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Abstract Background Microbial organisms hold significant potential for converting renewable substrates into valuable chemicals. Low pH fermentation in industrial settings offers key advantages, including reduced neutralizer usage and decreased wastewater generation, particularly in the production of amino acids and organic acids. Engineering acid-tolerant strains represents a viable strategy to enhance productivity in acidic environments. Synthetic biology provides dynamic regulatory tools, such as gene circuits, facilitating precise expression of acid resistance (AR) modules in a just-in-time and just-enough manner. Results In this study, we aimed to enhance the robustness and productivity of Escherichia coli, a workhorse for amino acid and organic acid production, in industrial fermentation under mild acidic conditions. We employed an Esa-type quorum sensing circuit to dynamically regulate the expression of an AR module (DsrA-Hfq) in a just-in-time and just-enough manner. Through careful engineering of the critical promoter PesaS and stepwise evaluation, we developed an optimal Esa-PBD(L) circuit that conferred upon an industrial E. coli strain SCEcL3 comparable lysine productivity and enhanced yield at pH 5.5 compared to the parent strain at pH 6.8. Conclusions This study exemplifies the practical application of gene circuits in industrial environments, which present challenges far beyond those of well-controlled laboratory conditions.

In industrial fermentation processes, microorganisms often encounter acid stress, which significantly impact their productivity. This study focused on the acid-resistant module composed of small RNA (sRNA) DsrA and the sRNA chaperone Hfq. Our previous study had shown that this module improved the cell growth of Escherichia coli MG1655 at low pH, but failed to obtain this desired phenotype in industrial strains. Here, we performed a quantitative analysis of DsrA-Hfq module to determine the optimal expression mode. We then assessed the potential of the CymR-based negative auto-regulation (NAR) circuit for industrial application, under different media, strains and pH levels. Growth assay at pH 4.5 revealed that NAR-05D04H circuit was the best acid-resistant circuit to improve the cell growth of E. coli MG1655. This circuit was robust and worked well in the industrial lysine-producing strain E. coli SCEcL3 at a starting pH of 6.8 and without pH control, resulting in a 250 % increase in lysine titer and comparable biomass in shaking flask fermentation compared to the parent strain. This study showed the practical application of NAR circuit in regulating DsrA-Hfq module, effectively and robustly improving the acid tolerance of industrial strains, which provides a new approach for breeding industrial strains with tolerance phenotype.

Abstract Background The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It’s unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents. Methods This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata. Results In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018–2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020–2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables. Conclusion Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection.

The prevalence of chronic diseases has increased in recent years among middle-aged and elderly men in China. This study focuses on the current prevalence and factors influencing chronic diseases among middle-aged and elderly men in the context of population ageing. The aim is to provide a reference for the development of preventive and control measures for chronic diseases and to improve the health of middle-aged and elderly men in China. Data was obtained from the 2018 China Health and Retirement Longitudinal Study (CHARLS), and the middle-aged and older population of men (aged 45 and above) were considered for analysis. The factors affecting the prevalence of chronic diseases were analysed using a binary logistic regression model, with the presence or absence of chronic diseases as the dependent variable and personal characteristics and lifestyle as the independent variables. The results of descriptive statistics showed that the prevalence of chronic diseases among middle-aged and elderly men in China was 42.6%, the top five diseases being hypertension (14.7%), arthritis and rheumatism (12.8%), stomach diseases (9.9%), dyslipidaemia (9.7%) and heart disease (6.6%). The results of the multivariate logistic regression analysis showed that ages between 60 and 70 years (OR (odds Ratio) = 0.565, 95% CI (confidence interval) = 0.398–0.802), living in a combination of urban and rural areas (OR = 1.276, 95% CI = 1.086–1.498), smoking (OR = 0.458, 95% CI = 0.357–0.587), sleeping for 6–7 h (OR = 1.255, 95% CI = 0.994–1.585), self-rated good health (OR = 1.846, 95% CI = 1.549–2.200) and self-rated very good health (OR = 1.758, 95% CI = 1.454–2.126) were factors that influenced the prevalence of chronic diseases among Chinese middle-aged and elderly men. The Chinese government should formulate NCD (Non-communicable diseases) prevention and control measures suitable for the middle-aged and elderly population of men according to different regions and groups. These measures can help improve the health levels of the middle-aged and elderly population and comprehensively promote the concept of healthy ageing.

