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In this work, a novel hot-dipped Zn–6Al–3Mg-0.1Si-0.05Ti alloy coating was designed through (Si, Ti) microalloying, and the related microstructure and corrosion behavior in Cl− containing environment were studied. The results show that the mainly microstructures of the coating consist of Al dendrites, primary MgZn2, peritectic and ternary eutectic. The addition of trace quantity of Si and Ti leads to the formation of (Al,Si)3Ti and Mg2Si intermetallic compounds. The corrosion process can be divided into four stages, including the formation of non-protective products and Si-based oxide, the formation protective products, the coverage of the coating surface by corrosion products and the establishment of stable double corrosion product layers. The corrosion products of Mg2Si are beneficial in enhancing the insulating properties of protective corrosion products. (Al,Si)3Ti, acting as a cathode in the corrosion process, leads to a decrease in the rate of corrosion by decreasing the current density at the anode. Additionally, the oxide passive film formed subsequent to its corrosion help inhibit the transfer of charge over the coating surface.

Abstract Alzheimer’s disease (AD) is the most common cause of dementia, characterized by memory loss, cognitive decline, personality changes, and various neurological symptoms. The role of blood–brain barrier (BBB) injury, extracellular matrix (ECM) abnormalities, and oligodendrocytes (ODCs) dysfunction in AD has gained increasing attention, yet the detailed pathogenesis remains elusive. This study integrates single-cell sequencing of AD patients’ cerebrovascular system with a genome-wide association analysis. It aims to elucidate the associations and potential mechanisms behind pericytes injury, ECM disorder, and ODCs dysfunction in AD pathogenesis. Finally, we identified that abnormalities in the pericyte PI3K–AKT–FOXO signaling pathway may be involved in the pathogenic process of AD. This comprehensive approach sheds new light on the complex etiology of AD and opens avenues for advanced research into its pathogenesis and therapeutic strategies.

Abstract There is considerable uncertainty regarding the associations between various risk factors and Parkinson’s Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson’s Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD.

Abstract Zinc ion hybrid capacitors (ZIHCs) show promise for large‐scale energy storage because of their low cost, highly intrinsic safety, and eco‐friendliness. However, their energy density has been limited by the lack of advanced cathodes. Herein, a high‐capacity cathode material named N‐doped porous carbon (CFeN‐2) is introduced for ZIHCs. CFeN‐2, synthesized through the annealing of coal pitch with FeCl3·6H2O as a catalytic activator and melamine as a nitrogen source, exhibits significant N content (10.95 wt%), a large surface area (1037.66 m2 g−1), abundant lattice defects and ultrahigh microporosity. These characteristics, validated through theoretical simulations and experimental tests, enable a dual‐ion energy storage mechanism involving Zn2+ ions and CF3SO3− anions for CFeN‐2. When used as a cathode in ZIHCs, CFeN‐2 achieves a high‐energy density of 142.5 W h kg−1 and a high‐power density of 9500.1 W kg−1. Furthermore, using CFeN‐2 ZIHCs demonstrate exceptional performance with 77% capacity retention and nearly 100% coulombic efficiency after 10 000 cycles at 10 A g−1, showcasing substantially superior performance to current ZIHCs. This study offers a pathway for developing high‐energy and high‐power cathodes derived from coal pitch carbon for ZIHC applications.

Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease. However, the definitive diagnosis of IPF is impeded by the limited capabilities of current diagnostic methods, which may fail to capture the optimal timing for treatment. The main goal of this study is to determine the feasibility of a nitroreductase (NTR) responsive probe, 18F-NCRP, for early detection and deterioration monitoring of IPF. 18F-NCRP was obtained with high radiochemical purity (>95 %). BLM-injured mice were established by intratracheal instillation with bleomycin (BLM) and characterized through histological analysis. Longitudinal PET/CT imaging, biodistribution study and in vitro autoradiography were performed. The correlations between the uptake of 18F-NCRP and mean lung density (tested by CT), as well as histopathological characteristics were analyzed. In PET imaging study, 18F-NCRP exhibited promising efficacy in monitoring the progression of IPF, which was earlier than CT. The ratio of uptake in BLM-injured lung to control lung increased from 1.4-fold on D15 to 2.2-fold on D22. Biodistribution data showed a significant lung uptake of 18F-NCRP in BLM-injured mice. There was a strong positive correlation between the 18F-NCRP uptake in the BLM-injured lungs and the histopathological characteristics. Given that, 18F-NCRP PET imaging of NTR, a promising biomarker for investigating the underlying pathogenic mechanism of IPF, is attainable as well as desirable, which might lay the foundation for establishing an NTR-targeted imaging evaluation system of IPF.

Purpose: An emergency rescue situation is an inevitable challenge in medical work, requiring collaborative efforts from healthcare professionals. Due to a lack of practical experience, novice nurses may encounter difficulties in successfully managing emergency resuscitation events. This study aimed to analyse the authentic psychological experiences of novice nurses participating in emergency resuscitation events by exploring applicable coping methods and management strategies. Methods: This study utilized a hermeneutic phenomenological qualitative research method. We employed purposive sampling to select 27 Novice nurses from West China Hospital of Sichuan University for face-to-face semistructured interviews. Data collection for this study was conducted from November 2023 to January 2024. The interviews were fully audio-recorded and transcribed verbatim. The data were coded, categorized and summarized with the help of Nvivo 20.0 software based on the interpretation of phenomenological research methods. Thematic analysis was performed to deeply analyse and extract corresponding themes. The COREQ criteria were used to guide the reporting of this study. Results: The authentic psychological experiences of novice nurses participating in emergency rescue events mainly include six aspects: lack of rescue knowledge reserves and related abilities, psychological and emotional changes, psychological stress after the rescue, rational arrangement of manpower, team cooperation, and postevent reflection and learning. Their authentic psychological experiences directly affect whether novice nurses can effectively respond to emergency rescue events. Conclusions: This study suggested enhancing novice nurses' knowledge, improving their resuscitation skills, and improving their psychological well-being during resuscitation events. It advocates for organized staffing, effective teamwork, and robust support systems to empower novice nurses and improve their overall capabilities in emergencies. These findings offer valuable insights for future research in this area.

Abstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. Results To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. Conclusion In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics. Graphical Abstract

Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease.

Lactate, a metabolic byproduct, has gained recognition as a highly influential signaling molecule. Lactylation, an emerging form of post-translational modification derived from lactate, plays a crucial role in numerous cellular processes such as inflammation, embryonic development, tumor proliferation, and metabolism. However, the precise molecular mechanisms through which lactylation governs these biological functions in both physiological and pathological contexts remain elusive. Hence, it is imperative to provide a comprehensive overview of lactylation in order to elucidate its significance in biological processes and establish a foundation for forthcoming investigations. This review aims to succinctly outline the process of lactylation modification and the characterization of protein lactylation across diverse organisms. Additionally, A summary of the regulatory mechanisms of lactylation in cellular processes and specific diseases is presented. Finally, this review concludes by delineating existing research gaps in lactylation and proposing primary directions for future investigations.

ABSTRACTPertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies.IMPORTANCEPertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.

