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Abstract Background Cancer remains a global health concern, with nearly 20 million new cancer cases and approximately 10 million cancer-related deaths reported in 2020.An increasing number of individuals with advanced-stage cancer are likely to confront the reality of mortality.In China, cancer-related deaths hold the top position among factors contributing to resident mortality, accounting for nearly a quarter of all deaths. Patients with advanced-stage cancer contend with both physical challenges such as pain, physical decline, and functional impairments, as well as psychological issues including death anxiety, fear of death, and feelings of meaninglessness and hopelessness during disease treatment. Death education serves as a method to educate patients on coping with death, alleviating death-related anxieties and fears, and approaching death calmly, thereby facilitating a peaceful end-of-life experience. Currently, there is a dearth of death education content tailored to patients’specific circumstances in China. Consequently, this study aims to explore the content of death education needs among patients with advanced-stage cancer in China. Methods A qualitative research based on phenomenology was used to select 19 patients with advanced cancer from November 2022 to June 2023. Semi-structured interviews were used to interview, and Colaizzi 7-step analysis method was used to organize and analyze the data. Results Six themes were extracted: 1. Death cognition and education; 2. Life review; 3. Ethics of death; 4. End-of-life decision-making; 5. Social support; 6. Disease treatment. Conclusions Patients with advanced-stage cancer face significant distress caused by their illness and the prospect of death. This distress can impact their quality of life and even influence treatment decisions. It’s essential to comprehensively assess the current state and needs of patients, engaging in ongoing interventions tailored to individual patient circumstances. This approach involves implementing targeted death education content and methods. When executing death education, it’s imperative to consider the patient’s knowledge framework and their level of acceptance. Integrating the patient’s disease progression and treatment, as well as addressing their negative emotional states, becomes crucial for enhancing the patient’s overall well-being and quality of life.

Abstract Long non-coding RNAs (lncRNAs) are typically described as RNA transcripts exceeding 200 nucleotides in length, which do not code for proteins. Recent advancements in technology, including ribosome RNA sequencing and ribosome nascent-chain complex sequencing, have demonstrated that many lncRNAs retain small open reading frames and can potentially encode micropeptides. Emerging studies have revealed that these micropeptides, rather than lncRNAs themselves, are responsible for vital functions, including but not limited to regulating homeostasis, managing inflammation and the immune system, moderating metabolism, and influencing tumor progression. In this review, we initially outline the rapidly advancing computational analytical methods and public tools to predict and validate the potential encoding of lncRNAs. We then focus on the diverse functions of micropeptides and their underlying mechanisms in the pathogenesis of disease. This review aims to elucidate the functions of lncRNA-encoded micropeptides and explore their potential applications as therapeutic targets in cancer.

Background: The homologous recombination deficiency (HRD) score serves as a promising biomarker to identify patients who are eligible for treatment with PARP inhibitors (PARPi). Previous studies have suggested a 3-biomarker Genomic Instability Score (GIS) threshold of ≥ 42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer. However, the GIS threshold for prostate cancer (PCa) is still lacking. Here, we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients. Methods: A total of 181 patients with metastatic castration-resistant PCa were included in this study. Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair (HRR) genes and copy number variation (CNV) analysis. The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms (SNP) distributed across the human genome, incorporating three SNP-based assays: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors. The relationship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed. Results: Genomic testing was succeeded in 162 patients. In our cohort, 61 patients (37.7%) had HRR mutations (HRRm). BRCA mutations occurred in 15 patients (9.3%). The median HRD score was 4 (ranged from 0 to 57) in the total cohort, which is much lower than that in breast and ovarian cancers. Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores. CNV occured more frequently in patients with HRRm. The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores ≥43. In the 16 patients who received PARPi in our cohort, 4 patients with a high HRD score achieved an objective response rate (ORR) of 100% while 12 patients with a low HRD score achieved an ORR of 8.3%. Progression-free survival (PFS) in HRD high patients was longer compared to HRD low patients, regardless of HRRm. Conclusions: A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study. Future studies are needed to further verify this threshold.

Summary: Background: China has the largest number of dementia patients in the world, posing a significant health and economic burden. Alzheimer's disease (AD) and other dementia patients face a higher risk of mortality during heatwaves, but relevant studies on this topic have been limited so far. Methods: The study extracted data from the China Cause of Death Reporting System (CDRS) on deaths of AD and other dementia patients aged 60 years and above between 2013 and 2020. Using an individual-level, time-stratified, and case-crossover study design, the effects of heatwaves across nine scenarios on dementia mortality were quantified by conditional logistic regression combined with distributed lag non-linear model (DLNM). Additionally, the attributable fractions (AFs) of deaths due to heatwaves were calculated. Findings: A total of 399,036 death cases were reported caused by AD and other dementias during the study period. It was found that heatwaves significantly increased the risk of death among people with AD and other dementias. As the intensities and durations of the heatwaves increased, the lag0-7 cumulative odds ratios (CORs) of mortality increased progressively from 1.140 (95% CI: 1.118, 1.163) under the mildest heatwave to 1.459 (95% CI: 1.403, 1.518) under the most severe one, across nine heatwave scenarios examined. Additionally, under specific heatwave scenarios, sex and regions modified the mortality risk, but no significant age differences were observed. The AFs of AD and other dementia mortality due to milder heatwaves were lower compared to more severe heatwaves, ranging from 12.281% (95% CI: 10.555%, 14.015%) to 31.460% (95% CI: 28.724%, 34.124%). Interpretation: The study provided critical insights into the substantial increase in heatwave-related mortality among AD and other dementia patients during and after heatwave events. The results from our quantitative analyses will provide needed scientific evidence for policymakers and practitioners to develop relevant policies and guidelines to protect the health and well-beings of vulnerable populations in future in the context of both seasonal changes and long-term climate change. Funding: This work was supported by the Project of Prevention and Intervention on Major Diseases for Elderly in China, NCNCD [00240201307], the National Key Research and Development Program of China [2022YFC2602301, 2023YFC2308703] and the Science and Technology Fundamental Resources Investigation Program of China [2017FY101201].

During the COVID-19, wastewater-based epidemiology (WBE) has become a powerful epidemic surveillance tool widely used worldwide. However, the development and application of this technology in Chinese Mainland are relatively lagging. Herein, we for the first time monitored the community circulation of SARS-CoV-2 lineages using WBE methods in Chinese Mainland. During the peak period of infection outbreak at the end of 2022, six precious sewage samples were collected from the manhole in the student dormitory area on Wangjiang Campus of Sichuan University. RT-qPCR revealed that the six sewage samples were all positive for SARS-CoV-2 RNA. Multiplex PCR amplicon sequencing of the sewage samples reflected the local transmission of SARS-CoV-2 variants. The results of two deconvolution methods indicate that the main virus lineages have clear evolutionary genetic correlations. Furthermore, the sampling time is consistent with the timeline of concern for these virus lineages, as well as the timeline of uploading the nucleic acid sequences from the corresponding lineages in Sichuan to the database. These results demonstrate the reliability of the sewage sequencing results. Multiplex PCR amplicon sequencing is by far the most powerful analytical tool of WBE, enabling quantitative detection of virus lineages transmission and evolution at the community level.

