Discovery and genetic characterization of novel paramyxoviruses from small mammals in Hubei Province, Central China.

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.

Diversity and genetic characterization of orthohantavirus from small mammals and humans during 2012-2022 in Hubei Province, Central China.

Hemorrhagic fever with renal syndrome (HFRS) is a significant public health problem in Hubei Province, China, where a novel strain of orthohantavirus, HV004, was reported in 2012. However, no systematic study has investigated the prevalence and variation of orthohantavirus in rodents and humans. Herein, 2137 small mammals were collected from ten HFRS epidemic areas in Hubei Province from 2012 to 2022, and 143 serum samples from patients with suspected hemorrhagic fever were collected from two hospitals from 2017 to 2021. Orthohantavirus RNA was recovered from 134 lung tissue samples from five rodent species, with a 6.27 % prevalence, and orthohantavirus was detected in serum samples from 25 patients. Genetic analyses revealed that orthohantavirus hantanense (HTNV), orthohantavirus seoulense (SEOV), and orthohantavirus dabieshanense (DBSV) are co-circulating in rodents in Hubei, and HTNV and SEOV were identified in patient serum. Phylogenetic analysis showed that most of the HTNV sequences were clustered with HV004, indicating that HV004-like orthohantavirus was the main HNTV subtype in rodents. Two genetic reassortments and six recombination events were observed in Hubei orthohantaviruses. In summary, this study identified the diversity of orthohantaviruses circulating in Hubei over the past decade, with the HV004-like subtype being the main genotype in rodents and patients. These findings highlight the need for continued attention and focus on orthohantaviruses, especially concerning newly identified strains.

Thermally engineered MSC-derived extracellular vesicles ameliorate colitis in mice by restoring the imbalanced Th17/Treg cell ratio.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have garnered extensive interest for their immunomodulatory properties in immune-mediated inflammatory diseases. However, the development of EVs as clinical drugs often faces challenges such as low production yield and suboptimal therapeutic efficacy. In this study, we discovered that thermally engineering was able to enhance the yield of MSC-EVs. Moreover, the PD-L1 expression of EVs released from the thermal engineering MSCs was found to be upregulated significantly, and these EVs ameliorated the symptoms and pathological damages in murine dextran sulfate sodium (DSS)-induced colitis model. The therapeutic effect on DSS-induced colitis was mediated through the regulation of the Th17/Treg cell balance, demonstrating the immunomodulatory properties of the thermally engineering MSC-EVs. Overall, our findings suggest that thermal engineering can be utilized as a promising strategy for enhancing EV production and may provide a potential therapeutic approach for clinical treatment of colitis.

Extensive genetic diversity of severe fever with thrombocytopenia syndrome virus circulating in Hubei Province, China, 2018-2022.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The clinical disease characteristics and case fatality rates of SFTSV may vary across distinct regions and among different variant genotypes. From 2018 to 2022, we surveyed and recruited 202 severe fever with thrombocytopenia syndrome (SFTS) patients in Hubei Province, a high-incidence area of the epidemic, and conducted timely and systematic research on the disease characteristics, SFTSV diversity, and the correlation between virus genome variation and clinical diseases. Our study identified at least 6 genotypes of SFTSV prevalent in Hubei Province based on the analysis of the S, M, and L genome sequences of 88 virus strains. Strikingly, the dominant genotype of SFTSV was found to change during the years, indicating a dynamic shift in viral genetic diversity in the region. Phylogenetic analysis revealed the genetic exchange of Hubei SFTSV strains was relatively frequent, including 3 reassortment strains and 8 recombination strains. Despite the limited sample size, SFTSV C1 genotype may be associated with higher mortality compared to the other four genotypes, and the serum amyloid A (SAA) level, an inflammatory biomarker, was significantly elevated in these patients. Overall, our data summarize the disease characteristics of SFTSV in Hubei Province, highlight the profound changes in viral genetic diversity, and indicate the need for in-depth monitoring and exploration of the relationship between viral mutations and disease severity.

Surveillance of Human Rotaviruses in Wuhan, China (2019-2022): Whole-Genome Analysis of Emerging DS-1-like G8P[8] Rotavirus.

