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Abstract Background Accumulating evidence suggests that exposure to air pollution acts as a potential trigger for neurological diseases (NDs), yet the current knowledge regarding the impact of ambient nitrogen dioxide (NO2) on the patients with NDs remains limited. In this study, we conducted a time-series study to evaluate the association between short-term exposure to NO2 and hospital visits for NDs in Xinxiang, China. Methods An over-dispersed Poisson generalized additive model was used to analyze the association between ambient NO2 concentrations and daily outpatient visits for NDs from January 1, 2015 to December 31, 2017. The model adjusted for meteorological factors, temporal trends, day of the week, and public holidays. The concentrations of air pollutants were collected from four air quality stations in Xinxiang. Results A total of 38, 865 outpatient visits for NDs were retrieved during the study period. 86.5% of the patients were below the age of 65 years. It was revealed that a 10 µg/m3 increase in NO2 at lag 0 was associated with a significant rise of 1.50% (95% CI: 0.45–2.56%) in outpatient visits for NDs, which was stronger during the cold season. However, the overall results from stratified analyses did not reach statistical significance. Conclusions Short-term exposure to NO2 is associated with increased outpatient visits for NDs. These findings underscore the need for implementing mitigating measures to reduce the neurological health effects of air pollutants.

Abstract Poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] is a highly promising valuable biodegradable material with good biocompatibility and degradability. Vibrio natriegens, owing to its fast-growth, wide substrate spectrum characteristics, was selected to produce P(3HB-co-LA). Herein, the crucial role of acetyltransferase PN96-18060 for PHB synthesis in V. natriegens was identified. Heterologous pathway of P(3HB-co-LA) was introduced into V. natriegens successfully, in addition, overexpression of the dldh gene led to 1.84 fold enhancement of the lactate content in P(3HB-co-LA). Finally, the production of P(3HB-co-LA) was characterized under different carbon sources. The lactate fraction in P(3HB-co-LA) was increased to 28.3 mol% by the modification, about 1.84 times of that of the control. This is the first successful case of producing the P(3HB-co-LA) in V. natriegens. Collectively, this study showed that V. natriegens is an attractive host organism for producing P(3HB-co-LA) and has great potential to produce other co-polymers.

Abstract Background At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. Methods A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. Results Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p

The Road of Tang Poetry in Eastern Zhejiang is a cultural route where nature and culture harmoniously intertwine. Mountain-type scenic areas play a vital role in providing core cultural ecosystem services (CES). To investigate the significance and distribution of landscape resources along the Poetry Road, a preliminary study was conducted in the densely concentrated areas of Shaoxing, Taizhou, and Ningbo. From these regions, six representative mountain-type scenic areas were selected for the research: Kuaiji Mountain, Qinwang Mountain, Wanwei Mountain, Tianmu Mountain, Tiantai Mountain, and Xuedou Mountain. Based on their designation status, these areas were categorized into national and non-national scenic areas. The research employed a combination of online and offline questionnaires, as well as semi-structured interviews. An importance-performance analysis (IPA) was introduced, and SPSS software was utilized to conduct U-tests on the statistical results. This analysis aimed to compare the differences in importance and performance of CES among the various mountain-type scenic areas. Furthermore, an overall evaluation of CES for the mountain-type scenic area was carried out using an optimization demand zoning approach, involving categories such as “Keeping up the good job”, “Concentrate here”, “Possible overkill”, and “Low priority”. Additionally, a comparative analysis was conducted between the two types of mountain-type scenic areas, considering aspects like aesthetic value, leisure tourism, cultural diversity, and nature education. The findings indicate that the overall importance of the core CES provided by mountain-type scenic areas significantly exceeds the performance score, implying that public expectations for these sites surpass the actual experience. Notably, the distinction between the two types of mountain-type scenic areas, national and non-national, lies primarily in their performance. Among the evaluation subcomponents, respondents’ perceptions are notably influenced by natural resource advantages, architectural style, recreation offerings, site iconicity, and historical heritage and preservation. The abundance of cultural activities emerges as a crucial factor contributing to the substantial performance disparity between the two types of scenic areas, underscoring the significant impact of cultural heritage on the development imbalance in mountain-type region. Furthermore, cultural heritage plays a pivotal role in promoting the establishment and enhancing the competitiveness and identity of mountain-type scenic areas. Consequently, prioritizing the protection and utilization of non-national mountain-type scenic areas cultural heritage can effectively elevate the level of CES supply and meet the demand in mountain-type scenic areas. The IPA has promoted the CES performance of mountain-type scenic areas to be closer to its importance, thereby fostering a more balanced CES of the Road of Tang Poetry in Eastern Zhejiang.

Abstract Alzheimer’s disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current Aβ-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between Aβ and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining Aβ and pTau vaccines, eliciting robust and enduring antibody responses against pathological Aβ and pTau in 3xTg transgenic mice. It significantly eradicated Aβ plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting Aβ and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.

Abstract Background Fatigue affects nurses negatively and may influence life satisfaction. According to the stress process model, active coping might influence the impact of adverse conditions such as fatigue on well-being measures such as life satisfaction. However, no research examined the associations among nurses’ fatigue, coping styles, and life satisfaction. Methods The cross-sectional study was conducted in Liaoning Province, China. 482 effective questionnaires were collected (effective response rate of 80.3%). The questionnaire included Fatigue Scale-14, Simplified Coping Style Questionnaire and Satisfaction with Life Scale. The association among fatigue, coping styles and fatigue × coping styles interaction with life satisfaction was examined by hierarchical multiple regression analysis. The interaction was visualized by simple slope analysis. Results Mean score of life satisfaction was 22.74 ± 6.11. Active coping moderated the relationship between mental fatigue and life satisfaction. The impacts of mental fatigue on life satisfaction gradually decreased in the low (1 SD below the mean, β=-0.400, P

Abstract This study deeply analyzes the ecocultural heritage of the Tiantai Mountain area in Eastern China, assesses its current status and explores effective mechanisms for its conservation and construction. Employing remote sensing technology, kernel density analysis and Minimum Cumulative Resistance Model, the study comprehensively evaluated the environmental characteristics of the region and its role in historical and modern conservation efforts. The results demonstrate the unique distribution patterns of ecocultural heritage in various conservation zones, such as restoration, controlled construction and core conservation zone. Furthermore, the study highlights the importance of religious beliefs and clan systems in the preservation of traditional knowledge and practices, with significant impacts of local community participation on conservation strategies. This research provides new theoretical and practical support for the implemention of ecocultural heritage conservation and development within religiously significant areas, highlights the need for conservation measures and synergistic strategies between ecological and cultural practices.