Abstract Developmental disabilities prevalence seem to be high in countries around the world. It’s worth understanding the most recent prevalence and trends of developmental disabilities. The objective of this study is to examine the prevalence and trends of developmental disabilities of US children and adolescents. A total of 26,422 individuals aged 3–17 years were included. Annual data were examined from the National Health Interview Survey (2018–2021). Weighted prevalence for each of the selected developmental disabilities were calculated. The prevalence of any developmental disabilities in individuals was 16.65% (95% CI 16.03–17.26%), prevalence of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), autism spectrum disorder (ASD), intellectual disability (ID), and other developmental delay were 9.57% (95% CI 9.09–10.06%), 7.45% (95% CI 7.00–7.89%), 2.94% (95% CI 2.67–3.21%), 1.72% (95% CI 1.51–1.93%), and 5.24% (95% CI 4.89–5.59%), respectively. Significant increases were observed for other developmental delay (4.02–6.05%) and co-occurring LD & ID (1.03–1.82%). Findings form this study highlight a high prevalence of any developmental disabilities, although no significant increase was observed. The prevalence of other developmental delay and co-occurring LD & ID were significantly increased. Further investigation is warranted to assess potentially modifiable risk factors and causes of developmental disabilities.

BackgroundDepression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma polyunsaturated fatty acids (PUFAs) levels and depression have yielded inconsistent results.ObjectiveTo evaluate whether plasma n-3 and n-6 PUFAs levels are associated with depression in American adults.MethodsA cross-sectional study included 2053 adults (aged ≥20 y) in the National Health and Nutrition Examination Survey (NHANES), 2011–2012. The level of plasma n-3 and n-6 PUFAs were obtained for analysis. Self-reported Patient Health Questionnaire-9 (PHQ-9) was used to identify the depression status. Binary logistic regression analysis was performed to evaluate the association between quartiles of plasma n-3 and n-6 PUFAs and depression after adjustments for confounders.ResultsThe study of 2053 respondents over 20 years of age with a weighted depression prevalence of 7.29% comprised 1,043 men (weighted proportion, 49.13%) and 1,010 women (weighted, 50.87%), with a weighted mean (SE) age of 47.58 (0.67) years. Significantly increased risks of depression over non-depression were observed in the third quartiles (OR = 1.65, 95% CI = 1.05–2.62) for arachidonic acid (AA; 20:4n-6); the third quartiles (OR = 2.20, 95% CI = 1.20–4.05) for docosatetraenoic acid (DTA; 22:4n-6); the third (OR = 2.33, 95% CI = 1.34–4.07), and highest quartiles (OR = 1.83, 95% CI = 1.03–3.26) for docosapentaenoic acid (DPAn-6; 22:5n-6); and the third (OR = 2.18, 95% CI = 1.18–4.03) and highest quartiles (OR = 2.47, 95% CI = 1.31–4.68) for docosapentaenoic acid (DPAn-3; 22:5n-3); the second (OR = 2.13, 95% CI = 1.24–3.66), third (OR = 2.40, 95% CI = 1.28–4.50), and highest quartiles (OR = 2.24, 95% CI = 1.08–4.69) for AA/docosahexaenoic acid (DHA; 22:6n-3) ratio compared with the lowest quartile after adjusting for confounding factors.ConclusionHigher plasma levels of AA, DTA, DPAn-6, DPAn-3 PUFAs, and AA/DHA ratio may be potential risk factors for depression in US adults.

BackgroundThe relationship between physical activity and hyperuricemia (HUA) remains inconsistent, and the dose-response association between moderate-to- vigorous physical activity (MVPA) level and HUA still unclear. In this study, we aimed to investigate the dose-response association of MVPA with HUA, and to explore an appropriate range of MVPA level for preventing HUA.MethodsData from the US National Health and Nutrition Examination Survey (NHANES) 2007-2018 were used, including 28740 non-gout adult Americans. MVPA level was self-reported using the Global Physical Activity Questionnaire and serum uric acid was measured using timed endpoint method. The dose-response relationship between MVPA level and HUA was modeled with restricted cubic spline analysis. Logistic regression analysis were applied to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of the relationships between MVPA level and HUA.ResultsA total of 28740 adults were included in the study (weighted mean age, 47.3 years; 46.5% men), with a prevalence rate of HUA was 17.6%. The restricted cubic spline functions depicted a general U-shaped relationship between MVPA level and HUA. The MVPA level of 933 and 3423 metabolic equivalent (MET) -min/wk were the cut-off discriminating for the risk of HUA. Participants with MVPA levels in the range of 933-3423 MET-min/wk had lower risk of HUA and they had the lowest risk when MVPA levels at around 1556 MET-min/wk. Compared with the moderate-activity group (600-2999 Met-min/wk), the low-activity group (< 600 Met-min/wk) had a greater risk of HUA (OR, 1.13 [95%CI, 1.02-1.26]) after fully adjusting for potential confounders.ConclusionsCompared with the moderate MVPA level, the low MVPA level was associated with the higher risk of HUA. And there may be a U-shaped dose-response relationship between MVPA level and HUA. When MVPA level was approximately 933-3423 MET-min/wk, the risk of HUA may at a lower level and the risk reached the lowest when MVPA level at around 1556 MET-min/wk.