Group A rotaviruses (RVAs) are major etiologic agents of gastroenteritis in infants and young children worldwide. To study the prevalence and genetic characteristics of RVAs, a hospital-based surveillance study was conducted in Wuhan, China from June 2019 through May 2022. The detection rates of RVAs were 19.40% (142/732) and 3.51% (8/228) in children and adults, respectively. G9P[8] was the predominant genotype, followed by G8P[8] and G3P[8]. G8P[8] emerged and was dominant in the 2021-2022 epidemic season. The genome constellation of six G8P[8] strains was assigned to G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that the VP7, VP4, VP2, VP3, NSP1, NSP2, NSP3, and NSP5 genes of these G8P[8] strains clustered closely with those of the G8P[8] strains in Asia and were distant from those of the P[8] and G2P[4] strains simultaneously detected in Wuhan. In contrast, the VP1, VP6, and NSP4 genes were closely related to the typical G2P[4] rotavirus, including those of G2P[4] strains simultaneously detected in Wuhan. The detection rate of RVAs decreased in the COVID-19 pandemic era. It was deduced that the G8P[8] rotaviruses that emerged in China may be reassortants, carrying the VP6, VP1, and NSP4 genes derived from the G2P[4] rotavirus in the backbone of the neighboring DS-1-like G8P[8] strains represented by CAU17L-103.

Study on the linkage between macro policy and market effectiveness in China's stock market: Based on run test of China's stock market index.

The macro policy of the stock market is an important market information. The implementation goal of the macro policy of the stock market is mainly to improve the effectiveness of the stock market. However, whether this effectiveness has achieved the goal is worth verifying through empirical data. The exertion of this information utility is closely related to the effectiveness of the stock market. Use the run test method in statistics to collect and sort out the daily data of stock price index in recent 30 years, the linkage between 75 macro policy events and 35 trading days of market efficiencies before and after the macro event are tested since 1992 to 2022. The results show that 50.66% of the macro policies are positively linked to the effectiveness of the stock market, while 49.34% of the macro policies have reduced the effectiveness of the market operation. This shows that the effectiveness of China's stock market is not high, and the nonlinear characteristics are obvious, so the policy formulation of the stock market needs further improvement.

Short-term associations of PM2.5 and PM2.5 constituents with immune biomarkers: A panel study in people living with HIV/AIDS.

Studies on associations of fine particulate matter (PM2.5) with immunity in people living with HIV/AIDS (PLWHA) were absent. We aimed to explore whether changes of immune biomarkers were associated with short-term exposure to PM2.5 in PLWHA. Based on a panel study in Wuhan, we selected 163 PLWHA as participants with up to 4 repeated visits from March 2020 to January 2021. Immune biomarkers, including CD4+T cell count, CD8+T cell count, HIV viral load (VL) and CD4+T/CD8+T ratio were tested for all participants at each visit. Residential exposures of PM2.5 and PM2.5 constituents for each participant were assessed using spatial-temporal models. Linear mixed-effect models and general linear mixed models were applied to evaluate the associations between PM2.5 and immune biomarkers. To estimate the combined effect of PM2.5 constituents, weighted quantile sum regression and Bayesian kernel machine regression were employed. Each 10 µg/m3 increase of 7-day average PM2.5 concentrations was associated with an 8.75 cells/mm3 (95%CI: -15.55, -1.98) decrease in CD4+T cell count and a 92% (OR: 1.92, 95%CI: 1.43, 2.58) increased odds ratio of detectable HIV VL. However, the odds ratio of inverted CD4+T/CD8+T was only positively associated with PM2.5 concentrations at lag2 day (OR:1.27, 95%CI:1.02, 1.57). CD4+T may be a potential mediator between PM2.5 and detectable HIV VL with 3.83% mediated proportion. Besides, the combined effect of PM2.5 chemical constituents indicated that NO3- and SO42- were the main constituents in reducing CD4+T cell count and increasing odds ratio of detectable HIV VL. Our finding revealed that short-term exposure to PM2.5 was negatively associated with CD4+T cell count but positively related to the odds ratio of detectable HIV VL in PLWHA. This research may provide new evidence in associations between PM2.5 and immune biomarkers as well as improving prognosis of PLWHA.