Abstract Background The identification of spotted leaf 50 (spl50), a novel lesion mimic mutant (LMM) in rice, provides critical insights into the mechanisms underlying programmed cell death (PCD) and innate immunity in plants. Results Based on ethyl methane sulfonate (EMS)-induced mutagenesis, the spl50 mutant mimics hypersensitive responses in the absence of pathogen by displaying spontaneous necrotic lesions after the tillering phase. SPL50, an ARM repeat protein essential for controlling reactive oxygen species (ROS) metabolism and boosting resistance to blast disease, was identified by map-based cloning techniques. This work also demonstrates the detrimental effects of spl50 on photosynthetic efficiency and chloroplast development. The crucial significance of SPL50 in cellular signaling and stress response is shown by its localization to the cytoplasm and constitutive expression in various plant tissues. In light of growing concerns regarding global food security, this study highlights the pivotal role of SPL50 in regulating programmed cell death (PCD) and enhancing the immune response in plants, contributing to strategies for improving crop disease resistance. Conclusions The novel identification of the SPL50 gene in rice, encoding an ARM repeat protein, reveals its pivotal role in regulating PCD and innate immune responses independently of pathogen attack.

Abstract Childhood overweight/obesity is a serious problem that has not been adequately addressed. As a key factor affecting weight gain, the association between dietary intake with childhood overweight and obesity is still unclear. The objective of this study was to analyze the association between sociodemographic, lifestyle factors and dietary intake with overweight or obesity. We used data from a large cross-sectional National Health and Nutrition Examination Survey (NHANES). The U.S. children aged 6–15 years with both weight data and dietary data were included. For univariate analysis of sociodemographic data, t tests was performed for continuous variables and chi-square tests was performed for discrete variables. Dietary intakes were described by median and quartile, and differences in dietary intake between children with normal weight and children with overweight or obesity were compared by rank sum tests. A modern statistical shrinkage technique, LASSO regression was used to examine the association between dietary intake and childhood obesity. Our study confirms that Hispanic ethnicity, increasing age, passive exposure to smoking, higher protein intake, and higher caffeine intake were positively associated with child overweight or obesity. Additionally, non-Hispanic White race, higher physical activity levels, higher household income, and higher vitamin A intake were negatively associated with child overweight or obesity.

Abstract Background Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision. Methods We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach. Discussion This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments. Systematic review registration PROSPERO CRD42023402365.

Copper-based alloys have garnered significant attention for their potential in antimicrobial applications aimed at mitigating medical-related infections. Nonetheless, the alloying elements in conventional copper alloys frequently exhibit biotoxicity. This study explored the corrosion behavior, antimicrobial activity, and ion release of Cu–Fe alloys with varying iron contents and aging treatment. The results indicate that increasing the iron content in Cu–Fe alloys and applying appropriate aging treatment can enhance both the antibacterial efficiency and corrosion rate. Transmission electron microscopy (TEM) observations revealed a corrosion mechanism in which dispersed iron phases act as nucleation sites. These nanoscale precipitates increase the Cu/Fe interfacial area, thereby promoting ion release at the interface. Furthermore, in-situ scanning electron microscopy (SEM) revealed that corrosion products are more likely to detach in iron-rich segregated areas, which effectively promotes the sustained release of copper ions.

Abstract Aims This investigation aims to elucidate the treatment status of advanced HR+/HER2- breast cancer patients in Hunan Province of Central Southern China from November 2021 to December 2022. Methods Data from 301 patients with advanced HR+/HER2- breast cancer were collected from the breast cancer investigation project in Hunan under the guidance of the Chinese Society of Clinical Oncolfogy (CSCO). The data included the clinical characteristics of patients and the status of first-line and second-line rescue treatment. Results First-line chemotherapy and endocrine therapy for mBC accounted for 40% (121/301) and 60% (180/301) of treatments, respectively. AI (21%), AI plus CDK4/6 inhibitor (28%), and fulvestrant (24%) or fulvestrant plus CDK4/6 inhibitor (18%) were the most common first-line endocrine therapies. Taxane-based chemotherapy was the most common first-line chemotherapy (59%). Second-line chemotherapy and endocrine therapy for mBC accounted for 43% (72/166) and 57% (94/166) of treatments, respectively. Fulvestrant (23%) or fulvestrant plus CDK4/6 inhibitor (29%) were the most common second-line endocrine therapies. The prevalences of AI and AI plus CDK4/6 inhibitor decreased to 19% and 11%, respectively. T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Third-line chemotherapy was more prevalent than endocrine therapy (57% vs. 41%). T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Fulvestrant plus CDK4/6 inhibitor was the most common endocrine therapy (33%). AI, AI plus CDK4/6 inhibitor, and fulvestrant accounted for 21%, 12% and 18% of third-line endocrine therapies, respectively. Conclusions Compared to chemotherapy, endocrine therapy was a more favorable choice for first-line and second-line treatment for HR+/HER2- advanced breast cancer patients in Hunan Province.

Abstract Background Andersen’s lesion (AL) is a rare complication of ankylosing spondylitis (AS), characterized by nonneoplastic bone destruction, typically manifested as bone destruction and sclerosis in the vertebral body and/or intervertebral disc area. At present, there is no consensus on the pathology and etiology of AL. Repeated trauma, inflammation in essence and part of the natural history of Ankylosing spondylitis itself are the most widely recognized theories of the etiology of AL. However, positive bacteria cultured in bone biopsy of Andersen’s lesion (AL) in Ankylosing spondylitis patients are extremely rare. Herein, we report a rare case of detecting Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by Metagenomic Next-Generation Sequencing (mNGS) Test. Case presentation This case involved a 39-year-old male with a history of AS for 11 years, who developed AL (T11/12) in the thoracic vertebrae. After sufficient preoperative preparation, we successfully performed one-stage posterior approach corrective surgery and collected bone biopsies samples for examination. Cultured bacteria were not found, and pathological histology indicated infiltration of inflammatory cells. However, it is worth noting that we discovered a gram-negative bacterium, the Ewingella americana, through mNGS testing. Further histopathological examination suggests chronic inflammatory cell infiltration. After one-stage posterior approach corrective surgery, the patient’s condition significantly improved. At the 6-month follow-up, the pain significantly decreased, and the patient returned to normal life. Conclusion We detected Ewinia americana in the bone biopsies of Andersson lesion (AL) in ankylosing spondylitis patient by mNGS.

