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Abstract Background Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor β (ERβ), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERβ-mediated endometriosis is still uncertain. This study aimed to assess that relation. Methods Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERβ were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERβ, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERβ-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERβ and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays. Results Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERβ overexpression. And ERβ promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERβ-mediated development and inflammatory response of endometriosis. Conclusions Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERβ-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis.

Abstract Since 2016, China has progressively relaxed family planning policies to stimulate birth rates. This paper examines the behavioral health repercussions of China’s 2016 universal two-child policy (UTCP) by analyzing sleep pattern data from China Family Panel Studies. Napping is a composite indicator that denotes health outcomes, job quality, and personal well-being. It reveals work conditions and environments to some extent. UTCP may lead to heightened social expectations regarding pregnancy likelihood, and changes in social expectations within the workplace may make work environments less equitable and more stressful for females. Leveraging a difference-in-difference model, this paper explores how napping behaviors among the working-age cohort have responded to the policy shifts. Our analysis reveals a gender discrepancy in response to the policy, specifically, females exhibit a discernible reduction in the likelihood of napping, as well as in the duration of both daytime naps and daily sleep. Conversely, such effects are not significant among males. These results suggest policy consequences extend beyond individuals directly impacted by childbirth or contemplating parenthood. Hence, while promoting fertility is still the government’s goal, policymakers are encouraged to consider the broader challenges the female population faces from social and workplace environment factors.

Abstract Background Mothers play a crucial role in influencing their daughters’ HPV vaccination decisions. Addressing barriers to receiving HPV vaccination among mothers of girls may achieve two goals in one strike: increasing vaccination coverage among both mothers and their daughters. This study aims to examine the HPV vaccination uptake and its determinants among mothers of girls in China at both the individual and interpersonal levels. Methods From July to October 2023, a cross-sectional online study was conducted to investigate HPV vaccine refusal for daughters aged 9–17 years among 11,678 mothers in Shenzhen, China. A randomized selection method was employed, targeting 11 primary schools and 13 secondary schools in Shenzhen. The research team invited mothers of girls to participate in an anonymous online survey. Multilevel logistic regression models (level 1: schools; level 2: individual participants) were employed to analyze the data. Results Among 11,678 mothers, 41.1% self-reported receiving at least one dose of HPV vaccination. Through multilevel logistic regression analysis, eight items measuring illness representations of HPV, which refers to how people think about HPV, were associated with higher HPV vaccination uptake (AOR: 1.02–1.14). These items included identity (identifying symptoms of HPV), timeline (whether HPV is acute/chronic), negative consequences, personal and treatment control (whether HPV is under volitional control), concern, negative emotions, and coherence (overall understanding of HPV). In addition, participants refusing HPV vaccines for the index daughters (AOR: 0.82, 95%CI: 0.76, 0.89) had lower vaccine uptake. Perceived more difficulties in accessing the 9-valent vaccines (AOR: 1.06, 95%CI: 1.04, 1.08) and more satisfaction with vaccine-related promotional materials (AOR: 1.50, 95%CI: 1.46, 1.54) at the individual level were associated with higher vaccine uptake. At the interpersonal factors, higher frequency of exposure to testimonials given by others about HPV vaccination on social media (AOR: 1.19, 95%CI: 1.14, 1.25) and thoughtful consideration of the veracity of the information (AOR: 1.11, 95%CI: 1.07, 1.16) were correlated with higher HPV vaccination uptake. Conclusions These findings offer essential implications for modifying HPV disease perceptions, addressing difficulties in accessing the 9-valent HPV vaccines, and enhancing health communication needs to improve HPV vaccine uptake among mothers of girls.

Abstract Depressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64–97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

Abstract This study delves into the correlation between childhood trauma and non-suicidal self-injury (NSSI) behaviors among high school students. Additionally, it examines the mediating role of stress perception and the moderating role of the teacher-student relationship in this association. A questionnaire survey was administered to 1,329 high school students in Yunnan Province to assess childhood trauma, NSSI behaviors, and stress perception. Firstly, the survey revealed a 12% prevalence of NSSI, with girls exhibiting a higher occurrence compared to boys (OR = 0.413, 95% CI: 0.280–0.609). Secondly, childhood trauma emerged as a significant predictor of NSSI behavior, irrespective of gender or whether the individual was an only child (r = 0.17, P

Abstract Background Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. Methods Utilizing patient data from the First Medical Center of the People’s Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. Results The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. Conclusions The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

Background: Children with ADHD demand for effective intervention with minimum side effect to improve executive function (EF) and health well-being. Method: This study used a three-arm partially-blinded randomized controlled trial to test the effects of two different kinds of 8-week game-based training programs (game-based HIIT program, GameHIIT; and game-based structured aerobic exercise program, GameSAE) on EF and other health indicators of children with ADHD, which was compared with a non-treatment control group. Results: A total of 49 children with ADHD completed the program. Analyses of EF tests and parental survey indicated that (i) there is no significant intragroup difference among all measures between pre-/post-intervention tests for two game-based intervention groups. The only significant intergroup difference was observed in self-monitor score of parent-reported child's EF between GameSAE group and the control (large effect). Similarly, cerebral hemodynamic responses also found no significant group effect for all EF tests. However, the time effects were observed in several channels in the GameHIIT group in two EF tests (Color Words Stroop Test and Tower of London Test). No significant change of participants' overall ADHD symptoms was found in the pre-/post-tests for three groups. Nonetheless, further analyses revealed that both of two game-based training programs exhibited the significant positive effects on child's PA levels and the large effects on levels of physical fitness, when they were compared to the control. Conclusion: By this study, a significant enhancement in physical fitness and PA levels were found in both game-based PA interventions when they were compared with control group. However, the effectiveness of game-based PA interventions on improving EF or reducing ADHD symptoms remains unclear. This implies that a larger intervention dosage or a tailored intervention design may be warranted to improve the EF of children with ADHD.