Development of Machine Learning Algorithms Incorporating Electronic Health Record Data, Patient-Reported Outcomes, or Both to Predict Mortality for Outpatients With Cancer.

PURPOSE: Machine learning (ML) algorithms that incorporate routinely collected patient-reported outcomes (PROs) alongside electronic health record (EHR) variables may improve prediction of short-term mortality and facilitate earlier supportive and palliative care for patients with cancer. METHODS: We trained and validated two-phase ML algorithms that incorporated standard PRO assessments alongside approximately 200 routinely collected EHR variables, among patients with medical oncology encounters at a tertiary academic oncology and a community oncology practice. RESULTS: Among 12,350 patients, 5,870 (47.5%) completed PRO assessments. Compared with EHR- and PRO-only algorithms, the EHR + PRO model improved predictive performance in both tertiary oncology (EHR + PRO v EHR v PRO: area under the curve [AUC] 0.86 [0.85-0.87] v 0.82 [0.81-0.83] v 0.74 [0.74-0.74]) and community oncology (area under the curve 0.89 [0.88-0.90] v 0.86 [0.85-0.88] v 0.77 [0.76-0.79]) practices. CONCLUSION: Routinely collected PROs contain added prognostic information not captured by an EHR-based ML mortality risk algorithm. Augmenting an EHR-based algorithm with PROs resulted in a more accurate and clinically relevant model, which can facilitate earlier and targeted supportive care for patients with cancer.

Association Between Nephrologist Ownership of Dialysis Facilities and Clinical Outcomes.

Importance: Ownership of US dialysis facilities presents a financial conflict of interest for nephrologists, who may change their clinical practice to improve facility profitability. Objective: To investigate the association between nephrologist ownership of freestanding dialysis facilities and clinical outcomes. Design, Setting, and Participants: This cross-sectional study was conducted using US Renal Data System data linked to a data set of freestanding nonpediatric dialysis facility owners. Participants were a sample of all adults with fee-for-service Medicare receiving dialysis for end-stage kidney disease from January 2017 to November 2017 at included facilities. Data were analyzed from April 2020 through August 2022. Exposures: Outcomes associated with nephrologist ownership were assessed using a difference-in-differences analysis comparing the difference in outcomes between patients treated by nephrologist owners and patients treated by nonowners within facilities owned by nephrologists after accounting for differences in patient outcomes between nephrologist owners and nonowners in other facilities. Main Outcomes and Measures: Outcomes plausibly associated with nephrologist ownership were evaluated: (1) treatment volumes (missed treatments and transplant waitlist status); (2) erythropoietin-stimulating agent (ESA) use and related outcomes (anemia, defined as hemoglobin level <10 g/dL, and blood transfusions), (3) quality metrics (mortality, hospitalizations, 30-day readmissions, hemodialysis adequacy, arteriovenous fistula use, and hemodialysis catheter use for ≥3 months), and (4) home dialysis use. Results: A cohort of 251 651 patients (median [IQR] age, 66 [46-85] years; 112 054 [44.5%] women; 9765 Asian [3.9%], 86 837 Black [34.5%], and 148 617 White [59.1%]; 38 938 Hispanic [15.5%]) receiving dialysis for end-stage kidney disease were included. Patient treatment by nephrologist owners at their owned facilities was associated with a 2.4 percentage point (95% CI, 1.1-3.8 percentage points) higher probability of home dialysis, a 2.2 percentage point (95% CI, 3.6-0.7 percentage points) lower probability of receiving an ESA, and no significant difference in anemia or blood transfusions. Patient treatment by nephrologist owners at their owned facilities was not associated with differences in missed treatments, transplant waitlisting, mortality, hospitalizations, 30-day readmissions, hemodialysis adequacy, or fistula or long-term dialysis catheter use. Conclusions and Relevance: This cross-sectional cohort study found that nephrologist ownership was associated with increased home dialysis use, decreased ESA use, and no change in anemia or blood transfusions.

Incidence of Timely Outpatient Follow-Up Care After Emergency Department Encounters for Acute Heart Failure.

