Exploring the Molecular Mechanisms of Huaier on Modulating Metabolic Reprogramming of Hepatocellular Carcinoma: A Study based on Network Pharmacology, Molecular Docking and Bioinformatics.

BACKGROUND: Huaier (Trametes robiniophila Murr), a traditional Chinese medicine, is widely used in China as a complementary and alternative therapy to treat hepatocellular carcinoma (HCC). Past studies have shown that Huaier can arrest the cell cycle, promote apoptosis and inhibit the proliferation of cancer cells. However, how it regulates the metabolism of HCC is still unclear. OBJECTIVE: This study explores the metabolic-related function of Huaier in treating HCC with an in-silico approach. METHODS: A network pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of metabolic reprogramming in HCC with Huaier. The compounds of Huaier were obtained from public databases. Oral bioavailability and drug likeness were screened using the TCMSP platform. The differential gene expressions between HCC and non-tumor tissue were calculated and used to find the overlap from the targets of Huaier. The enrichment analysis of the overlapped targets by Metascape helped filter out the metabolism-related targets of Huaier in treating HCC. Protein-protein interaction (PPI) network construction and topological screening revealed the hub nodes. The prognosis and clinical correlation of these targets were validated from the cancer genome atlas (TCGA) database, and the interactions between the hub nodes and active ingredients were validated by molecular docking. RESULTS: The results showed that Peroxyergosterol, Daucosterol, and Kaempferol were the primary active compounds of Huaier involved in the metabolic reprogramming of HCC. The top 6 metabolic targets included AKR1C3, CYP1A1, CYP3A4, CYP1A2, CYP17A1, and HSD11B1. The decreased expression of CYP3A4 and increased expression of AKR1C3 were related to the poor overall survival of HCC patients. The molecular docking validated that Peroxyergosterol and Kaempferol exhibited the potential to modulate CYP3A4 and AKR1C3 from a computational perspective. CONCLUSION: This study provided a workflow for understanding the mechanism of Huaier in regulating the metabolic reprogramming of HCC.

Enhanced bovine genome annotation through integration of transcriptomics and epi-transcriptomics datasets facilitates genomic biology.

BACKGROUND: The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues. RESULTS: A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5' untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue-tissue interconnection involved in different traits and construct the first bovine trait similarity network. CONCLUSIONS: These validated results show significant improvement over current bovine genome annotations.

Postnatal Growth and Development of the Rumen: Integrating Physiological and Molecular Insights.

The rumen plays an essential role in the physiology and production of agriculturally important ruminants such as cattle. Functions of the rumen include fermentation, absorption, metabolism, and protection. Cattle are, however, not born with a functional rumen, and the rumen undergoes considerable changes in size, histology, physiology, and transcriptome from birth to adulthood. In this review, we discuss these changes in detail, the factors that affect these changes, and the potential molecular and cellular mechanisms that mediate these changes. The introduction of solid feed to the rumen is essential for rumen growth and functional development in post-weaning calves. Increasing evidence suggests that solid feed stimulates rumen growth and functional development through butyric acid and other volatile fatty acids (VFAs) produced by microbial fermentation of feed in the rumen and that VFAs stimulate rumen growth and functional development through hormones such as insulin and insulin-like growth factor I (IGF-I) or through direct actions on energy production, chromatin modification, and gene expression. Given the role of the rumen in ruminant physiology and performance, it is important to further study the cellular, molecular, genomic, and epigenomic mechanisms that control rumen growth and development in postnatal ruminants. A better understanding of these mechanisms could lead to the development of novel strategies to enhance the growth and development of the rumen and thereby the productivity and health of cattle and other agriculturally important ruminants.

Chromatin profiling reveals TFAP4 as a critical transcriptional regulator of bovine satellite cell differentiation.