In practical engineering applications, the prevalence of buried pipelines characterized by substantial filling heights and diameters is steadily increasing. The conventional approach to evaluating the stress in buried pipelines typically relies on elastic behavior assumptions. However, when dealing with significant deformations of pipelines, there tends to be a noticeable disparity between calculated results and actual measurements. The main goal of this research is to examine the mechanical properties of steel corrugated pipe culverts subjected to large deformations. We use the Maston-Spangler model theory to figure out the deformation and bending stress of steel corrugated pipe culverts that are deforming a lot. Following this, we utilize finite element analysis using ANSYS software to perform numerical simulations. The simulation presented in this study involves the modeling of a steel corrugated pipe culvert as an ideal elastic-plastic structure. Incremental external loading is given to the culvert until it achieves its limit condition. This study aims to conduct a thorough analysis on the influence of two key variables, namely filling height and pipe diameter, on steel corrugated pipe culverts. The objective is to establish quantitative expressions and descriptive coefficients that accurately depict the impact of these elements. The determination of deformation and bending stress in a steel corrugated pipe culvert, when subjected to significant deformation, is achieved by utilizing a customized mathematical formula. The aforementioned formula is a useful tool for informing the design of steel corrugated pipe culverts, specifically in terms of their ability to endure substantial filling heights and notable deformations.

Abstract Aims To explore the role and mechanism of Notch signaling and ERK1/2 pathway in the inhibitory effect of sacubitril/valsartan on the proliferation of vascular smooth muscle cells (VSMCs). Main methods Human aortic vascular smooth muscle cells (HA-VSMCs) were cultured in vitro. The proliferating VSMCs were divided into three groups as control group, Ang II group and Ang II + sacubitril/valsartan group. Cell proliferation and migration were detected by CCK8 and scratch test respectively. The mRNA and protein expression of PCNA, MMP-9, Notch1 and Jagged-1 were detected by qRT-PCR and Western blot respectively. The p-ERK1/2 expression was detected by Western blot. Key findings Compared with the control group, proliferation and migration of VSMCs and the expression of PCNA, MMP-9, Notch1, Jagged-1 and p-ERK1/2 was increased in Ang II group. Sacubitril/valsartan significantly reduced the proliferation and migration. Additionally, pretreatment with sacubitril/valsartan reduced the PCNA, MMP-9, Notch1, Jagged-1 and p-ERK1/2 expression.

Abstract Objective PD-L1, a target of immune checkpoint blockade, has been proven to take the role of an oncogene in most human tumors. However, the role of PD-L1 in human pan-cancers has not yet been fully investigated. Materials and methods Pan-cancer analysis was conducted to analyze expression, genetic alterations, prognosis analysis, and immunological characteristics of PD-L1. Estimating the correlation between PD-L1 expression and survival involved using pooled odds ratios and hazard ratios with 95% CI. The Kaplan–Meier (K-M) technique, COX analysis, and receiver operating characteristic (ROC) curves were applied to the survival analysis. Additionally, we investigated the relationships between PD-L1 and microsatellite instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers using Spearman's correlation analysis. Also, immunohistochemical analysis and qRT-PCR were employed in evaluating PD-L1’s protein and mRNA expression in pan-caner. Results PD-L1 showed abnormal mRNA and protein expression in a variety of cancers and predicted prognosis in cancer patients. Furthermore, across a variety of cancer types, the aberrant PD-L1 expression was connected to the MSI, MMR, TMB, drug sensitivity, and tumor immune microenvironment (TIME). Moreover, PD-L1 was significantly correlated with infiltrating levels of immune cells (T cell CD8 + , neutrophil, and so on). Conclusion Our study provides a better theoretical basis and guidance for the clinical treatment of PD-L1.

To understand the asymmetric flow of a slender body with low-aspect ratio fins, a wind tunnel experiment was carried out, and the asymmetric flow was observed when the pair of fins had a symmetric deflection angle of 30° at a small angle of attack and zero sideslip angle at transonic speeds. The unsteady characteristics of flow around the moving fins, especially for the evolution of the asymmetric flow, was carefully numerically investigated via the RANS method. To verify the numerical method, the experimental steady wind tunnel data of the NACA 0012 airfoil with sinusoidal pitching motion were adopted. A hysteresis loop exists as a function of the deflection angle during the upstroke and downstroke motions. The side force is periodic due to the asymmetric flow peaks at the downstroke and their peak value appeared at around δz = 25°, which was independent of the deflection frequency. As the deflection frequency increased, the asymmetric flow formed at a higher deflection angle during the upstroke motion, but decayed at a lower deflection angle during the downstroke motion, resulting in a more significant unsteady hysteresis effect.

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.

Abstract The size of plant lateral organs is determined by well-coordinated cell proliferation and cell expansion. Here, we report that miR159, an evolutionarily conserved microRNA, plays an essential role in regulating cell division in rose (Rosa hybrida) petals by modulating cytokinin catabolism. We uncover that Cytokinin Oxidase/Dehydrogenase6 (CKX6) is a target of miR159 in petals. Knocking down miR159 levels results in the accumulation of CKX6 transcripts and earlier cytokinin clearance, leading to a shortened cell division period and smaller petals. Conversely, knocking down CKX6 causes cytokinin accumulation and a prolonged developmental cell division period, mimicking the effects of exogenous cytokinin application. MYB73, a R2R3-type MYB transcription repressor, recruits a co-repressor (TOPLESS) and a histone deacetylase (HDA19) to form a suppression complex, which regulates MIR159 expression by modulating histone H3 lysine 9 acetylation levels at the MIR159 promoter. Our work sheds light on mechanisms for ensuring the correct timing of the exit from the cell division phase and thus organ size regulation by controlling cytokinin catabolism.