Abstract Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1–14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.

Abstract Background Nosocomial infections with heavy disease burden are becoming a major threat to the health care system around the world. Through long-term, systematic, continuous data collection and analysis, Nosocomial infection surveillance (NIS) systems are constructed in each hospital; while these data are only used as real-time surveillance but fail to realize the prediction and early warning function. Study is to screen effective predictors from the routine NIS data, through integrating the multiple risk factors and Machine learning (ML) methods, and eventually realize the trend prediction and risk threshold of Incidence of Nosocomial infection (INI). Methods We selected two representative hospitals in southern and northern China, and collected NIS data from 2014 to 2021. Thirty-nine factors including hospital operation volume, nosocomial infection, antibacterial drug use and outdoor temperature data, etc. Five ML methods were used to fit the INI prediction model respectively, and to evaluate and compare their performance. Results Compared with other models, Random Forest showed the best performance (5-fold AUC = 0.983) in both hospitals, followed by Support Vector Machine. Among all the factors, 12 indicators were significantly different between high-risk and low-risk groups for INI (P

Abstract Background Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia. Methods We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel–Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach. Discussion Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients. Systematic review registration PROSPERO-ID CRD42023410645.

Abstract Effects of short-term exposure to ambient air pollution on systemic immunological and inflammatory biomarkers in rural population have not been adequately characterized. From May to July 2021, 5816 participants in rural villages of northern Henan Province, China, participated in this cross-sectional study. Blood biomarkers of systemic inflammation were determined including peripheral white blood cells (WBC), eosinophils (EOS), basophils (BAS), monocytes (MON), lymphocytes (LYM), neutrophils (NEU), neutrophil-lymphocyte ratio (NLR), and serum high-sensitivity C-reactive protein (hs-CRP). The concentrations of ambient fine particulate matter (PM2.5), PM10, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were assessed up to 7 days prior to the blood draw. A generalized linear model was used to analyze the associations between air pollution exposure and the above-mentioned blood biomarkers. Significantly positive associations were revealed between PM2.5, CO and WBC; CO, O3 and LYM; PM2.5, PM10, SO2, CO and NEU; PM2.5, PM10, SO2, CO and NLR; PM2.5, PM10, SO2, NO2, CO, O3 and hs-CRP. Meanwhile, negative associations were found between SO2 and WBC; PM2.5, PM10, NO2, CO, or O3 and EOS; PM2.5, SO2, or CO and BAS; SO2, NO2 or O3 and MON; PM2.5, PM10, SO2, or NO2 and LYM. Moreover, men, individuals with normal body mass index (BMI), current smokers, and those older than 60 years were found vulnerable to air pollution effects. Taken together, short-term exposure to air pollution was associated with systemic inflammatory responses, providing insight into the potential mechanisms for air pollution-induced detrimental systemic effects in rural residents.

Abstract The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of

Abstract The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Abstract Flexible sensors have been widely studied for use in motion monitoring, human‒machine interactions (HMIs), personalized medicine, and soft intelligent robots. However, their practical application is limited by their low output performance, narrow measuring range, and unidirectional force detection. Here, to achieve flexibility and high performance simultaneously, we developed a flexible wide-range multidimensional force sensor (FWMFS) similar to bones embedded in muscle structures. The adjustable magnetic field endows the FWMFS with multidimensional perception for detecting forces in different directions. The multilayer stacked coils significantly improved the output from the μV to the mV level while ensuring FWMFS miniaturization. The optimized FWMFS exhibited a high voltage sensitivity of 0.227 mV/N (0.5–8.4 N) and 0.047 mV/N (8.4–60 N) in response to normal forces ranging from 0.5 N to 60 N and could detect lateral forces ranging from 0.2–1.1 N and voltage sensitivities of 1.039 mV/N (0.2–0.5 N) and 0.194 mV/N (0.5–1.1 N). In terms of normal force measurements, the FWMFS can monitor finger pressure and sliding trajectories in response to finger taps, as well as measure plantar pressure for assessing human movement. The plantar pressure signals of five human movements collected by the FWMFS were analyzed using the k-nearest neighbors classification algorithm, which achieved a recognition accuracy of 92%. Additionally, an artificial intelligence biometric authentication system is being developed that classifies and recognizes user passwords. Based on the lateral force measurement ability of the FWMFS, the direction of ball movement can be distinguished, and communication systems such as Morse Code can be expanded. This research has significant potential in intelligent sensing and personalized spatial recognition.

Abstract Currently, three carnivorous bat species, namely Ia io, Nyctalus lasiopterus, and Nyctalus aviator, are known to actively prey on seasonal migratory birds (hereinafter referred to as “avivorous bats”). However, the absence of reference genomes impedes a thorough comprehension of the molecular adaptations of avivorous bat species. Herein, we present the high-quality chromosome-scale reference genome of N. aviator based on PacBio subreads, DNBSEQ short-reads and Hi-C sequencing data. The genome assembly size of N. aviator is 1.77 Gb, with a scaffold N50 of 102 Mb, of which 99.8% assembly was anchored into 21 pseudo-chromosomes. After masking 635.1 Mb repetitive sequences, a total of 19,412 protein-coding genes were identified, of which 99.3% were functionally annotated. The genome assembly and gene prediction reached 96.1% and 96.1% completeness of Benchmarking Universal Single-Copy Orthologs (BUSCO), respectively. This chromosome-level reference genome of N. aviator fills a gap in the existing information on the genomes of carnivorous bats, especially avivorous ones, and will be valuable for mechanism of adaptations to dietary niche expansion in bat species.