BACKGROUND: Satellite cells are myogenic precursor cells in adult skeletal muscle and play a crucial role in skeletal muscle regeneration, maintenance, and growth. Like embryonic myoblasts, satellite cells have the ability to proliferate, differentiate, and fuse to form multinucleated myofibers. In this study, we aimed to identify additional transcription factors that control gene expression during bovine satellite cell proliferation and differentiation. RESULTS: Using chromatin immunoprecipitation followed by sequencing, we identified 56,973 and 54,470 genomic regions marked with both the histone modifications H3K4me1 and H3K27ac, which were considered active enhancers, and 50,956 and 59,174 genomic regions marked with H3K27me3, which were considered repressed enhancers, in proliferating and differentiating bovine satellite cells, respectively. In addition, we identified 1,216 and 1,171 super-enhancers in proliferating and differentiating bovine satellite cells, respectively. Analyzing these enhancers showed that in proliferating bovine satellite cells, active enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation whereas repressed enhancers were associated with genes essential for myoblast differentiation, and that in differentiating satellite cells, active enhancers were associated with genes essential for myoblast differentiation or muscle contraction whereas repressed enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation. Active enhancers in proliferating bovine satellite cells were enriched with binding sites for many transcription factors such as MYF5 and the AP-1 family transcription factors; active enhancers in differentiating bovine satellite cells were enriched with binding sites for many transcription factors such as MYOG and TFAP4; and repressed enhancers in both proliferating and differentiating bovine satellite cells were enriched with binding sites for NF-kB, ZEB-1, and several other transcription factors. The role of TFAP4 in satellite cell or myoblast differentiation was previously unknown, and through gene knockdown and overexpression, we experimentally validated a critical role for TFAP4 in the differentiation and fusion of bovine satellite cells into myofibers. CONCLUSIONS: Satellite cell proliferation and differentiation are controlled by many transcription factors such as AP-1, TFAP4, NF-kB, and ZEB-1 whose roles in these processes were previously unknown in addition to those transcription factors such as MYF5 and MYOG whose roles in these processes are widely known.

Molecular and Cellular Mechanisms of Intramuscular Fat Development and Growth in Cattle.

Intramuscular fat, also referred to as marbling fat, is the white fat deposited within skeletal muscle tissue. The content of intramuscular fat in the skeletal muscle, particularly the longissimus dorsi muscle, of cattle is a critical determinant of beef quality and value. In this review, we summarize the process of intramuscular fat development and growth, the factors that affect this process, and the molecular and epigenetic mechanisms that mediate this process in cattle. Compared to other species, cattle have a remarkable ability to accumulate intramuscular fat, partly attributed to the abundance of sources of fatty acids for synthesizing triglycerides. Compared to other adipose depots such as subcutaneous fat, intramuscular fat develops later and grows more slowly. The commitment and differentiation of adipose precursor cells into adipocytes as well as the maturation of adipocytes are crucial steps in intramuscular fat development and growth in cattle. Each of these steps is controlled by various factors, underscoring the complexity of the regulatory network governing adipogenesis in the skeletal muscle. These factors include genetics, epigenetics, nutrition (including maternal nutrition), rumen microbiome, vitamins, hormones, weaning age, slaughter age, slaughter weight, and stress. Many of these factors seem to affect intramuscular fat deposition through the transcriptional or epigenetic regulation of genes directly involved in the development and growth of intramuscular fat. A better understanding of the molecular and cellular mechanisms by which intramuscular fat develops and grows in cattle will help us develop more effective strategies to optimize intramuscular fat deposition in cattle, thereby maximizing the quality and value of beef meat.

Evaluation of phase-adjusted interventions for COVID-19 using an improved SEIR model.

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2-5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.

Prediction of Oncomelania hupensis distribution in association with climate change using machine learning models.