BACKGROUND: Patients who are discharged from the emergency department (ED) after an encounter for acute heart failure are at high risk for return hospitalization. These patients may benefit from timely outpatient follow-up care to reassess volume status, adjust medications, and reinforce self-care strategies. This study examines the incidence of outpatient follow-up care after ED encounters for acute heart failure and describes patient characteristics associated with obtaining timely follow-up care. METHODS: We conducted a retrospective cohort study using an administrative claims database for a large US commercial insurer, from January 1, 2012 to June 30, 2019. Participants included adult patients discharged from the ED with principal diagnosis of acute heart failure. The primary outcome was obtaining an in-person outpatient clinic visit for heart failure within 30 days. We also examined the competing risk of all-cause hospitalization within 30 days and without an intervening outpatient clinic visit. We estimated competing risk regression models to identify patient characteristics associated with obtaining outpatient follow-up and report cause-specific hazard ratios. RESULTS: The cohort included 52 732 patients, with mean age of 73.9 years (95% CI, 73.8-74.0) and 27 395 (52.0% [95% CI, 51.5-52.4]) female patients. Within 30 days of the ED encounter, 12 279 (23.2%) patients attended an outpatient clinic visit for heart failure, with 8382 (15.9%) patients hospitalized before they could obtain an outpatient clinic visit. In the adjusted analysis, patients that were younger, women, reporting non-Hispanic Black race, and had fewer previous clinic visits were less likely to obtain outpatient follow-up care. CONCLUSIONS: Few patients obtain timely outpatient follow-up after ED visits for heart failure, although nearly 20% require hospitalization within 30 days. Improved transitions following discharge from the ED may represent an opportunity to improve outcomes for patients with acute heart failure.

Oncologist phenotypes and associations with response to a machine learning-based intervention to increase advance care planning: Secondary analysis of a randomized clinical trial.

BACKGROUND: While health systems have implemented multifaceted interventions to improve physician and patient communication in serious illnesses such as cancer, clinicians vary in their response to these initiatives. In this secondary analysis of a randomized trial, we identified phenotypes of oncology clinicians based on practice pattern and demographic data, then evaluated associations between such phenotypes and response to a machine learning (ML)-based intervention to prompt earlier advance care planning (ACP) for patients with cancer. METHODS AND FINDINGS: Between June and November 2019, we conducted a pragmatic randomized controlled trial testing the impact of text message prompts to 78 oncology clinicians at 9 oncology practices to perform ACP conversations among patients with cancer at high risk of 180-day mortality, identified using a ML prognostic algorithm. All practices began in the pre-intervention group, which received weekly emails about ACP performance only; practices were sequentially randomized to receive the intervention at 4-week intervals in a stepped-wedge design. We used latent profile analysis (LPA) to identify oncologist phenotypes based on 11 baseline demographic and practice pattern variables identified using EHR and internal administrative sources. Difference-in-differences analyses assessed associations between oncologist phenotype and the outcome of change in ACP conversation rate, before and during the intervention period. Primary analyses were adjusted for patients' sex, age, race, insurance status, marital status, and Charlson comorbidity index. The sample consisted of 2695 patients with a mean age of 64.9 years, of whom 72% were White, 20% were Black, and 52% were male. 78 oncology clinicians (42 oncologists, 36 advanced practice providers) were included. Three oncologist phenotypes were identified: Class 1 (n = 9) composed primarily of high-volume generalist oncologists, Class 2 (n = 5) comprised primarily of low-volume specialist oncologists; and 3) Class 3 (n = 28), composed primarily of high-volume specialist oncologists. Compared with class 1 and class 3, class 2 had lower mean clinic days per week (1.6 vs 2.5 [class 3] vs 4.4 [class 1]) a higher percentage of new patients per week (35% vs 21% vs 18%), higher baseline ACP rates (3.9% vs 1.6% vs 0.8%), and lower baseline rates of chemotherapy within 14 days of death (1.4% vs 6.5% vs 7.1%). Overall, ACP rates were 3.6% in the pre-intervention wedges and 15.2% in intervention wedges (11.6 percentage-point difference). Compared to class 3, oncologists in class 1 (adjusted percentage-point difference-in-differences 3.6, 95% CI 1.0 to 6.1, p = 0.006) and class 2 (adjusted percentage-point difference-in-differences 12.3, 95% confidence interval [CI] 4.3 to 20.3, p = 0.003) had greater response to the intervention. CONCLUSIONS: Patient volume and time availability may be associated with oncologists' response to interventions to increase ACP. Future interventions to prompt ACP should prioritize making time available for such conversations between oncologists and their patients.