Abstract. Background:. Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. Methods:. Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. Results:. A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4+ T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg 2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P

Abstract Background Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). Methods We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. Results Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84–21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08–0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. Conclusions Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

Abstract Microbial flora plays an important role in microorganism-enhanced technology. The pollutant degradation ability and viable counts of these agents are crucial to guarantee their practical application. In this study, an efficient pollutant-degrading microbial flora was screened, its medium components and culture conditions were optimized, and its effect was verified in zeolite trickling filter towers. After a 24 h culture under the optimal conditions, the viable count reached 4.76 × 109 cfu/mL, with the degradation rates of ammonia nitrogen (NH4 +-N), nitrate nitrogen (NO3 −-N), total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) increased to 93.5%, 100%, 68.3%, 32.6%, and 85%, respectively. After optimizing the feeding strategy, the concentration of viable bacteria reached 5.80 × 109 cfu/mL. In the application effect verification experiment, the degradation rates of NH4 +-N, TN, TP, and COD in the experimental group reached 96.69%, 75.18%, 73.82%, and 90.83%, respectively, showing a significant improvement compared to the results of the control group. The main components in the control group were Dokdonella, Brevundimonas, Alishewanella, Rhodobacter, Pseudoxanthomonas, and Thauera, whereas those in the experimental group were Dokdonella, Proteocatella, Rhodobacter, Dechlomonas, and Nitrospira. Proteocatella, Dechlomonas, and Nitrosra, which were unique to the experimental group, are common bacteria used for nitrogen and phosphorus removal. This explains the difference in the sewage treatment capacity between the two groups. This study provides an alternative sewage treatment microbial flora with a reasonable production cost and high degradation efficiency for NH4 +-N, TN, TP, and COD.

One of the major factors inhibiting the construction of deep underground projects is the risk posed by rockbursts. A study was conducted on the access tunnel of the Shuangjiangkou hydropower station to determine the evolutionary mechanism of microfractures within the surrounding rock mass during rockburst development and develop a rockburst warning model. The study area was chosen through the combination of field studies with an analysis of the spatial and temporal distribution of microseismic (MS) events. The moment tensor inversion method was adopted to study rockburst mechanism, and a dynamic Bayesian network (DBN) was applied to investigating the sensitivity of MS source parameters for rockburst warnings. A MS multivariable rockburst warning model was proposed and validated using two case studies. The results indicate that fractures in the surrounding rock mass during the development of strain-structure rockbursts initially show shear failure and are then followed by tensile failure. The effectiveness of the DBN-based rockburst warning model was demonstrated using self-validation and K-fold cross-validation. Moment magnitude and source radius are the most sensitive factors based on an investigation of the influence on the parent and child nodes in the model, which can serve as important standards for rockburst warnings. The proposed rockburst warning model was found to be effective when applied to two actual projects.

ABSTRACT: Objectives: Emergence of carbapenemase and tigecycline resistance genes in pathogens threatens the efficacy of last-resort antibiotics. High attention should be paid to the spread and convergence of such resistance genes. This study reports an extensively drug-resistant (XDR) Providencia rettgeri clinical strain co-harbouring carbapenemase genes blaNDM-1, blaOXA-10 and the tmexCD3-toprJ1b gene cluster. Methods: The phenotype and genotype of P. rettgeri Pre20-95 were investigated by antimicrobial susceptibility testing, conjugation assay, stability testing and whole genome sequencing. Bioinformatics tools were used to uncover the genetic structures of its multidrug-resistant (MDR) plasmid pPre20-95-1 and SXT/R391 integrative and conjugative element ICEPreChn20-95. Results: P. rettgeri strain Pre20-95 was isolated from a human clinical infection and displayed an extensively drug-resistant (XDR) phenotype. Whole genome sequencing (WGS) analysis identified a pPrY2001-like MDR plasmid, namely pPre20-95-1, co-harbouring blaNDM-1 and blaOXA-10 genes in Pre20-95. The multidrug resistance region of pPre20-95-1 was composed of a Tn6625-derived module and a ∆Tn1696 structure, and blaNDM-1 and blaOXA-10 were located in a composite Tn structure consisting of insertion sequences ISCR1 and ISAba125 and an In125-like class 1 integron, respectively. Furthermore, the novel RND efflux pump gene cluster tmexCD3-toprJ1b was identified on the SXT/R391 ICE ICEPreChn20-95 of its chromosome, and reverse PCR showed that it could form a circular intermediate for transmission. Conclusion: Our findings highlight further dissemination of the tmexCD3-toprJ1b gene cluster into a clinical isolate of P. rettgeri and convergence with multiple carbapenemase genes, which increases the risk of the emergence of XDR strains and threatens the treatment of Enterobacterales bacterial infections.

Introduction Hysterectomy is the most common surgical procedure in the field of gynaecology. The traditional multiport laparoscopy, transumbilical laparoendoscopic single-site surgery (TU-LESS) and transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy approaches have been implemented to varying degrees in clinical practice. At present, although their feasibility has been proven, there are no large randomised controlled studies on postoperative rehabilitation. This study aims to evaluate postoperative recovery and assess the safety and effectiveness of these three surgical approaches for total laparoscopic hysterectomy.Method and analysis This is a multicentre, randomised, single-blind, three-arm, parallel-group, interventional clinical trial. Recruitment will be carried out in five tertiary hospitals in China. Patients diagnosed with benign uterine disease or precancerous lesions will be assigned to the vNOTES group, TU-LESS group and conventional laparoscopy group at a 1:1:1 ratio. The achievement rate of comprehensive indices of enhanced recovery after surgery (ERAS) within 24 hours postoperatively will be considered the primary outcome (the comprehensive indicators of ERAS include fluid intake, passing flatus, urination after catheter removal, ambulation and a Visual Analogue Scale score ≤3.) This study will use a non-inferiority test, with a power (1−ß) of 80% and a margin of −0.15, at a one-sided α of 0.0125. The sample size will be 480 patients (including an assumed 15% dropout rate), calculated according to the primary outcome.Ethics and dissemination This study was approved on 25 April 2022 by the Medical Ethics Committee of West China Second University Hospital (2022(057)), Sichuan University, Chengdu, China. All participants will be required to provide informed consent before their participation in the study. The results of the trial will be submitted for publication in a peer-reviewed journal and presented at international conferences.Protocol version V.3.0, 31 August 2023.Trial registration number ChiCTR2200057405.

With the increasingly widespread application of CMOS image sensors (CIS) in radiation environments, such as aerospace, their radiation effects have gained attention. This paper investigates single-event transient (SET) caused by the proton direct ionization on CIS, combining both experimental and simulation methods. The proton beam energy used in the experiment is 12 MeV, with a flux up to 3.5 × 108 p/(cm2 s). Due to the periodicity of the proton beam, the CIS output displays a phenomenon of alternating brightness and darkness. When the proton beam flux is low, numerous SET bright spots with different outputs are observed. To comprehensively analyze these experimental phenomena, a typical three-dimensional 4T pinned photodiode model is constructed in TCAD, and relevant SET simulation is carried out. The results indicate that incident position, incident time, and the number of incident protons significantly affect the output of SET-generated bright spots, which are key factors contributing to the different bright spots observed in the experiment.