BACKGROUND: Oncomelania hupensis is the sole intermediate host of Schistosoma japonicum. Its emergence and recurrence pose a constant challenge to the elimination of schistosomiasis in China. It is important to accurately predict the snail distribution for schistosomiasis prevention and control. METHODS: Data describing the distribution of O. hupensis in 2016 was obtained from the Yunnan Institute of Endemic Disease Control and Prevention. Eight machine learning algorithms, including eXtreme Gradient Boosting (XGB), support vector machine (SVM), random forest (RF), generalized boosting model (GBM), neural network (NN), classification and regression trees (CART), k-nearest neighbors (KNN), and generalized additive model (GAM), were employed to explore the impacts of climatic, geographical, and socioeconomic variables on the distribution of suitable areas for O. hupensis. Predictions of the distribution of suitable areas for O. hupensis were made for various periods (2030s, 2050s, and 2070s) under different climate scenarios (SSP126, SSP245, SSP370, and SSP585). RESULTS: The RF model exhibited the best performance (AUC: 0.991, sensitivity: 0.982, specificity: 0.995, kappa: 0.942) and the CART model performed the worst (AUC: 0.884, sensitivity: 0.922, specificity: 0.943, kappa: 0.829). Based on the RF model, the top six important variables were as follows: Bio15 (precipitation seasonality) (33.6%), average annual precipitation (25.2%), Bio2 (mean diurnal temperature range) (21.7%), Bio19 (precipitation of the coldest quarter) (14.5%), population density (13.5%), and night light index (11.1%). The results demonstrated that the overall suitable habitats for O. hupensis were predominantly distributed in the schistosomiasis-endemic areas located in northwestern Yunnan Province under the current climate situation and were predicted to expand north- and westward due to climate change. CONCLUSIONS: This study showed that the prediction of the current distribution of O. hupensis corresponded well with the actual records. Furthermore, our study provided compelling evidence that the geographical distribution of snails was projected to expand toward the north and west of Yunnan Province in the coming decades, indicating that the distribution of snails is driven by climate factors. Our findings will be of great significance for formulating effective strategies for snail control.

In vivo bioluminescence imaging of labile iron in xenograft models and liver using FeAL-1, an iron-activatable form of D-luciferin.

Dysregulated iron homeostasis underlies diverse pathologies, from ischemia-reperfusion injury to epithelial-mesenchymal transition and drug-tolerant "persister" cancer cell states. Here, we introduce ferrous iron-activatable luciferin-1 (FeAL-1), a small-molecule probe for bioluminescent imaging of the labile iron pool (LIP) in luciferase-expressing cells and animals. We find that FeAL-1 detects LIP fluctuations in cells after iron supplementation, depletion, or treatment with hepcidin, the master regulator of systemic iron in mammalian physiology. Utilizing FeAL-1 and a dual-luciferase reporter system, we quantify LIP in mouse liver and three different orthotopic pancreatic ductal adenocarcinoma tumors. We observed up to a 10-fold increase in FeAL-1 bioluminescent signal in xenograft tumors as compared to healthy liver, the major organ of iron storage in mammals. Treating mice with hepcidin further elevated hepatic LIP, as predicted. These studies reveal a therapeutic index between tumoral and hepatic LIP and suggest an approach to sensitize tumors toward LIP-activated therapeutics.

Do gut microbiome-targeted therapies improve liver function in cirrhotic patients? A systematic review and meta-analysis.

BACKGROUND AND AIM: Microbiome-targeted therapies (MTTs) are considered as promising interventions for cirrhosis, but the impact of gut microbiome modulation on liver function and disease severity has not been fully assessed. We comprehensively evaluated the efficacy of MTTs in patients with liver cirrhosis. METHODS: Data from randomized controlled trials were collected through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov from inception to February 20, 2023. Clinical outcomes were pooled and expressed in terms of risk ratios or mean differences (MD). Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A trial sequential analysis was applied to calculate the required information size and evaluate the credibility of the meta-analysis results. RESULTS: Twenty-one studies with a total of 1699 cirrhotic patients were included for meta-analysis. MTTs were associated with a significant reduction in aspartate aminotransferase (MD, -3.62; 95% CI, -6.59 to -0.65), the risk of hepatic encephalopathy (risk ratio = 0.56, 95% CI: 0.46 to 0.68), model for end-stage liver disease score (MD, -0.90; 95% CI, -1.17 to -0.11), ammonia (MD, -11.86; 95% CI, -16.39 to -7.33), and endotoxin (MD, -0.14; 95% CI, -0.23 to -0.04). The trial sequential analysis yielded reliable results of these outcomes. No effects were observed on the changes of other hepatic function indicators. CONCLUSION: MTTs appeared to be associated with a slowed deterioration in liver cirrhosis, which could provide reference for clinicians in treatment of cirrhotic patients based on their conditions.