Trichosporon species are part of the normal microbiota of humans which can cause both superficial and invasive infections, primarily affecting immunocompetent and immunocompromised hosts, respectively. Giant ulcer caused by Trichosporon asahii is relatively uncommon in immunocompetent hosts. Increased drug resistance and biofilm-associated virulence makes the treatment of infectious ulcers challenging. Herein, we present a case of a massive ulcer caused by T. asahii which resulted in completed healing when treated with photodynamic therapy (PDT) and voriconazole. It provided the feasibility for PDT combined with antifungal drugs to treat similar refractory cases.

ObjectiveAlthough guidelines support the efficacy of Modified Qing’ E Formula (MQEF) in treating postmenopausal osteoporosis (PMOP), its underlying mechanisms remain incompletely understood. This retrospective investigation aims to elucidate MQEF’s impact on serum exosomal miRNA expression in postmenopausal osteoporosis patients and to explore potential therapeutic mechanisms.MethodsFollowing ethical approval and registration, postmenopausal osteoporosis patients aged 50–85 years, meeting the diagnostic criteria were randomly selected and received MQEF decoction supplementary therapy. Serum samples were collected pre- and post-treatment, followed by isolation and sequencing of exosomal miRNAs. Differential miRNAs in serum exosomes were identified, and bioinformatics analysis was conducted to discern the principal exosomal miRNAs involved in MQEF’s effects on PMOP and the associated signaling pathways.ResultsEighteen clinical blood samples were collected. A total of 282,185 target genes were detected across the three groups. 306 miRNAs exhibited altered expression in serum exosomes of PMOP patients, while MQEF intervention resulted in changes in 328 miRNAs. GO enrichment analysis revealed the immune and endocrine systems was pertained. KEGG enrichment analysis indicated associations between PMOP occurrence and MQEF treatment with cytokine interactions, oxidative phosphorylation, and the renin-angiotensin system. Intersectional analysis identified 17 miRNAs, including 2 consistent trends. miR-3188 as a potentially pivotal miRNA implicated in both PMOP occurrence and MQEF treatment.ConclusionThis study constitutes the first randomized, retrospective clinical exploration confirming that MQEF demonstrates regulatory influence over exosomal miRNA expression in PMOP patients’ serum, its impact likely involves modulation of the immune and endocrine systems, as well as the renin-angiotensin system.

IntroductionSpecialized care is essential for the recovery of children with cerebral palsy (CP). This study investigates how different care modes impact the gut microbiota.MethodsFecal samples from 32 children were collected, among whom those cared for by family (n = 21) were selected as the observation group, and those cared for by children's welfare institutions (n = 11) were selected as the control group (registration number of LGFYYXLL-024). The gut microbiota profiles were analyzed.ResultsThere was no significant difference in the α-diversity of the gut microbiota and the abundance at the phylum level. However, at the genus level, the observation group showed a significant increase in the abundance of butyrate-producing bacteria Bacteroides and Lachnospiracea incertae sedis (P

Abstract Objective Cancer-related fatigue (CRF) has been considered the biggest influencing factor for cancer patients after surgery. This study aimed to develop and validate a nomogram for severe cancer-related fatigue (CRF) patients with cervical cancer (CC). Methods A cross-sectional study was conducted to develop and validate a nomogram (building set = 196; validation set = 88) in the Department of Obstetrics and Gynecology of a Class III hospital in Shenyang, Liaoning Province. We adopted the questionnaire method, including the Cancer Fatigue Scale (CFS), Medical Uncertainty in Illness Scale (MUIS), Medical Coping Modes Questionnaire (MCMQ), Multidimensional Scale of Perceived Social Support (MSPSS), and Sense of Coherence-13 (SOC-13). Binary logistic regression was used to test the risk factors of CRF. The R4.1.2 software was used to develop and validate the nomogram, including Bootstrap resampling method, the ability of Area Under Curve (AUC), Concordance Index (C-Index), Hosmer Lemeshow goodness of fit test, Receiver Operating Characteristic (ROC) curve, Calibration calibration curve, and Decision Curve Analysis curve (DCA). Results The regression equation was Logit(P) = 1.276–0.947 Monthly income + 0.989 Long-term passive smoking − 0.952 Physical exercise + 1.512 Diagnosis type + 1.040 Coping style − 0.726 Perceived Social Support − 2.350 Sense of Coherence. The C-Index of the nomogram was 0.921 (95% CI: 0.877 $$ \sim $$ 0.958). The ROC curve showed the sensitivity of the nomogram was 0.821, the specificity was 0.900, and the accuracy was 0.857. AUC was 0.916 (95% CI: 0.876 $$ \sim $$ 0.957). The calibration showed that the predicted probability of the nomogram fitted well with the actual probability. The DCA curve showed when the prediction probability was greater than about 10%, the benefit of the nomogram was positive. The results in the validation group were similar. Conclusion This nomogram had good identifiability, accuracy and clinical practicality, and could be used as a prediction and evaluation tool for severe cases of clinical patients with CC.

Abstract Escherichia coli MLB (MG1655 ΔpflB ΔldhA), which can hardly grow on glucose with little succinate accumulation under anaerobic conditions. Two-stage fermentation is a fermentation in which the first stage is used for cell growth and the second stage is used for product production. The ability of glucose consumption and succinate production of MLB under anaerobic conditions can be improved significantly by using acetate as the solo carbon source under aerobic condition during the two-stage fermentation. Then, the adaptive laboratory evolution (ALE) of growing on acetate was applied here. We assumed that the activities of succinate production related enzymes might be further improved in this study. E. coli MLB46-05 evolved from MLB and it had an improved growth phenotype on acetate. Interestingly, in MLB46-05, the yield and tolerance of succinic acid in the anaerobic condition of two-stage fermentation were improved significantly. According to transcriptome analysis, upregulation of the glyoxylate cycle and the activity of stress regulatory factors are the possible reasons for the elevated yield. And the increased tolerance to acetate made it more tolerant to high concentrations of glucose and succinate. Finally, strain MLB46-05 produced 111 g/L of succinic acid with a product yield of 0.74 g/g glucose. Synopsis