DNMT3A participates in de novo methylation, yet its impact on the proliferation of testicular Sertoli cells remains unclear. Development-specific methylation has been proven to be associated with cellular development. Therefore, in this study, we simulated DNMT3A expression pattern during testicular development by DNMT3A interference. Then, RRBS and RNA-seq were used to decipher DNMT3A regulatory mechanisms on Sertoli cell proliferation. Immunofluorescence staining revealed the expression of DNMT3A in the Sertoli cells of the prepubertal testis. DNMT3A was demonstrated to inhibit the cell cycle and proliferation of Sertoli cells, while promoting cell apoptosis. After transfected with DNMT3A interference, a total of 560 DEGs and 2,091 DMGs produced by DNMT3A interference were identified between two treated groups, respectively. Integrating the results from RRBS and RNA-seq, the overlapping genes between DMGs and DEGs were found to be enriched in the Gene Ontology (GO) terms related to cellular development and the Apelin signaling pathway. The present study demonstrated the impact of DNMT3A on the proliferation of porcine testicular Sertoli cells, suggesting that DNMT3A primarily acts through the Apelin signaling pathway. These findings provide valuable insights into how DNMT3A influences testicular development and health, offering new perspectives.

Transient γ-radiation and laser-simulated experiments were carried out to investigate the transient dose rate effect (TDRE) in SiGe heterojunction bipolar transistors (HBTs) for the first time. The results indicate that IBM43RF0100 SiGe HBTs experience a significant sensitivity of TDRE. For the laser-simulated experiment, the duration of transient current and charge collection are matched well with that of transient γ-radiation. The amplitude of transient photocurrent induced by the lower energy order of μJ approaches the transient photocurrent induced by transient γ-radiation. It is demonstrated that laser-simulated experiments are a candidate and a convenient method to evaluate the TDRE response of SiGe HBTs, which avoids serious electromagnetic interference in the transient γ-radiation environment.

ABSTRACTThe length of stay (LOS) in hospital varied considerably in different patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The study aimed to explore the clinical characteristics of Omicron patients, identify prognostic factors, and develop a prognostic model to predict the LOS of Omicron patients. This was a single center retrospective study in a secondary medical institution in China. A total of 384 Omicron patients in China were enrolled. According to the analyzed data, we employed LASSO to select the primitive predictors. The predictive model was constructed by fitting a linear regression model using the predictors selected by LASSO. Bootstrap validation was used to test performance and eventually we obtained the actual model. Among these patients, 222 (57.8%) were female, the median age of patients was 18 years and 349 (90.9%) completed two doses of vaccination. Patients on admission diagnosed as mild were 363 (94.5%). Five variables were selected by LASSO and a linear model, and those with P < 0.05 were integrated into the analysis. It shows that if Omicron patients receive immunotherapy or heparin, the LOS increases by 36% or 16.1%. If Omicron patients developed rhinorrhea or occur familial cluster, the LOS increased by 10.4% or 12.3%, respectively. Moreover, if Omicron patients’ APTT increased by one unit, the LOS increased by 0.38%. Five variables were identified, including immunotherapy, heparin, familial cluster, rhinorrhea, and APTT. A simple model was developed and evaluated to predict the LOS of Omicron patients. The formula is as follows: Predictive LOS = exp(1*2.66263 + 0.30778*Immunotherapy + 0.1158*Familiar cluster + 0.1496*Heparin + 0.0989*Rhinorrhea + 0.0036*APTT).

Abstract Treated AML patients often have measurable residual disease (MRD) due to persisting low-level clones. This study assessed whether residual post-treatment somatic mutations, detected by NGS, were significantly prognostic for subsequent clinical outcomes. AML patients (n = 128) underwent both pre-and post-treatment testing with the same 42-gene MRD-validated NGS assay. After induction, 59 (46%) patients were mutation-negative (0.0024 VAF detection limit) and 69 (54%) had ≥1 persisting NGS-detectable mutation. Compared with NGS-negative patients, NGS-positive patients had shorter overall survival (17 months versus median not reached; P = 0.004; hazard ratio = 2.2 [95% CI: 1.3–3.7]) and a shorter time to relapse (14 months versus median not reached; P = 0.014; HR = 1.9 [95% CI: 1.1–3.1]). Among 95 patients with a complete morphologic remission (CR), 43 (45%) were MRD-positive by NGS and 52 (55%) were MRD-negative. These MRD-positive CR patients had a shorter overall survival (16.8 months versus median not reached; P = 0.013; HR = 2.1 [95% CI: 1.2–3.9]) than did the MRD-negative CR patients. Post-treatment persisting MRD positivity, defined by the same NGS-based test used at diagnosis, is thus a more sensitive biomarker for low-level leukemic clones compared to traditional non-molecular methods and is prognostic of subsequent relapse and death.

Abstract To model the COVID-19 infection and develop effective control measures, this paper proposes an SEIR-type epidemic model considering the impact of face-mask wearing and vaccination. Firstly, the effective reproduction number and the threshold conditions are obtained. Secondly, based on the data of South Korea from January 20, 2022 to March 21, 2022, the model parameters are estimated. Finally, a sensitivity analysis and the numerical study are conducted. The results show that the face-mask wearing is associated with $$83\%$$ 83 % and $$90\%$$ 90 % reductions in the numbers of cumulative cases and newly confirmed cases, respectively, after a period of 60 days, when the face mask wearing rate increases by $$15\%$$ 15 % . Furthermore, the vaccination rate is associated with $$75\%$$ 75 % and $$80\%$$ 80 % reductions in the numbers of cumulative cases and the newly confirmed cases, respectively, after the same period of 60 days when the vaccination rate is increased by $$15\%$$ 15 % . A combined measure involving face-mask wearing and vaccination may be more effective and reasonable in preventing and controlling this infection. It is also suggested that disease control departments should strongly recommended the wearing of face masks s as well as vaccination to prevent the unvaccinated people from becoming infected.

Abstract Thiol/disulfide‐based redox regulation in plant chloroplasts is essential for controlling the activity of target proteins in response to light signals. One of the examples of such a role in chloroplasts is the activity of the chloroplast ATP synthase (CFoCF1), which is regulated by the redox state of the CF1γ subunit and involves two cysteines in its central domain. To investigate the mechanism underlying the oxidation of CF1γ and other chloroplast redox‐regulated enzymes in the dark, we characterized the Arabidopsis cbsx2 mutant, which was isolated based on its altered NPQ (non‐photochemical quenching) induction upon illumination. Whereas in dark‐adapted WT plants CF1γ was completely oxidized, a small amount of CF1γ remained in the reduced state in cbsx2 under the same conditions. In this mutant, reduction of CF1γ was not affected in the light, but its oxidation was less efficient during a transition from light to darkness. The redox states of the Calvin cycle enzymes FBPase and SBPase in cbsx2 were similar to those of CF1γ during light/dark transitions. Affinity purification and subsequent analysis by mass spectrometry showed that the components of the ferredoxin‐thioredoxin reductase/thioredoxin (FTR‐Trx) and NADPH‐dependent thioredoxin reductase (NTRC) systems as well as several 2‐Cys peroxiredoxins (Prxs) can be co‐purified with CBSX2. In addition to the thioredoxins, yeast two‐hybrid analysis showed that CBSX2 also interacts with NTRC. Taken together, our results suggest that CBSX2 participates in the oxidation of the chloroplast redox‐regulated enzymes in darkness, probably through regulation of the activity of chloroplast redox systems in vivo.

