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The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1–HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

Abstract Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is marked by impaired immune tolerance and heightened activity in both innate and adaptive immune systems. Hallmarks of SLE include elevated type I interferons and autoantibody production, though the exact causes of SLE remain elusive despite advances in research techniques. Crucial to SLE research is understanding its pathogenesis and developing effective diagnostic and therapeutic methods. Recent studies have highlighted a significant link between mitochondrial abnormalities and SLE's development and progression. Mitochondrial dysfunction plays a key role in SLE pathogenesis through various mechanisms such as mitochondrial DNA mutations, oxidative stress, immune metabolic reprogramming, and cellular death. These factors collectively contribute to the loss of self‐tolerance, increased autoantibody production, and impaired clearance of immune complexes, leading to their deposition. This triggers sustained inflammatory responses and damages multiple organs. This review focuses on the diagnostic and therapeutic approaches related to mitochondrial abnormalities in SLE. Targeting mitochondrial pathways presents a promising strategy for treating SLE, potentially improving prognosis and quality of life for those affected. Future research should further investigate the role of mitochondria in the onset and progression of SLE, providing new avenues for understanding and managing this complex disease.

Background: Ozone can enhance the expression of some growth factors (GFs) in platelet rich plasma (PRP), recent study showed oxygen-rich PRP (ozonized PRP) have better therapeutic effects on bone and joint diseases. PRP injection has been widely used in the treatment of facial rejuvenation, but the efficacy of sufficient oxygen-rich PRP in facial rejuvenation has not been studied. Objective: Firstly, we examined whether ozone treatment can increase the concentration of GFs of PRP in vitro. And then a variety of subjective and objective detection methods were used to evaluate the effect of sufficient(10–12 mL each time for the injection of face and neck) oxygen-rich (ozonized PRP) PRP injection in facial rejuvenation by follow-up for 6 months. At last, we investigated the satisfaction, side effects and pain score of the treatment through a questionnaire survey. Methods: The concentration of main GFs in PRP treated with different dose of ozone in vitro was measured by ELISA. Clinical picture, the collagen thickness of dermis by reflectance confocal microscope(RCM), skin conditions (including spots, ultraviolet (UV) spots, brown spots, red area, pores, wrinkles, texture and porphyrin) by VISIA were collected before treatment and each month follow-up visit after treatment until 6-month follow-up period was finished. Patients’ satisfaction, side effects and pain score were collected at the end of follow-up period. Results: PRP treated by high-dose ozone (57 μg/mL, ozone/PRP volume ratio:1/1) in vitro showed a significant increase in endothelial growth factor (EGF) and transforming growth factor-β (TGF-β) compared to baseline(P

Abstract Introduction Persistent nasal carriage has been associated with Staphylococcus aureus infection. Previous S. aureus studies in Asia have primarily focused on clinical patients, providing limited information on persistent nasal carriage among the general adult population. Methods This study examined 143 healthy adults in a community in Jiangsu, China. Nasal swab samples were collected 10 times. The colonization status was identified using SPA typing. We also determined antimicrobial susceptibility, genotype, and genomic characteristics of S. aureus. Results The prevalence of S. aureus nasal carriage among the community individuals was on average 16.78%. The carriage rates of methicillin-resistant S. aureus and multidrug-resistant S. aureus were 6.29% and 7.69%, respectively. We identified 8.39% persistent carriers, 39.16% intermittent carriers, and 52.45% noncarriers. Furthermore, family members displayed concordance in terms of genotype and genomic characteristics. Conclusion Persistent nasal sampling captured intermittent carriers that were missed during short-term sampling, thus highlighting the necessity for regular community testing. SPA typing can serve as a rapid method for determining S. aureus colonization. The potential for intrafamilial transmission of S. aureus is evident, with persistent carriers being the most probable source of infection.

