors, the constituent ratios of no, mild, moderate and above depressive symptoms were 9.9%, 30.5% and 59.6%, respectively. Additionally, college students who had three Lying Flat behaviors were more likely to show mild, moderate and above depressive symptoms [OR(95%CI)=2.49(1.60-3.87), 7.69(5.01-11.79), P<0.01].@*Conclusions@#Academic Lying Flat behavior is most prevalent among college students. Academic, life and social Lying Flat behaviors are all significantly positively correlated with depressive symptoms. Attention should be paid to the Lying Flat behaviors and college students psychological health conditions to promote their physical and mental health development.

Longitudinal associations between organophosphate esters exposure and blood pressure among school aged children in Beijing / 中国学校卫生

Objective@#To explore the longitudinal association between organophosphate esters (OPEs) exposure and blood pressure in children, so as to provide a reference for identifying the effects of OPEs exposure on child health.@*Methods@#A total of 404 children from the Beijing Child Growth and Health Cohort (PROC) were enrolled using a case cohort study design, baseline physical examination, urine collection, questionnaires survey were administered in 2018 and follow up surveys in 2019-2020 and 2023. Participants were divided into case group ( n =140) and control group ( n =264) according to the observation of new onset of high blood pressure during the follow up period. High performance liquid chromatography tandem mass spectrometry was used to detect diethyl phosphate (DEP)，bis (2-chloroethyl) phosphate (BCEP)，bis (1-chloro-2-propyl) phosphate, (BCIPP), diphenyl phosphate(DPHP), dibutyl phosphate (DnBP), bis (1,3-dichloro-2-propyl) phosphate(BDCIPP), bis(2-butoxyethyl) phosphate(BBOEP), bis (2-butoxyethyl) 2-hydroxyethyl phosphate (BBOEHEP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP). Generalized linear mixed models and Quantile g computation models were developed to analyze the longitudinal associations between OPEs individual/mixed exposure and blood pressure in children.@*Results@#The detection range of 9 OPEs metabolites,including DEP, BCEP, BCIPP, DPHP, DnBP, BDCIPP, BBOEP, BBOEHEP and 4-OH-TPHP at three time points (baseline, first follow up and second follow up) were 27.7%-92.1%, 24.0%-99.3% and 39.2%-90.9% respectively. Without adjustment for covariates such as gender, age, body mass index, Tanner stage, parental education, and monthly household income, and family history of hypertension, the increase of BDCIPP concentration and mixed exposure of OPEs may reduce children s systolic blood pressure( β= -0.85，-2.40，95%CI=-1.69--0.01，-3.30--1.50，P <0.05). After adjusting for the covariates, the longitudinal association of individual OPEs or mixed exposure with pediatric BP was not statistically significant ( P >0.05).@*Conclusion@#Children are commonly exposed to OPEs, and although no significant longitudinal associations are observed between exposure to OPEs and blood pressure among school aged children in Beijing, it is recommended that child exposure should be minimized whenever possible.

Promoting healthy lifestyles among children and adolescents to enhance primary prevention of non-communicable diseases / 中国学校卫生

Abstract@#Healthy lifestyles are the most effective means of promoting the physical and mental health of children and adolescents. In China, unhealthy lifestyles, such as insufficient physical activity, inadequate sleep, poor dietary choices, smoking, and alcohol consumption are prevalent among this population, posing a threat to healthy growth and development. An initial review of global research examining healthy lifestyles reveals a continually evolving landscape, emphasizing the pressing need to update intervention strategies and theories for children and adolescents health promotion in China. The article presents the most recent state of the art healthy lifestyle indicators and the development of healthy lifestyle intervention strategies. In the future, interventions and monitoring of the health lifestyles of children and adolescents should be conducted in conjunction with schools and families which provide optimal settings, while utilizing advanced methods such as the Internet and digital technologies, artificial intelligence, and integrated omics technologies incorporating genetics and the environment.