Aquaporins (AQPs) are one of the most ancient superfamily proteins, which are essential for maintaining the fluid homeostasis of most organisms against various environments. Here, the latest findings for function of AQPs in cell signal transduction in plants are summarized. We also put forward several issues that still need to be addressed in the future.

Bionic herringbone riblets are applied to relieve the flow near the blade endwall in a linear compressor cascade under the incidence angle of −4° to 6° at a Reynolds number of 382,000. The herringbone riblets are placed at the endwall upstream of the blade, and the Reynolds-averaged Navier–Stokes simulations are performed to explore their effects on corner separation and the control mechanism. The results show that the herringbone riblets can effectively improve the corner separation over the stable operating range, and the control effect is affected by the riblet height and the yaw angle. The implementation of herringbone riblets with a height of only 0.08 boundary layer thickness and a yaw angle of 30 degrees can reduce the total pressure loss by up to 9.89% and increase the static pressure coefficient by 12.27%. Flow details indicate that small-scale vortices in the riblet channels can accumulate and form a high-intensity large-scale vortex close to the bottom of the boundary layer downstream. Compared with traditional vortex generators, the herringbone riblets induce a vortex closer to the wall due to their smaller size, which can reduce the damage of an induced vortex to the mainstream and enhance its control over the bottom of the boundary layer, thereby effectively reducing additional losses. The induced vortex enhances mixing and injects kinetic energy into the low-energy fluid, thus inhibiting the transverse migration of low-energy fluid in the endwall boundary layer, delaying the formation of the separating vortex, further suppressing the development of corner separation and improving the aerodynamic performance of the cascade.

This paper introduces a new finding regarding single event upsets (SEUs) in configuration memory, and their potential impact on enhancing the performance of deep neural networks (DNNs) on the multiprocessor system on chip (MPSoC) platform. Traditionally, SEUs are considered to have negative effects on electronic systems or designs, but the current study demonstrates that they can also have positive contributions to the DNN on the MPSoC. The assertion that SEUs can have positive contributions to electronic system design was supported by conducting fault injections through dynamic reconfiguration on DNNs implemented on a 16nm FinFET technology Zynq UltraScale+ MPSoC. The results of the current study were highly significant, indicating that an SEU in configuration memory could result in an impressive 8.72% enhancement in DNN recognition on the MPSoC. One possible cause is that SEU in the configuration memory leads to slight changes in weight or bias values, resulting in improved activation levels of neurons and enhanced final recognition accuracy. This discovery offers a flexible and effective solution for boosting DNN performance on the MPSoC platform.

Energetic particle strikes the device and induces data corruption in the configuration memory (CRAM), causing errors and even malfunctions in a system on chip (SoC). Software-based fault injection is a convenient way to assess device performance. In this paper, dynamic partial reconfiguration (DPR) is adopted to make fault injection on a Xilinx 16 nm FinFET Ultrascale+ MPSoC. And the reconfiguration module implements the Sobel and Gaussian image filtering, respectively. Fault injections are executed on the static and reconfiguration modules' bitstreams, respectively. Another contribution is that the failure modes and effects analysis (FMEA) method is applied to evaluate the system reliability, according to the obtained injection results. This paper proposes a software-based solution to estimate programmable device vulnerability.

BackgroundFew studies have focused on the performance of Briganti 2012, Briganti 2017 and MSKCC nomograms in the Chinese population in assessing the risk of lymph node invasion(LNI) in prostate cancer(PCa) patients and identifying patients suitable for extended pelvic lymph node dissection(ePLND). We aimed to develop and validate a novel nomogram based on Chinese PCa patients treated with radical prostatectomy(RP) and ePLND for predicting LNI.MethodsWe retrospectively retrieved clinical data of 631 patients with localized PCa receiving RP and ePLND at a Chinese single tertiary referral center. All patients had detailed biopsy information from experienced uropathologist. Multivariate logistic-regression analyses were performed to identify independent factors associated with LNI. The discrimination accuracy and net-benefit of models were quantified using the area under curve(AUC) and Decision curve analysis(DCA).The nonparametric bootstrapping were used to internal validation.ResultsA total of 194(30.7%) patients had LNI. The median number of removed lymph nodes was 13(range, 11-18). In univariable analysis, preoperative prostate-specific antigen(PSA), clinical stage, biopsy Gleason grade group, maximum percentage of single core involvement with highest-grade PCa, percentage of positive cores, percentage of positive cores with highest-grade PCa and percentage of cores with clinically significant cancer on systematic biopsy differed significantly. The multivariable model that included preoperative PSA, clinical stage, biopsy Gleason grade group, maximum percentage of single core involvement with highest-grade PCa and percentage of cores with clinically significant cancer on systematic biopsy represented the basis for the novel nomogram. Based on a 12% cutoff, our results showed that 189(30%) patients could have avoided ePLND while only 9(4.8%) had LNI missing ePLND. Our proposed model achieved the highest AUC (proposed model vs Briganti 2012 vs Briganti 2017 vs MSKCC model: 0.83 vs 0.8 vs 0.8 vs 0.8, respectively) and highest net-benefit via DCA in the Chinese cohort compared with previous nomograms. In internal validation of proposed nomogram, all variables had a percent inclusion greater than 50%.ConclusionWe developed and validated a nomogram predicting the risk of LNI based on Chinese PCa patients, which demonstrated superior performance compared with previous nomograms.

Wastewater-based epidemiology has become a powerful surveillance tool for monitoring the pandemic of COVID-19. Although it is promising to quantitatively correlate the SARS-CoV-2 RNA concentration in wastewater with the incidence of community infection, there is still no consensus on whether the viral nucleic acid concentration in sewage should be normalized against the abundance of endogenous biomarkers and which biomarker should be used as a reference for the normalization. Here, several candidate endogenous reference biomarkers for normalization of SARS-CoV-2 signal in municipal sewage were evaluated. The human fecal indicator virus (crAssphage) is a promising candidate of endogenous reference biomarker for data normalization of both DNA and RNA viruses for its intrinsic viral nature and high and stable content in sewage. Without constructing standard curves, the relative quantification of sewage viral nucleic acid against the abundance of the reference biomarker can be used to correlate with community COVID-19 incidence, which was proved via mimic experiments by spiking pseudovirus of different concentrations in sewage samples. Dilution of pseudovirus-seeded wastewater did not affect the relative abundance of viral nucleic acid, demonstrating that relative quantification can overcome the sewage dilution effects caused by the greywater input, precipitation and/or groundwater infiltration. The process of concentration, recovery and detection of the endogenous biomarker was consistent with that of SARS-CoV-2 RNA. Thus, it is necessary to co-quantify the endogenous biomarker because it can be not only an internal reference for data normalization, but also a process control.