Abstract Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new therapeutic schemes, but most of which are not satisfactory. Single-cell RNA sequencing was performed in PDX mouse models with or without TCC therapy. 2-’O-Methylation modification and multiplex immunofluorescence staining were used to explore the function and mechanism of SAMD4B in the immune context of HCC. Here, we propose for the first time a synergistic immunochemotherapy that exerts a potent antitumour effect for patients with advanced hepatocellular carcinoma (HCC) in clinical practice based on three common antitumour drugs and found that HCC patients with new synergistic immunochemotherapy had better three-year overall survival (p = 0.004) and significantly higher survival ratio (increased by 2.3 times) than the control group. We further reveal the immunoregulatory mechanism of synergistic immunochemotherapy through 2’-O-Methylation modification mediated by SAMD4B, a tumour suppressor gene. Mechanistically, SAMD4B, increased by the reduced mutations of upstream genes NOTCH1 and NOTCH2, affected the instability of APOA2 mRNA by 2-’O-Methylation modification of the C-terminus. The decreased APOA2 further attenuated programmed death ligand 1 (PD-L1) level with a direct interaction pattern. The high-SAMD4B tumour tissues contained fewer native CD29+CD8+ T cells, which improved immune microenvironment to achieve the effect of antitumour effect. Overall, we developed a potent synergistic immunochemotherapy strategy that exerts an efficient anti-HCC effect inducing SAMD4B-APOA2-PD-L1 axis to inhibit tumour immune evasion.

Mpox is a zoonotic infectious disease caused by the mpox virus (MPXV). Historically, the majority of mpox cases have been documented in Central Africa. However, since May 2022, there has been a notable rise in reported cases from regions beyond Africa. Currently, over 110 countries spanning Europe, North America, South America, Asia, and other territories have reported mpox infections. This report details a case involving a patient who identifies as a man who has sex with men (MSM) and is concurrently infected with MPXV, human immunodeficiency virus type 1 (HIV-1), Pneumocystis jiroveci, as well as extensively drug-resistant tuberculosis (XDR-TB). This patient had also received a vaccination for smallpox in the past. Additionally, we provide photographic documentation charting the progression of dermatological manifestations associated with mpox. This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox. The rapid and widespread dissemination of the MPXV across various regions, especially among MSM communities, underscores the importance of enhancing preventive education efforts targeted at high-risk populations.

Abstract Background Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998–2001). Results Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76–0.96], 0.84 [0.74–0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03–1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26–1.62], 1.70 [1.31–2.21], and 1.36 [1.18–1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13–1.49], 1.5 [1.12–1.99], respectively). Conclusions In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations.

Acinetobacter baumannii is a pathogenic bacterium widespread in human environments, especially in intensive care units, and is associated with high morbidity and infection rates. Multiple drug resistance in A. baumannii frequently leads to the death of patients, making the development of multi-effect antibacterial agents against this bacterium a research hotspot. We have previously found that the X33 antimicrobial oligopeptide can effectively inhibit the growth of Penicillium digitatum and Candida albicans. Herein, we evaluated the antibacterial activity of X33 antimicrobial oligopeptide against A. baumannii by determining the minimum inhibitory concentration, inhibition zone, and growth curve. The increase in extracellular alkaline phosphatase and the leakage of intracellular compounds confirmed the effect of X33 antimicrobial oligopeptide on the cell wall and membrane. Changes in reactive oxygen species, malondialdehyde, ATP, reducing sugar, soluble protein, and pyruvate content demonstrated that the incubation with X33 antimicrobial oligopeptide affected energy metabolism and oxidative stress. Consistent with the physiological characteristics, transcriptomics analysis indicated that incubation with X33 antimicrobial oligopeptide significantly induced changes in the expression of 2339 genes, including 1262 upregulated and 1077 downregulated genes, which participate in oxidative phosphorylation, ribosome, quorum sensing, fatty acid degradation, glycolysis/gluconeogenesis, and citrate cycle pathways. These results provide a fundamental basis for investigating the mechanism of X33 antimicrobial oligopeptide as a potential drug against A. baumannii.

Abstract Background Alcohol screening and brief intervention (SBI) is an evidence-based intervention recommended by the World Health Organization. This study applied the Consolidated Framework for Implementation Research (CFIR) to understand facilitators and barriers of SBI implementation in primary care settings in Hong Kong, China. Methods This was a sequential mixed-method study. In-depth interviews of 21 physicians and 20 nurses working in the primary care settings from the public and private sectors were first conducted to identify CFIR constructs that were relevant to SBI implementation in the Chinese context and potential factors not covered by the CFIR. A questionnaire was then developed based on the qualitative findings to investigate factors associated with SBI implementation among 282 physicians and 295 nurses. Results The in-depth interviews identified 22 CFIR constructs that were facilitators or barriers of SBI implementation in Hong Kong. In addition, the stigmatization of alcohol dependence was a barrier and the belief that it was important for people to control the amount of alcohol intake in any situation was mentioned as a facilitator to implement SBI. In the survey, 22% of the participants implemented SBI in the past year. Factors associated with the SBI implementation echoed most of the qualitative findings. Among physicians and nurses in both sectors, they were more likely to implement SBI when perceiving stronger evidence supporting SBI, better knowledge and self-efficacy to implement SBI, more available resources, and clearer planning for SBI implementation in the clinics but less likely to do so when perceiving SBI implementation to be complicated and of higher cost, and drinking approved by the Chinese culture. Participants were more likely to implement SBI when perceiving SBI fit better with the existing practice and better leadership engagement in the public sector, but not in the private sector. Perceiving a stronger need and greater importance to implement SBI were associated with higher likelihood of SBI implementation among physicians, but not among nurses. Perceiving better organizational culture supporting SBI was positively associated with SBI implementation among nurses, but not among physicians. Conclusions There was a significant gap between SBI evidence and its implementation. Some strategies to improve SBI implementation may be different between physicians and nurses and between those in the public and private sectors. The CFIR is a useful framework for understanding facilitators and barriers of SBI implementation in primary care settings.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. Methods Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. Results A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8+ T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. Conclusions We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell–cell communication in the tumor microenvironment.

Abstract Background Urinary incontinence is highly prevalent in women while pelvic floor muscle training is recommended as the first-line therapy. However, the exact treatment regimen is poorly understood. Also, patients with pelvic floor muscle damage may have decreased muscle proprioception and cannot contract their muscles properly. Other conservative treatments including electromagnetic stimulation are suggested by several guidelines. Thus, the present study aims to compare the effectiveness of electromagnetic stimulation combined with pelvic floor muscle training as a conjunct treatment for urinary incontinence and different treatment frequencies will be investigated. Methods/design This is a randomized, controlled clinical trial. We will include 165 patients with urinary incontinence from the outpatient center. Participants who meet the inclusion criteria will be randomly allocated to three groups: the pelvic floor muscle training group (active control group), the low-frequency electromagnetic stimulation group (group 1), and the high-frequency electromagnetic stimulation group (group 2). Both group 1 and group 2 will receive ten sessions of electromagnetic stimulation. Group 1 will be treated twice per week for 5 weeks while group 2 will receive 10 days of continuous treatment. The primary outcome is the change in International Consultation on Incontinence Questionnaire–Short Form cores after the ten sessions of the treatment, while the secondary outcomes include a 3-day bladder diary, pelvic floor muscle function, pelvic organ prolapse quantification, and quality of life assessed by SF-12. All the measurements will be assessed at baseline, after the intervention, and after 3 months of follow-up. Discussion The present trial is designed to investigate the effects of a conjunct physiotherapy program for urinary incontinence in women. We hypothesize that this strategy is more effective than pelvic floor muscle training alone, and high-frequency electromagnetic stimulation will be superior to the low-frequency magnetic stimulation group.