Abstract Bacterial biofilm is an important factor in bacterial drug resistance. Recently, it has been proved that electret films can inhibit the bacterial biofilm, while its mechanism of action on biofilms is under further investigation. In this work, taking Staphylococcus aureus as an example, the inhibition of positive electret on bacterial biofilm was verified and its mechanism was explained. Two factors have been found to explain the inhibition mechanism of electret on bacterial biofilms. One is probably due to its inhibition of the expression of key genes related to bacterial biofilms induced by the electric field of positive electret, and the other is to prevent the aggregation of bacteria rather than the direct bactericidal effect. The conclusions are expected to be extended to other types of bacteria and expand the application of electrostatic materials in the field of biomedicine.

Abstract Introduction Tofacitinib, a selective inhibitor of JAK1 and/or JAK3, is considered to alleviate the pulmonary condition of primary Sjögren’s syndrome (pSS)-associated interstitial lung disease (ILD) through its anti-inflammatory and antifibrotic effects. Methods and analysis This is a single-center, prospective, randomized, open-label trial. The trial will compare a 52-week course of oral tofacitinib with traditional therapy cyclophosphamide (CYC) combined with azathioprine (AZA) in the treatment of pSS-ILD. A total of 120 patients will be randomly assigned into two treatment groups with a 1:1 ratio and followed for 52 weeks from the first dose. The primary endpoint of the study is the increase of forced vital capacity (FVC) at 52 weeks. Secondary endpoints include high-resolution computed tomography (HRCT), diffusion capacity for carbon monoxide of the lung (DLCO), the Mahler dyspnea index, the health-related quality of life (HARQoL) score, the cough symptom score, EULAR Sjögren's syndrome disease activity index (ESSDAI), and safety. Discussion This study will be the first randomized controlled trial to investigate tofacitinib compared to the traditional regimen of CYC in combination with AZA in the treatment of pSS-ILD, which will provide data on efficacy and safety and further elucidate the role of the JAK-STAT signaling pathway in the development of pSS-ILD. Ethics and dissemination Before starting the experiment, the research proposal, informed consent (ICF) and relevant documents in accordance with the ethical principles of the Helsinki Declaration and the relevant requirements of the local GCP rules for ethical approval shall be submitted to the ethics committee of the hospital. The ethical approval of this study is reviewed by the Ethics Committee of Tongji Hospital and the ethical approval number is 2021-LCYJ-007. When the experiment is completed, the results will also be disseminated to patients and the public through publishing papers in international medical journals. Trial registration The study was registered on the Chinese Clinical Trial Registry, www.chictr.org.cn ; ID ChiCTR2000031389.

Bacterial diseases of the gastrointestinal (GI) tract continue to be a major worldwide cause of human morbidity and mortality. Among various enteric pathogens, Shigella spp. are some of the most common and deadly bacterial pathogens. They are responsible for ~125 million worldwide cases of shigellosis, and ~14,000 deaths annually, the majority in children under the age of 5 and occurring in developing countries. Preventing and treating shigellosis with conventional drugs (e.g., vaccines and antibiotics) has proven to be very difficult. Here, we assessed the safety and tolerability of ShigActive™, a lytic bacteriophage preparation targeting Shigella spp., in a randomized, placebo-controlled, double-blind Phase 1 clinical trial. Ten participants randomized 4:1 received ShigActive™ or placebo co-administered with sodium bicarbonate orally three times daily for 7 days. Solicited and unsolicited adverse events (AEs) were observed for 29 days. Fifty percent of the subjects receiving ShigActive™ reported mild GI-related symptoms, while one participant experienced moderate fatigue. No serious or medically attended AEs occurred through day 90. Additionally, no significant differences in GI-associated inflammatory mediators or fecal microbiome changes were observed between placebo- and ShigActive™-treated subjects, or from a participants’ baseline value. The results of this first-in-human (FIH) randomized, controlled Phase 1 trial of ShigActive™ demonstrate that it is safe and well tolerated when orally administered with no significant differences compared to placebo controls.

Abstract Background Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown. Methods Infants from two birth cohorts in Malawi were monitored at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria. Poisson regression and linear mixed effects models measured the effect of exposure to malaria in infancy on subsequent malaria incidence, weight-for-age z-scores (WAZ), and haemoglobin concentrations after 6 months. Results Infants with at least one P. falciparum infection during their first 6 months had increased incidence ratio (IRR) of P. falciparum infection (IRR = 1.27, 95% CI, 1.06–1.52) and clinical malaria (IRR = 2.37, 95% CI, 2.02–2.80) compared to infants without infection. Infants with clinical malaria had increased risk of P. falciparum infection incidence between 6 and 24 months (IRR = 1.64, 95% CI, 1.38–1.94) and clinical malaria (IRR = 1.85, 95% CI, 1.48–2.32). Exposure to malaria was associated with lower WAZ over time (p = 0.02) and lower haemoglobin levels than unexposed infants at every time interval (p = 0.02). Conclusions Infants experiencing malaria infection or clinical malaria are at increased risk of subsequent infection and disease, have poorer growth, and lower haemoglobin concentrations.

Sjögren’s syndrome (SjS) is a systemic, highly diverse, and chronic autoimmune disease with a significant global prevalence. It is a complex condition that requires careful management and monitoring. Recent research indicates that epigenetic mechanisms contribute to the pathophysiology of SjS by modulating gene expression and genome stability. DNA methylation, a form of epigenetic modification, is the fundamental mechanism that modifies the expression of various genes by modifying the transcriptional availability of regulatory regions within the genome. In general, adding a methyl group to DNA is linked with the inhibition of genes because it changes the chromatin structure. DNA methylation changes the fate of multiple immune cells, such as it leads to the transition of naïve lymphocytes to effector lymphocytes. A lack of central epigenetic enzymes frequently results in abnormal immune activation. Alterations in epigenetic modifications within immune cells or salivary gland epithelial cells are frequently detected during the pathogenesis of SjS, representing a robust association with autoimmune responses. The analysis of genome methylation is a beneficial tool for establishing connections between epigenetic changes within different cell types and their association with SjS. In various studies related to SjS, most differentially methylated regions are in the human leukocyte antigen (HLA) locus. Notably, the demethylation of various sites in the genome is often observed in SjS patients. The most strongly linked differentially methylated regions in SjS patients are found within genes regulated by type I interferon. This demethylation process is partly related to B-cell infiltration and disease progression. In addition, DNA demethylation of the runt-related transcription factor (RUNX1) gene, lymphotoxin-α (LTA), and myxovirus resistance protein A (MxA) is associated with SjS. It may assist the early diagnosis of SjS by serving as a potential biomarker. Therefore, this review offers a detailed insight into the function of DNA methylation in SjS and helps researchers to identify potential biomarkers in diagnosis, prognosis, and therapeutic targets.