Compared to linear accelerators, pulsed lasers have the characteristics of high efficiency, low cost, stable pulse output, and low environment interference for researching the transient dose rate effect (TDRE) on semiconductor devices. In this paper, pulsed laser radiation experiments are performed on a level-shifting transceiver. The experimental results are consistent with the results of the transient γ-ray radiation experiment, demonstrating the feasibility of using the pulsed laser in TDRE research on the level-shifting transceiver. This paper obtains theoretical and experimental conversion factors (CFs) through theoretical analysis and equivalency of the peak photocurrents, which are measured in pulsed laser and transient γ-ray radiation experiments. The CF results from the two approaches are within 7% of each other. In pulsed laser radiation experiments, an uncommon phenomenon is found. At the I/O (Input/Output) ports of the level-shifting transceiver, a trend of a positive photocurrent followed by a negative pulse is observed. A hypothesis is proposed that this photocurrent is produced by the turn-on and turn-off of the parasitic PNP (Positive-Negative-Positive) transistors in electrostatic discharge circuits at the level-shifting transceiver I/O ports. In addition, this hypothesis is verified by TCAD (Technology Computer Aided Design) simulations.

Low temperature is one of the environmental factors that restrict the growth and geographical distribution of peach (Prunus persica L. Batsch). To explore the molecular mechanisms of peach brunches in response to cold, we analyzed the metabolomics and transcriptomics of ‘Donghe No.1’ (cold-tolerant, CT) and ‘21st Century’ (cold-sensitive, CS) treated by different temperatures (-5 to -30°C) for 12 h. Some cold-responsive metabolites (e.g., saccharides, phenolic acids and flavones) were identified with upregulation only in CT. Further, we identified 1991 cold tolerance associated genes in these samples and they were significantly enriched in the pathways of ‘galactose metabolism’, ‘phenylpropanoid biosynthesis’ and ‘flavonoids biosynthesis’. Weighted gene correlation network analysis showed that soluble sugar, flavone, and lignin biosynthetic associated genes might play a key role in the cold tolerance of peach. In addition, several key genes (e.g., COMT, CCR, CAD, PER and F3’H) were substantially expressed more in CT than CS under cold stress, indicating that they might be major factors during the adaptation of peach to low temperature. This study will not only improve our understanding towards the molecular mechanisms of peach trees under cold stress but also contribute to the screening and breeding program of peach in the future.

Abstract Multidrug resistance gene 1 (MDR1), a key factor contributing to drug insensitivity, has been associated with treatment failure and poor prognoses in various cancers, including bladder urothelial carcinoma (UC). Here we show that positive Nkx2.8 expression was associated with better prognosis of UC patients received chemotherapy. Patients with positive Nkx2.8 expression had promising prognosis from adjuvant chemotherapy. Enforced expression of Nkx2.8 promotes drug sensitivity of UC cells. Mechanistic investigations showed that Nkx2.8 negatively regulated expression of MDR1 by binds directly to the MDR1 promoter and transcriptionally represses MDR1 expression. P-gp inhibitor reversed chemosensitivity inhibition by Nkx2.8 scilencing. In clinical UC specimens, expression of Nkx2.8 inversely correlated with P-gp expression, and UC patients with Nkx2.8 positivity and low P-gp expression displayed the best prognosis. Our findings uncovered a new mechanism of chemosensitivity in UC cells and proposing Nkx2.8-MDR1 axis as a novel candidate target for therapeutic intervention of UC.

Abstract Background Effective and accurate screening of oncological biomarkers in peripheral blood circulation plays an increasingly vital role in diagnosis and prognosis. High-sensitivity assays can effectively aid clinical decision-making and intervene in cancer in a localized status before they metastasize and become unmanageable. Meanwhile, it is equally pivotal to prevent overdiagnosis of non-life-threatening cancer by eliminating unnecessary treatment and repeated blood draws. Unfortunately, current clinical screening methodologies can hardly simultaneously attain sufficient sensitivity and specificity, especially under resource-restrained circumstances. To circumvent such limitations, particularly for cancer biomarkers from early-onset and recurrence, we aim to develop a universal plasmonic platform for clinical applications, which macroscopically amplifies multiplexed fluorescence signals in a broad spectral window and readily adapts to current assay setups without sophisticated accessories or expertise at low cost. Methods The plasmonic substrate was chemically synthesized in situ at the solid–liquid interface by rationally screening a panel of reducing monosaccharides and tuning the redox reactions at various catalyst densities and precursor concentrations. The redox properties were studied by Benedict’s assay and electrochemistry. We systemically characterized the morphologies and optical properties of the engineered plasmonic Ag structures by scanning electron microscopy (SEM) and spectroscopy. The structure-fluorescence enhancement correlation was explicitly explained by the finite-difference time-domain (FDTD) simulation and a computational model for gap distribution. Next, we established an enhanced fluoroimmunoassay (eFIA) using a model biomarker for prostate cancer (PCa) and validated it in healthy and PCa cohorts. Prognosis was explored in patients subject to surgical and hormonal interventions following recommended PCa guidelines. Results The monosaccharide-mediated redox reaction yielded a broad category of Ag structures, including sparsely dispersed nanoparticles (NPs) of various sizes, semi-continuous nanoislands, and crackless continuous films. Optimal broad-spectral fluorescence enhancement from green to far-red was observed for the inhomogeneous, irregularly-shaped semi-continuous Ag nanoisland substrate (AgNIS), synthesized from a well-balanced redox reaction at a stable rate mediated by mannose. In addition, different local electric field intensity distributions in response to various incident excitations were observed at the nanoscale, elucidating the need for irregular and inhomogeneous structures. AgNIS enabled a maximized 54.7-fold macroscopically amplified fluorescence and long-lasting photostability. Point-of-care availability was fulfilled using a customized smartphone prototype with well-paired optics. The eFIA effectively detected the PCa marker in cell lines, xenograft tumors, and patient sera. The plasmonic platform rendered a diagnostic sensitivity of 86.0% and a specificity of 94.7% and capably staged high-grade PCa that the clinical gold standard test failed to stratify. Patient prognosis of robotic-assisted surgeries and hormone therapies was non-invasively monitored following efficient medical interventions. The assay time was significantly curtailed on the plasmonic platform upon microwave irradiation. Conclusions By investigating the effects of reducing monosaccharides on the seed-mediated chemical synthesis of plasmonic Ag structures, we deduced that potent multiplexed fluorescence enhancement originated from both an adequate reducing power and a steady reduction rate. Furthermore, the inhomogeneous structure with adequate medium gap distances afforded optimal multiwavelength fluorescence enhancement, thus empowering an effective eFIA for PCa. The clinically validated diagnostic and prognostic features, along with the low sample volume, point-of-care feasibility with a smartphone, and microwave-shortened assay time, warrant its potential clinical translation for widespread cancer biomarker analysis. Graphical Abstract