Identifying determinants for the seropositive rate of schistosomiasis in Hunan province, China: A multi-scale geographically weighted regression model.

BACKGROUND: Schistosomiasis is of great public health concern with a wide distribution and multiple determinants. Due to the advances in schistosomiasis elimination and the need for precision prevention and control, identifying determinants at a fine scale is urgent and necessary, especially for resource deployment in practice. Our study aimed to identify the determinants for the seropositive rate of schistosomiasis at the village level and to explore their spatial variations in local space. METHODOLOGY: The seropositive rates of schistosomiasis were collected from 1714 villages or communities in Human Province, and six spatial regression models including ordinary least squares (OLS), spatial lag model (SLM), spatial error model (SEM), geographically weighted regression (GWR), robust GWR (RGWR) and multiscale GWR (MGWR) were used to fit the data. PRINCIPAL/FINDINGS: MGWR was the best-fitting model (R2: 0.821, AICc:2727.092). Overall, the nearest distance from the river had the highest mean negative correlation, followed by proportion of households using well water and the annual average daytime surface temperature. The proportions of unmodified toilets showed the highest mean positive correlation, followed by the snail infested area, and the number of cattle. In spatial variability, the regression coefficients for the nearest distance from the river, annual average daytime surface temperature and the proportion of unmodified toilets were significant in all villages or communities and varied little in local space. The other significant determinants differed substantially in local space and had significance ratios ranging from 41% to 70%, including the number of cattle, the snail infested area and the proportion of households using well water. CONCLUSIONS/SIGNIFICANCE: Our study shows that MGWR was well performed for the spatial variability of schistosomiasis in Hunan province. The spatial variability was different for different determinants. The findings for the determinants for the seropositive rate and mapped variability for some key determinants at the village level can be used for developing precision intervention measure for schistosomiasis control.

Three Gorges Dam: Potential differential drivers and trend in the spatio-temporal evolution of the change in snail density based on a Bayesian spatial-temporal model and 5-year longitudinal study.

BACKGROUND: Snail abundance varies spatially and temporally. Few studies have elucidated the different effects of the determinants affecting snail density between upstream and downstream areas of the Three Gorges Dam (TGD). We therefore investigated the differential drivers of changes in snail density in these areas, as well as the spatial-temporal effects of these changes. METHODS: A snail survey was conducted at 200 sites over a 5-year period to monitor dynamic changes in snail abundance within the Yangtze River basin. Data on corresponding variables that might affect snail abundance, such as meteorology, vegetation, terrain and economy, were collected from multiple data sources. A Bayesian spatial-temporal modeling framework was constructed to explore the differential determinants driving the change in snail density and the spatial-temporal effects of the change. RESULTS: Volatility in snail density was unambiguously detected in the downstream area of the TGD, while a small increment in volatility was detected in the upstream area. Regarding the downstream area of the TGD, snail density was positively associated with the average minimum temperature in January of the same year, the annual Normalized Difference Vegetation Index (NDVI) of the previous year and the second, third and fourth quartile, respectively, of average annual relative humidity of the previous year. Snail density was negatively associated with the average maximum temperature in July of the previous year and annual nighttime light of the previous year. An approximately inverted "U" curve of relative risk was detected among sites with a greater average annual ground surface temperature in the previous year. Regarding the upstream area, snail density was positively associated with NDVI and with the second, third and fourth quartile, respectively, of total precipitation of the previous year. Snail density was negatively associated with slope. CONCLUSIONS: This study demonstrated a rebound in snail density between 2015 and 2019. In particular, temperature, humidity, vegetation and human activity were the main drivers affecting snail abundance in the downstream area of the TGD, while precipitation, slope and vegetation were the main drivers affecting snail abundance in the upstream area. These findings can assist authorities to develop and perform more precise strategies for surveys and control of snail populations.