Abstract Objective Coronavirus Disease-19 (COVID-19) has become a global pandemic, and mental health of children and parents are affected by confinement in home. Since the outbreak of COVID-19 is still global pandemic currently, it is important to examine how the changes of children’s behaviors and parent–child relationship affect parental anxiety during this difficult time. Methods A cross-sectional online investigation was conducted with snowball sampling to collect the information about the behavioral changes of children and the anxiety of parents from February 23 to March 3, 2020. 642 participants who had children aged 3–17 years included in this study. Information about behavioral change of children was reported by parents with a questionnaire, parental anxiety was assessed with Self-rating Anxiety Scale (SAS, Chinese Version). Results Among children’s behaviors, decreased time of outdoor activity was associated with a lower odds of parental anxiety, with an adjusted odds ratios (ORs) of 0.31 (95% CI, 0.11–0.87). Parents’ satisfaction with children's behaviors was associated with a lower odds of parental anxiety (ORs, 0.13; 95% CI, 0.05–0.35). In addition, we observed a significant association of worse behavioral performance and worse family relationship with anxiety among parents with the adjusted ORs of 2.78 (95% CI, 1.35–5.73), and 2.67 (95% CI, 1.13–6.32), respectively. Conclusion Under COVID-19 outbreak in China, changes in children’s behavioral and family relationship were associated with parental anxiety. Our finding suggested that family mental health support and promotion should consider the children’s behavioral regulation and parent–child relationship as essential components.

Abstract Aims There is an increasing proportion of hospitalized heart failure (HF) patients classified as HF with preserved ejection fraction (HFpEF) around the world. Growth differentiation factor 15 (GDF‐15) is a promising biomarker in HFpEF prognostication; however, the majority of the existing data has been derived from the research on undifferentiated HF, whereas the studies focusing on HFpEF are still limited. This study aimed to determine the prognostic power of GDF‐15 in the hospitalized patients with HFpEF in a Chinese cohort. Methods and results We analysed the levels of serum GDF‐15 in 380 patients hospitalized for acute onset of HFpEF measured by heart ultrasound at admission in a prospective cohort. The associations of GDF‐15 with 1 year risk of all‐cause death and 1 year HF readmission were assessed by the Cox proportional hazards model. Area under the receiver operating characteristic curves was used to compare predictive accuracy. GDF‐15 was strongly correlated with 1 year HF readmission and 1 year all‐cause death, with event rates of 24.8%, 40.0%, and 50.0% for 1 year HF readmission (P

AbstractWith the increasing popularity of computer-assisted language learning in the past decades, how to teach English reading in the new educational landscape created has become a challenge. Abundant literature has contributed to reading strategy instruction worldwide, however, empirical studies on computer-aided schema strategy training for Chinese university students in the EFL context have been relatively uncommon. This research aimed to find out whether there was a significant improvement in Chinese university students’ reading comprehension after schema strategy instruction (SSI) using digital mind mapping (DMM) or not. This research also aimed to demonstrate students’ perceptions regarding the positive and negative influencing factors of SSI using DMM. A mixed case study approach was applied due to its complexity and the small number of participants. The data were collected by using semi-structured group interview and reading comprehension tests. The interview data were analyzed quantitatively by using simple percentage analysis and described qualitatively as well. The reading comprehension test data were analyzed quantitatively by using descriptive statistics and non-parametric statistics. It was found that SSI using DMM effectively promoted participants’ awareness of schema strategy in reading, however, no significant improvement in reading comprehension scores was found. Furthermore, visualization of DMM, cooperation among participants, and personalized schemata were perceived as positive influencing factors while imbalanced time arrangement, difficulty in cooperative work, and problems with DMM use were considered negative influencing factors of SSI using DMM. In conclusion, this study highlights the potential of concentrated strategy intervention with DMM to enhance EFL learners’ reading literacy.

Abstract Background Quality is the most important factor in satisfaction. However, the existing satisfaction index model of urban and rural resident-based basic medical insurance scheme (SIM_URRBMI) lacks the segmentation of perceived quality elements, it couldn’t provide a reference for quality improvement and satisfaction promotion. This study aims to construct a revised SIM_URRBMI that can accurately and detailly measure perceived quality and provide feasible and scientific suggestions for improving the satisfaction of urban and rural residents' basic medical insurance scheme (URRBMI) in China. Methods Based on the theoretical framework of the American Customer Satisfaction Index, the elements of perceived quality were refined through literature review and expert consultation, and a pool of alternative measurement variables was formed. A three-stage randomized stratified cluster sampling was adopted. The main decision makers of URRBMI in the families of primary school students in 8 primary schools in Changsha were selected. Both the classic test theory and the item response theory were used for measurement variables selection. The reliability and validity of the model were tested by partial least squares (PLS)-related methods. Results A total of 1909 respondents who had URRBMI for their children were investigated. The SIM_URRBMI1.0 consists of 11 latent variables and 28 measurement variables with good reliability and validity. Among the three explanatory variables of public satisfaction, perceived quality had the largest total effect (path coefficient) (0.737). The variable with the greatest effect among the five first-order latent variables on perceived quality was the quality of the medical insurance policy (0.472). Conclusions The SIM_URRBMI1.0 consists of 28 measurement variables and 11 latent variables. It is a reliable, valid, and standard satisfaction measurement tool for URRBMI with good prediction ability for public satisfaction. In addition, the model provides an accurate evaluation of the perceived quality, which will greatly help with performance improvement diagnosis. The most critical aspects of satisfaction improvement are optimizing the scope and proportion of reimbursement as well as setting appropriate level of deductible and capitation of URRBMI.