Introduction: The Panyu low uplift is located in the middle of the Central Uplift Belt of the Pearl River Mouth Basin, which has experienced multiple episodes of tectonic movements since the Cenozoic, and the faults are extensively developed there. The fault activities had a significant influence on the migration and accumulation of oil and gas, as well as the sedimentation.Methods: In order to recognize the effect of the faults on the tectono-straigraphy evolution in the Panyu low uplift, based on the high-resolution seismic and latest drilling well data, the study has comprehensively analyzed the geometry and kinematics of these faults, as well as the sedimentary filling evolution of the residual depressions.Results: The results show that two major fault systems has developed in the Panyu low uplift: the deep and shallow fault systems. The former was dominated by a series of NEE and NW-trending high-angle listric/plane faults, along with several low-angle detachment normal faults, which were under the joint control of the NW-SE and NS-trending extensional stress during the Eocene. The latter was dominated by NW-NWW trending strike-slip normal faults with tension-shear properties under the NEE trending dextral strike-slip stress field in the late Miocene. The uplift had undergone five tectonic evolution stages: the initial rifting stage (Tg-T83), the intensive rifting stage (T83-T80), the rifting and depression transitional stage (T80-T70), the thermal subsidence depression stage (T70-T35), and the tectonic reactivation stage (T35-T10).Discussion: Based on the 3D seismic phase interpretation and drilling sample analyses, the study also indicates that during the initial rifting stage, the Panyu low uplift manifested as multistage depositional center. The sedimentary strata were distributed in the downthrown wall of the depression-controlling faults, exhibiting multiple subsidence and sedimentary centers, and the depressions was supplied by multi-provenance systems. During the intense rifting period, the depression widened, the lacustrine basins were connected with each other, and the sedimentary center migrated. During the rifting and depression transitional stage, the faults controlling on deposition weakened. The thick Enping formation from the northwest provenance direction is unconformably overlaid on the Panyu low uplift. Meanwhile, the depressions was characterized by the sedimentary deposits of lacustrine basin. Various types of sedimentary facies were developed, including the delta, semi-deep lacustrine, shallow lacustrine, and shore-shallow lacustrine deposits, and the mudstone of the semi-deep lacustrine facies could serve as a high-quality source rock for the hydrocarbon production.

Abstract Bacterial biofilm formation is an important factor in bacterial resistance. The commonly used methods to inhibit bacterial biofilms are synthetic drugs such as antimicrobial peptides, but physical methods are often safe, non‐toxic and simple to prepare. This work proposes an environmentally friendly method to use electret films to provide a stable electric field during the formation of bacterial biofilms, inhibit the formation of bacterial biofilms through the action of the electric field and weaken the adhesion of bacterial biofilms. The total amount of Staphylococcus aureus biofilm decreased by 20% compared to the control group after the treatment of positive electret. The distribution of exopolysaccharides showed that the activity of biofilm also decreased. In addition, the negative electret can also inhibit the formation of bacterial biofilm. The result can be generalised to other Gram‐positive bacteria and could contribute to reduce the resistance of bacteria, improve the effect of related antibiotics, reduce the dosage of antibiotics and reduce the side effects of drugs.

This study aims to verify the application effect of Fluvic acid (FA) with different molecular weights (MW) on the growth and quality of winter wheat. FA extracted from lignite was divided into 3 MWs (W1≤3000 D, 3000 D10000 D) by dialysis, and its structure was analyzed. Three application rates were set for each MW FA in the pot experiment, which were 10, 25 and 50 mg/kg in soil, respectively, and water was the control. There were significant interactive effects of MW and application rates of FAs. Compared with the control, all the FA treatments significantly increased grain yields, nitrogen uptake efficiencies, grain iron concentration, and soil available nitrogen concentration. Heatmap analysis revealed that the W1C2 (10 mg/kg W1) treatment had the most significant impacts for all analyzed indexes, whereas W3C3 (50 mg/kg W3) showed the weakest impacts. The results showed that at a low application rate (10 mg/kg in soil), the promotion effects of the three MW FAs were similar. W1 showed the most significant promotion effects, which was attributed to the combined effects of its lower MW and functional group characteristics.

Abstract Background Widespread establishment of home-based healthy energy balance-related behaviors (EBRBs), like diet, physical activity, sedentary behavior, screen time, and sleep, among low-income preschool-aged children could curb the childhood obesity epidemic. We examined the effect of an 8-month multicomponent intervention on changes in EBRBs among preschool children enrolled in 12 Head Start centers. Methods The Head Start (HS) centers were randomly assigned to one of three treatment arms: center-based intervention group (CBI), center-based plus home-based intervention group (CBI + HBI), or control. Before and following the intervention, parents of 3-year-olds enrolled in participating HS centers completed questionnaires about their child’s at-home EBRBs. Adult-facilitated physical activity (PA) was measured by an index based on questions assessing the child’s level of PA participation at home, with or facilitated by an adult. Fruit, vegetable, and added sugar intake were measured via a short food frequency questionnaire, and sleep time and screen time were measured using 7-day logs. A linear mixed effects model examined the intervention’s effect on post-intervention changes in PA, intake of fruit, vegetable, and added sugar, sleep time, and screen time from baseline to post-intervention. Results A total of 325 parents participated in the study (CBI n = 101; CBI + HBI n = 101; and control n = 123). Compared to control children, CBI and CBI + HBI parents reported decreases in children’s intake of added sugar from sugar-sweetened beverages. Both CBI and CBI + HBI parents also reported smaller increases in children’s average weekday screen time relative to controls. In addition, CBI + HBI parents reported CBI + HBI parents reported increases in children’s adult-facilitated PA, fruit and vegetable intake, and daily sleep time during weekdays (excluding weekends) and the total week from baseline to post-intervention, while children in the CBI increased sleep time over the total week compared to the children in the control group. Conclusions Parent engagement strengthened the improvement in parent-reported EBRBs at home in young children participating in an evidence-based obesity prevention program in a childcare setting. Future studies should investigate equity-related contextual factors that influence the impact of obesity prevention in health-disparity populations. Trial registration ClinicalTrials.gov, NCT03590834. Registered July 18, 2018, https://clinicaltrials.gov/ct2/show/NCT03590834

Abstract Objective: To test a culturally tailored obesity prevention intervention in low-income, minority preschool age children. Design: A three-group clustered randomised controlled trial. Setting: Twelve Head Start centres were randomly assigned to a centre-based intervention, a combined centre- and home-based intervention, or control using a 1:1:1 ratio. The centre-based intervention modified centre physical activity and nutrition policies, staff practices, and child behaviours, while the home-based intervention supported parents for obesity prevention at home. Study outcomes: The primary end point was change in children’s BMI (kg/m2) at post-test immediately following completion of the 8-month intervention. Secondary end points included standardised scores for BMI (BMIz) and body weight (WAZ), and BMI percentiles (BMI pctl). Participants: Three-year-old children enrolled in Head Start in San Antonio, Texas, with written parent consent (n 325), 87 % Latino, 57 % female with mean age (sd) of 3·58 years (0·29). Results: Change in BMI at post-test was 1·28 (0·97), 1·28 (0·87) and 1·41 (0·71) in the centre + home-based intervention, centre-based intervention and control, respectively. There was no significant difference in BMI change between centre + home-based intervention and control or centre-based intervention and control at post-test. BMIz (adjusted difference –0·12 (95 % CI, –0·24, 0·01), P = 0·06) and WAZ (adjusted difference, –0·09 (–0·17, –0·002), P = 0·04) were reduced for children in centre + home-based intervention compared with control group. Conclusions: There was no reduction in BMI at post-test in children who received the intervention. Findings shed light on methodological challenges in childhood obesity research and offer future directions to explore health equity-oriented obesity prevention.