Climate change and human activities have caused a range of impacts on the ecological environment. The Loess Plateau (LP) is critical to the stability and health of ecosystems in central and western China, but there is still a lack of research on spatial and temporal heterogeneity in the effects of climate and human activities on the EEQ of the LP. We quantified the ecological environment quality of the study area from 2001 to 2019 based on the improved remote sensing ecological index (RSEI-2) and studied the spatial and temporal evolution of EEQ and its drivers during this period by trend analysis and multiscale geographic weighted regression (MGWR) model. The EEQ of the LP showed an increasingly slowing trend during 2001–2019, with apparent spatial heterogeneity, the south-central part was the hot spot area of change, and the center of gravity of change shifted 124.56 km to the southwest. The driving effects and ranges of each factor changed over time during the study period, and the positive effects of precipitation (PRE) and temperature (TEM) on the EEQ of the southern LP became more apparent, but the negative effects of TEM on the northwestern part have expanded. The negative effect of the intensity of land utilization (LUI) has increased from north to south and has the most profound impact, while population growth has less impact on the central region. The results of this research indicate that the execution of the Grain to Green Program (GGP) in the LP over the last two decades has been effective, but more attention should be paid to the maintenance of the restoration effect in the central region and the reasonable development of the land in the southern area. This research can enhance the comprehension of alterations in ecological factors that impact the environment of the LP. Additionally, it serves as a foundation for investigating strategies for ecological preservation and sustainable land development.

Key points A novel co-culture system was established. Medium composition for the coculture of C. butyricum and B. coagulans was optimized. The optimal medium cost is lower than what was reported.

Abstract Highly infectious illnesses caused by pathogens constitute severe threats to public health and lead to global economic loss. The use of robust and programmable clustered regularly interspaced short palindromic repeat and CRISPR-associated protein (CRISPR-Cas) systems, repurposed from genome-engineering applications has markedly improved traditional nucleic acid detection for precise identification, independently enabling rapid diagnostics of multiplex biomarker with genetic and mutation related to tumors, and microbial pathogens. In this review, we delineate the utility of the current CRISPR-Cas enzyme as biosensors by which these effector toolkits achieve recognition, signaling amplification, and finally, accurate detection. Additionally, we discuss the details of the dominance and hurdles related to expanding this revolutionary technology into an effective and convenient contraption crucial for improving the rational redesign to CRISPR/Cas biosensing. Overall, this review provides an insight into the current status of rapid and POC diagnostic systems by CRISPR/Cas tools.

As new ways to solve partial differential equations (PDEs), physics-informed neural network (PINN) algorithms have received widespread attention and have been applied in many fields of study. However, the standard PINN framework lacks sufficient seepage head data, and the method is difficult to apply effectively in seepage analysis with complex boundary conditions. In addition, the differential type Neumann boundary makes the solution more difficult. This study proposed an improved prediction method based on a PINN with the aim of calculating PDEs with complex boundary conditions such as Neumann boundary conditions, in which the spatial distribution characteristic information is increased by a small amount of measured data and the loss equation is dynamically adjusted by loss weighting coefficients. The measured data are converted into a quadratic regular term and added to the loss function as feature data to guide the update process for the weight and bias coefficient of each neuron in the neural network. A typical geotechnical problem concerning seepage phreatic line determination in a rectangular dam is analyzed to demonstrate the efficiency of the improved method. Compared with the standard PINN algorithm, due to the addition of measurement data and dynamic loss weighting coefficients, the improved PINN algorithm has better convergence and can handle more complex boundary conditions. The results show that the improved method makes it convenient to predict the phreatic line in seepage analysis for geotechnical engineering projects with measured data.

Dryland ecosystems are crucial components within the Earth and atmospheric systems, and a number of projects have been implemented to restore vegetation in drylands in the recent years. However, these regions are experiencing extreme climatic changes, and the impact of these projects are unclear. To gain a better understanding of the effectiveness of these projects, we employed water use efficiency (WUE), the ratio of gross primary production (GPP) to terrestrial evapotranspiration (ET), to predict future dryland ecosystem dynamics, and detected the underlying causes of WUE changes. We analysed the WUE trends and the decomposed components of WUE, namely the GPP to plant transportation ratio (GPP/T) and the plant transportation to terrestrial evapotranspiration (T/ET) ratio, between 2003 and 2018 in China’s drylands. The results indicated that 70.3 % of the study area had an upward WUE trend, and T/ET was the dominant factor of the WUE trend in 74.9 % of the areas investigated. Furthermore, the increase in T/ET was associated with growth in leaf area index (LAI). The rising WUE rate in the vegetation restoration project areas was significantly higher than that in other areas along with the drought gradient (P

Abstract In clinical trials, vitamin D supplementation has been reported to reduce serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) but not high-density lipoprotein cholesterol (HDL-C). In this cohort study we evaluated the association between changes in vitamin D (25-hydroxyvitamin D) and changes in lipid levels in a real-world setting. Changes in lipid levels over a 1-year period were evaluated among individuals whose vitamin D levels increased (group 1) or decreased (group 2) by ≥ 10 ng/mL in year 2018 versus 2017 (cohort 1; n = 5580), in 2019 versus 2018 (cohort 2, n = 6057), or in 2020 versus 2019 (cohort 3, n = 7249). In each cohort, levels of TC, LDL-C, and TG decreased in group 1 and increased in group 2. Between-group differences in average changes in the 3 cohorts ranged from 10.71 to 12.02 mg/dL for TC, from 7.42 to 8.95 mg/dL for LDL-C, and from 21.59 to 28.09 mg/dL for TG. These differences were significant after adjusting for age, sex, race, education, body mass index, blood pressure, smoking status, geographical location, and baseline levels of vitamin D and lipids (P

Abstract The initial in situ stress field influences underground engineering design and construction. Since the limited measured data, it is necessary to obtain an optimized stress field. Although the present stress field can be obtained by valley evolution simulation, the accuracy of the ancient stress field has a remarkable influence. This paper proposed a method using the generative adversarial network (GAN) to obtain optimized lateral stress coefficients of the ancient stress field. A numerical model with flat ancient terrain surfaces is established. Utilizing the nonlinear relationship between measured stress components and present burial depth, lateral stress coefficients of ancient times are estimated to obtain the approximate ancient stress field. Uniform designed numerical tests are carried out to simulate the valley evolution by excavation. Coordinates, present burial depth, present lateral stress coefficients and ancient regression factors of lateral stress coefficients are input to GAN as real samples for training, and optimized ancient regression factors can be predicted. The present stress field is obtained by excavating strata layers. Numerical results show the magnitude and distribution law of the present stress field match well with measured points, thus the proposed method for the stress field inversion is effective.