Background Improving health status is one of the major goals in the management of heart failure (HF). However, little is known about the long‐term individual trajectories of health status in patients with acute HF after discharge. Methods and Results We enrolled 2328 patients hospitalized for HF from 51 hospitals prospectively and measured their health status via the Kansas City Cardiomyopathy Questionnaire–12 at admission and 1, 6, and 12 months after discharge, respectively. The median age of the patients included was 66 years, and 63.3% were men. Six patterns of Kansas City Cardiomyopathy Questionnaire–12 trajectories were identified by a latent class trajectory model: persistently good (34.0%), rapidly improving (35.5%), slowly improving (10.4%), moderately regressing (7.4%), severely regressing (7.5%), and persistently poor (5.3%). Advanced age, decompensated chronic HF, HF with mildly reduced ejection fraction, HF with preserved ejection fraction, depression symptoms, cognitive impairment, and each additional HF rehospitalization within 1 year of discharge were associated with unfavorable health status (moderately regressing, severely regressing, and persistently poor) (P

Abstract Background This study was designed for the research and development (R&D) and application of a storage inflow and outflow management system enabling departments to perform efficient, scientific, and information-based consumable management. Methods In the endocrinology department of a hospital, expert and R&D teams in consumable management were set up, and an information-based storage inflow and outflow management system for consumables was designed and developed. The system was operated on a personal computer and was divided into three modules: public consumables, bed consumables, and quality control management. The functions of the system included storage inflow and outflow, early warnings, response to user queries, and statistics on consumables. Data were derived from the hospital information system (HIS,ZHIY SOFTWARE HIS VERSION4.0) and a questionnaire survey. Economic indicators, work efficiency of consumable management, nurse burnout, consumable stockroom management, and staff satisfaction were compared under manual management, Excel-based management, and the consumable storage inflow and outflow management system. The results of the questionnaire were analysed using the R software, version 4.1.0. Results Dates were obtained from manual management, Excel-based management and the consumable storage inflow and outflow management system. Under these three methods, the daily prices of department consumables per bed were 53.43 ± 10.27 yuan, 38.65 ± 8.56 yuan, and 31.98 ± 7.36 yuan, respectively, indicating that the new management system reduced costs for the department. The time spent daily on consumable management was shortened from 119.5 (106.75, 123.5) min to 56.5 (48.5, 60.75) to 20 (17.25, 24.25) min. Nurses’ emotional fatigue and job indifference scores, respectively, decreased from 22.90 ± 1.65 and 8.75 ± 1.25 under manual management to 19.70 ± 1.72 and 6.90 ± 1.37 under Excel-based management and to 17.20 ± 2.04 and 6.00 ± 1.30 under the novel system; the satisfaction of the warehouse keeper and collection staff, respectively, increased from 76.62% and 80.78% to 91.6% and 90.5% to 98.8% and 98.5% under the three successive systems. Conclusions The storage inflow and outflow management system achieved produced good results in the storage and classification of consumables.

Aims: Patient-reported outcome measures have become an important part of routine care. The aim of this study was to determine if Patient-Reported Outcomes Measurement Information System (PROMIS) measures can be used to create patient subgroups for individuals seeking orthopaedic care. Methods: This was a cross-sectional study of patients from Duke University Department of Orthopaedic Surgery clinics (14 ambulatory and four hospital-based). There were two separate cohorts recruited by convenience sampling (i.e. patients were included in the analysis only if they completed PROMIS measures during a new patient visit). Cohort #1 (n = 12,141; December 2017 to December 2018,) included PROMIS short forms for eight domains (Physical Function, Pain Interference, Pain Intensity, Depression, Anxiety, Sleep Quality, Participation in Social Roles, and Fatigue) and Cohort #2 (n = 4,638; January 2019 to August 2019) included PROMIS Computer Adaptive Testing instruments for four domains (Physical Function, Pain Interference, Depression, and Sleep Quality). Cluster analysis (K-means method) empirically derived subgroups and subgroup differences in clinical and sociodemographic factors were identified with one-way analysis of variance. Results: Cluster analysis yielded four subgroups with similar clinical characteristics in Cohort #1 and #2. The subgroups were: 1) Normal Function: within normal limits in Physical Function, Pain Interference, Depression, and Sleep Quality; 2) Mild Impairment: mild deficits in Physical Function, Pain Interference, and Sleep Quality but with Depression within normal limits; 3) Impaired Function, Not Distressed: moderate deficits in Physical Function and Pain Interference, but within normal limits for Depression and Sleep Quality; and 4) Impaired Function, Distressed: moderate (Physical Function, Pain Interference, and Sleep Quality) and mild (Depression) deficits. Conclusion: These findings suggest orthopaedic patient subgroups differing in physical function, pain, and psychosocial distress can be created from as few as four different PROMIS measures. Longitudinal research is necessary to determine whether these subgroups have prognostic validity.