Association of growth hormone deficiency with an increased number of preadipocytes in subcutaneous fat.

The inhibitory effect of growth hormone (GH) on adipose tissue growth is well known, but the underlying mechanism is not fully understood. In this study, we determined the possibility that GH inhibits adipose tissue growth by inhibiting adipogenesis, the process of formation of adipocytes from stem cells, in the lit/lit mice. The lit/lit mice are GH deficient because of a spontaneous mutation to the GH releasing hormone receptor (ghrhr) gene, and they have more subcutaneous fat despite being smaller than the lit/+ mice at the same age. We found that cells of the stromal vascular fraction (SVF) of subcutaneous fat from the lit/lit mice had greater adipogenic potential than those from the lit/+ mice, as evidenced by forming greater numbers of lipid droplets-containing adipocytes and having greater expression of adipocyte marker genes during induced adipocyte differentiation in culture. However, addition of GH to the culture did not reverse the superior adipogenic potential of subcutaneous SVF from the lit/lit mice. Through florescence-activated cell sorting and quantification of mRNAs of preadipocyte markers, including CD34, CD29, Sca-1, CD24, Pref-1, and PPARγ, we found that subcutaneous SVF from the lit/lit mice contained more preadipocytes than that from the lit/+ mice. These results support the notion that GH inhibits adipose tissue growth in mice at least in part by inhibiting adipogenesis. Furthermore, these results suggest that GH inhibits adipogenesis in mice not by inhibiting the terminal differentiation of preadipocytes into adipocytes, rather by inhibiting the formation of preadipocytes from stem cells or the recruitment of stem cells to the fat depot.

Three Gorges Dam: the changing trend of snail density in the Yangtze River basin between 1990 and 2019.

BACKGROUND: The area of Oncomelania hupensis snail remains around 3.6 billion m2, with newly emerging and reemergent habitats continuing to appear in recent years. This study aimed to explore the long-term dynamics of snail density before and after the operation of Three Gorges Dam (TGD). METHODS: Data of snail survey between 1990 and 2019 were collected from electronic databases and national schistosomiasis surveillance. Meta-analysis was conducted to estimate the snail density. Joinpoint model was used to identify the changing trend and inflection point. Inverse distance weighted interpolation (IDW) was used to determine the spatial distribution of recent snail density. RESULTS: A total of 3777 snail survey sites with a precise location of village or beach were identified. For the downstream area, snail density peaked in 1998 (1.635/0.11 m2, 95% CI: 1.220, 2.189) and fluctuated at a relatively high level before 2003, then declined steadily from 2003 to 2012. Snail density maintained lower than 0.150/0.11 m2 between 2012 and 2019. Joinpoint model identified the inflection of 2003, and a significant decreasing trend from 2003 to 2012 with an annual percentage change (APC) being - 20.56% (95% CI: - 24.15, - 16.80). For the upstream area, snail density peaked in 2005 (0.760/0.11 m2, 95% CI: 0.479, 1.207) and was generally greater than 0.300/0.11 m2 before 2005. Snail density was generally lower than 0.150/0.11 m2 after 2011. Snail density showed a significant decreasing trend from 1990 to 2019 with an APC being - 6.05% (95% CI: - 7.97, - 7.09), and no inflection was identified. IDW showed the areas with a high snail density existed in Poyang Lake, Dongting Lake, Jianghan Plain, and the Anhui branch of the Yangtze River between 2015 and 2019. CONCLUSIONS: Snail density exhibited a fluctuating downward trend in the Yangtze River basin. In the downstream area, the operation of TGD accelerated the decline of snail density during the first decade period, then snail density fluctuated at a relatively low level. There still exists local areas with a high snail density. Long-term control and monitoring of snails need to be insisted on and strengthened.