Abstract Background Mental health problems (e.g., depression and anxiety) are among the most commonly reported comorbidities of HIV. Antiretroviral therapy (ART) coverage has increased sharply. The purposes of this prospective cohort study were to investigate the ART-related experiences and whether they were associated with mental health problems among a sample of people living with HIV undergoing ART in China. Methods The participants were 400 people living with HIV who had started ART for the first time in Guangzhou city. They were followed-up 1-year after ART initiation. Probable depression and moderate/severe anxiety were measured at baseline and Month 12, while experiences related to ART (e.g., side effects and regained self-confidence) were measured at Month 6. Univariate and multivariate logistic regressions were used to explore the associations between baseline characteristics, ART-related experiences and mental health status. Results Among the 300 participants (75.0%) who completed all three surveys, a significant decline in prevalence of probable depression (23.0% at baseline vs. 14.0% at Month 12, P = 0.002) and moderate/severe anxiety (14.7% at baseline vs. 8.7% at Month 12, P = 0.023) was observed during the follow-up period. After adjustment for mental health status and potential confounders at baseline, a number of ART-related experiences at Month 6 were associated with probable depression and/or moderate/severe anxiety measured at Month 12. Improved physical health, relationships with sexual partners, and self-confidence were associated with decreased mental health issues, while the side effects of ART, AIDS-related symptoms, and inconvenience in daily life due to ART use were associated with increased mental health issues. Conclusions ART-related experiences were associated with mental health problems, tailored mental health promotion interventions targeting these experiences are needed.

Since 2000, the Chinese government has implemented a series of ecological restoration policies to combat ecological degradation and land desertification in drylands. However, it remains unclear whether ecosystem services (ES) in drylands have improved since then. To this end, we analyzed the long-term trends (2000–2020) of four ES (NPP, sandstorm prevention, soil retention, and water retention) and the associated drivers in the Hunshandak sandy land of Inner Mongolia by using multi-scale trend analysis. We found that: (1) all the four ES types, including NPP, soil retention, sand prevention, and water retention showed increasing trends, with Zhenglan banner and Kashiketeng banner showing the most significant growth. (2) The changes in ES showed significant spatial heterogeneity, with 54%, 18%, and 53% of the total area still being degraded for NPP, sandstorm prevention, soil retention, and water retention, respectively. The degradation hotspots of ES are mainly located in Sunit Left Banner, Sunit Right Banner, Zhengxiangbai Banner, and Duolun County. (3) Both the conversion of sandy land into grassland due to ecological policies and the improvement of climatic conditions contributed to the enhancement of ES in this region. Our results indicate that ecological restoration policies have improved ES in the Hunshandak Sandy Land, but the effects of the policies show regional unevenness. Future ecological restoration policies should pay more attention to areas with a decreasing trend of ES and to the problem of overgrazing in fragile pastoral areas.

Chloroplast ribulose-5-phosphate-3-epimerase (RPE) is a critical enzyme involved in the Calvin-Benson cycle and oxidative pentose phosphate pathways in higher plants. Three Arabidopsis rpe mutants with reduced level of RPE were identified through their high NPQ (nonphotochemical quenching) phenotype upon illumination, and no significant difference of plant size was found between these rpe mutants and WT (wild type) plants under growth chamber conditions. A decrease in RPE expression to a certain extent leads to a decrease in CO2 fixation, Vcmax and Jmax. Photosynthetic linear electron transport was partially inhibited and activity of ATP synthase was also decreased in the rpe mutants, but the levels of thylakoid protein complexes and other Calvin-Benson cycle enzymes in rpe mutants were not affected. These results demonstrate that some degree of reduction in RPE expression decreases carbon fixation in chloroplasts, which in turn feedback inhibits photosynthetic electron transport and ATP synthase activity due to the photosynthetic control. Taken together, this work provides evidence that RPE plays an important role in the Calvin-Benson cycle and influences the photosynthetic capacity of chloroplasts.

BackgroundThe continued ‘evolution’ of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of the Omicron variant after the Delta variant, resulting in a significant increase in the number of people with COVID-19. This increase in the number of cases continues to have a significant impact on lives. Therefore, a more detailed understanding of the clinical characteristics of Omicron infection is essential.MethodsUsing medical charts, we extracted clinical information for 384 patients infected with the Omicron variant in Anyang City, Henan Province, China. Epidemiology and clinical characteristics were compared with a cohort of people infected with the Delta variant in Zhengzhou in 2021.FindingsCommon initial symptoms at onset of illness were cough [240 (63%)], expectoration [112 (29%)], fever [96 (25%)], nasal congestion [96 (25%)] and myalgia or fatigue [30 (6%)]. In patients with the Omicron variant, levels of total cholesterol, low-density lipoprotein and creatinine increased in 52 (14%), 36 (9%) and 58 (15%) patients, respectively, compared with patients with the Delta variant [one (1%), one (1%) and two (2%)]. Levels of triglyceride and high-density lipoprotein also increased. In patients with the Omicron variant, the levels of specific gravity and the erythrocyte sedimentation rate were increased in 115 (30%) and 81 (21%) patients, and serum levels of complement 3 decreased in 93 (41%).ResultsCompared with patients infected with Delta, no major differences in initial clinical symptoms were identified in patients infected with Omicron. However, dyslipidemia and kidney injury were much more severe in patients with the Omicron variant, and the erythrocyte sedimentation rate was increased. Due to decreased levels of complement 3, the immunity of patients with the Omicron variant was weak.

Background: Many studies have shown that various kinds of diseases were associated with the variation of ambient temperature. However, there’s only a scrap of evidence paying attention to the link between temperature and skin diseases, and no relevant national research was performed in China. Objective: This study aimed to quantify the effect of heat on skin diseases and identify the vulnerable populations and areas in China. Methods: Daily meteorological data, air pollutant data and outpatient data were collected from in 18 sites of China during 2014–2018. A time-series study with distributed lag nonlinear model and multivariate meta-analysis was applied to analyze the site-specific and pooled associations between daily mean temperature and daily outpatient visits of skin diseases by using the data of warm season (from June to September). Stratified analysis by age, sex and climate zones and subtypes of skin diseases were also conducted. Results: We found a positive linear relationship between the ambient temperature and risk of skin diseases, with a 1.25% (95%CI: 0.34%, 2.16%) increase of risk of outpatient visits for each 1 °C increase in daily mean temperature during the warm season. In general, groups aged 18–44 years, males and people living in temperate climate regions were more susceptible to high temperature. Immune dysfunction including dermatitis and eczema were heat-sensitive skin diseases. Conclusions: Our findings suggested that people should take notice of heat-related skin diseases and also provided some references about related health burden for strategy-makers. Targeted measures for vulnerable populations need to be taken to reduce disease burden, including monitoring and early warning systems, and sun-protection measures.

Abstract Background To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P). Methods Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety. Results One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS. Conclusions A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.