Abstract Introduction Post-stroke depression (PSD) is a prevalent complication that has been shown to have a negative impact on rehabilitation outcomes and quality of life and poses a significant risk for suicidal intention. However, models for discriminating and predicting PSD in stroke survivors for effective secondary prevention strategies are inadequate as the pathogenesis of PSD remains unknown. Prognostic prediction models that exhibit greater rule-in capacity have the potential to mitigate the issue of underdiagnosis and undertreatment of PSD. Thus, the planned study aims to systematically review and critically evaluate published studies on prognostic prediction models for PSD. Methods and analysis A systematic literature search will be conducted in PubMed and Embase through Ovid. Two reviewers will complete study screening, data extraction, and quality assessment utilizing appropriate tools. Qualitative data on the characteristics of the included studies, methodological quality, and the appraisal of the clinical applicability of models will be summarized in the form of narrative comments and tables or figures. The predictive performance of the same model involving multiple studies will be synthesized with a random effects meta-analysis model or meta-regression, taking into account heterogeneity. Ethics and dissemination Ethical approval is considered not applicable for this systematic review. Findings will be shared through dissemination at academic conferences and/or publication in peer-reviewed academic journals. Systematic review registration PROSPERO CRD42023388548.

Abstract Improving the absorption of electromagnetic waves at low-frequency bands (2-8 GHz) is crucial for the increasing electromagnetic (EM) pollution brought about by the innovation of the fifth generation (5G) communication technology. However, the poor impedance matching and intrinsic attenuation of material in low-frequency bands hinders the development of low-frequency electromagnetic wave absorbing (EMWA) materials. Here we propose an interface-induced dual-pinning mechanism and establish a magnetoelectric bias interface by constructing bilayer core-shell structures of NiFe2O4 (NFO)@BiFeO3 (BFO)@polypyrrole (PPy). Such heterogeneous interface could induce distinct magnetic pinning of the magnetic moment in the ferromagnetic NFO and dielectric pinning of the dipole rotation in PPy. The establishment of the dual-pinning effect resulted in optimized impedance and enhanced attenuation at low-frequency bands, leading to better EMWA performance. The minimum reflection loss (RLmin) at thickness of 4.43 mm reaches -65.30 dB (the optimal absorption efficiency of 99.99997%), and the effective absorption bandwidth (EAB) can almost cover C-band (4.72 ~ 7.04 GHz) with low filling of 15.0 wt.%. This work proposes a mechanism to optimize low-frequency impedance matching with electromagnetic wave (EMW) loss and pave an avenue for the research of high-performance low-frequency absorbers.

Abstract Background Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). Methods Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. Results A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan–Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P

Abstract Background Clinical characteristics and long-term data on the safety and efficacy of LAAC in preventing cerebrovascular accident and thromboembolism among Chinese patients with non-valvular AF (NVAF) remain limited. Methods Data of consecutive NVAF patients who underwent LAAC at Beijing Anzhen Hospital, Capital Medical University, from June 1, 2014, to December 31, 2021, were collected and analyzed retrospectively. The primary effectiveness endpoint was the composite endpoint of stroke/transient ischemic attack, systemic embolism, and death from cardiovascular causes. The primary safety endpoint is the severe bleeding defined by the LAAC Munich consensus. Results Of the 222 patients enrolled, the mean age was 66.90 ± 9.62 years, with a majority being male (77.03%). Many patients are non-paroxysmal AF (71.19%) with a median duration of AF of 4.00 years. The mean CHA2DS2-VASc score was 3.78 ± 1.49, and the mean HAS-BLED score was 1.68 ± 0.86. Thromboembolic events (76.58%) were the most common indication for LAAC. The device, technical, and procedural success rates were 98.65%, 98.65%, and 93.69%, respectively. The anticoagulation continuation rate was 56.36%, 31.25%, and 22.60% at 3-, 6- and 12 months post-procedure, respectively. Throughout a mean 2.81 years of follow-up, the incidence of the primary efficacy endpoint was 4.27 per 100 patient-years, predominantly attributable to stroke/TIA (3.12 per 100 PYs). Five patients experienced major bleeding during the follow-up period. Post-procedure imaging revealed minimal complications, with only one substantial peri-device leak. Device-related thrombus occurred in 2.33% of patients, resolving with anticoagulation. Conclusion The study demonstrates that LAAC is a safe and effective alternative option for Chinese patients with AF, with a high success rate, few complications as well as fewer long-term adverse outcome events.