BackgroundHealthy lifestyle is one of the important factors affecting individual health. How to promote residents' cognition of healthy lifestyle has become an urgent practical problem for the whole society. However, there is no residents' healthy lifestyle cognitive indexes available with consideration of carbon peaking and carbon neutrality. ObjectiveTo construct a cognitive index system for providing effective assessment on residents' cognition of healthy lifestyle under the background of carbon peaking and carbon neutrality. MethodsBased on the health belief model, a preliminary cognitive index system of residents' healthy lifestyle under the background of carbon peaking and carbon neutrality was proposed after literature study and relevant policy review. Then three rounds of indicator importance evaluation and screening by Delphi method were conducted before the index system was finally constructed. The weights of all levels of indicators were determined using analytic hierarchy process. In addition, a self-assessment questionnaire was developed based on the index system. The questionnaire was utilized to conduct a survey among 200 residents by convenience sampling in Shenyang, Liaoning Province from November to December 2021. The survey was used to examine the reliability and validity of the indicator system. ResultsThe effective recovery rates of the three rounds of Delphi method were all 100%. The authority coefficient was 0.84. The Kendall's W consistency test showed good expert consistency (P

Abstract Background This study aims to identify the risk factors contributing to spinal cord injury (SCI) following a type A acute aortic dissection (TA-AAD). Methods This retrospective study was conducted at a single center and involved 481 patients who received frozen elephant trunk stent implantation for TA-AAD. Additionally, these patients underwent total arch replacement with deep hypothermic circulatory arrest. This study was performed at Fuwai Hospital between September 2016 and April 2020. Results The resulting data of the multivariate logistic regression analysis demonstrated that preoperative platelet count (odds ratio [OR] = 0.774) and D-dimer levels (OR = 2.247) could serve as independent predictors for postoperative SCI in patients with TA-AAD. Conclusion The findings indicate that preoperative platelet count and D-dimer levels are independent risk factors for postoperative SCI in patients with TA-AAD. This study holds significant clinical implications regarding the prognosis and therapeutic responses for patients with TA-AAD.

Abstract Background Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. Method Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. Results Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P

Chronic spontaneous urticaria (CSU) is a common immune skin disease in clinic. Mast cells are the key effector cells in the pathogenesis of CSU. With the continuous understanding of the pathogenesis of CSU in recent years, many new biologics have been used to treat CSU. Biologics can effectively treat CSU by targeting different stages of mast cell activation, blocking their activation and degranulation. According to the target and mechanisms of their action, biologics can be classified into inhibition of mast cell activation and intracellular signaling transduction, and activation of inhibitory receptor. This article will review the applications of biologics in the treatment of CSU.

Abstract Background A stable public health workforce plays an indispensable role in the realization of the goal of health for all. However, there is an exodus of public health workers from the Centers for Disease Control and Prevention (CDC). Given the limited evidence on the mechanisms shaping turnover intention (TI) among public health workers, the study aims to investigate the triggering mechanisms of high and low turnover intention by combining job demands, job resources, and personal resources through a set theory perspective based on the Job-Demand-Resources (JD-R) model. Methods The cross-sectional study was conducted from September 7 to 18, 2020 at district (county) level CDC in Liaoning Province, China. A total of 584 public health professionals were included. Overcommitment, effort, social respect, occupational identity, job rewards, self-efficacy, and psychological resilience were included in the study as configuration factors. The data were gathered through an online questionnaire and were analyzed using multiple regression and fuzzy-set Qualitative Comparative Analysis (fsQCA). Results Social respect (B = -0.682, P

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG35-55 antigen, was attenuated ex vivo. Mechanistically, inulin treatment altered the composition of gut microbiota. It increased Lactobacillus and Dubosiella whereas decreased g_Prevotellaceae_NK3B31_group at the genus level, alongside with elevated concentration of butyric acid in fecal content and serum. In vitro, butyrate, but not inulin, could inhibit the activation of MOG35-55 stimulated lymphocytes. Furthermore, fecal microbiota transplantation assay confirmed that fecal contents of inulin-treated normal mice had an ameliorative effect on EAE mice. In contrast, antibiotic cocktail (ABX) treatment diminished the therapeutic effect of inulin in EAE mice as well as the reduction of Th17 cells, while supplementation with Lactobacillus reuteri restored the amelioration effect. These results confirmed that the attenuation of inulin on Th17 cells and inflammatory demyelination in EAE mice was dependent on its modulation on gut microbiota and metabolites. Our findings provide a potential therapeutic regimen for prebiotic inulin supplementation in patients with multiple sclerosis.

Norovirus (NV) infection causes acute gastroenteritis in children and adults. Upon infection with NV, specific CD8+ T cells, which play an important role in anti-infective immunity, are activated in the host. Owing to the NV’s wide genotypic variability, it is challenging to develop vaccines with cross-protective abilities against infection. To aid effective vaccine development, we examined specific CD8+ T-cell responses towards viral-structural protein (VP) epitopes, which enable binding to host susceptibility receptors. We isolated peripheral blood mononuclear cells from 196 participants to screen and identify predominant core peptides towards NV main and small envelope proteins using ex vivo and in vitro intracellular cytokine staining assays. Human leukocyte antigen (HLA) restriction characteristics were detected using next-generation sequencing. Three conservative immunodominant VP-derived CD8+ T-cell epitopes, VP294–102 (TDAARGAIN), VP2153–161 (RGPSNKSSN), and VP1141–148 (FPHIIVDV), were identified and restrictively presented by HLA-Cw * 0102, HLA-Cw * 0702, and HLA-A *1101 alleles, separately. Our findings provide useful insights into the development of future vaccines and treatments for NV infection.

AbstractOpioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.