ObjectiveAs a major source of added sugar, the consumption of sugar-sweetened beverages (SSBs) continues to increase worldwide. The adverse health effects associated with SSBs are also risk factors for cognitive development, but studies on the relationship between SSBs and adolescents' cognitive function are limited. We used data released by the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) to explore the association between the consumption of SSBs and cognitive function among children and adolescents aged 12–16 years in the United States.Methods and proceduresA nationally representative population sample included 1,809 adolescents aged 12–16 years who participated in the United States NHANES from 1988 to 1994 and provided samples for the dietary intake frequency questionnaire and measures of cognitive function. Binary logistic regression was used to estimate the association between the frequency of SSB consumption and scores on cognitive function tests.ResultsThis study of 1,809 adolescents aged 12–16 years comprised 963 girls (weighted proportion, 48.17%) and 846 boys (weighted, 51.83%), with a weighted mean (SE) age of 13.99 (0.05) years. Compared with adolescents who intake SSBs 0–1 times per week, those who drank 4–7 times per week had better scores in arithmetic, reading, and digit span tests, with odds ratios (ORs) of 0.36 (95% CI = 0.16–0.82), 0.35 (95% CI = 0.18–0.70), and 0.19 (95% CI = 0.08–0.44), respectively. The ORs for abnormal block design scores increase with the frequency of SSB intake after being adjusted for potential confounders (P for trend 0.02). Stratified analyses showed that compared with normal or below BMI, among overweight or obese individuals, the frequency of SSB intake had significant ORs for abnormal digit span scores (OR = 4.76, 95% CI = 1.19–18.96 vs. 0.35, 95% CI = 0.10–1.25; P for interaction = 0.01).ConclusionThe positive associations of SSBs at moderate level intake with better scores in arithmetic, reading, and digit span were observed, but no dose-response relationship was identified at the overall level. Additionally, with the increasing frequency of SSB consumption, the risk of anomalous block design scores increased among US adolescents. Further investigation is warranted to confirm the association and mechanism between SSBs and cognitive function among adolescents.

Cholangiocarcinoma (CCA) is a highly invasive malignant tumor with high mortality. Most cases of CCA are already advanced when they are detected, resulting in poor prognosis. As such, there is an ongoing need for the identification of effective biomarkers for CCA. The long noncoding RNA DLGAP1‐AS2 has been reported to have prognostic value in glioma and Wilms' tumor. Here, we investigated the function of DLGAP1‐AS2 in CCA. The differential expression of DLGAP1‐AS2 in CCA tissues and normal tissues was first examined using data from the The Cancer Genome Atlas database and then in CCA cell lines by quantitative RT‐PCR (qRT‐PCR). The target gene was predicted by bioinformatics analysis, and the binding sites were confirmed using luciferase assay. DLGAP1‐AS2 is up‐regulated in CCA, and high DLGAP1‐AS2 expression promotes cell viability and is associated with poor prognosis. Notably, DLGAP1‐AS2 acts as a sponge to suppress miR‐505 expression, and miR‐505 reduces the expression of N‐acetylgalactosaminyltransferase 10 (GALNT10) in CCA cells. Biofunctional experiments revealed that a miR‐505 inhibitor almost completely removed the inhibitory effect of si‐DLGAP1‐AS2 on CCA cell malignant progression, whereas the malignant phenotype of cells cotransfected with si‐DLGAP1‐AS2 and si‐GALNT10 was significantly reduced as compared with the control. In summary, the DLGAP1‐AS2/miR‐505/GALNT10 axis may contribute to regulating the malignant progression of CCA and may have potential as a novel target for CCA therapy.

The effects of exposure to the environmental toxicant cadmium, in combination with obesity, on the metal content in mouse testis were evaluated. Starting in utero and continuing through to 10 or 24 weeks post-weaning, male mice were exposed to cadmium (0, 0.5 or 5 ppm), and fed either a low (LFD) or high fat diet (HFD) post-weaning. Testicular levels of cadmium and essential metals were determined 10 and 24 weeks post-weaning by ICP-MS. Similar to what has been previously observed in the liver, kidney, heart and brain, significant levels of cadmium accumulated in the testis under all exposure conditions. Additionally, HFD-fed animals accumulated more cadmium than did their LFD-treated counterparts. Both treatments affected essential metal homeostasis in the testis. These findings suggest that cadmium and obesity may compromise the reproductive potential in the male mouse by disrupting essential metal levels.