Abstract Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan–Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.

BackgroundMale factory workers in China are vulnerable to HIV transmission. Commercial and nonmarital noncommercial contacts are the driving forces of heterosexual HIV transmission among male factory workers in China. There is a lack of effective HIV interventions for male factory workers in China. ObjectiveThe primary objective of this randomized controlled trial was to compare the efficacy of an enhanced versus the standard version of a WeChat mini program in reducing sexual intercourse with nonregular female sex partners and female sex workers among male factory workers in Shenzhen, China. MethodsA nonblinded 2-arm parallel randomized controlled trial was conducted between December 2021 and April 2023. Participants were adult male factory workers in Shenzhen who had access to a smartphone and WeChat. Those who had oral or anal sex with a man or self-reported as HIV positive were excluded. A total of 247 participants were randomly assigned to the intervention group (n=125, 50.6%) or the control group (n=122, 49.4%); 221 (89.5%) and 220 (89.1%) completed follow-up surveys at T1 (6 months after completion of the interventions) and T2 (6 months after T1). Participants in the control group had access to the standard WeChat mini program that provided basic HIV-related knowledge and information about local free HIV testing services. Participants in the intervention group had access to the enhanced WeChat mini program. The enhanced mini program covered all the information in the standard mini program. In addition, the enhanced mini program assessed users’ behaviors and invited users to watch different web-based videos on reducing nonmarital sexual contacts and promoting HIV testing based on their behavioral characteristics at months 0 and 1. The videos were developed based on in-depth interviews with male factory workers. Intention-to-treat analysis was used for outcome analyses. Multiple imputation was used to replace missing outcome values at T1 and T2. ResultsAt T1, fewer participants in the intervention group reported sexual intercourse with a nonregular female sex partner in the past 6 months compared with the control group (1/125, 0.8% vs 8/122, 6.6%; relative risk=0.12, 95% CI 0.02-0.96; P=.02). However, there were no between-group differences in sexual intercourse with a nonregular female sex partner at T2 (10/125, 8% vs 14/122, 11.5%; P=.36) or sexual intercourse with a female sex worker at T1 (2/125, 1.6% vs 2/122, 1.6%; P=.98) or T2 (8/125, 6.4% vs 8/122, 6.6%; P=.96). ConclusionsThe enhanced WeChat mini program was more effective than the standard WeChat mini program in reducing sexual intercourse with nonregular female sex partners among male factory workers in the short term but not in the longer term. Improvements should be made to the WeChat mini program before implementation. Trial RegistrationClinicalTrials.gov NCT05811611; https://clinicaltrials.gov/study/NCT05811611

BackgroundThe Herpesviridae family contains several human-related viruses, which are able to establish colonizing and latency in the human body, posing a significant threat to the prognosis of patients. Pulmonary infections represent one of the predominant infectious diseases globally, characterized by diverse and multifaceted clinical manifestations that have consistently attracted clinician’s concern. However, the relationship of herpesviruses on the prognosis of pulmonary infections and the respiratory microbiota remains poorly understood.MethodsHere, we retrospectively analyzed respiratory samples from 100 patients with pulmonary infection detected by metagenomic next-generation sequencing (mNGS).ResultsEmploying mNGS, five herpesvirus species were detected: Human alphaherpesvirus 1 (HSV-1), Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), Human betaherpesvirus 7 (HHV-7), and Human betaherpesvirus 6B (HHV-6B). Regression analysis showed that the age and positivity of herpesviruses in patients were independently correlated with ICU admission rates. In addition, positivity of herpesvirus was related with increased ICU days and total hospital stay. The herpesvirus-positive group demonstrated markedly higher incidences of co-infections and fungi-positive, predominantly involving Pneumocystis jirovecii and Aspergillus fumigatus. Analysis of respiratory microbiota revealed a substantially altered community composition within the herpesvirus-positive group, and herpesviruses were significantly positively correlated with the diverse respiratory opportunistic pathogens.ConclusionOverall results substantiate that the active herpesviruses in patients with pulmonary infections were significantly associated with high ICU admission rate. Moreover, the herpesviruses promotes the dysbiosis of the respiratory microbiota and an increased proportion of co-infections. These insights could contribute to unraveling the underlying mechanisms connecting active herpesviruses to the progression of severe illnesses.

Abstract Mammalian cochlear hair cells (HCs) are essential for hearing, and damage to HCs results in severe hearing impairment. Damaged HCs can be regenerated by neighboring supporting cells (SCs), thus the functional regeneration of HCs is the main goal for the restoration of auditory function in vivo. Here, cochlear SC trans‐differentiation into outer and inner HC by the induced expression of the key transcription factors Atoh1 and its co‐regulators Gfi1, Pou4f3, and Six1 (GPAS), which are necessary for SCs that are destined for HC development and maturation via the AAV‐ie targeting the inner ear stem cells are successfully achieved. Single‐cell nuclear sequencing and lineaging tracing results showed that the majority of new Atoh1‐derived HCs are in a state of initiating differentiation, while GP (Gfi1, Pou4f3) and GPS (Gfi1, Pou4f3, and Six1) enhanced the Atoh1‐induced new HCs into inner and outer HCs. Moreover, the patch‐clamp analysis indicated that newborn inner HCs induced by GPAS forced expression have similar electrophysiological characteristics to those of native inner HCs. Also, GPAS can induce HC regeneration in the HC‐damaged mice model. In summary, the study demonstrates that AAV‐mediated co‐regulation of multiple genes, such as GPAS, is an effective means to achieve functional HC regeneration in the mouse cochlea.