Depression is a psychological disorder associated with prolonged stress, which involves abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated levels of glucocorticoids (GC). Excessive GC can cause damage to the structure and function of the hippocampus, thereby triggering depressive symptoms. Studies suggest that the bile acid receptor farnesoid X receptor (FXR) may play a role in adrenal GC synthesis. This study aimed to explore the potential therapeutic effects of dried bear bile (DBB) on depression and its mechanism. We used the chronic unpredictable mild stress (CUMS) mouse model and FXR agonist GW4064 stimulated mice, as well as H295R human adrenal cortical carcinoma cells, employing behavioral tests, biochemical analysis, and gene expression analysis to assess the effects of DBB treatment on depressive behavior, serum corticosterone (CORT) levels, and adrenal FXR and steroid biosynthesis-related gene expression. The results showed that in both CUMS and GW4064-stimulated mice, DBB treatment significantly improved depressive-like behaviors and reversed serum CORT levels. Additionally, DBB suppressed the expression of steroidogenic regulatory genes in the adrenal glands of CUMS mice. In H295R cells, DBB treatment effectively reduced cortisol secretion induced by Forskolin, inhibited the expression of steroid biosynthesis-related genes, and suppressed cortisol production and HSD3B2 expression under conditions of FXR overexpression and FXR activation. Our findings suggest that DBB regulates adrenal FXR to modulate glucocorticoid synthesis and exerts antidepressant effects. DBB may serve as a potential therapeutic agent for depression by regulating GC levels and steroidogenesis pathway. Further research is underway to test the antidepressant effects of each DBB component to understand their specific contribution.

Hexavalent chromium (Cr(VI)) is a hazardous metallic compound commonly used in industrial processes. The liver, responsible for metabolism and detoxification, is the main target organ of Cr(VI). Toxicity experiments were performed to investigate the impacts of low-dose exposure to Cr(VI) on rat livers. It was revealed that exposure of 0.05 mg/kg potassium dichromate (K2Cr2O7) and 0.25 mg/kg K2Cr2O7 notably increased malondialdehyde (MDA) levels and the expressions of P-AMPK, P-ULK, PINK1, P-Parkin, and LC3II/LC3I, and significantly reduced SOD activity and P-mTOR and P62 expression levels in liver. Electron microscopy showed that CR(VI) exposure significantly increased mitophagy and the destruction of mitochondrial structure. This study simulates the respiratory exposure mode of CR(VI) workers through intratracheal instillation of CR(VI) in rats. It confirms that autophagy in hepatocytes is induced by low concentrations of CR(VI) and suggest that the liver damage caused by CR(VI) may be associated with the AMPK-related PINK/Parkin signaling pathway.

ABSTRACT Early childhood dental caries (ECC) is the most common chronic disease among children, especially among low socioeconomic populations. Streptococcus mutans is most frequently associated with initiation of ECC. Although many studies report children with multiple S. mutans strains (i.e., genotypes) have greater odds of developing ECC, studies investigating intraspecies interactions in dental caries are lacking. This study investigates the impact of intraspecies interactions on cariogenic and fitness traits of clinical S. mutans isolates using in vitro and in vivo approaches. Association analysis evaluated if presence of multiple S. mutans genotypes within the first year of colonization was associated with caries. Initially, clinical S. mutans isolates from 10 children were evaluated. S. mutans strains (G09 and G18, most prevalent) isolated from one child were used for subsequent analysis. Biofilm analysis was performed for single and mixed cultures to assess cariogenic traits, including biofilm biomass, intra-polysaccharide, pH, and glucan. Confocal laser scanning microscopy (CLSM) and time-lapse imaging were used to evaluate spatial and temporal biofilm dynamics, respectively. A Drosophila model was used to assess colonization in vivo. Results showed the mean biofilm pH was significantly lower in co-cultured biofilms versus monoculture. Doubling of S. mutans biofilms was observed by CLSM and in vivo colonization in Drosophila for co-cultured S. mutans. Individual strains occupied specific domains in co-culture and G09 contributed most to increased co-culture biofilm thickness and colonization in Drosophila. Biofilm formation and acid production displayed distinct signatures in time-lapsed experiments. This study illuminates that intraspecies interactions of S. mutans significantly impacts biofilm acidity, architecture, and colonization.IMPORTANCEThis study sheds light on the complex dynamics of a key contributor to early childhood dental caries (ECC) by exploring intraspecies interactions of different S. mutans strains and their impact on cariogenic traits. Utilizing clinical isolates from children with ECC, the research highlights significant differences in biofilm architecture and acid production in mixed versus single genotype cultures. The findings reveal that co-cultured S. mutans strains exhibit increased cell density and acidity, with individual strains occupying distinct domains. These insights, enhanced by use of time-lapsed confocal laser scanning microscopy and a Drosophila model, offer a deeper understanding of ECC pathogenesis and potential avenues for targeted interventions.

BackgroundMale urethral stricture disease (USD) is predominantly characterized by scar formation. There are few effective therapeutic drugs, and comprehensive molecular characterizations of USD formation remain undefined.MethodsThe proteomic profiling of twelve scar tissues and five matched normal adjacent tissues (NATs). Proteomic analysis methods were applied to explore the molecular characterizations of USD formation, including uncovering mechanistic pathways and providing novel biomarkers for scar formation.ResultsComparative proteomic analysis showed that the extracellular matrix (ECM) and complement cascade signaling were predominant in scar tissues. COL11A1 and CD248 significantly contributed to the accumulation of ECM components. Our study presented diverse molecular mechanisms of scar formation across different ages and suggested the potential effects of PXK in Age 1 (

Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1β), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Purpose: This umbrella review summarized the factors influencing parents’ hesitancy to vaccinate their children against COVID-19 and the evidence to reduce it. Methods: The analysis included PubMed, Embase, Cochrane Library, Web of Science, and Scopus articles published before March 22, 2024. It considered all meta-analyses that investigated parental COVID-19 vaccine hesitancy. Results: Eight studies were included. Hesitancy rate of parents from five continents to vaccinate their children against COVID-19 was between 0.69 % and 95.0 %. The comprehensive synthesis in this review shows that the influencing factors originate from four aspects: Parents’ attitudes, including their trust in the scientific community, concerns about COVID-19 complications, perceptions of children's susceptibility, and support from the social environment, including government incentives, low vaccination costs, and specific sociodemographic characteristics, were positive factors that reduced parental vaccine hesitancy in children. Conversely, negative aspects, including vaccine distrust, the spread of misinformation, poor economic status, and concern about unprecedentedly short development time, were associated with increased hesitancy. Conclusion: Our study identified positive and negative factors for parental COVID-19 vaccine hesitancy in children and highlighted that parental attitude was the most important determinant.