Autoantibodies against type I interferons in COVID-19 infection: A systematic review and meta-analysis.

OBJECTIVES: In this study, we aimed to study the rate of autoantibodies against type I interferons (IFNs) in patients with COVID-19 and analyze its dependence on severity of infection and some other variables. METHODS: A systemic review with the search terms: "COVID-19" or "SARS-CoV-2" and "autoantibodies" or "autoantibody" and "IFN" or "interferon" for the period 20 December 2019 to 15 August 2022 was carried out using PubMed, Embase, Cochrane, and Web of Science. R 4.2.1 software was used for meta-analysis of the published results. Pooled risk ratios and 95% confidence intervals (CIs) were calculated. RESULTS: We identified eight studies involving 7729 patients, of whom 5097 (66%) had severe COVID-19 and 2632 (34%) had mild or moderate symptoms. The positive rate of anti-type-I-IFN-autoantibodies in the total dataset was 5% (95% CI, 3-8%), but reached 10% (95% CI, 7-14%) in those with severe infection. The most common subtypes were anti-IFN-α (89%) and anti-IFN-ω (77%). The overall prevalence in male patients was 5% (95% CI, 4-6%), and in female patients 2% (95% CI, 1-3%). CONCLUSION: Severe COVID-19 is associated with high rates of autoantibodies against type-I-IFN and more so in male than female patients.

Global Distribution of Culex tritaeniorhynchus and Impact Factors.

Culex tritaeniorhynchus is the primary vector of Japanese encephalitis (JE) and has a wide global distribution. However, the current and future geographic distribution maps of Cx. tritaeniorhynchus in global are still incomplete. Our study aims to predict the potential distribution of Cx. tritaeniorhynchus in current and future conditions to provide a guideline for the formation and implementation of vector control strategies all over the world. We collected and screened the information on the occurrence of Cx. tritaeniorhynchus by searching the literature and online databases and used ten algorithms to investigate its global distribution and impact factors. Cx. tritaeniorhynchus had been detected in 41 countries from 5 continents. The final ensemble model (TSS = 0.864 and AUC = 0.982) indicated that human footprint was the most important factor for the occurrence of Cx. tritaeniorhynchus. The tropics and subtropics, including southeastern Asia, Central Africa, southeastern North America and eastern South America, showed high habitat suitability for Cx. tritaeniorhynchus. Cx. tritaeniorhynchus is predicted to have a wider distribution in all the continents, especially in Western Europe and South America in the future under two extreme emission scenarios (SSP5-8.5 and SSP1-2.6). Targeted strategies for the control and prevention of Cx. tritaeniorhynchus should be further strengthened.

Artificial Neural Network Modeling to Predict Neonatal Metabolic Bone Disease in the Prenatal and Postnatal Periods.