Background: China started to implement the HPV vaccination program for females in 2016. This study investigated associations between mothers’ decisional conflicts, satisfaction with governmental health promotion materials, and their daughters’ HPV vaccination uptake. Methods: A cross-sectional online survey was conducted between July and October 2023 among mothers of girls aged 9–17 years in Shenzhen, China. Participants were mothers having a daughter aged 9–17 years at the survey date and a smartphone with internet access. About 3 % of all primary and secondary schools in Shenzhen were randomly selected by the research team (11 primary schools and 13 secondary schools). Teachers at the selected schools invited mothers of female students aged 9–17 years to complete an anonymous online questionnaire. Multivariate logistic regression was fitted. Results: Among 11,728 mothers who completed the survey, 18.9% of their index daughters received at least one dose of HPV vaccination. In multivariate analysis, less decisional conflict about the choice of HPV vaccines for their daughters (AOR: 1.07, 95%CI: 1.05, 1.10), more satisfaction with the government’s health promotional materials related to HPV vaccines (AOR: 1.15, 95%CI: 1.12, 1.19), receiving more cue to action from significant others (AOR: 1.23, 95%CI: 1.19, 1.27), and perceived higher self-efficacy related to HPV vaccines (AOR: 1.79, 95%CI: 1.67, 1.92) were associated with a higher uptake of HPV vaccines. Perceived susceptibility to HPV (AOR: 0.79, 95%CI: 0.74, 0.85), perceived barriers to having the index daughter receive HPV vaccines (AOR: 0.82, 95%CI: 0.80, 0.84), and mothers who were hesitant to receive HPV vaccination (AOR: 0.75, 95%CI: 0.68, 0.84) were associated with a lower uptake. Conclusion: HPV vaccination uptake was low among girls in China. Future health promotion should address mothers’ decisional conflicts about the choice of HPV vaccines for their daughters and improve the health promotional materials. School-based HPV vaccination programs might be useful.

BackgroundThis study aims to screen inflammation-related genes closely associated with the prognosis of hepatocellular carcinoma (HCC) to accurately forecast the prognosis of HCC patients.MethodsGene expression matrices and clinical information for liver cancer samples were obtained from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An intersection of differentially expressed genes of HCC and normal and GeneCards yielded inflammation-related genes associated with HCC. Cox regression and the minor absolute shrinkage and selection operator (LASSO) regression analysis to filter genes associated with HCC prognosis. The prognostic value of the model was confirmed by drawing Kaplan–Meier and ROC curves. Select differentially expressed genes between the high-risk and low-risk groups and perform GO and KEGG pathways analyses. CIBERSORT analysis was conducted to assess associations of risk models with immune cells and verified using real-time qPCR.ResultsA total of six hub genes (C3, CTNNB1, CYBC1, DNASE1L3, IRAK1, and SERPINE1) were selected using multivariate Cox regression to construct a prognostic model. The validation evaluation of the prognostic model showed that it has an excellent ability to predict prognosis. A line plot was drawn to indicate the HCC patients’ survival, and the calibration curve revealed satisfactory predictability. Among the six hub genes, C3 and DNASE1L3 are relatively low expressed in HCCLM3 and 97H liver cancer cell lines, while CTNNB1, CYBC1, IRAK1, and SERPINE1 are relatively overexpressed in liver cancer cell lines.ConclusionOne new inflammatory factor-associated prognostic model was constructed in this study. The risk score can be an independent predictor for judging the prognosis of HCC patients’ survival.

Buckling restrained brace is an important structure for improving the seismic resistance of structures. Conducting research on new types of buckling restrained brace can improve the seismic performance and reliability of buckling resistant support. Four different types of buckling restrained braces specimens were designed and manufactured: cross-shaped square steel pipe members, cross-shaped round steel pipe members, cross-shaped carbon fiber members, and in-line carbon fiber members. By conducting quasi-static tests, the force displacement hysteresis curves, skeleton curves, stiffness degradation, equivalent viscous damping coefficient, and energy dissipation ratio of four different types of buckling restrained brace were analyzed. The research results showed that all four buckling restrained brace specimens have good hysteresis performance. The load-bearing capacity and energy consumption performance of the three specimens of square steel pipe, round steel pipe and carbon fiber with the same core unit are the same, but the inline type is worse than the cross type. The core unit specimen with a width of 80 mm is about 60% higher in bearing capacity and energy consumption than a specimen with a width of 50 mm. The core unit of some specimens undergoes multi-wave buckling. For carbon fiber specimens, the CFRP is prone to breakage due to the lateral thrust of the restraining unit. Therefore, steel hoop or stirrup should be added to the end to improve the restraint effect when designing and manufacturing.

Abstract Objectives To develop a multiparameter magnetic resonance imaging (MRI)-based radiomics approach that can accurately predict the tumor cell proliferation status of serous ovarian carcinoma (SOC). Materials and methods A total of 134 patients with SOC who met the inclusion and exclusion criteria were retrospectively screened from institution A, spanning from January 2016 to March 2022. Additionally, an external validation set comprising 42 SOC patients from institution B was also included. The region of interest was determined by drawing each ovarian mass boundaries manually slice-by-slice on T2-weighted imaging fat-suppressed fast spin-echo (T2FSE) and T1 with contrast enhancement (T1CE) images using ITK-SNAP software. The handcrafted radiomic features were extracted, and then were selected using variance threshold algorithm, SelectKBest algorithm, and least absolute shrinkage and selection operator. The optimal radiomic scores and the clinical/radiological independent predictors were integrated as a combined model. Results Compared with the area under the curve (AUC) values of each radiomic signature of T2FSE and T1CE, respectively, the AUC value of the radiomic signature (T1CE-T2FSE) was the highest in the training set (0.999 vs. 0.965 and 0.860). The homogeneous solid component of the ovarian mass was considered the only independent predictor of tumor cell proliferation status among the clinical/radiological variables. The AUC of the radiomic–radiological model was 0.999. Conclusions The radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can accurately predict tumor cell proliferation status of SOC which has high repeatability and may enable more targeted and effective treatment strategies. Critical relevance statement The proposed radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can predict tumor cell proliferation status of SOC which has high repeatability and may guide individualized treatment programs. Key points • The radiomic–radiological nomogram may guide individualized treatment programs of SOC. • This radiomic–radiological nomogram showed a favorable prediction ability. • Homogeneous slightly higher signal intensity on T2FSE is vital for Ki-67. Graphical Abstract

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.