Abstract Background There have been few studies on satisfaction with integrated basic medical insurance for urban and rural residents (URRBMI), and satisfaction with URRBMI is not very high because of the complexity of its policies and differences among the insured. The aim of the present study was to explore the factors that influence satisfaction with URRBMI in China and to provide scientific suggestions to the government for how to effectively manage and improve the policy. Methods An explanatory sequential design of mixed methods research was used. A quantitative research using a three-stage stratified cluster sampling method was used to randomly select the guardians of pupils who participated in URRBMI (n = 1335). The quantitative research was conducted to calculate the latent variables’ scores and path coefficients between latent variables using SmartPLS3.0. With public trust, public satisfaction, and perceived quality as the target variables, important-performance analysis (IPA) was used to explore the important but underperforming factors, which were the key elements to improving satisfaction with URRBMI. A purposeful sampling strategy according to satisfaction level was used to obtain qualitative research subjects from among the quantitative research subjects. A qualitative research was conducted using semi-structured interviews, and the thematic analysis method was used to summarize the interview data. Results The three strongest paths were perceived quality to public satisfaction, with a total effect of 0.737 (t = 41.270, P

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a major global public health burden and lacks effective risk stratification. We aimed to assess a multi-biomarker model in improving risk prediction in HFpEF.Methods: We analyzed 18 biomarkers from the main pathophysiological domains of HF in 380 patients hospitalized for HFpEF from a prospective cohort. The association between these biomarkers and 2-year risk of all-cause death was assessed by Cox proportional hazards model. Support vector machine (SVM), a supervised machine learning method, was used to develop a prediction model of 2-year all-cause and cardiovascular death using a combination of 18 biomarkers and clinical indicators. The improvement of this model was evaluated by c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The median age of patients was 71-years, and 50.5% were female. Multiple biomarkers independently predicted the 2-year risk of death in Cox regression model, including N-terminal pro B-type brain-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), tumor necrosis factor-α (TNFα), endoglin, and 3 biomarkers of extracellular matrix turnover [tissue inhibitor of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-2, and MMP-9) (FDR < 0.05). The SVM model effectively predicted the 2-year risk of all-cause death in patients with acute HFpEF in training set (AUC 0.834, 95% CI: 0.771–0.895) and validation set (AUC 0.798, 95% CI: 0.719–0.877). The NRI and IDI indicated that the SVM model significantly improved patient classification compared to the reference model in both sets (p < 0.05).Conclusions: Multiple circulating biomarkers coupled with an appropriate machine-learning method could effectively predict the risk of long-term mortality in patients with acute HFpEF. It is a promising strategy for improving risk stratification in HFpEF.

Objectives Little is known about contemporary characteristics and management of valvular heart disease (VHD) in China. This study aimed to examine the clinical characteristics, aetiology and type of VHD, interventions and in-hospital outcomes of patients with VHD hospitalised in China.Methods We used a two-stage random sampling design to create a nationally representative sample of patients with VHD hospitalised in 2015 in China and included adult patients with mild, moderate or severe VHD. We abstracted data from medical records, including echocardiogram reports, on patient characteristics, aetiology, type and severity of VHD, interventions and in-hospital outcomes. We weighted our findings to estimate nationally representative hospitalisations. We performed multivariable logistic regression analysis to identify factors associated with valve intervention.Results In 2015, 38 841 patients with VHD were hospitalised in 188 randomly sampled hospitals, representing 662 384 inpatients with VHD in China. We sampled 9363 patients, mean age 68.7 years (95% CI 42.2 to 95.2) and 46.8% (95% CI 45.8% to 47.8%) male, with an echocardiogram. Degenerative origin was the predominant aetiology overall (33.3%, 95% CI 32.3% to 34.3%), while rheumatic origin was the most frequent aetiology among patients with VHD as the primary diagnosis (37.4%, 95% CI 35.9% to 38.8%). Rheumatic origin was also the most common aetiology among patients with moderate or severe VHD (27.3%, 95% CI 25.6% to 29.0% and 33.6%, 95% CI 31.9% to 35.2%, respectively). The most common VHD was mitral regurgitation (79.1%, 95% CI 78.2% to 79.9%), followed by tricuspid regurgitation (77.4%, 95% CI 76.5% to 78.2%). Among patients with a primary diagnosis of severe VHD who were admitted to facilities capable of valve intervention, 35.6% (95% CI 33.1% to 38.1%) underwent valve intervention during the hospitalisation. The likelihood of intervention decreased significantly among patients with higher operative risk.Conclusions Among patients with VHD hospitalised in China, the predominant aetiology was degenerative in origin; among patients with moderate or severe VHD, rheumatic origin was the most common aetiology. Targeted strategies and policies should be promoted to address degenerative VHD. Patients with severe VHD may be undertreated, particularly those with high operative risk.