Sex differences in cardiovascular health among children aged 6-8 years in Beijing City / 中国学校卫生

Objective@#To explore sex difference in the cardiovascular health (CVH) status of 6-8 year old children in Beijing, so as to inform the early intervention of CVH related lifestyles.@*Methods@#Based on the Beijing Children s Growth and Health Cohort (PROC), baseline physical examination, sequential questionnaire survey, and laboratory tests were conducted among 1 914 grade 1 students. Children s CVH and its subscales (health behaviors and health factors) scores were calculated according to the Life s Essential 8 (LE 8) index and categorized into high, moderate, and low CVH. CVH scores were reported as medians and interquartile ranges; sex differences were compared using the Chi square test and Wilcoxon test.@*Results@#Among the 1 914 participants, the percentages of high, moderate, and low CVH were 35.7%, 63.5%, and 0.8%, respectively, and the percentages of high, moderate, and low health behavior scores were 25.9%, 67.5%, and 6.6%, respectively, with no statistically significant differences between sex ( χ 2=2.30, 0.07, P >0.05). The rates of high, moderate, and low health factor scores for boys and girls were 61.1%, 36.0%, 2.9% and 71.1%, 28.4%, 0.5%, respectively, with a statistically significant sex difference ( χ 2=31.88, P < 0.01). The overall CVH score was 76.0(70.0, 83.0), 76.0(69.0, 82.0) for boys, and 77.0(71.0, 83.0) for girls. Among the health behavior metrics, sleep scores were the best and physical activity scores were the worst[100.0(90.0,100.0), 40.0(20.0, 80.0 )]; among the health factor metrics, blood glucose scores were the best and lipid scores were the worst[100.0(100.0,100.0), 60.0(40.0,100.0)]. In respect to health factors, there were significant gender differences in body mass index, blood lipids, blood sugar, and blood pressure scores ( Z =-6.92, 3.01, -6.60, -2.30, <0.05), but there were no significant gender differences in diet, physical activity, nicotine exposure, or sleep scores with regards to health behaviors ( Z =0.99, 0.88, -0.13, 0.36, P > 0.05 ). Compared to boys, girls in the low and moderate CVH groups had high health factor scores despite low health behavior scores.@*Conclusion@#Most 6 to 8-year-old children in Beijing were found to have relatively good CVH, and optimization of children s CVH status can be achieved by promoting healthier lifestyles and monitoring health factors, especially among boys.

Relationship between depressive symptoms, negative life events, and resilience in primary and secondary school teachers / 中国学校卫生

Objective@#To explore the relationship between depressive symptoms, negative life events and resilience among primary and secondary school teachers, so as to provide a reference for mental health promotion in school teachers.@*Methods@#During November to December 2022, a questionnaire survey was conducted using convenient cluster sampling method to select 11 332 in service teachers from 38 schools in 8 provinces (cities) including Beijing, Guangdong, Anhui, Hubei, Sichuan, Xinjiang, Liaoning, and Heilongjiang. The Patient Health Questionnaire-9 items, a self developed 21-item Adverse Life Events questionnaire, and a 10-item Conner-Davidson Resilience Scale were used to assess depressive symptoms, experiences of negative life events, and resilience levels of the teachers, respectively. The relationship between depressive symptoms, negative life events and psychological resilience were analyzed by multiple linear regression and stratified regression.@*Results@#The detection rate of depressive symptoms among primary and secondary school teachers was 14.0%. Negative life events of primary and secondary school teachers were positively correlated with depressive symptoms ( r =0.35), while psychological resilience was negatively correlated with depressive symptoms ( r =-0.45) ( P <0.05). After adjusting for possible covariates including gender and marital status, negative life events were positively correlated with depressive symptoms ( β=0.22, P <0.01). Resilience played a moderating role in the association of negative life events with depressive symptoms among primary and secondary school teachers ( B=-0.15, P <0.01).@*Conclusions@#Negative life events experiences are associated with higher level of depressive symptoms among school teachers. However, resilience might mitigate the negative effects of negative life events on depressive symptoms, playing a protective role in teachers mental health.

pan-MHC and cross-Species Prediction of T Cell Receptor-Antigen Binding.