Abstract Background Hepatocellular carcinoma (HCC) is characterized by aggressive progression and elevated mortality rates. This study aimed to investigate the regulatory effects of RBBP7 on HCC pathogenesis and the underlying mechanisms. Methods The expression and clinical feature of RBBP7 were evaluated using bioinformatics analysis and the assessment of clinical HCC samples. CCK8 and colony formation were employed to estimate cell proliferation function of RBBP7. Aerobic glycolysis levels of RBBP7 were evaluated by measuring ATP levels, lactic acid production, glucose uptake capacity, and the expression of relevant enzymes (PFKM, PKM2, and LDHA). The phosphorylation levels in PI3K/AKT signaling were measured by western blotting. The regulatory effect of transcription factors of specificity protein 1 (SP1) on RBBP7 mRNA expression was confirmed in dual-luciferase reporter assays and chromatin immunoprecipitation experiments. The proliferation- and glycolysis-associated proteins were assessed using immunofluorescence staining in vivo. Results We found that RBBP7 is expressed at high levels in HCC and predicts poor survival. Functional assays showed that RBBP7 promoted HCC proliferation and glycolysis. Mechanistically, it was demonstrated that RBBP7 activates the PI3K/AKT pathway, a crucial pathway in glycolysis, contributing to the progression of HCC. The outcomes of the dual-luciferase assay further confirmed that SP1 is capable of activating the promoter of RBBP7. Conclusions RBBP7, which is up-regulated by SP1, promotes HCC cell proliferation and glycolysis through the PI3K/AKT pathway. The findings of this study suggest that RBBP7 is a potential biomarker for HCC.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and lethal hepatobiliary tumor with few therapeutic strategies. The metabolic reprogramming of tumor cells plays an essential role in the development of tumors, while the metabolic molecular classification of iCCA is largely unknown. Here, we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients, hoping to provide a novel perspective to understand and treat iCCA. Methods We performed integrated multiomics analysis in 116 iCCA samples, including whole‐exome sequencing, bulk RNA‐sequencing and proteome analysis. Based on the non‐negative matrix factorization method and the protein abundance of metabolic genes in human genome‐scale metabolic models, the metabolic subtype of iCCA was determined. Survival and prognostic gene analyses were used to compare overall survival (OS) differences between metabolic subtypes. Cell proliferation analysis, 5‐ethynyl‐2'‐deoxyuridine (EdU) assay, colony formation assay, RNA‐sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinase α (DGKA) in iCCA cells. Results Three metabolic subtypes (S1‐S3) with subtype‐specific biomarkers of iCCA were identified. These metabolic subtypes presented with distinct prognoses, metabolic features, immune microenvironments, and genetic alterations. The S2 subtype with the worst survival showed the activation of some special metabolic processes, immune‐suppressed microenvironment and Kirsten rat sarcoma viral oncogene homolog (KRAS)/AT‐rich interactive domain 1A (ARID1A) mutations. Among the S2 subtype‐specific upregulated proteins, DGKA was further identified as a potential drug target for iCCA, which promoted cell proliferation by enhancing phosphatidic acid (PA) metabolism and activating mitogen‐activated protein kinase (MAPK) signaling. Conclusion Via multiomics analyses, we identified three metabolic subtypes of iCCA, revealing that the S2 subtype exhibited the poorest survival outcomes. We further identified DGKA as a potential target for the S2 subtype.

Purposes Traffic flow prediction is crucial for the effective management and operation of urban transportation systems. The flows of different road sections or intersections in a traffic network change dynamically with time, meanwhile the flows of spatially neighboring road sections or intersections affect each other. In order to better learn the spatial and temporal correlation of the traffic flow of different road sections or intersections from the traffic flow sequences, and to improve the performance of short-term prediction of traffic flow, in this paper we propose a traffic flow prediction method based on Dynamic Graph Convolution Network with Multi-head Attention (DGCNMA). Methods The DGCNMA model first introduces graph convolution networks into the Transformer framework to learn the spatial embedding of traffic flow sequences and incorporate them into the traffic flow sequences, and then adopts the mechanism of Multi-head Attention to capture the temporal and spatial correlation of the traffic flow sequences from multiple perspectives at the same time; second, the Interactive Dynamic Graph Convolution Network is introduced to simultaneously learn the local and global spatial-temporal correlations of traffic flow sequences through the interactive learning of convolutional network and dynamic graph convolutional network, and the interactive fusion of parity subsequence features. Findings Experiments on highway traffic flow datasets (PEMS03, PEMS04, PEMS08) and subway crowd flow datasets (HZME inflow and HZME outflow) show that the proposed DGCNMA model has better traffic flow prediction performance than the baseline models.

Marine fishing is related to the balance of marine natural ecosystem and national food security. At present, marine fishing industry in China develops rapidly and its market prospect is broad, but there are still some problems to be solved. This paper analyzes the current situation of marine fishery and related laws in China, and puts forward development suggestions for a series of problems, such as the defects of the fishing license system, the weak operability of the quota fishing system, and the lack of scientificity of the "one-size-fits-all" off-season fishing moratorium. The following development suggestions are provided: (1) Improve the restrictive management measures of the fishing license system, strengthen supervision and raise the threshold for entry; (2) Increase the operational legal provisions of fishing quotas, and to establish a database of total available catches for marine fisheries and to establish a corresponding system of government financial subsidies; (3) Learn from Canada, the United States and other marine fishery developed countries’ advanced experience to improve the fishing moratorium in the summer.

Abstract Background The diagnostic assay leveraging multiple reverse transcription loop-mediated isothermal amplification (RT-LAMP) could meet the requirements for rapid nucleic acid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods The devised assay merged the lateral flow assay with the RT-LAMP technology and designed specific primers for the simultaneous detection of the target and human-derived internal reference genes within a single reaction. An inquiry into the assay's limit of detection (LOD), sensitivity, and specificity was carried out. The effectiveness of this assay was validated using 498 clinical specimens. Results This LOD of the assay was determined to be 500 copies/mL, and there was no observed cross-reaction with other respiratory pathogens. The detection results derived from clinical specimens showed substantial concordance with those from real-time reverse transcription-polymerase chain reaction (RT-qPCR) (Cohen's kappa, 0.876; 95% CI: 0.833-0.919; p

ABSTRACTThis study investigated the influences of mother-daughter communication and social media on mothers’ HPV vaccine refusal for their daughters aged 9–17. A cross-sectional online survey among 11,728 mothers of girls aged 9–17 in Shenzhen, China was implemented between July and October 2023. Multi-level logistic regression models were fitted. Among 11,728 participants, 43.2% refused to have their daughters receive an HPV vaccination. In multivariate analysis, more openness in the mother-daughter communication (AOR: 0.99, 95%CI: 0.98, 0.99), perceived more positive outcomes of mother-daughter communication (AOR: 0.77, 95%CI: 0.75, 0.79), higher frequency of exposure to testimonials about daughters’ HPV vaccination (AOR: 0.81, 95%CI: 0.78, 0.85) and information encouraging parents to vaccinate their daughters against HPV on social media (AOR: 0.76, 95%CI: 0.73, 0.79), and thoughtful consideration of the veracity of the information specific to HPV vaccines (AOR: 0.80, 95%CI: 0.77, 0.83) were associated with lower vaccine refusal. Mothers who were not the main decision-makers of daughters’ HPV vaccination (AOR: 1.28 to 1.46), negative outcome expectancies of mother-daughter communication (AOR: 1.06, 95%CI: 1.04, 1.08), and mothers’ HPV vaccine refusal (AOR: 2.81, 95%CI: 2.58, 3.06) were associated with higher vaccine refusal for their daughters. The level of mothers’ HPV vaccine refusal for their daughters was high in China. Openness and outcome expectancies of mother-daughter communication and information exposure on social media were considered key determinants of HPV vaccine refusal for daughters. Future HPV vaccination programs should consider these interpersonal factors.