Background: To identify long non-coding RNAs (lncRNAs) that may be used as potential biomarkers of sensitivity to antiretroviral therapy (ART) against human immunodeficiency virus (HIV) infection. Method: A two-stage matched case-control study was conducted. First, in the screening stage, peripheral blood lymphocytes (PBLs) of six subjects receiving lamivudine-based ART (3 ART-resistant and 3 ART-sensitive subjects with matching durations of ART) were subjected to comprehensive microarray expression profiling in order to screen out lncRNAs associated with ART sensitivity. Secondly, during the validation stage, promising lncRNAs were evaluated via a 1:4 matched case-control study using 50 subjects (10 ART-resistant and 40 ART-sensitive subjects with matching durations of ART). Results: Seven lncRNAs were screened out (P

Background: Patients with primary Sjögren’s syndrome (pSS) are at increased risk of cardiovascular morbidity as compared with the general population. Objectives: A retrospective study on 349 Chinese patients with pSS was conducted to identify potential risk factors for cardiovascular events and develop a cardiovascular risk nomogram. Design: This is a retrospective observational study. Methods: The study included 349 patients who were diagnosed with pSS at Tongji Hospital, School of Medicine, Tongji University, China from January 2010 to March 2022. The least absolute shrinkage and selection operator (LASSO) was used to select features for the cardiovascular risk model. The features selected in LASSO were used to build the cardiovascular risk model in a multivariate logistic regression analysis. C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis were used to assess the predictive model. Internal validation was performed by bootstrapping. Results: Sex, joint pain as an initial symptom, dry mouth, oral ulcers, dental caries, Raynaud’s phenomenon, fatigue, diabetes, elevated thyroid-stimulating hormone (TSH) level, and elevated systolic blood pressure were included in the nomogram for the prediction of cardiovascular risk. Our model had good discrimination (C-index: 0.824, 95% confidence interval: 0.712–0.936) and good calibration (C-index in the interval validation: 0.8). Decision curve analysis indicated that our nomogram demonstrated clinical usefulness for intervention in a cardiovascular disease possibility threshold of 3%. Conclusion: The cardiovascular risk nomogram incorporating sex, initial joint pain, dry mouth, oral ulcer, dental caries, Raynaud’s phenomenon, fatigue, diabetes, elevated TSH, and systolic blood pressure could be used in the prediction of cardiovascular risk in patients with pSS and the guidance of further treatment.

This paper investigates the problem of cooperative payload delivery by two quadrotors with a novel “Y”-shaped cable that improves payload carrying and dropping efficiency. Compared with the existing “V”-shaped suspension, the proposed suspension method adds another payload swing degree of freedom to the quadrotor–payload system, making the modeling and control of such a system more challenging. In the modeling, the payload swing motion is decomposed into a forward–backward process and a lateral process, and the swing motion is then transmitted to the dynamics of the two quadrotors by converting it into disturbance cable pulling forces. A novel guidance and control framework is proposed, where a guidance law is designed to not only achieve formation transformation but also generate a local reference for the quadrotor, which does not have access to the global reference, based on which a cooperative controller is developed by incorporating an uncertainty and disturbance estimator to actively compensate for payload swing disturbance to achieve the desired formation trajectory tracking performance. A singular perturbation theory-based analysis shows that the proposed parameter mapping method, which unifies the parameter tuning of different control channels, allows us to tune a single parameter, ε, to quantitatively enhance both the formation control performance and system robustness. Simulation results verify the effectiveness of the proposed approach in different scenarios.

This study explores whether children’s refractive errors and visual behaviors reverted to pre-COVID-19 levels a year after normal schooling resumed in Hong Kong as well as the impact of corneal and internal astigmatism on refractive astigmatism development. Vision survey data and questionnaire results collected in 2022 (n = 119) and 2020 (n = 173) were compared. Cross-sectional data showed similar proportions of astigmatism (cylindrical power ≥ 0.75 D) in the 2020 (49.1%) and 2022 cohorts (55.5%). Despite a 0.28 D increase in corneal astigmatism, a compensatory 0.24 D increase in internal astigmatism of opposite direction kept refractive astigmatism relatively stable. The questionnaire data showed that children spent an additional 0.5 h/day outdoors on weekends post-resumption of normal schooling but engaged in more near-work activities, especially non-screen near-work, by approximately 1 h/day on both weekdays and weekends. These findings were supported by longitudinal data from 72 children who participated in both surveys. This study highlights the significant role of corneal and internal astigmatism in refractive astigmatism changes. Despite the return to in-person classes, children’s total near-work time increased and astigmatism remained high. These findings underscore the need for comprehensive strategies to reduce the high environmental risks for refractive error development in children.

Abstract This study focusses on the target detection problem in the distributed multiple‐input multiple‐output (MIMO) radar. The observation environment is assumed to be partially homogeneous in one transmitter‐receiver path and simultaneously non‐homogeneous for different paths. By characterising the disturbance signals with a series of auto‐regressive (AR) processes, two parametric detectors based on the Wald test are developed. The first one utilises an iterative scheme to estimate the unknown parameters that were involved in the derivation, and the second one obtains these estimations sequentially. One of the most attractive features of the two distributed MIMO radar detectors is that they can be used in the presence/absence of the training data. More specifically, they can take advantage of the training data to boost the detection performances effectively even if the training data are very limited. The simulation results of several scenarios demonstrate the remarkable detection performances of authors’ proposed methods compared with that of the competitors. Furthermore, the amplitude estimation performances of the two detectors are evaluated via the corresponding Cramér–Rao bound (CRB).

Background: The mobile integrated health-community paramedicine (MIH-CP) program affiliated with the University of Maryland Medical Center focuses on improving patient transitions from hospital to home by addressing both medical and social determinants of health. Until recently, only self-contained health systems could integrate inpatient and outpatient medication data. Without some means to track patients in transition, there is a significant risk of medication-related problems and errors. Objective: To evaluate the impact of the MIH-CP program on medication adherence among patients with congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD). Methods: This is a pilot observational study designed to compare adherence to drug regimens prescribed at hospital discharge (measured by the proportion of days covered [PDC]) between patients enrolled in the MIH-CP program and a propensity-matched control group. Propensity scores were calculated using 11 demographic, diagnostic, third-party payer, and patient care-associated variables. Discharge medication details were obtained from electronic medical records. PDC for each of the medications were calculated from pharmacy claims data. Results: Eighty-three patients were included in the study; forty-three patients were placed in the intervention group and 40 were propensity-matched controls. After adjusting for age, sex, and third-party payer, findings indicated that medication adherence was higher among patients enrolled in the MIH-CP program compared with control during the first 30 days post-discharge, specifically among patients diagnosed with CHF (8% difference in PDC, 95% confidence interval [CI], ‐0.12-0.28%) and COPD (14% difference, 95% CI, ‐0.15-0.43%), although neither result achieved statistical significance. The differences in medication adherence between patients who were enrolled and those who were not enrolled in the MIH-CP program diminished after 30 days post-discharge. Conclusion: This pilot study demonstrated a trend toward improved medication adherence among patients enrolled in the MIH-CP program. Future research involving a larger patient cohort will be required to confirm these preliminary findings.

Objectives: In 2017, the World Health Organisation (WHO) pre-qualified a single-dose typhoid conjugate vaccine (TCV) and identified TCV co-administration studies as a research priority. Accordingly, we tested co-administration of Typbar TCV® (Bharat Biotech International) with measles-rubella (MR) and yellow fever (YF) vaccines. Methods: We conducted a randomized, double-blind, and controlled, phase 2 trial in Ouagadougou, Burkina Faso. Healthy children aged 9–11 months were randomized 1:1 to receive TCV (Group 1) or control vaccine (inactivated polio vaccine (IPV), Group 2). Vaccines were administered intramuscularly with routine MR and YF vaccines. Safety was assessed by (1) local and systemic reactions on days 0, 3, and 7; (2) unsolicited adverse events within 28 days; and (3) serious adverse events (SAEs) within six months after immunization. Results: We enrolled, randomized, and vaccinated 100 eligible children (49 Group 1 and 51 Group 2). Safety outcomes occurred with similar frequency in both groups: local/solicited reactions (Group 1: 1/49, Group 2: 3/50), systemic/solicited reactions (Group 1: 4/49, Group 2: 9/50), unsolicited adverse events (Group 1: 26/49, Group 2: 33/51), and SAEs (Group 1: 2/49, Group 2: 3/51). TCV conferred robust immunogenicity without interference with MR or YF vaccines. Conclusion: TCV can be safely co-administered with MR and YF vaccines to children at the 9-month vaccination visit.