Importance: Early recognition of metabolic bone disease (MBD) in infants is necessary but difficult; an appropriate tool to screen infants at risk of developing MBD is needed. Objectives: To develop a predictive model for neonates at risk for MBD in the prenatal and postnatal periods and detect the pivotal exposed factors in each period. Design, Setting, and Participants: A diagnostic study was conducted from January 1, 2012, to December 31, 2021, in Shanghai, China. A total of 10 801 pregnant women (singleton pregnancy, followed up until 1 month after parturition) and their infants (n = 10 801) were included. An artificial neural network (ANN) framework was used to build 5 predictive models with different exposures from prenatal to postnatal periods. The receiver operating characteristic curve was used to evaluate the model performance. The importance of each feature was examined and ranked. Results: Of the 10 801 Chinese women who participated in the study (mean [SD] age, 29.7 [3.9] years), 7104 (65.8%) were local residents, 1001 (9.3%) had uterine scarring, and 138 (1.3%) gave birth to an infant with MBD. Among the 5 ANN models, model 1 (significant prenatal and postnatal factors) showed the highest AUC of 0.981 (95% CI, 0.970-0.992), followed by model 5 (postnatal factors; AUC, 0.977; 95% CI, 0.966-0.988), model 4 (all prenatal factors; AUC, 0.850; 95% CI, 0.785-0.915), model 3 (gestational complications or comorbidities and medication use; AUC, 0.808; 95% CI, 0.726-0.891), and model 2 (maternal nutritional conditions; AUC, 0.647; 95% CI, 0.571-0.723). Birth weight, maternal age at pregnancy, and neonatal disorders (anemia, respiratory distress syndrome, and septicemia) were the most important model 1 characteristics for predicting infants at risk of MBD; among these characteristics, extremely low birth weight (importance, 50.5%) was the most powerful factor. The use of magnesium sulfate during pregnancy (model 4: importance, 21.2%) was the most significant predictor of MBD risk in the prenatal period. Conclusions and Relevance: In this diagnostic study, ANN appeared to be a simple and efficient tool for identifying neonates at risk for MBD. Combining prenatal and postnatal factors or using postnatal exposures alone provided the most precise prediction. Extremely low birth weight was the most significant predictive factor, whereas magnesium sulfate use during pregnancy could be an important bellwether for MBD before delivery.

Prediction of the Risk Distributions for Anopheles sinensis, a Vector for Malaria in Shanghai, China.

Malaria is a parasitic disease caused by Plasmodium, and Anopheles sinensis is a vector of malaria. Although malaria is no longer indigenous to China, a high risk remains for local transmission of imported malaria. This study aimed to identify the risk distribution of vector An. sinensis and malaria transmission. Using data collected from routine monitoring in Shanghai from 2010 to 2020, online databases for An. sinensis and malaria, and environmental variables including climate, geography, vegetation, and hosts, we constructed 10 algorithms and developed ensemble models. The ensemble models combining multiple algorithms (An. sinensis: area under the curve [AUC] = 0.981, kappa = 0.920; malaria: AUC = 0.959, kappa = 0.800), with the best out-of-sample performance, were used to identify important environmental predictors for the risk distributions of An. sinensis and malaria transmission. For An. sinensis, the most important predictor in the ensemble model was moisture index, which reflected degree of wetness; the risk of An. sinensis decreased with higher degrees of wetness. For malaria transmission, the most important predictor in the ensemble model was the normalized differential vegetation index, which reflected vegetation cover; the risk of malaria transmission decreased with more vegetation cover. Risk levels for An. sinensis and malaria transmission for each district of Shanghai were presented; however, there was a mismatch between the risk classification maps of An. sinensis and malaria transmission. Facing the challenge of malaria transmission in Shanghai, in addition to precise An. sinensis monitoring in risk areas of malaria transmission, malaria surveillance should occur even in low-risk areas for An. sinensis.

Life expectancy and healthy life expectancy of patients with advanced schistosomiasis in Hunan Province, China.