Objectives Characterise the health status of patients newly consulting an orthopaedic specialist across eight clinical subspecialties.Design Retrospective cohort.Setting 18 orthopaedic clinics, including 8 subspecialties (14 ambulatory and 4 hospital based) within an academic health system.Participants 14 910 patients consulting an orthopaedic specialist for a new patient consultation who completed baseline Patient-Reported Outcomes Measurement Information System (PROMIS) measures associated with their appointment from 17 November 2017 to 13 May 2019. Patients were aged 55.72±5.8 years old, and 61.3% were female and 79.3% were Caucasian and 13.4% were black or African American. Patients who did not complete PROMIS measures or cancelled their appointment were excluded from the study.Primary outcome PROMIS domains of physical function, pain interference, pain intensity, depression, anxiety, fatigue, sleep disturbance and the ability to participate in social roles.Results Mean PROMIS scores for physical function were (38.1±9.2), pain interference (58.9±8.1), pain intensity (4.6±2.5), depression (47.9±8.9), anxiety (49.9±9.5), fatigue (50.5±10.3), sleep disturbance (51.1±9.8) and ability to participate in social roles (49.1±10.3) for the entire cohort. Across the clinical subspecialties, neurosurgery, spine and trauma patients were most profoundly affected across almost all domains and patients consulting with a hand specialist reported the least limitations or symptoms across domains. There was a moderate, negative correlation between pain interference and physical functioning (r=−0.59) and low correlations between pain interference with anxiety (r=0.36), depression (r=0.39) as well as physical function and anxiety (r=−0.32) and depression(r=−0.30) and sleep (r=−0.31).Conclusions We directly compared clinically meaningful PROMIS domains across eight orthopaedic subspecialties, which would not have been possible with legacy measures alone. These results support PROMIS’s utility as a common metric to assess and compare patient health status across multiple orthopaedic subspecialties.

We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased oestrogen levels are reported to be associated with increased BC risk. Herein, we assessed if oestrogens, including oestrone (E1), oestradiol (E2) and oestriol (E3), are associated with A-FABP in the obesity-related BC development. We collected 249 serum samples from women with or without BC and measured serum levels of E1, E2, E3 and A-FABP. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause individuals. E3 and E1 levels were higher in non-obese than in obese women. When samples were separated by BC status, E2 levels were significantly higher, while E1 and E3 levels were significantly lower in postmenopausal obese than non-obese women without BC. These differences based on body mass index (BMI) were not observed among women with BC. E3 levels were higher in obese women with BC than those without. A-FABP levels were significantly higher in postmenopausal obese women regardless of BC status. In addition, A-FABP was not associated with E1, E2 or E3. Altogether, our data suggest that A-FABP is independently regulated by obesity and menopausal status compared to oestrogens, thus playing a unique role in the development of BC.

Ubiquitination-mediated protein degradation plays a crucial role in the turnover of immune proteins through rapid alteration of protein levels. Specifically, the over-accumulation of immune proteins and consequent activation of immune responses in uninfected cells is prevented through degradation. Protein post-translational modifications can influence and affect ubiquitination. There is accumulating evidence that suggests sumoylation, phosphorylation, and acetylation differentially affect the stability of immune-related proteins, so that control over the accumulation or degradation of proteins is fine-tuned. In this paper, we review the function and mechanism of sumoylation, phosphorylation, acetylation, and ubiquitination in plant disease resistance responses, focusing on how ubiquitination reacts with sumoylation, phosphorylation, and acetylation to regulate plant disease resistance signaling pathways. Future research directions are suggested in order to provide ideas for signaling pathway studies, and to advance the implementation of disease resistance proteins in economically important crops.

Abstract Traditional Proportional-Integral-Derivative (PID) control systems often encounter challenges related to nonlinearity and time-variability. Original dung beetle optimizer (DBO) offers fast convergence and strong local exploitation capabilities. However, they are limited by poor exploration capabilities, imbalance between exploration and exploitation phases, and insufficient precision in global search. This paper proposes a novel adaptive PID control algorithm based on enhanced dung beetle optimizer (EDBO) and back propagation neural network (BPNN). Firstly, the diversity of exploration is increased by incorporating a merit-oriented mechanism into the rolling behavior. Then, a sine learning factor is introduced to balance the global exploration and local exploitation capabilities. Additionally, a dynamic spiral search strategy and adaptive $$t$$ -distribution disturbance are presented to enhance search precision and global search capability. The BPNN is employed to fine-tune both PID and network parameters, leveraging its powerful generalization and learning ability to model nonlinear system dynamics. In the simplified motor experiments, the proposed controller achieved the lowest overshoot (0.5%) and the shortest response time (0.012 s), with a settling time of 0.02 s and a steady-state error of just 0.0010. In another set of experiments, the proposed controller recorded an overshoot and response time of 0.7% and 0.0010 s, across five DC motor tests. These results demonstrate the proposed adaptive PID control algorithm has superior performance in optimizing control system parameters, as well as improving system robustness and stability.