Abstract Background Pseudomonas aeruginosa is a major Gram-negative pathogen that can exacerbate lung infections in the patients with cystic fibrosis, which can ultimately lead to death. Methods From 2016 to 2021, 103 strains of P. aeruginosa were isolated from hospitals and 20 antibiotics were used for antimicrobial susceptibility determination. Using next-generation genome sequencing technology, these strains were sequenced and analyzed in terms of serotypes, ST types, and resistance genes for epidemiological investigation. Results The age distribution of patients ranged from 10 days to 94 years with a median age of 69 years old. The strains were mainly isolated from sputum (72 strains, 69.9%) and blood (14 strains, 13.6%). The size of these genomes ranged from 6.2 Mb to 7.4 Mb, with a mean value of 6.5 Mb. In addition to eight antibiotics that show inherent resistance to P. aeruginosa, the sensitivity rates for colistin, amikacin, gentamicin, ceftazidime, piperacillin, piperacillin-tazobactam, ciprofloxacin, meropenem, aztreonam, imipenem, cefepime and levofloxacin were 100%, 95.15%, 86.41%, 72.82%, 71.84%, 69.90%, 55.34%, 52.43%, 50.49%, 50.49%, 49.51% and 47.57% respectively, and the carriage rate of MDR strains was 30.69% (31/101). Whole-genome analysis showed that a total of 50 ST types were identified, with ST244 (5/103) and ST1076 (4/103) having a more pronounced distribution advantage. Serotype predictions showed that O6 accounted for 29.13% (30/103), O11 for 23.30% (24/103), O2 for 18.45% (19/103), and O1 for 11.65% (12/103) of the highest proportions. Notably, we found a significantly higher proportion of ExoU in P. aeruginosa strains of serotype O11 than in other cytotoxic exoenzyme positive strains. In addition to this, a total of 47 crpP genes that mediate resistance to fluoroquinolones antibiotics were found distributed on 43 P. aeruginosa strains, and 10 new variants of CrpP were identified, named 1.33, 1.34, 1.35, 1.36, 1.37, 1.38, 1.39, 1.40, 1.41 and 7.1. Conclusions We investigated the antibiotic susceptibility of clinical isolates of P. aeruginosa and genomically enriched the diversity of P. aeruginosa for its prophylactic and therapeutic value.

ObjectiveSevere cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs.MethodsWe analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out.ResultsAmong 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups.ConclusionThe identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

Multiple myeloma (MM) is a malignancy arisen from the abnormal proliferation of clonal plasma cells. It has a high risk of developing bleeding and thrombotic complications, which are related to poor prognosis and decreased survival. Multiple factors are involved in the breaking of the hemostasis balance, including disease specific factors, patient-specific factors, and drug factors that change pro-and anticoagulant and fibrinolysis. Recently, with the introduction of new treatments such as monoclonal antibodies, chimeric antigen receptor modified T-cell therapy, antibody-drug conjugates directed against BCMA, programmed death-1 inhibitor, export protein 1 inhibitors, histone deacetylase inhibitors, immunomodulatory drugs, proteasome inhibitors and Bcl-2 inhibitors, the therapy of MM patients has entered into a new era. Furthermore, it arouses a question whether these new treatments would alter the hemostasis balance in MM patients, which highlights the importance of the underlying pathophysiology of hemostasis abnormalities in MM, and on prophylaxis approaches. In this review, we updated the mechanisms of hemostasis abnormalities in MM, the impact of the new drugs on hemostasis balance and reliable therapeutic strategies.

Background and objectives: Many studies suggested that short-term exposure to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5–10) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM2.5 and PM2.5–10 on various types of cerebrovascular disease. Methods: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season. Results: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10 μg/m3 rise in PM2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10 μg/m3 rise in PM2.5–10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season. Conclusions: Short-term exposures to both PM2.5 and PM2.5–10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae.

Abstract Recent studies have demonstrated great values of deep‐learning (DL) methods for improving El Niño‐Southern Oscillation (ENSO) predictions. However, the black‐box nature of DL makes it challenging to physically interpret mechanisms responsible for successful ENSO predictions. Here, we demonstrate an interpretable method by performing perturbation experiments to predictors and quantifying input‐output relationships in predictions by using a transformer‐based model; ENSO‐related thermal precursors serving as initial conditions during multi‐month time intervals (TIs) are identified in the equatorial‐northern Pacific, acting to precondition input predictors to provide for long‐lead ENSO predictability. Results reveal the existence of upper‐ocean temperature anomaly pathways and consistent phase propagations of thermal precursors around the tropical Pacific. It is illustrated that three‐dimensional thermal fields and their basinwide evolution during long TIs act to enhance long‐lead prediction skills of ENSO. These physically explainable results indicate that neural networks can adequately represent predictable precursors in the input predictors for successful ENSO predictions.