Appraising regional anthropogenic heat flux using high spatial resolution NTL and POI data: A case study in the Beijing-Tianjin-Hebei region, China.

Rapid urbanization and the aggregation of human activities in cities have resulted in large amounts of anthropogenic heat (AH) emission, which affects urban climate. Quantifying and assessing the AH emission values accurately and analyzing their spatial distribution characteristics is important to understand the energy exchange processes of urban areas. In this study, the high spatial resolution anthropogenic heat flux (AHF) quantification and spatial distribution analysis were conducted using multi-source data in the Beijing-Tianjin-Hebei region (BTH region) of China. First, the AH emission in district and city level were estimated using inventory method based on energy consumption and socio-economic statistical data; Then, AHF spatial quantification models were constructed based on high spatial resolution nighttime light (NTL) data and Point of interests (POI) data, and 130 m × 130 m gridded AHF quantification result in BTH region was realized; Finally, the potential numerical and spatial distribution patterns of AHF were analyzed using various indicators including contribution rate and aggregation index. The results show that: (1) The parameterized index constructed based on NTL and POI data shows a strong correlation with AHF, with R2 ranging from 0.79 to 0.94 and a mean absolute error (MAE) value of 0.72 w·m-2, which can be applied to the quantification of gridded AHF values with high resolution. The highest total AHF in the study area is 214 w·m-2, and the average value is 2.24 w·m-2. (2) Considering the sources of AHF, industrial emission sources in BTH region contribute the most to the total AHF, but commercial building emission sources in Beijing have a higher contribution, which can reach 33.8%. (3) Different types of AHF have different spatial aggregation levels. Commercial building emission and human metabolic emission have the highest aggregation level, and transportation emission has the lowest aggregation level.

Pathogenic Leptospira Infections in Hubei Province, Central China.

Leptospirosis is an important zoonosis that is caused by pathogenic Leptospira, which is considered to be a re-emerging infectious disease in many countries. Rodents are the most important reservoirs for both human and animal infection. An epidemiological survey of pathogenic Leptospira in rodents is important for the prevention and control of leptospirosis. In this study, a total of 964 rodents were captured from six cities in Hubei Province, and two pathogenic Leptospira species (L. interrogans and L. borgpetersenii) were detected using nested PCR with an overall prevalence of 4.8%. L. interrogans was distributed in five sampling sites, which may be the dominant species of pathogenic Leptospira in Hubei Province. In addition, Rattus norvegicus showed a relatively high infection rate, which may play an important role in the transmission and infection of pathogenic Leptospira. This study reveals the prevalence of pathogenic Leptospira in wild rodents in Hubei Province, suggesting that the risk of leptospirosis infection in Hubei Province still exists.

Differences in Cancer Care Expenditures and Utilization for Surgery by Hospital Type Among Patients With Private Insurance.