Abstract Development of efficient, stable, and recyclable photocatalysts for organic synthesis is vital for transformation of traditional thermal organic chemistry into green sustainable organic chemistry. In this work, the study reports an electrostatic approach to assemble meso‐tetra (4‐sulfonate phenyl) porphyrin (TPPS)tetra (4‐sulfonate phenyl) porphyrin (TPPS) as a donor and benzyl viologen (BV) as an acceptor into stable and recyclable photocatalyst for an efficient organic transformation reaction – aryl sulfide oxidation. By use of the electrostatic TPPS‐BV photocatalysts, 0.1 mmol aryl sulfide with electron‐donating group can be completely transformed into aryl sulfoxide in 60 min without overoxidation into sulfone, rendering near 100% yield and selectivity. The photocatalyst can be recycled up to 95% when 10 mg amount is used. Mechanistic study reveals that efficient charge separation between TPPS and BV results in sufficient formation of superoxide which further reacts with the oxidized sulfide by the photocatalyst to produce the sulfoxide. This mechanistic pathway differs significantly from the previously proposed singlet oxygen‐dominated process in homogeneous TPPS photocatalysis.

IntroductionThe contamination of farmland soil with the heavy metal cadmium (Cd) has consistently been a globally recognized environmental issue, especially with the rapid development of the central part of the Hanjiang River basin. The Cd contamination has become increasingly serious, and the accumulation and translocation of Cd in the soil-crop system warrant further research.MethodsIn this study, representative yellowish-brown soil and limestone soil from Hubei Province in China, as well as five varieties of potato (Solanum tuberosum L), were selected to investigate Cd accumulation and transfer regulation from soil to plants using pot tests at varying Cd concentration levels.Results and discussionFor Eshu-12, Favorita, Huashu-6, Mira, and Zhongshu-5, the accumulation capacity of Cd in different parts exhibits a consistent pattern: Cdroot > Cdstem > Cdleaf > Cdtuber. The potato varieties exhibited distinct differences in Cd concentration, as follows: CdFavorita > CdMira > CdEshu-12 > CdHuashu-6 > CdZhongshu-5. The yellowish-brown soil demonstrated a higher accumulation and lower transport capacity to the plants of Cd, while limestone soil exhibited the opposite trend. The bio-concentration factor and transfer coefficients in yellowish-brown soil revealed significant (p

BACKGROUND: The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. OBJECTIVE: This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. STUDY DESIGN: Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. RESULTS: Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25–39.50] vs 28.00 [range, 24.00–36.00]; P

The adenosine monophosphate (AMP)-activated protein kinase (AMPK) sits at a central node in the regulation of energy metabolism and tumor progression. AMPK is best known to sense high cellular ADP or AMP levels, which indicate the depletion of energy stores. Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer. In this study, we report that AMPK is also highly sensitive to extracellular matrix (ECM) stiffness. We found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM stiffness. This regulation of AMPK requires the Hippo kinases but not LKB1/CaMKKβ. Hippo kinases directly phosphorylate AMPKα at Thr172 to activate AMPK at low ECM stiffness. Furthermore, we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma (PDAC) with high ECM stiffness and is associated with a poor survival outcome. The activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC growth. Together, these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness–Hippo kinases–AMPK signaling and low glucose–LKB1–AMPK signaling pathways as an effective therapeutic strategy against PDAC.

Abstract Plastid ribosomal proteins play a crucial role in the growth and development of plants, mainly in the gene expression and translation of key genes in chloroplasts. While some information is known about the regulatory processes of plastid ribosomal proteins in various plant species, there is limited knowledge about the underlying mechanisms in rice. In this study, ethyl methanesulfonate (EMS) mutagenesis was used to generate a new mutant called wlp3 (white leaf and panicle3), characterized by white or albino leaves and panicles, which exhibited this phenotype from the second leaf stage until tillering. Furthermore, after a certain period, the newly emerging leaves developed the same phenotype as the rice variety ZH11, while the albino leaves of wlp3 showed an incomplete chloroplast structure and significantly low chlorophyll content. A transition mutation (T to C) at position 380 was identified in the coding region of the LOC_Os03g61260 gene, resulting in the substitution of isoleucine by threonine during translation. WLP3 encodes the ribosomal L18 subunit, which is localized in the chloroplast. Complementation experiments confirmed that LOC_Os03g61260 was responsible for the albino phenotype in rice. WLP3 has high expression in the coleoptile, leaves at the three-leaf stage, and panicles at the heading stage. Compared to the wild-type (WT), wlp3 exhibited reduced chlorophyll synthesis and significantly decreased expression levels of genes associated with plastid development. Yeast two-hybrid (Y2H) analysis revealed that WLP3 interacts with other ribosomal subunits, to influence chloroplast development. These results contribute to a better understanding of the underlying molecular mechanisms of chloroplast development and plastid gene translation.

Abstract Background Age-related hearing loss (ARHL) signifies the bilateral, symmetrical, sensorineural hearing loss that commonly occurs in elderly individuals. Several studies have suggested a higher risk of dementia among patients diagnosed with ARHL. Although the precise causal association between ARHL and cognitive decline remains unclear, ARHL has been recognized as one of the most significant factors that can be modified to reduce the risk of developing dementia potentially. Mild cognitive impairment (MCI) typically serves as the initial stage in the transition from normal cognitive function to dementia. Consequently, the objective of our randomized controlled trial (RCT) is to further investigate whether the use of hearing aids can enhance cognitive function in older adults diagnosed with ARHL and MCI. Methods and design This study is a parallel-arm, randomized controlled trial conducted at multiple centers in Shanghai, China. We aim to enlist a total of 688 older adults (age ≥ 60) diagnosed with moderate-to-severe ARHL and MCI from our four research centers. Participants will be assigned randomly to either the hearing aid fitting group or the health education group using block randomization with varying block sizes. Audiometry, cognitive function assessments, and other relevant data will be collected at baseline, as well as at 6, 12, and 24 months post-intervention by audiologists and trained researchers. The primary outcome of our study is the rate of progression to dementia among the two groups of participants. Additionally, various evaluations will be conducted to measure hearing improvement and changes in cognitive function. Apart from the final study results, we also plan to conduct an interim analysis using data from 12-month follow-up. Discussion In recent years, there has been a notable lack of randomized controlled trials (RCTs) investigating the possible causal relationship between hearing fitting and the improvement of cognitive function. Our findings may demonstrate that hearing rehabilitation can be a valuable tool in managing ARHL and preventing cognitive decline, which will contribute to the development of a comprehensive framework for the prevention and control of cognitive decline. Trial registration Chinese Clinical Trial Registry chictr.org.cn ChiCTR2000036139. Registered on 21 August 2020.