Abstract Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), is a widely distributed soilborne disease that poses a serious threat to banana production. Many control measures have been implemented but have not been effective. Here, we evaluated a combined strategy for Fusarium wilt control that involves a biological agent (Bacillus velezensis strain EB1) and a bioactive compound (potassium sorbate). Our results showed that potassium sorbate inhibited Foc TR4 in a dose-dependent manner. Potassium sorbate did not limit the growth of EB1 in vitro; instead, it promoted the growth and antagonistic ability of EB1 by upregulating the expression of antagonism-related genes. In greenhouse experiments, the combined application of EB1 and potassium sorbate significantly reduced the disease index of Fusarium wilt by suppressing fungal growth in the roots and promoting plant growth. Overall, our results demonstrated that potassium sorbate and B. velezensis EB1 can be used together for the sustainable management of banana Fusarium wilt.

Abstract Background Dexmedetomidine is considered to have neuroprotective effects and may reduce postoperative delirium in both cardiac and major non-cardiac surgeries. Compared with non-cardiac surgery, the delirium incidence is extremely high after cardiac surgery, which could be caused by neuroinflammation induced by surgical stress and CPB. Thus, it is essential to explore the potential benefits of dexmedetomidine on the incidence of delirium in cardiac surgery under CPB. Methods Randomized controlled trials studying the effect of perioperative dexmedetomidine on the delirium incidence in adult patients undergoing cardiac surgery with CPB were considered to be eligible. Data collection was conducted by two reviewers independently. The pre-specified outcome of interest is delirium incidence. RoB 2 was used to perform risk of bias assessment by two reviewers independently. The random effects model and Mantel-Haenszel statistical method were selected to pool effect sizes for each study. Results PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception to June 28, 2023. Sixteen studies including 3381 participants were included in our systematic review and meta-analysis. Perioperative dexmedetomidine reduced the incidence of postoperative delirium in patients undergoing cardiac surgery with CPB compared with the other sedatives, placebo, or normal saline (RR 0.57; 95% CI 0.41–0.79; P = 0.0009; I2 = 61%). Conclusions Perioperative administration of dexmedetomidine could reduce the postoperative delirium occurrence in adult patients undergoing cardiac surgery with CPB. However, there is relatively significant heterogeneity among the studies. And the included studies comprise many early-stage small sample trials, which may lead to an overestimation of the beneficial effects. It is necessary to design the large-scale RCTs to further confirm the potential benefits of dexmedetomidine in cardiac surgery with CPB. Registration number CRD42023452410.

ABSTRACTThis cross-sectional epidemiological study aimed to investigate awareness regarding human papillomavirus (HPV) and willingness for vaccination among college students with or without medical background in Guizhou Province, China. A logistic regression model was used for univariate and multivariate analyses of cognition to determine factors influencing willingness for vaccination. In total, 2,540 questionnaires were collected, of which 2,360 were valid. The medical and nonmedical groups included 737 (31.2%) and 1,623 (68.8%) individuals, respectively. The medical group had heard of HPV and its vaccines more frequently than the nonmedical group, with the former also having greater awareness than the latter (P

Afforestation is recognized as a crucial strategy for mitigating global warming. Therefore, appropriate areas and scales of afforestation needed to be accurate identify and plan, due to the varying levels of economic development and ecological protection across different regions and future scenarios. This study utilized land use data, natural and socio-economic data as the indicators from 2000 to 2020. The Patch-level Land Use Simulation Model (PLUS) was employed to simulate and analyze afforestation potential areas (APAs) under four scenarios: Natural Development (NDS), Ecological Protection (EPS), Urban Development (UDS), and Cultivated Land Protection (CLPS) for the years 2035 and 2050. The results shown that: (1) the spatial distribution of APAs in Yunnan Province under different scenarios shown significant spatial heterogeneity. The APAs are mainly concentrated in economically backward areas with favorable natural conditions. Moreover, the APAs are primarily found around existing forests. (2) The EPS scenario revealed the highest afforestation potential, with 14,132.14 km2 and 13,825.76 km2 of high-APAs, and 5,204.17 km2 and 5,262.4 km2 of low-APAs expected by 2035 and 2050, respectively. The CLPS scenario shown the lowest afforestation potential. (3) The APAs are mainly influenced by natural conditions, the strictness of forest management, and the level of local economic development. Climate and soil, as fundamental natural elements, constitute the foundational conditions for these potential areas. (4) Afforestation strategies should have emphasized ’adapting to local conditions and time’ at different development stages. The program would be dynamically adjusted according to future development scenarios to maximize afforestation potential areas and ecological value. These strategies could provide valuable suggestions for future afforestation planning in Yunnan Province.

Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear.Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored.Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133+ subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells. Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis.Conclusions: Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified.Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids.Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa.Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.