BackgroundPublic health service is an important component and pathway to achieve universal health coverage (UHC), a major direction goal of many countries. China’s National Basic Public Health Service Program (the Program) is highly consistent with this direction. ObjectiveThe aim of this study was to analyze the key experience and challenges of the Program so as to present China’s approach to UHC, help other countries understand and learn from China’s experience, and promote UHC across the world. MethodsA literature review was performed across five main electronic databases and other sources. Some data were obtained from the Department of Primary Health, National Health Commission, China. Data obtained included the financing share of the national/provincial/prefectural government among the total investment of the program in 32 provinces in 2016, their respective per capita funding levels, and some indicators related to program implementation from 2009 to 2016. The Joinpoint regression model was adopted to test the time trend of changes in program implementation indicators. Face-to-face individual interviews and group discussions were conducted with 48 key insiders. ResultsThe program provided full life cycle service to the whole population with an equitable and affordable financing system, enhanced the capability and quality of the health workforce, and facilitated integration of the public health service delivery system. Meanwhile, there were also some shortcomings, including lack of selection and an exit mechanism of service items, inadequate system integration, shortage of qualified professionals, limited role played by actors outside the health sector, and a large gap between the subsidy standard and the actual service cost. The Joinpoint regression analysis demonstrated that 13 indicators related to program implementation showed a significant upward trend (P

PurposeTrials of non-operative management (NOM) have become the standard of care for blunt splenic injury (BSI) in hemodynamically stable patients. However, there is a lack of consensus regarding the utility of follow-up CT exams and relevant CT features. The purpose of this study is to determine imaging predictors of splenectomy on follow-up CT using quantitative volumetric measurements.MethodsAdult patients who underwent a trial of non-operative management (NOM) with follow-up CT performed for BSI between 2017 and 2019 were included (n = 51). Six patients (12% of cohort) underwent splenectomy; 45 underwent successful splenic salvage. Voxelwise measurements of splenic laceration, hemoperitoneum, and subcapsular hematoma were derived from portal venous phase images of admission and follow-up scans using 3D slicer. Presence/absence of pseudoaneurysm on admission and follow-up CT was assessed using arterial phase images. Multivariable logistic regression was used to determine independent predictors of decision to perform splenectomy.ResultsFactors significantly associated with splenectomy in bivariate analysis incorporated in multivariate logistic regression included final hemoperitoneum volume (p = 0.003), final subcapsular hematoma volume (p = 0.001), change in subcapsular hematoma volume between scans (p = 0.09) and new/persistent pseudoaneurysm (p = 0.003). Independent predictors of splenectomy in the logistic regression were final hemoperitoneum volume (unit OR = 1.43 for each 100 mL change; 95% CI: 0.99–2.06) and new/persistent pseudoaneurysm (OR = 160.3; 95% CI: 0.91–28315.3). The AUC of the model incorporating both variables was significantly higher than AAST grading (0.91 vs. 0.59, p = 0.025). Mean combined effective dose for admission and follow up CT scans was 37.4 mSv.ConclusionFollow-up CT provides clinically valuable information regarding the decision to perform splenectomy in BSI patients managed non-operatively. Hemoperitoneum volume and new or persistent pseudoaneurysm at follow-up are independent predictors of splenectomy.

Introduction: Young adults may be facing growing threats from vaccine-preventable diseases (VPDs). However, vaccination of young adults may not have drawn adequate attention. In Asia, adensely populated region with ahigh proportion of low-income countries, VPDs impose more of an economic and social burden than in western countries. However, knowledge about attitudes toward vaccines among young Asians is limited. This study aims to fill that gap by describing attitudes toward vaccines and how well they are accepted among young Asian adults through asystematic review of relevant Chinese and English publications. Methods: A three-stage searching strategy was adopted to identify eligible studies published during 2009–2019 according to the selection criteria, resulting in 68 articles being included. Results: The review finds that vaccination coverage among young Asians is generally lower than among their western peers, and there is a lack of relevant study in many Asian countries. Factors influencing young Asians’ attitudes toward vaccines are categorized into contextual level, individual and social level, and vaccine-specific level. Conclusion: These suggest that there is a need to strengthen young adults’ vaccination programs and to promote vaccine-related information and government.

Objectives: The World Health Organization pre-qualified single-dose typhoid conjugate vaccine (TCV) and requested data on co-administration with routine vaccines. The co-administration of Typbar TCV (Bharat Biotech International) with routine group A meningococcal conjugate vaccine (MCV-A) and measles–rubella (MR) vaccine was tested. Methods: This was a double-blind, randomized controlled trial performed in Ouagadougou, Burkina Faso. Children were recruited at the 15-month vaccination visit and were assigned randomly (1:1:1) to three groups. Group 1 children received TCV plus control vaccine (inactivated polio vaccine) and MCV-A 28 days later; group 2 children received TCV and MCV-A; group 3 children received MCV-A and control vaccine. Routine MR vaccine was administered to all participants. Safety was assessed at 0, 3, and 7 days after immunization, and unsolicited adverse events and serious adverse events were assessed for 28 days and 6 months after immunization, respectively. Results: A total of 150 children were recruited and vaccinated. Solicited symptoms were infrequent and similar for TCV and control recipients, as were adverse events (group 1, 61.2%; group 2, 64.0%; group 3, 68.6%) and serious adverse events (group 1, 2.0%; group 2, 8.0%; group 3, 5.9%). TCV generated robust immunity without interference with MCV-A vaccine. Conclusions: TCV can be safely co-administered at 15 months with MCV-A without interference. This novel study on the co-administration of TCV with MCV-A provides data to support large-scale uptake in sub-Saharan Africa.

Background: The value of rectal anorectal manometry (ARM) in the diagnosis of Hirschsprung's disease (HD), especially in newborns, has been controversial. This study aims to further explore the value of ARM in the diagnosis of HD. Methods: This study prospectively collected the rectal and anal canal pressure records of children with high suspicion of HD diagnosed by rectal suction biopsy (RSB) from the West China Hospital of Sichuan University from November 2019 to September 2021. With RSB results as the diagnostic gold standard, the value of ARM examination in the diagnosis of HD was explored through age stratification. Results: Among 170 children, the sensitivity of ARM in diagnosing HD was 98%, the specificity was 65%, and the accuracy was 93%. The positive likelihood ratio was 2.83, and the negative likelihood ratio was 0.03. The positive result of ARM is more important to HD. The positive predictive value was 94%, the negative predictive value of the ARM negative result for HD was 85%, the kappa value was 0.680, and the Yuedeng index was 0.63. Through age stratification, it was found that the sensitivity of ARM for HD diagnosis in each age group was relatively close, but the neonatal specificity was only 33%, which was significantly lower than that of children of other age groups. Conclusion: ARM has high sensitivity in HD children of all ages. In neonates, ARM has a high false positive rate in the diagnosis of HD.