Importance: With rising expenditures on cancer care outpacing other sectors of the US health system, national attention has focused on insurer spending, particularly for patients with private insurance, for whom price transparency has historically been lacking. The type of hospital at which cancer care is delivered may be an important factor associated with insurer spending for patients with private insurance. Objective: To examine differences in spending and utilization for patients with private insurance undergoing common cancer surgery at National Cancer Institute (NCI) centers vs community hospitals. Design, Setting, and Participants: This retrospective cross-sectional study included adult patients with an incident diagnosis of breast, colon, or lung cancer who underwent cancer-directed surgery from 2011 to 2014. Mean risk-adjusted spending and utilization outcomes were examined for each hospital type using multilevel generalized linear mixed-effects models, adjusting for patient, hospital, and region characteristics. Data were collected from the Health Care Cost Institute's national multipayer commercial claims data set, which encompasses claims paid by 3 of the 5 largest commercial health insurers in the United States (ie, Aetna, Humana, and UnitedHealthcare). Data analyses were conducted from February 2018 to February 2019. Exposures: Hospital type at which cancer surgery was performed: NCI, non-NCI academic, or community. Main Outcomes and Measures: Spending outcomes were surgery-specific insurer prices paid and 90-day postdischarge payments. Utilization outcomes were length of stay (LOS), emergency department (ED) use, and hospital readmission within 90 days of discharge. Results: The study included 66 878 patients (51 569 [77.1%] women; 31 585 [47.2%] aged ≥65 years) with incident breast (35 788 [53.5%]), colon (21 378 [32.0%]), or lung (9712 [14.5%]) cancer undergoing cancer surgery at 2995 hospitals (5522 [8.3%] at NCI centers; 10 917 [16.3%] at non-NCI academic hospitals; 50 439 [75.4%] at community hospitals). Treatment at NCI centers was associated with higher surgery-specific insurer prices paid compared with community hospitals ($18 526 [95% CI, $16 650-$20 403] vs $14 772 [95% CI, $14 339-$15 204]; difference, $3755 [95% CI, $1661-$5849]; P < .001) and 90-day postdischarge payments ($47 035 [95% CI, $43 289-$50 781] vs $41 291 [95% CI, $40 350-$42 231]; difference, $5744 [95% CI, $1659-9829]; P = .006). There were no significant differences in LOS, ED use, or hospital readmission within 90 days of discharge. Conclusions and Relevance: In this cross-sectional study, surgery at NCI centers vs community hospitals was associated with higher insurer spending for a surgical episode without differences in care utilization among patients with private insurance undergoing cancer surgery. A better understanding of the factors associated with prices and spending at NCI cancer centers is needed.

TMEM182 interacts with integrin beta 1 and regulates myoblast differentiation and muscle regeneration.

BACKGROUND: Transmembrane proteins are vital for intercellular signalling and play important roles in the control of cell fate. However, their physiological functions and mechanisms of action in myogenesis and muscle disorders remain largely unexplored. It has been found that transmembrane protein 182 (TMEM182) is dramatically up-regulated during myogenesis, but its detailed functions remain unclear. This study aimed to analyse the function of TMEM182 during myogenesis and muscle regeneration. METHODS: RNA sequencing, quantitative real-time polymerase chain reaction, and immunofluorescence approaches were used to analyse TMEM182 expression during myoblast differentiation. A dual-luciferase reporter assay was used to identify the promoter region of the TMEM182 gene, and a chromatin immunoprecipitation assay was used to investigate the regulation TMEM182 transcription by MyoD. We used chickens and TMEM182-knockout mice as in vivo models to examine the function of TMEM182 in muscle growth and muscle regeneration. Chickens and mouse primary myoblasts were used to extend the findings to in vitro effects on myoblast differentiation and fusion. Co-immunoprecipitation and mass spectrometry were used to identify the interaction between TMEM182 and integrin beta 1 (ITGB1). The molecular mechanism by which TMEM182 regulates myogenesis and muscle regeneration was examined by Transwell migration, cell wound healing, adhesion, glutathione-S-transferse pull down, protein purification, and RNA immunoprecipitation assays. RESULTS: TMEM182 was specifically expressed in skeletal muscle and adipose tissue and was regulated at the transcriptional level by the myogenic regulatory factor MyoD1. Functionally, TMEM182 inhibited myoblast differentiation and fusion. The in vivo studies indicated that TMEM182 induced muscle fibre atrophy and delayed muscle regeneration. TMEM182 knockout in mice led to significant increases in body weight, muscle mass, muscle fibre number, and muscle fibre diameter. Skeletal muscle regeneration was accelerated in TMEM182-knockout mice. Furthermore, we revealed that the inhibitory roles of TMEM182 in skeletal muscle depend on ITGB1, an essential membrane receptor involved in cell adhesion and muscle formation. TMEM182 directly interacted with ITGB1, and this interaction required an extracellular hybrid domain of ITGB1 (aa 387-470) and a conserved region (aa 52-62) within the large extracellular loop of TMEM182. Mechanistically, TMEM182 modulated ITGB1 activation by coordinating the association between ITGB1 and laminin and regulating the intracellular signalling of ITGB1. Myogenic deletion of TMEM182 increased the binding activity of ITGB1 to laminin and induced the activation of the FAK-ERK and FAK-Akt signalling axes during myogenesis. CONCLUSIONS: Our data reveal that TMEM182 is a novel negative regulator of myogenic differentiation and muscle regeneration.