ABSTRACT Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) is a traditional non-culture technique that can provide a fingerprint of the microbial community. In the field of gut microbiota analysis, PCR-DGGE still holds potential for development. In the present study, we utilized an improved nested PCR-DGGE approach targeting the V3 region of 16S ribosomal DNA to investigate the impact of whole grain highland hull-less barley (WHLB), a cereal known for its significant hypocholesterolemic effect, on the gut microbiota profiles of high-fat diet rats. Seventy-two male Sprague–Dawley rats were divided into four groups and fed a normal control diet, a high-fat diet, or a high-fat diet supplemented with a low or high dose of WHLB for 4 or 8 weeks. The results revealed that the dominant bands varied among different dose groups and further changed with different treatment times. The compositions of bacterial communities in feces and cecal content were similar, but the dominant bacterial bands differed. After performing double DGGE, extracting the bands, sequencing the DNA, and aligning the sequences, a total of 19 bands were classified under the Firmicutes and Bacteroidetes phyla, while two bands were identified as unclassified uncultured bacteria. The relative abundance of Lactobacillus gasseri, Uncultured Prevotella sp., and Clostridium sp. increased following the administration of WHLB. Illumina-based sequencing was employed to assess the reliability of DGGE, demonstrating its reliability in analyzing the dominant taxonomic composition, although it may have limitations in accurately detecting the alpha diversity of bacterial species.IMPORTANCEWhile next-generation sequencing has overshadowed polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), the latter still holds promise for advancing gut microbiota analysis due to its unique advantages. In this study, we used optimized nested PCR-DGGE to investigate the gut microbiota profile of high-fat diet rats after administering whole grain highland hull-less barley. High-throughput sequencing was employed to validate the DGGE results. Our results proved the reliability of PCR-DGGE for analyzing the dominant taxonomic composition while also providing visual evidence of a notable relationship between the composition of cecal and fecal microbial communities, highlighting substantial differences in both richness and abundance.

The energy demand has increased significantly in recent years and it is urgent to develop a renewable energy system that is highly efficient and non-noble metal-based. Hydrogen energy is an environmentally friendly energy source with abundant resources, which can be used to solve the problem of high energy demand without greenhouse gas emissions. However, the development of catalysts for hydrogen production technology by electrolysis of water is slow, mainly due to the complexity of the electrolysis hydrogen generation process, low hydrogen production efficiency, weak electrode material activity and high cost. Among the non-noble metal-based catalysts, carbon-based materials have high conductivity, tunable chemical bonding, and easily modified morphology, making them beneficial to achieving efficient hydrogen production, though pure carbon composites suffer from few surface-active sites and unmoderated hydrogen bonding energy, which need to be further optimized. The principle of electrocatalytic hydrogen production from the perspectives of reaction thermodynamics and kinetics is analyzed and discussed in this paper. Thermodynamics of electrocatalytic hydrogen production is reflected by the Gibbs free energy of hydrogen adsorption (ΔGH*) and electrode potential (E). Reaction kinetics of the electrocatalytic hydrogen production process are reflected by overpotential, Tafel slope and exchange current density. Structural optimization methods of carbon-based composite materials and hydrogen production performance after structural optimization are also summarized. Structural optimization methods of carbon-based composite materials mainly include introducing active sites, improving conductivity, increasing specific surface area and introducing self-supporting materials. Finally, prospects are proposed for the development direction and existing problems of electrocatalytic hydrogen production performance of carbon-based composites.

The gene delivery systems (GDS) for lung cancer (LC) has made significant progress over the past 12 years, yet, there is a great challenge in its clinical application due to low delivery efficiency. This study aims to explore research fields related to gene therapy for LC and predict future directions from a bibliometric perspective. The Web of Science Core Collection collects articles and reviews on GDS for LC published from 2010 to 2022. Comprehensive bibliometric and visual analyses were performed using CiteSpace, VOSviewer, R-Bibliometrix, and Microsoft Excel. The analysis showed that the number of publications on GDS for LC has been increasing over the past 12 years, highlighting the growing interest and research efforts in this area. A rigorous examination of keywords and research hotspots revealed that the themes such as “complex,” “transfection,” “RNA interference,” “extracellular vesicle,” “co-deliver,” “resistance,” etc. dominate the field of GDS for LC. These findings indicated that the research in GDS for LC is evolving, with a noticeable shift toward addressing challenges related to delivery efficiency, transfection methods, and overcoming resistance mechanisms in gene therapy. The comprehensive study provides an overview of the literature on GDS for LC and identifies areas that require further exploration and development. By highlighting emerging research hotspots, our bibliometric analysis offers valuable insights to scholars and researchers, aiding in the identification of gaps, and guiding future efforts toward the development of GDS with more efficiency for LC therapy.