BACKGROUND: Few studies have investigated the change in life expectancy (LE) and the healthy lifespan among patients with advanced schistosomiasis. This study was to evaluate the LE and healthy life expectancy (HLE) for patients and assess the mechanism responsible for the LE inequality. METHODS: We utilized data from a dynamic advanced schistosomiasis cohort (10,362 patients) for the period from January 2008 to December 2019 in Hunan Province, China, to calculate the LEs of patients, and made a comparison with that of general population (19,642 schistosomiasis-free individuals) in the schistosomiasis endemic areas. LEs were estimated from 15 years of age by constructing period life tables. Arriaga's decomposition method was applied to quantify the influence of the age structure on the difference in LE. HLE for advanced schistosomiasis patients was calculated by using Sullivan method with age-specific disability weight. The LE and HLE were calculated for both males and females to perform further analyses on gender gap. RESULTS: The estimated LE for advanced schistosomiasis patients aged 15-19 was 49.51 years (48.86 years for males and 51.07 years for females), which was 20.14 years lower compared with general population (69.65 years), and the LE gap between patients and general population decreased with age. The largest age-specific mortality contribution to the gap (32.06%) occurred at age 80-84 years. Women had a lower LE and HLE than men at age ≥ 60 years (both gender gaps in LE and HLE < 0). For advanced schistosomiasis patients, the gender gap in LE was largely attributed to the difference in mortality among those under the age of 55; the age-specific mortality in women exerted positive influence on the gap at age 25-64 and 75-79 years, with the contribution rate ranging from 0.59% to 57.02%, and made the negative contribution at other age groups. CONCLUSIONS: The LE of advanced schistosomiasis patients was still much lower compared with general population. Strengthened prevention strategies and targeted treatments are needed to reduce morbidity and mortality due to advanced schistosomiasis, especially for younger population and elderly female patients.

Changing trend of sickness absenteeism among students during 2010-2017 academic years and its correlation with the incidence of acute infectious diseases in Jiading District，Shanghai / 中国学校卫生

Objective@#To describe the sickness absenteeism among primary and secondary school students in Jiading District and to analyze its correlation with the incidence of infectious diseases and associated lead or lag times, so as,to provide a scientific basis for the health and education departments to take measures.@*Methods@#The regularity and symptom composition of school sickness absenteeism among primary and secondary school students in Jiading District from the 2010-2017 were described. The Joinpoint model was applied to analyze the changing trend of absenteeism. And the rate of school sickness absenteeism and incidences of 7 acute infectious diseases were compared through visual analysis. The time lagged correlation coefficients and Granger causality tests were applied to quantitatively analyze the correlation and lead/lag patterns.@*Results@#The average rate of school sickness absenteeism among primary and secondary school students in Jiading District, Shanghai was 0.27%. Since the 2012 academic year, the overall rate of sickness absenteeism has been on the rise. Fever was the most common symptom of absenteeism (47.49%). The trend of sickness absenteeism rate was mainly consistent with the incidence of influenza, and showed a one way Granger causality. The maximum time lagged correlation coefficient was obtained in the second semester of the 2017 academic year with a value of 0.43 (95% CI =0.25-0.58). The maximum time lagged correlation coefficient between the rate of sickness absenteeism with fever and other respiratory symptoms and the incidence of influenza was also obtained in the second semester of the 2017 academic year and the maximum correlation coefficient was 0.50(95% CI =0.33-0.65).@*Conclusion@#The sickness absenteeism rate in primary and secondary school students is correlated to influenza incidence, and it has potential application value in supplementing early warning of influenza activities in the community.

RNA-Sequencing Reveals Upregulation and a Beneficial Role of Autophagy in Myoblast Differentiation and Fusion.

Myoblast differentiation is a complex process whereby the mononuclear muscle precursor cells myoblasts express skeletal-muscle-specific genes and fuse with each other to form multinucleated myotubes. The objective of this study was to identify potentially novel mechanisms that mediate myoblast differentiation. We first compared transcriptomes in C2C12 myoblasts before and 6 days after induction of myogenic differentiation by RNA-seq. This analysis identified 11,046 differentially expressed genes, of which 5615 and 5431 genes were upregulated and downregulated, respectively, from before differentiation to differentiation. Functional enrichment analyses revealed that the upregulated genes were associated with skeletal muscle contraction, autophagy, and sarcomeres while the downregulated genes were associated with ribonucleoprotein complex biogenesis, mRNA processing, ribosomes, and other biological processes or cellular components. Western blot analyses showed an increased conversion of LC3-I to LC3-II protein during myoblast differentiation, further demonstrating the upregulation of autophagy during myoblast differentiation. Blocking the autophagic flux in C2C12 cells with chloroquine inhibited the expression of skeletal-muscle-specific genes and the formation of myotubes, confirming a positive role for autophagy in myoblast differentiation and fusion.