Profiling the binding of T cell receptors (TCRs) of T cells to antigenic peptides presented by MHC proteins is one of the most important unsolved problems in modern immunology. Experimental methods to probe TCR-antigen interactions are slow, labor-intensive, costly, and yield moderate throughput. To address this problem, we developed pMTnet-omni, an Artificial Intelligence (AI) system based on hybrid protein sequence and structure information, to predict the pairing of TCRs of αß T cells with peptide-MHC complexes (pMHCs). pMTnet-omni is capable of handling peptides presented by both class I and II pMHCs, and capable of handling both human and mouse TCR-pMHC pairs, through information sharing enabled this hybrid design. pMTnet-omni achieves a high overall Area Under the Curve of Receiver Operator Characteristics (AUROC) of 0.888, which surpasses competing tools by a large margin. We showed that pMTnet-omni can distinguish binding affinity of TCRs with similar sequences. Across a range of datasets from various biological contexts, pMTnet-omni characterized the longitudinal evolution and spatial heterogeneity of TCR-pMHC interactions and their functional impact. We successfully developed a biomarker based on pMTnet-omni for predicting immune-related adverse events of immune checkpoint inhibitor (ICI) treatment in a cohort of 57 ICI-treated patients. pMTnet-omni represents a major advance towards developing a clinically usable AI system for TCR-pMHC pairing prediction that can aid the design and implementation of TCR-based immunotherapeutics.

National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data.

BACKGROUND: Cancer has been the leading cause of death since 2010 in China, with increasing incidence, mortality, and burden. We aimed to assess national and subnational changes in the cancer burden from 2005 to 2020 in China using data from the National Mortality Surveillance System. METHODS: We extracted data on cancer-related deaths from the National Mortality Surveillance System, which accounts for 24·3% of the country's population with national and provincial representativeness. Data for the surveillance population stratified by age and sex were extracted from the National Bureau of Statistics of China. We estimated mortality and years of life lost (YLLs) for all cancers and for 23 cancer groups by age and sex, nationally, and for 31 provinces in China between 2005 and 2020. We calculated age-standardised mortality and YLL rates using the China 2020 census as the reference population. Average annual percent changes in age-standardised rates for mortality and YLLs were calculated to assess trends over the study period. Decomposition analysis was used to assess the drivers of changes in cancer-related death due to three explanatory components: population growth, population ageing, and age-specific mortality rates in China. FINDINGS: The total number of cancer-related deaths increased by 21·6% to 2 397 772 and YLLs increased by 5·0% to 56 598 975 between 2005 and 2020. The three leading fatal cancer types remained stable for both sexes over the study period: tracheal, bronchus, and lung cancer; liver cancer; and stomach cancer. The fourth and fifth leading cancers also remained stable among males (oesophageal, and colon and rectum), while colon and rectum cancer replaced oesophageal cancer as the fourth and breast cancer replaced colon and rectum cancer as the fifth leading cause of cancer-related death among females. Age-standardised mortality rates and age-standardised YLL rates for almost all cancer types (except for prostate for male and multiple myeloma for female) decreased significantly in both sexes in urban areas. Age-standardised YLL rates increased for about half of all cancers for both sexes in rural areas. Leading fatal types were leukaemia and brain and nervous system cancer in younger groups (aged 0-19 years); liver, tracheal, bronchus, and lung, or breast cancers in middle-aged groups (aged 40-59 years); and tracheal, bronchus, and lung, liver, or stomach cancers in older adults (aged ≥60 years) in 2020. The leading causes of cancer-related mortality varied for each province, with tracheal, bronchus, and lung or liver cancer at the top in 30 provinces. INTERPRETATION: The cancer burden in China appeared to be shifting towards that in high-income countries from 2005 to 2020. Adjustments to existing health plans and actions are needed to reduce the burdens of tracheal, bronchus, and lung cancer or other leading and emerging cancers. FUNDING: National Key Research and Development Program of China.

Transfer learning with false negative control improves polygenic risk prediction.

Polygenic risk score (PRS) is a quantity that aggregates the effects of variants across the genome and estimates an individual's genetic predisposition for a given trait. PRS analysis typically contains two input data sets: base data for effect size estimation and target data for individual-level prediction. Given the availability of large-scale base data, it becomes more common that the ancestral background of base and target data do not perfectly match. In this paper, we treat the GWAS summary information obtained in the base data as knowledge learned from a pre-trained model, and adopt a transfer learning framework to effectively leverage the knowledge learned from the base data that may or may not have similar ancestral background as the target samples to build prediction models for target individuals. Our proposed transfer learning framework consists of two main steps: (1) conducting false negative control (FNC) marginal screening to extract useful knowledge from the base data; and (2) performing joint model training to integrate the knowledge extracted from base data with the target training data for accurate trans-data prediction. This new approach can significantly enhance the computational and statistical efficiency of joint-model training, alleviate over-fitting, and facilitate more accurate trans-data prediction when heterogeneity level between target and base data sets is small or high.