MicroRNA (miRNA) is a class of endogenous non-coding small RNA with regulatory activities, which generally regulates the expression of target genes at the post-transcriptional level. Multiple Sclerosis (MS) is thought to be an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that typically affect young adults. T lymphocytes play an important role in the pathogenesis of MS, and studies have suggested that miRNAs are involved in regulating the proliferation, differentiation, and functional maintenance of T lymphocytes in MS. Dysregulated expression of miRNAs may lead to the differentiation balance and dysfunction of T lymphocytes, and they are thus involved in the occurrence and development of MS. In addition, some specific miRNAs, such as miR-155 and miR-326, may have potential diagnostic values for MS or be useful for discriminating subtypes of MS. Moreover, miRNAs may be a promising therapeutic strategy for MS by regulating T lymphocyte function. By summarizing the recent literature, we reviewed the involvement of T lymphocytes in the pathogenesis of MS, the role of miRNAs in the pathogenesis and disease progression of MS by regulating T lymphocytes, the possibility of differentially expressed miRNAs to function as biomarkers for MS diagnosis, and the therapeutic potential of miRNAs in MS by regulating T lymphocytes.

Abstract Background The goal of this study was to describe the expenses related to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) management and care in Nantong Infectious Disease Hospital from October 2013 through June 2017. Methods The information of 610 HIV/AIDS inpatients were collected from the Electronic Medical Record System of the hospital. Univariate and path analysis were employed to evaluate the association between hospitalization expense and its related factors. Results The average hospitalization expenses per person was 5454 RMB (Renminbi, the currency of China, about $808 USD) and 23,555 RMB (about $3489 USD), respectively for HIV/AIDS patients. The average length of hospital stay was 10.0 ± 5.5 days for HIV patients and 21.7 ± 12.4 days for AIDS patients. For HIV patients, laboratory test fees constituted 37.46% of total expenses; while drug fees accounted for the largest proportion for AIDS patients. Path analysis indicated that the length of hospital stay was the most important factor affecting total expenses (total path coefficient = 0.563 for HIV patients and 0.649 for AIDS patients). Total expenses for HIV-infected females was higher than that of males (total path coefficient = 0.217), and the more complications led to higher expenses for AIDS patients. Conclusions Though antiretroviral therapy (ART) is provided for free in China, associated medical care, particularly hospitalizations and fees, continue to drive up the medical costs of patients living with HIV and AIDS. Understanding the factors influencing these costs are crucial for determining policies and strategies that can reduce the economic burden of HIV/AIDS patients in China.

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (Psa), is a catastrophic disease affecting kiwifruit worldwide. As no effective cure has been developed, planting Psa-resistant cultivars is the best way to avoid bacterial canker in kiwifruit cultivation. However, the differences in the mechanism of resistance between cultivars is poorly understood. In the present study, five local kiwifruit cultivars were used for Psa resistance evaluation and classified into different resistance categories, tolerant (T), susceptible (S), and highly susceptible (HS), based on their various symptoms of lesions on the cane. Susceptible and highly susceptible varieties had a higher sucrose concentration, and a greater decrease in sucrose content was observed after Psa inoculation in phloem than in tolerant varieties. Three invertase activities and their corresponding gene expressions were detected in the phloem with lesions and showed the same trends as the variations in sucrose concentration. Meanwhile, after Psa inoculation, enzyme activities involved in antioxidant defense responses, such as PAL, POD, and CAT, were also altered in the phloem of the lesion position. With no differences among cultivars, PAL and POD activities in phloem first increased and then decreased after Psa inoculation. However, great differences in CAT activities were observed between T and S/HS categories. Our results demonstrate that sucrose content was negatively correlated with the disease resistance of different cultivars and that the increase in immune response enzymes is likely caused by increased sucrose metabolism in the phloem.

Alzheimer’s disease (AD) is the most common cause of senile dementia. Although AD research has made important breakthroughs, the pathogenesis of this disease remains unclear, and specific AD diagnostic biomarkers and therapeutic strategies are still lacking. Recent studies have demonstrated that neuroinflammation is involved in AD pathogenesis and is closely related to other health effects. MicroRNAs (miRNAs) are a class of endogenous short sequence non-coding RNAs that indirectly inhibit translation or directly degrade messenger RNA (mRNA) by specifically binding to its 3′ untranslated region (UTR). Several broadly expressed miRNAs including miR-21, miR-146a, and miR-155, have now been shown to regulate microglia/astrocytes activation. Other miRNAs, including miR-126 and miR-132, show a progressive link to the neuroinflammatory signaling. Therefore, further studies on these inflamma-miRNAs may shed light on the pathological mechanisms of AD. The differential expression of inflamma-miRNAs (such as miR-29a, miR-125b, and miR-126-5p) in the peripheral circulation may respond to AD progression, similar to inflammation, and therefore may become potential diagnostic biomarkers for AD. Moreover, inflamma-miRNAs could also be promising therapeutic targets for AD treatment. This review provides insights into the role of inflamma-miRNAs in AD, as well as an overview of general inflamma-miRNA biology, their implications in pathophysiology, and their potential roles as biomarkers and therapeutic targets.

Objectives: This meta-analysis was conducted to evaluate the effects of hydroxychloroquine (HCQ) in the treatment of primary Sjögren’s syndrome (pSS).Methods: Nine databases were searched for data collection. We used clinical features, including involvement in superficial tissues and visceral systems, and experimental findings, including Schirmer’s test, unstimulated salivary flow rate (uSFR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and immunoglobulins (IgG, IgM and IgA) as major outcome measures. The Downs and Black quality assessment tool and RevMan 5.3 were used to assess the methodological quality and statistical analysis, respectively.Results: Thirteen studies with pSS patients, consisting of two randomized controlled studies, four retrospective studies and seven prospective studies were analyzed. Results showed that HCQ treatment significantly improved the oral symptoms of pSS patients compared to non-HCQ treatment (P = 0.003). Similar trends favoring HCQ treatment were observed for uSFR (p = 0.05), CRP (p = 0.0008), ESR (p < 0.00001), IgM (p = 0.007) and IgA (p = 0.05). However, no significant improvement was observed in other clinical features, including ocular involvement, fatigue, articular lesions, pulmonary, neurological and lymphoproliferative symptoms, renal organs and other experimental parameters in the HCQ treatment group compared to the non-HCQ treatment group.Conclusion: HCQ treatment showed moderate efficacy to improve oral symptoms, uSFR, ESR, CRP, IgM and IgA. However, HCQ could not alleviate organ-specific systemic involvement.Systematic Review Registration:We have registered on the PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], and the registration number is identifier [CRD42020205624]

Crassocephalum crepidioides is an African orphan crop that is used as a leafy vegetable and medicinal plant. Although it is of high regional importance in Sub-Saharan Africa, the plant is still mainly collected from the wild and therefore efforts are made to promote its domestication. However, in addition to beneficial properties, there was first evidence that C. crepidioides can accumulate the highly toxic pyrrolizidine alkaloid (PA) jacobine and here it was investigated, how jacobine production is controlled. Using ecotypes from Africa and Asia that were characterized in terms of their PA profiles, it is shown that the tetraploid C. crepidioides forms jacobine, an ability that its diploid close relative Crassocephalum rubens appears to lack. Evidence is provided that nitrogen (N) deficiency strongly increases jacobine in the leaves of C. crepidioides, that this capacity depends more strongly on the shoot than the root system, and that homospermidine synthase (HSS) activity is not rate-limiting for this reaction. A characterization of HSS gene representation and transcription showed that C. crepidioides and C. rubens possess two functional versions, one of which is conserved, that the HSS transcript is mainly present in roots and that its abundance is not controlled by N deficiency. In summary, this work improves our understanding of how environmental cues impact PA biosynthesis in plants and provides a basis for the development of PA-free C. crepidioides cultivars, which will aid its domestication and safe use.