The incidence of chronic wound healing is promoted by the growing trend of elderly population, obesity, and type II diabetes. Although numerous wound dressings have been studied over the years, it is still challenging for many wound dressings to perfectly adapt to the healing process due to the dynamic and complicated wound microenvironment. Aiming at an optimal reproduction of the physiological environment, multifunctional electrospinning nanofibrous membranes (ENMs) have emerged as a promising platform for the wound treatment owing to their resemblance to extracellular matrix (ECM), adjustable preparation processes, porousness, and good conformability to the wound site. Moreover, profiting from the booming development of human-machine interaction and artificial intelligence, a next generation of intelligent electrospinning nanofibrous membranes (iENMs) based wound dressing substrates that could realize the real-time monitoring of wound proceeding and individual-based wound therapy has evoked a surge of interest. In this regard, general wound-related biomarkers and process are overviewed firstly and representative iENMs stimuli-responsive materials are briefly summarized. Subsequently, the emergent applications of iENMs for the wound healing are highlighted. Finally, the opportunities and challenges for the development of next-generation iENMs as well as translating iENMs into clinical practice are evaluated.

Aims: Doxorubicin is a powerful chemotherapeutic agent for cancer, whose use is limited due to its potential cardiotoxicity. Semaglutide (SEMA), a novel analog of glucagon-like peptide-1 (GLP-1), has received widespread attention for the treatment of diabetes. However, increasing evidence has highlighted its potential therapeutic benefits on cardiac function. Therefore, the objective of this study was to examine the efficacy of semaglutide in ameliorating doxorubicin-induced cardiotoxicity. Methods and results: Doxorubicin-induced cardiotoxicity is an established model to study cardiac function. Cardiac function was studied by transthoracic echocardiography and invasive hemodynamic monitoring. The results showed that semaglutide significantly ameliorated doxorubicin-induced cardiac dysfunction. RNA sequencing suggested that Bnip3 is the candidate gene that impaired the protective effect of semaglutide in doxorubicin-induced cardiotoxicity. To determine the role of BNIP3 on the effect of semaglutide in doxorubicin-induced cardiotoxicity, BNIP3 with adeno-associated virus serotype 9 (AAV9) expressing cardiac troponin T (cTnT) promoter was injected into tail vein of C57/BL6J mice to overexpress BNIP3, specifically in the heart. Overexpression of BNIP3 prevented the improvement in cardiac function caused by semaglutide. In vitro experiments showed that semaglutide, via PI3K/AKT pathway, reduced BNIP3 expression in the mitochondria, improving mitochondrial function. Conclusion: Semaglutide ameliorates doxorubicin-induced mitochondrial and cardiac dysfunction via PI3K/AKT pathway, by reducing BNIP3 expression in mitochondria. The improvement in mitochondrial function reduces doxorubicin-mediated cardiac injury and improves cardiac function. Therefore, semaglutide is a potential therapy to reduce doxorubicin-induced acute cardiotoxicity.

Background: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. Objectives: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. Methods: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. Results: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0–3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7–12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. Discussion: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Purpose PIWI-interacting RNAs (piRNAs) are a type of noncoding small RNA that can interact with PIWI-like RNA-mediated gene silencing (PIWIL) proteins to affect biological processes such as transposon silencing through epigenetic effects. Recent studies have found that piRNAs are widely dysregulated in tumors and associated with tumor progression and a poor prognosis. Therefore, this study aimed to investigate the effect of piR-1919609 on the proliferation, apoptosis, and drug resistance of ovarian cancer cells. Methods In this study, we used small RNA sequencing to screen and identify differentially expressed piRNAs in primary ovarian cancer, recurrent ovarian cancer, and normal ovaries. A large-scale verification study was performed to verify the expression of piR-1919609 in different types of ovarian tissue, including ovarian cancer tissue and normal ovaries, by RT–PCR and to analyze its association with the clinical prognosis of ovarian cancer. The expression of PIWILs in ovarian cancer was verified by RT–PCR, Western blotting and immunofluorescence. The effects of piR-1919609 on ovarian cancer cell proliferation, apoptosis and drug resistance were studied through in vitro and in vivo models. Results (1) piR-1919609 was highly expressed in platinum-resistant ovarian cancer tissues (p