Trajectories of mortality risk among patients with cancer and associated end-of-life utilization.

Machine learning algorithms may address prognostic inaccuracy among clinicians by identifying patients at risk of short-term mortality and facilitating earlier discussions about hospice enrollment, discontinuation of therapy, or other management decisions. In the present study, we used prospective predictions from a real-time machine learning prognostic algorithm to identify two trajectories of all-cause mortality risk for decedents with cancer. We show that patients with an unpredictable trajectory, where mortality risk rises only close to death, are significantly less likely to receive guideline-based end-of-life care and may not benefit from the integration of prognostic algorithms in practice.

Novel 61-bp Indel of RIN2 Is Associated With Fat and Hatching Weight Traits in Chickens.

The Ras and Rab interactor 2 (RIN2) gene, which encodes RAS and Rab interacting protein 2, can interact with GTP-bound Rab5 and participate in early endocytosis. This study found a 61-bp insertion/deletion (indel) in the RIN2 intron region, and 3 genotypes II, ID, and DD were observed. Genotype analysis of mutation sites was performed on 665 individuals from F2 population and 8 chicken breeds. It was found that the indel existed in each breed and that yellow feathered chickens were mainly of the DD genotype. Correlation analysis of growth and carcass traits in the F2 population of Xinghua and White Recessive Rock chickens showed that the 61-bp indel was significantly correlated with abdominal fat weight, abdominal fat rate, fat width, and hatching weight (P < 0.05). RIN2 mRNA was expressed in all the tested tissues, and its expression in abdominal fat was higher than that in other tissues. In addition, the expression of the RIN2 mRNA in the abdominal fat of the DD genotype was significantly higher than that of the II genotype (P < 0.05). The transcriptional activity results showed that the luciferase activity of the pGL3-DD vector was significantly higher than that of the pGL3-II vector (P < 0.01). Moreover, the results indicate that the polymorphisms in transcription factor binding sites (TFBSs) of 61-bp indel may affect the transcriptional activity of RIN2, and thus alter fat traits in chicken. The results of this study showed that the 61-bp indel was closely related to abdominal fat-related and hatching weight traits of chickens, which may have reference value for molecular marker-assisted selection of chickens.

Whole Transcriptome Analysis Reveals a Potential Regulatory Mechanism of LncRNA-FNIP2/miR-24-3p/FNIP2 Axis in Chicken Adipogenesis.

Lipid biosynthesis is a complex process, which is regulated by multiple factors including lncRNA. However, the role of lncRNA in chicken abdominal fat accumulation is still unclear. In this research, we collected liver tissues from six high abdominal fat rate Sanhuang broilers and six low abdominal fat rate Sanhuang broilers to perform lncRNA sequencing and small RNA sequencing. A total of 2,265 lncRNAs, 245 miRNAs, and 5,315 mRNAs were differently expressed. Among of them, 1,136 differently expressed genes were enriched in the metabolic process. A total of 36 differently expressed genes, which were considered as differently expressed lncRNAs' targets, were enriched in the metabolic process. In addition, we also found out that eight differently expressed miRNAs could target 19 differently expressed genes. FNIP2 and PEX5L were shared in a cis-regulatory network and a differently expressed miRNA target relationship network. LncRNA-FNIP2/miR-24-3p/FNIP2 axis was considered as a potential candidate that may participate in lipid synthesis. Experimentally, the objective reality of lncRNA-FNIP2/miR-24-3p/FNIP2 axis was clarified and the regulation effect of lncRNA-FNIP2/miR-24-3p/FNIP2 axis on synthesis was validated. In brief, our study reveals a potential novel regulatory mechanism that lncRNA-FNIP2/miR-24-3p/FNIP2 axis was considered as being involved in lipid synthesis during chicken adipogenesis in liver.