The second messenger Ap4A contributes to mast cell activation by interacting with HINT1 but the molecular mechanism is not fully understood. Here, the authors show that Ap4A regulates downstream signaling by polymerizing HINT1 and provide insights into how specificity over other second messengers is achieved.

Abstract Background One in three Head Start children is either overweight or obese. We will test the efficacy of an early childhood obesity prevention program, “¡Míranos! Look at Us, We Are Healthy!” (¡Míranos!), which promotes healthy growth and targets multiple energy balance-related behaviors in predominantly Latino children in Head Start. The ¡Míranos! intervention includes center-based (policy changes, staff development, gross motor program, and nutrition education) and home-based (parent engagement/education and home visits) interventions to address key enablers and barriers in obesity prevention in childcare. In partnership with Head Start, we have demonstrated the feasibility and acceptability of the proposed interventions to influence energy balance-related behaviors favorably in Head Start children. Methods Using a three-arm cluster randomized controlled design, 12 Head Start centers will be randomly assigned in equal number to one of three conditions: 1) a combined center- and home-based intervention, 2) center-based intervention only, or 3) comparison. The interventions will be delivered by trained Head Start staff during the academic year. A total of 444 3-year-old children (52% females; n = 37 per center at baseline) in two cohorts will be enrolled in the study and followed prospectively 1 year post-intervention. Data collection will be conducted at baseline, immediately post-intervention, and at the one-year follow-up and will include height, weight, physical activity (PA) and sedentary behaviors, sleep duration and screen time, gross motor development, dietary intake and food and activity preferences. Information on family background, parental weight, PA- and nutrition-related practices and behaviors, PA and nutrition policy and environment at center and home, intervention program costs, and treatment fidelity will also be collected. Discussion With endorsement and collaboration of two local Head Start administrators, ¡Míranos!, as a culturally tailored obesity prevention program, is poised to provide evidence of efficacy and cost-effectiveness of a policy and environmental approach to prevent early onset of obesity in low-income Latino preschool children. ¡Míranos! can be disseminated to various organized childcare settings, as it is built on the Head Start program and its infrastructure, which set a gold standard for early childhood education, as well as current PA and nutrition recommendations for preschool children. Trial registration ClinicalTrials.Gov (NCT03590834) July 18, 2018.

Oxidative stress induced by hydrogen peroxide (H2O2) triggers human lens epithelial cell (HLEC) apoptosis and initiates cataract formation. Oxyresveratrol (Oxy) was reported to possess antioxidant and free radical scavenging activities. Herein, we investigated the effects of Oxy on H2O2-induced oxidative stress and apoptosis in HLECs and the associated mechanisms. Cell viability was detected by MTT assay. The oxidative damage was assessed by measuring the activities of superoxide dismutases-1 (SOD-1), catalase (CAT), glutathione reductase (GSH), and malondialdehyde (MDA). Apoptosis was analyzed by flow cytometry analysis. The changed expressions of heme oxygenase-1 (HO-1) and protein kinase B (Akt) pathways were evaluated by qRT-PCR and western blot. We found that exposure to H2O2 dose-dependently reduced cell viability, and induced oxidative stress and apoptosis in HLECs, which were reversed by pretreatment with Oxy. Oxy increased p-Akt and HO-1 expressions in H2O2-stimulated HLECs. Akt and HO-1 expressions form a regulatory axis and Oxy activated the Akt/HO-1 pathway in H2O2-stimulated HLECs. Inhibition of the Akt/HO-1 pathway by LY294002 or ZnPP attenuated the effects of Oxy on oxidative stress and apoptosis in H2O2-stimulated HLECs. In conclusion, Oxy protected H2O2-induced oxidative stress and apoptosis through activating the Akt/HO-1 pathway, suggesting the protective effect of Oxy against H2O2-induced cataract. Keywords: Oxyresveratrol, Hydrogen peroxide, Oxidative stress, The Akt/HO-1 pathway, Cataract

Radiotherapy remains an effective conventional method of treatment for patients with cancer. However, the clinical efficacy of radiotherapy is compromised by the development of radioresistance of the tumor cells during the treatment. Consequently, there is need for a comprehensive understanding of the regulatory mechanisms of tumor cells in response to radiation to improve radiotherapy efficacy. The current study aims to highlight new developments that illustrate various forms of cancer cell death after exposure to radiation. A summary of the cellular pathways and important target proteins that are responsible for tumor radioresistance and metastasis is also provided. Further, the study outlines several mechanistic descriptions of the interaction between ionizing radiation and the host immune system. Therefore, the current review provides a reference for future research studies on the biological effects of new radiotherapy technologies, such as ultra-high-dose-rate (FLASH) radiotherapy, proton therapy, and heavy-ion therapy.

Objectives: We aimed to assess the effectiveness and safety of iguratimod (IGU) in treating primary Sjögren’s syndrome (pSS) by meta-analysis.Methods: Eight databases and two clinical trial websites were searched from conception to August 10, 2020, for relevant randomized controlled trials (RCTs) on outcomes of patients with pSS treated with IGU. Revman 5.4 was used for statistical analysis and creating plots.Results: A total of 1,384 patients with pSS from 19 RCTs were included in this meta-analysis. Pooled results demonstrated that patients treated with IGU + hydroxychloroquine (HCQ) + glucocorticoid (GC) showed significant differences in erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) level, platelet (PLT) count, immunoglobulin G (IgG) level, salivary flow rate, Schirmer’s test result, EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), and efficacy rate (p ≤ 0.01) compared to patients treated with HCQ + GC. Compared to treatment with HCQ and GC, co-administration of IGU with GC showed significant differences in ESR and RF level (p ≤ 0.01); however, no significant differences were noted in IgG level. Conversely, the IgG level showed a significant improvement in the IGU + HCQ + GC group compared to the HCQ + GC group. The results of safety analysis revealed that seven trials showed no significant differences in adverse events (AEs) between the IGU + HCQ + GC and HCQ + GC groups (p = 0.15). Although no severe AEs were noted, gastrointestinal discomfort was the most common AE in the IGU group. No significant differences in AEs were observed between the IGU + GC and HCQ + GC groups.Conclusion: IGU improved the clinical symptoms of patients with pSS, including inflammatory indicators (ESR, IgG, and RF levels), PLT count, secretion function of the salivary and lacrimal glands (salivary flow rate and Schirmer’s test result), and disease indexes (ESSDAI and ESSPRI), when co-administered with HCQ + GC therapy without increasing the risks of AEs. Therefore, IGU can be considered as an effective and safe drug for clinical therapy of pSS. Considering the limitations of the present trials, more long-term, multicenter, and high-quality RCTs are required to assess the effectiveness and safety of IGU for treating patients with pSS.