Abstract Background The 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) has been widely used to measure depressive symptoms in many large-scale surveys. Due to its brevity, it can lower costs, relieve respondent burdens, and ensure data quality. However, its factor structure and measurement invariance across gender and time among adolescents have not been adequately evaluated. This study investigated its factor structure and measurement invariance across gender and time among adolescents. Methods The data was drawn from the China Family Panel Studies (CFPS) conducted in 2018 and 2020, with 3099 participants (46.82% girls) aged 11 to 18 in 2018. First, exploratory and confirmatory factor analyses were used to examine the factor structure of the CES-D 8. Next, multi-group confirmatory factor analysis was conducted to test its measurement invariance across gender and time. Finally, a longitudinal cross-gender test was conducted to further confirm the stability of the scale. Results A two-factor structure was identified among the adolescents, including Negative Symptoms and Diminished Happiness Feeling. Measurement invariance across gender and time, as well as the longitudinal cross-gender invariance, was supported, with configural, factor loadings, thresholds and residual invariance. Conclusions The factor structure of the CES-D 8 remains stable across gender and time among adolescents, indicating that it is a promising instrument for measuring depressive symptoms, especially in large-scale and longitudinal surveys.

Abstract Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE+ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.

Lysimachia cavicola (Subgen. Idiophyton, Primulaceae), a new species from Guangxi, China, is here described and illustrated based on morphological data. Although it shares similarities with L. microcarpa, L. fooningensis, and L. capillipes, there are distinguishing characteristics that set it apart. These include erect stems either solitary or in clusters of 1 to 2, herbaceous, terete, and densely glandular hairy. The leaves are either ovate or elliptical lanceolate, with inconspicuously reticulate veins. The petiole measures 2–4 mm in length covered with minute glandular hairy. The corolla is deeply parted, measuring 6–8 mm in length, with narrowly elliptic or narrowly oblong lobes that are 1–2 mm wide. The capsule is globose, measuring 2–3 × 2–3 mm, and possesses a chalky, brittle texture, which splits into 5-valved segments. The calyx of the plant appears yellowish-white during fruiting. This newly discovered species is endemic to limestone areas in Fengshan County, Guangxi, China.

The economic benefits of tourism are an important indicator for evaluating the tourism economic activities and their impact. In order to maximize the tourism economic benefits, this article studied the economic benefits of tourism from the perspective of agricultural water resource transformation. This paper took the relevant data of Shandong Province from 2010 to 2022 as the object of study and established the evaluation index system of tourism economic benefits of Shandong Province. The coupling relationship between tourism economic benefits and ecological environment (EE) was studied, and the systemic evaluation index system of Shandong tourism economy and EE was constructed. The range method and entropy method were used to calculate indicator weights, thereby constructing a coupled collaborative model between the tourism economy and the EE. Based on the relationship between tourism economic benefits and EE, research has been conducted on the transformation methods of agricultural water resources in EE construction to improve tourism economic benefits. With the continuous improvement of the EE index, the coupling degree between the tourism economic index and the EE index in many cities in Shandong Province has improved, and the tourism economic benefits have greatly improved. HIGHLIGHTS This article studies the economic benefits of tourism from the perspective of agricultural water resources conversion, aiming to maximize the economic benefits of tourism..; This article uses the range method and the entropy method to calculate the index weights and construct a coupled synergy model of tourism economy and environmental benefits.; Research shows that as the ecological environment index continues to improve, the coupling degree between the urban tourism economic index and the ecological environment index will also increase, and the tourism economic benefits will increase significantly.;

Abstract Background Premature ovarian insufficiency (POI) is an important cause of infertility characterized by the functional decline of the ovary. Granulosa cells (GCs) around oocytes are critical for folliculogenesis, and GC dysfunction is one of the important etiologies of POI. The aim of this study was to explore the potential biomarkers of POI by identifying hub genes and analyze the correlation of biomarkers with immune infiltration in POI using RNA profiling and bioinformatics analysis. Methods RNA sequencing was performed on GCs from biochemical POI (bPOI) patients and controls. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to explore the candidate genes. qRT‒PCR was performed to verify the expression of hub genes. Western blot, Cell Counting Kit-8, 5‐ethynyl‐2’‐deoxyuridine (EdU) assays, TUNEL (TdT-mediated dUTP Nick-End Labeling) and flow cytometry analysis were used to validate the possible role of ubiquitin-conjugating enzyme 2C (UBE2C) in POI. CIBERSORT was adopted to explore immune cell infiltration and the correlation between UBE2C and immune cells in bPOI. Results Through analysis of differentially expressed genes (DEGs) and WGCNA, we obtained 143 candidate genes. After construction of the protein‒protein interaction (PPI) network and analysis with Cytoscape, 10 hub genes, including UBE2C, PBK, BUB1, CDC20, NUSAP1, CENPA, CCNB2, TOP2A, AURKB, and FOXM1, were identified and verified by qRT‒PCR. Subsequently, UBE2C was chosen as a possible biomarker of POI because knockdown of UBE2C could inhibit the proliferation and promote the apoptosis of GCs. Immune infiltration analysis indicated that monocytes and M1 macrophages may be associated with the pathogenesis of POI. In addition, UBE2C was negatively correlated with monocytes and M1 macrophages in POI. Conclusions This study identified a hub gene in GCs that might be important in the pathogenesis of POI and revealed the key role of UBE2C in driving POI. Immune infiltration may be highly related with the onset and etiology of POI.