Streaming applications are being extensively run on portable embedded systems, which are battery-operated and with limited memory. Thus, minimizing the total energy consumption of such a system is important. We investigate the problem of offline scheduling for streaming applications composed of non-preemptible periodic dependent tasks on homogeneous Network-on-Chip (NoC)-based Multiprocessor System-on-Chip (MPSoCs) such that their total energy consumption is minimized under memory constraints. We propose a novel unified approach that integrates task-level software pipelining with Dynamic Voltage and Frequency Scaling (DVFS) to solve the problem. Our approach is supported by a set of novel techniques, which include constructing an initial schedule based on a list scheduling where the priority of each task is its approximate successor-tree-consistent deadline such that the workload across all the processors is balanced, a retiming heuristic to transform intra-period dependencies into inter-period dependencies for enhancing parallelism, assigning an optimal discrete frequency for each task and each message using a Non-Linear Programming (NLP)-based algorithm and an Integer-Linear Programming (ILP)-based algorithm, and an incremental approach to reduce the memory usage of the retimed schedule in case of memory size violations. Using a set of real and synthetic benchmarks, we have implemented and compared our unified approach with two state-of-the-art approaches, RDAG+GeneS (Wang et al., 2011) , and JCCTS (Wang et al., 2013a). Experimental results show that our approach’s maximum, average, and minimum improvements over RDAG+GeneS (Wang et al., 2011) are 31.72%, 14.05%, and 7.00%, respectively. Our approach’s maximum, average, and minimum improvement over JCCTS (Wang et al., 2013a) are 35.58%, 17.04%, and 8.21%, respectively.

Exposure to ambient PM2.5 is associated with neurodegenerative disorders, in which microglia activation plays a critical role. Thus far, the underlying mechanisms for PM2.5-induced microglia activation have not been well elucidated. In this study, a human microglial cell line (HMC3) was used as the in vitro model to examine the inflammatory effect (hall marker of microglia activation) of PM2.5 and regulatory pathways. The expression of inflammatory mediators including interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) as well as the brain derived neurotrophic factor (BDNF) were determined by ELISA and/or real-time PCR, respectively. Flow cytometry was used to measure the production of intracellular reactive oxygen species (ROS). Western blot was used to measure protein levels of Toll-like receptor 4 (TLR4), NF-κB inhibitor α (IκBα) and COX-2. It was shown that PM2.5 stimulation increased IL-6 and COX-2 expression but decreased BDNF expression in a dose-dependent manner. Further studies showed that PM2.5 triggered the formation of ROS and pre-treatment with the ROS scavenger acetylcysteine (NAC) significantly suppressed PM2.5-induced IL-6 and COX-2 expression. Moreover, the nuclear factor kappa B (NF-κB) inhibitor BAY11–7085 or the TLR4 neutralizing antibody markedly blocked PM2.5-induced IL-6 and COX-2 expression. However, NAC or BAY11–7085 exhibited minimal effect on PM2.5-induced BDNF down-regulation. In addition, pre-treatment with BAY11–7085 or TLR4 neutralizing antibody reduced ROS production induced by PM2.5, and NAC pre-treatment inhibited TLR4 expression and NF-κB activation induced by PM2.5. Collectively, PM2.5 treatment induced IL-6 and COX-2 but suppressed BDNF expression. PM2.5-induced IL-6 and COX-2 expression was mediated by interactive oxidative stress and TLR4/NF-κB pathway.

Study region: The midstream of the Hei River Basin (HRB). Study focus: The study investigated the changes in hydrological elements at different time scales in the basin from 1982 to 2020. We used the Budyko coupled balance equation to quantitatively assess the contributions of climate change and human activity-induced land surface changes to runoff during different periods. In addition, the driving factors of flow consumption within the basin were analyzed using wavelet coherence and generalized additive model (GAM). New hydrological insights for the region: Prior to 2001, there was a significant decrease in annual-scale runoff in the midstream. After that, a partial recovery was observed due to the influence of the Ecological Water Transfer Project (EWTP), while the NDVI trend exhibited an opposite pattern. The study indicates that human-induced modification of the underlying surface is the primary driving factor for the decrease in runoff, with land surface factors contributing 84.69% and 65.27% to the runoff reduction during two periods of change, respectively. Further research on the driving forces of runoff consumption reveals that vegetation cover and climate factors jointly regulate the variations in runoff consumption in the midstream, with multifactor effects surpassing those of individual factors, and NDVI emerges as the predominant controlling factor for runoff consumption. Moreover, all anthropogenic factors exhibit a high explanatory power for runoff consumption.

Abstract SnO2 has been extensively investigated as an anode material for sodium‐ion batteries (SIBs) and potassium‐ion batteries (PIBs) due to its high Na/K storage capacity, high abundance, and low toxicity. However, the sluggish reaction kinetics, low electronic conductivity, and large volume changes during charge and discharge hinder the practical applications of SnO2‐based electrodes for SIBs and PIBs. Engineering rational structures with fast charge/ion transfer and robust stability is important to overcoming these challenges. Herein, S‐doped SnO2 (S–SnO2) quantum dots (QDs) (≈3 nm) encapsulated in an N, S codoped carbon fiber networks (S–SnO2–CFN) are rationally fabricated using a sequential freeze‐drying, calcination, and S‐doping strategy. Experimental analysis and density functional theory calculations reveal that the integration of S–SnO2 QDs with N, S codoped carbon fiber network remarkably decreases the adsorption energies of Na/K atoms in the interlayer of SnO2–CFN, and the S doping can increase the conductivity of SnO2, thereby enhancing the ion transfer kinetics. The synergistic interaction between S–SnO2 QDs and N, S codoped carbon fiber network results in a composite with fast Na+/K+ storage and extraordinary long‐term cyclability. Specifically, the S–SnO2–CFN delivers high rate capacities of 141.0 mAh g−1 at 20 A g−1 in SIBs and 102.8 mAh g−1 at 10 A g−1 in PIBs. Impressively, it delivers ultra‐stable sodium storage up to 10,000 cycles at 5 A g−1 and potassium storage up to 5000 cycles at 2 A g−1. This study provides insights into constructing metal oxide‐based carbon fiber network structures for high‐performance electrochemical energy storage and conversion devices.