Abstract Objectives: Evidence supporting collection of follow-up blood cultures for Gram-negative bacteremia is mixed. We sought to understand why providers order follow-up blood cultures when managing P. aeruginosa bacteremia and whether follow-up blood cultures in this context are associated with short- and long-term survival. Methods: We conducted a retrospective cohort study of adult inpatients with P. aeruginosa bacteremia at the University of Maryland Medical Center in 2015–2020. Kaplan-Meier survival curves and Cox regression with time-varying covariates were used to evaluate the association between follow-up blood cultures and time to mortality within 30 days of first positive blood culture. Provider justifications for follow-up blood cultures were identified through chart review. Results: Of 159 eligible patients, 127 (80%) had follow-up blood cultures, including 9 (7%) that were positive for P. aeruginosa and 10 (8%) that were positive for other organisms. Follow-up blood cultures were typically collected “to ensure clearance” or “to guide antibiotic therapy.” Overall, 30-day mortality was 25.2%. After risk adjustment for patient characteristics, follow-up blood cultures were associated with a nonsignificant reduction in mortality risk (hazard ratio, 0.43; 95% confidence interval, 1.08; P = .071). In exploratory analyses, the potential mortality reduction from follow-up blood cultures was driven by their use in patients with Pitt bacteremia scores >0. Conclusions: Follow-up blood cultures are commonly collected for P. aeruginosa bacteremia but infrequently identify persistent bacteremia. Targeted use of follow-up blood cultures based on severity of illness may reduce unnecessary culturing.

Wheat (Triticum aestivum L) production on the Huang-Huai Plain of China has substantially affected in the past 50 years as a result of the decreasing total solar radiation and sunshine hours. Potassium has a significant effect on improving leaf photosynthesis ability under stress conditions. Five potassium application rates (K), 0 (K0), 50 (K50), 100 (K100), 150 (K150), and 250 (K250) mg K2O kg-1 soil, combined with two shading levels, no shading (NS) and shading at early filling stage for 10 days (SE), were used to investigate the effects of K application on winter wheat growth under SE condition. Under NS condition, the parameters related to chlorophyll fluorescence characteristics, dry matter productivity and grain yields reached the maximum values at a middle K application rate (100 mg K2O kg-1 soil). Shading stress significantly reduced leaf SPAD value, showed negative effects on chlorophyll fluorescence characteristics and reduced grain yield of winter wheat. However, as the result of the interaction of K×S, compared to NS condition, higher K application rate (150 mg and 250 K2O kg-1 soil) was beneficial in terms of achieving a higher grain yield of winter wheat under SE by improving leaf SPAD value, alleviating the damage of SE on the winter wheat photosynthetic system, and increasing fructan content and dry matter translocation percentage.

MicroRNAs are a set of highly conserved non-coding RNAs that control gene expression at the post-transcriptional/translational levels by binding to the 3′-UTR of diverse target genes. Increasing evidence indicates that miRNAs not only play a vital role in many biological processes, but they are also frequently deregulated in pathological conditions, including cancer. The miR-320 family is one of many tumor suppressor families and is composed of five members, which has been demonstrated to be related to the repression of epithelial-mesenchymal transition (EMT) inhibition, cell proliferation, and apoptosis. Moreover, this family has been shown to regulate drug resistance, and act as a potential biomarker for the diagnosis, prognosis, and prediction of cancer. In this review, we summarized recent research with reference to the tumor suppressor function of miR-320 and the regulation mechanisms of miR-320 expression. The collected evidence shown here supports that miR-320 may act as a novel biomarker for cancer prognosis and therapeutic response to cancer treatment.

Abstract Background Effective community-partnered and patient-centered outcomes research needs to address community priorities. However, optimal sampling methods to engage stakeholders from hard-to-reach, vulnerable communities to generate research priorities have not been identified. Methods In two similar rural, largely Hispanic communities, a community advisory board guided recruitment of stakeholders affected by chronic pain using a different method in each community: 1) snowball sampling, a chain- referral method or 2) purposive sampling to recruit diverse stakeholders. In both communities, three groups of stakeholders attended a series of three facilitated meetings to orient, brainstorm, and prioritize ideas (9 meetings/community). Using mixed methods analysis, we compared stakeholder recruitment and retention as well as priorities from both communities’ stakeholders on mean ratings of their ideas based on importance and feasibility for implementation in their community. Results Of 65 eligible stakeholders in one community recruited by snowball sampling, 55 (85 %) consented, 52 (95 %) attended the first meeting, and 36 (65 %) attended all 3 meetings. In the second community, the purposive sampling method was supplemented by convenience sampling to increase recruitment. Of 69 stakeholders recruited by this combined strategy, 62 (90 %) consented, 36 (58 %) attended the first meeting, and 26 (42 %) attended all 3 meetings. Snowball sampling recruited more Hispanics and disabled persons (all P

Background:. There is a paucity of patient-reported outcome measures for facial trauma reconstruction. To measure satisfaction and health-related quality of life (HRQOL), following repair of traumatic facial fractures, we used the FACE-Q, a set of patient-reported outcome instruments designed for aesthetic facial surgery. As a step toward validating the scales for facial trauma, we evaluated their reliability. Methods:. This is a prospective study of patients following primary repair of traumatic facial fractures at a level 1 trauma center from 2016 to 2018. Six FACE-Q scales with relevance to the facial trauma population were completed by patients at their 1-month postoperative visits. Predictors of satisfaction were examined using multiple linear regression models. Reliability of the scales in this population was evaluated using psychometric methods. Results:. One hundred eighty-five participants fulfilled inclusion criteria. Mean scores for the 6 scales ranged from 59 (SD = 15) for Recovery-Early Life Impact to 94 (SD = 13) for Satisfaction with Medical Team. Predictors of lower satisfaction and/or HRQOL include current tobacco smoking status, mandibulomaxillary fixation, and Le Fort pattern fractures. All scales were found to have good to excellent reliability (Cronbach’s alpha = 0.824–0.969). Conclusions:. Following repair of facial fractures, patient-reported outcomes can be reliably measured using FACE-Q scales. On average, patients report poor health-related quality of life in the early postoperative period. Predictors of low satisfaction and/or poor HRQOL include current smoking habit, mandibulomaxillary fixation, and Le Fort fractures.

Cancer and cardiovascular disease (CVD) are leading causes of morbidity and mortality in the United States. Vascular endothelial dysfunction, an important contributor in the development of CVD, improves with exercise training in patients with CVD. However, the role of regular exercise to improve vascular function in cancer survivors remains equivocal. We performed a meta-analysis to determine the effect of exercise training on vascular endothelial function in cancer survivors. We searched PubMed (1975 to 2016), EMBASE CINAHL (1937 to 2016), OVID MEDLINE (1948 to 2016), and Cochrane Central Registry of Controlled Trials (1991 to 2016) using search terms: vascular function , endothelial function , flow-mediated dilation [FMD], reactive hyperemia , exercise , and cancer . Studies selected were randomized controlled trials of exercise training on vascular endothelial function in cancer survivors. We calculated pooled effect sizes and performed a meta-analysis. We identified 4 randomized controlled trials (breast cancer, n=2; prostate cancer, n=2) measuring vascular endothelial function by FMD (n=3) or reactive hyperemia index (n=1), including 163 cancer survivors (exercise training, n=82; control, n=81). Aerobic exercise training improved vascular function (n=4 studies; standardized mean difference [95% CI]=0.65 [0.33, 0.96], I 2 =0%; FMD, weighted mean difference [WMD]=1.28 [0.22, 2.34], I 2 =23.2%) and peak exercise oxygen uptake (3 trials; WMD [95% CI]=2.22 [0.83, 3.61] mL/kg/min; I 2 =0%). Our findings indicate that exercise training improves vascular endothelial function and exercise capacity in breast and prostate cancer survivors.