Abstract Background Wearable sensors have become a complementary means for evaluation of body function and gait in lower limb osteoarthritis. This study aimed to review the applications of wearable sensors for gait analysis after total knee arthroplasty (TKA). Methods Five databases, including Web of Science Core Collection, Embase, Cochrane, Medline, and PubMed, were searched for articles published between January 2010 and March 2023, using predetermined search terms that focused on wearable sensors, TKA, and gait analysis as broad areas of interest. Results A total of 25 articles were identified, involving 823 TKA patients. Methodologies varied widely across the articles, with inconsistencies found in reported patient characteristics, sensor data and experimental protocols. Patient-reported outcome measures (PROMs) and gait variables showed various recovery times from 1 week postoperatively to 5 years postoperatively. Gait analysis using wearable sensors and PROMs showed differences in controlled environments, daily life, and when comparing different surgeries. Conclusion Wearable sensors offered the potential to remotely monitor the gait function post-TKA in both controlled environments and patients’ daily life, and covered more aspects than PROMs. More cohort longitudinal studies are warranted to further confirm the benefits of this remote technology in clinical practice.

This paper introduces innovative approaches to enhance and develop one-equation RANS models using gene-expression programming. Two distinct strategies are explored: overcoming the limitations of the Boussinesq hypothesis and formulating a novel one-equation turbulence model that can accurately predict a wide range of turbulent wall-bounded flows. A comparative analysis of these strategies highlights their potential for advancing RANS modeling capabilities. The study employs a single-case CFD-driven machine learning framework, demonstrating that machine-informed models significantly improve predictive accuracy, especially when baseline RANS predictions diverge from established benchmarks. Using existing training data, symbolic regression provides valuable insights into the underlying physics by eliminating ineffective strategies. This highlights the broader significance of machine learning beyond developing turbulence closures for specific cases.

Pneumococcal vaccination (PV) is effective in preventing vaccine-type pneumococcal diseases. This study investigated the changes in PV uptake and its determinants before, during, and after the Coronavirus Disease 2019 (COVID-19) pandemic among community-living older adults aged ≥65 years in Hong Kong, China. Three rounds of random telephone surveys were conducted every two years from May 2019 to October 2023. Multivariate logistic regression models were fitted to examine the between-round differences in PV uptake rate and factors associated with PV uptake in each round. This study included 1563 participants. The standardized PV uptake rate in Round 1, 2, and 3 was 17.3%, 28.3%, and 35.5%, respectively. A significant difference in the PV uptake rate was found between Rounds 2 and 1 (p = 0.02), but not between Rounds 3 and 2 (p = 0.98). Perceived barriers, cue to action and self-efficacy, were significant determinants of PV uptake in all rounds. Perceived benefits were significant determinants of PV uptake in the first and second rounds, but not in the third round. Continuous monitoring of PV uptake and its determinants, and evaluating and adjusting the PV program, might contribute to the success of such a vaccination program in the post-pandemic era.

Powdery mildew disease (PMD) is caused by the obligate biotrophic fungus Microsphaera diffusa Cooke & Peck (M. diffusa) and results in significant yield losses in soybean (Glycine max (L.) Merr.) crops. By identifying disease-resistant genes and breeding soybean accessions with enhanced resistance, we can effectively mitigate the detrimental impact of PMD on soybeans. We analyzed PMD resistance in a diversity panel of 315 soybean accessions in two locations over 3 years, and candidate genes associated with PMD resistance were identified through genome-wide association studies (GWAS), haplotype analysis, qRT-PCR, and EMS mutant analysis. Based on the GWAS approach, we identified a region on chromosome 16 (Chr16) in which 21 genes form a gene cluster that is highly correlated with PMD resistance. In order to validate and refine these findings, we conducted haplotype analysis of 21 candidate genes and indicated there are single nucleotide polymorphisms (SNPs) and insertion-deletions (InDels) variations of Glyma.16G214000, Glyma.16G214200, Glyma.16G215100 and Glyma.16G215300 within the coding and promoter regions that exhibit a strong association with resistance against PMD. Subsequent structural analysis of candidate genes within this cluster revealed that in 315 accessions, the majority of accessions exhibited resistance to PMD when Glyma.16G214300, Glyma.16G214800 and Glyma.16G215000 were complete; however, they demonstrated susceptibility to PMD when these genes were incomplete. Quantitative real-time PCR assays (qRT-PCR) of possible candidate genes showed that 14 candidate genes (Glyma.16G213700, Glyma.16G213800, Glyma.16G213900, Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214500, Glyma.16G214585, Glyma.16G214669, Glyma.16G214700, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300) were involved in PMD resistance. Finally, we evaluated the PMD resistance of mutant lines from the Williams 82 EMS mutations library, which revealed that mutants of Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300, exhibited sensitivity to PMD. Combined with the analysis results of GWAS, haplotypes, qRT-PCR and mutants, the genes Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300 were identified as highly correlated with PMD resistance. The candidate genes identified above are all NLR family genes, and these discoveries deepen our understanding of the molecular basis of PMD resistance in soybeans and will be useful for guiding breeding strategies.

Abstract Macroinvertebrates play a vital role in coastal ecosystems and are an important indicator of ecosystem quality. Both anthropogenic activity and environmental changes may lead to significant changes in the marine macroinvertebrate community. However, the assembly process of benthic biodiversity and its mechanism driven by environmental factors at large scales remains unclear. Here, using the benthic field survey data of 15 years at large spatial and temporal scales from the Yellow Sea Large Marine Ecosystem, we investigated the relative importance of environmental selection, dispersal processes, random‐deterministic processes of macroinvertebrates community diversity assembly, and the responses of this relative importance driven by temperature and nutrients. Results showed that the macroinvertebrates community diversity is mainly affected by dispersal. Nitrogen and phosphorus are the most important negative factors among environmental variables, while geographical distance is the main limiting factor of β diversity. Within the range of 0.35–0.70 mg/L of nutrients, increasing nutrient concentration can significantly facilitate the contribution of the decay effect to β diversity. Within the temperature range studied (15.0–18.0°C), both warming and cooling can lead to a greater tendency for species diversity assembly processes to be dominated by deterministic processes. The analysis contributes to a better understanding of the assembly process of the diversity of coastal marine macroinvertebrates communities and how they adapt to global biogeochemical processes.

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelial cells. Common treatment methods for NPC include radiotherapy, chemotherapy, and surgical intervention. Despite these approaches, the prognosis for NPC remains poor due to treatment resistance and recurrence. Hence, there is a crucial need for more comprehensive research into the mechanisms underlying treatment resistance in NPC. Long non coding RNAs (LncRNAs) are elongated RNA molecules that do not encode proteins. They paly significant roles in various biological processes within tumors, such as chemotherapy resistance, radiation resistance, and tumor recurrence. Recent studies have increasingly unveiled the mechanisms through which LncRNAs contribute to treatment resistance in NPC. Consequently, LncRNAs hold promise as potential biomarkers and therapeutic targets for diagnosing NPC. This review provides an overview of the role of LncRNAs in NPC treatment resistance and explores their potential as therapeutic targets for managing NPC.