Background: Chemotherapy-induced nausea and vomiting (CINV) is the most common adverse effect of chemotherapy and affects the continuation of chemotherapy in cancer patients. Electrical acupoint stimulation (EAS), which includes electroacupuncture and transcutaneous electrical stimulation (TES), has been used to treat CINV. This meta-analysis aimed to evaluate the efficacy of EAS in the treatment of CINV. Methods: Randomized controlled trials (RCTs) of EAS for CINV retrieved form five key databases. Two researchers independently performed article screening, data extraction and data integration. The Cochrane Collaboration's tool for assessing risk of bias was used to assesse the methodological quality according to Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.4 was used to perform analyses. Results: 10 RCTs with a total of 950 participants were included. The results showed that there was no significant difference between EAS compared to sham EAS in terms of increasing the rate of complete control of CINV and decreasing the overall incidence of CINV [RR = 1.26, 95 % CI (0.96, 1.66), P = 0.95; RR = 1.16, 95 % CI (0.97, 1.40), p = 0.71]. In terms of CINV severity, EAS reduced the occurrence of moderate-to-severe CINV [RR = 0.60, 95 % CI (0.38, 0.94), P = 0.03; RR = 0.50, 95 % CI (0.33, 0.76), P = 0.001]. Conclusion: EAS could improve moderate-to-severe CINV. However, EAS did not show a significant difference in reducing overall incidence and improving complete control rates compared with sham EAS. Due to limitations in the quality of the included articles, the available studies are insufficient to have sufficient evidence to confirm the efficacy of EAS for CINV. Validation with rigorously designed, large-sample, high-quality clinical trial studies may also be needed.

Solar photovoltaic (PV) is one of the most environmental-friendly and promising resources for achieving carbon peak and neutrality targets. Despite their ecological fragility, China’s vast desert regions have become the most promising areas for PV plant development due to their extensive land area and relatively low utilization value. Artificial ecological measures in the PV plants can reduce the environmental damage caused by the construction activity and promote the ecological condition of fragile desert ecosystems, therefore yield both ecological and economic benefits. However, the understanding of the current status and ecological benefits of this approach in existing desert PV plants is limited. Here we surveyed 40 PV plants in northern China’s deserts to identify the ecological construction modes and their influencing factors. We quantified the ecosystem service value (ESV) provided by these PV plants using remote sensing data and estimated the potential for ESV enhancement. Our results show that PV plant construction in desert regions can significantly improve the ecosystem, even with natural restoration measures (M1) alone, resulting in a 74% increase in average fractional vegetation cover (FVC) during the growing season, although the maximum average FVC of only about 10%. The integrated mode M4, which combined artificial vegetation planting M2 and sand control measures M3, further enhance the average growing season FVC to 14.53%. Currently, 22.5% of plants lack ecological measures, 40% employ only a single measure, but 92% of new plants since 2017 have adopted at least one ecological construction mode. The main influencing factors include surface type, policy support, water resources, ecological construction costs, and scientific management guidance. If artificial ecological construction were incorporated, a significant ESV could be achieved in these PV plants, reaching $8.9 million (a 7.7-fold increase) if assuming a targeted 50% vegetation coverage. This study provides evidence for evaluating the ecological benefit and planning of large-scale PV farms in deserts.

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD’s inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

ABSTRACTThe tenacious biofilms formed by Streptococcus mutans are resistant to conventional antibiotics and current treatments. There is a growing need for novel therapeutics that selectively inhibit S. mutans biofilms while preserving the normal oral microenvironment. Previous studies have shown that increased levels of cyclic di-AMP, an important secondary messenger synthesized by diadenylate cyclase (DAC), favored biofilm formation in S. mutans. Thus, targeting S. mutans DAC is a novel strategy to inhibit S. mutans biofilms. We screened a small NCI library of natural products using a fluorescence detection assay. (+)-Brazilin, a tetracyclic homoisoflavanoid found in the heartwood of Caesalpinia sappan, was identified as one of the 11 “hits,” with the greatest reduction (>99%) in fluorescence at 100 µM. The smDAC inhibitory profiles of the 11 “hits” established by a quantitative high-performance liquid chromatography assay revealed that (+)-brazilin had the most enzymatic inhibitory activity (87% at 100 µM) and was further studied to determine its half maximal inhibitory concentration (IC50 = 25.1 ± 0.98 µM). (+)-Brazilin non-competitively inhibits smDAC’s enzymatic activity (Ki = 140.0 ± 27.13 µM), as determined by a steady-state Michaelis-Menten kinetics assay. In addition, (+)-brazilin’s binding profile with smDAC (Kd = 11.87 µM) was illustrated by a tyrosine intrinsic fluorescence quenching assay. Furthermore, at low micromolar concentrations, (+)-brazilin selectively inhibited the biofilm of S. mutans (IC50 = 21.0 ± 0.60 µM) and other oral bacteria. S. mutans biofilms were inhibited by a factor of 105 in colony-forming units when treated with 50 µM (+)-brazilin. In addition, a significant dose-dependent reduction in extracellular DNA and glucan levels was evident by fluorescence microscopy imaging of S. mutans biofilms exposed to different concentrations of (+)-brazilin. Furthermore, colonization of S. mutans on a representative model of enamel using suspended hydroxyapatite discs showed a >90% reduction with 50 µM (+)-brazilin. In summary, we have identified a drug-like natural product inhibitor of S. mutans biofilm that not only binds to smDAC but can also inhibit the function of smDAC. (+)-Brazilin could be a good candidate for further development as a potent therapeutic for the prevention and treatment of dental caries.IMPORTANCEThis study represents a significant advancement in our understanding of potential therapeutic options for combating cariogenic biofilms produced by Streptococcus mutans. The research delves into the use of (+)-brazilin, a natural product, as a potent inhibitor of Streptococcus mutans’ diadenylate cyclase (smDAC), an enzyme crucial in the formation of biofilms. The study establishes (+)-brazilin as a non-competitive inhibitor of smDAC while providing initial insights into its binding mechanism. What makes this finding even more promising is that (+)-brazilin does not limit its inhibitory effects to S. mutans alone. Instead, it demonstrates efficacy in hindering biofilms in other oral bacteria as well. The broader spectrum of anti-biofilm activity suggests that (+)-brazilin could potentially serve as a versatile tool in a natural product-based treatment for combating a range of conditions caused by resilient biofilms.