Abstract Floods have affected billions worldwide. Yet, the indirect health impacts of floods on vulnerable groups, particularly women in the developing world, remain underexplored. Here, we evaluated the risk of pregnancy loss for women exposed to floods. We analyzed 90,465 individual pregnancy loss records from 33 developing countries, cross-referencing each with spatial-temporal flood databases. We found that gestational flood exposure is associated with increased pregnancy loss with an odds ratio of 1.08 (95% confidence interval: 1.04 - 1.11). This risk is pronounced for women outside the peak reproductive age range (35) or during the mid and late-stage of pregnancy. The risk escalated for women dependent on surface water, with lower income or education levels. We estimated that, over the 2010s, gestational flood events might be responsible for approximately 107,888 (CIs: 53,944 - 148,345) excess pregnancy losses annually across 33 developing countries. Notably, there is a consistent upward trend in annual excess pregnancy losses from 2010 to 2020, and was more prominent over Central America, the Caribbean, South America, and South Asia. Our findings underscore the disparities in maternal and child health aggravated by flood events in an evolving climate.

Abstract Purpose Benign skin lesions in zygomatic-infraorbital regions severely influence pediatric patients’ appearance as well as mental health. Treatments are difficult for the high requirements of patients’ guardians in both function and aesthetics. The present study aims to introduce a surgical method, Expanded Multi-Lobe Cervicofacial Flap, which combines the advantages of the classical cervicofacial advancement rotation flap and the tissue expansion technique. Methods A total of 21 pediatric patients were enrolled. The treatment process included 2 stages: implantation of the skin tissue expander and flap transfer. The excessive skin created by tissue expansion extended the coverage area of the multi-lobe flap. Results In this retrospective study, follow-up periods were all more than 12 months (20.8 ± 6.7). In the last follow-ups, the flaps were all in good condition, and No facial organ displacement was observed. The patients’ guardians were satisfied with the outcomes. Conclusions Using the expanded multi-lobe cervicofacial flap for the zygomatic-infraorbital benign skin lesion repair is effective, and this method is especially applicable to the pediatric population.

Emerging evidence suggested that zinc finger protein 831 (ZNF831) was associated with immune activity and stem cell regulation in breast cancer. Whereas, the roles and molecular mechanisms of ZNF831 in oncogenesis remain unclear. ZNF831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not mutation. Ectopic over-expression of ZNF831 suppressed breast cancer cell proliferation and colony formation and promoted apoptosis in vitro, while knockdown of ZNF831 resulted in an opposite phenotype. Anti-proliferation effect of ZNF831 was verified in vivo. Bioinformatic analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT pathway. ChIP and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of STAT3. As a result, the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic progression. Augmentation of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell lines. Furthermore, ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell lines. Our findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer, suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

Abstract Background Klebsiella pneumoniae is a pathogen that often infects patients in clinical practice. Due to its high virulent and drug resistance, infected patients are difficult to treat. In clinical practice, Klebsiella pneumoniae can infect patients' intestines, intestines, blood, etc., causing pathological changes. However, there is relatively little information on the impact of Klebsiella pneumoniae on intestinal inflammation and microbial populations. Zebrafish is an excellent biomedical model that has been successfully applied to the virulence assessment of Klebsiella pneumoniae. Methods In this study, three clinically isolated representative strains of Klebsiella pneumoniae (high virulence non-resistant, high virulence resistant, and low virulence resistant) were used to infect zebrafish, and their effects on intestinal colonization, inflammation, pathology, and microbial diversity were tested. Results Enzyme-linked immunoassay (ELISA) showed that Klebsiella pneumoniae significantly increased levels of the cytokines interleukin-1α (Il-1α), interleukin-1β (Il-1β), and tumor necrosis factor-α (Tnf-α), which increased inflammatory symptoms. Hematoxylin eosin staining(H&S) showed that Klebsiella pneumoniae treatment caused intestinal lesions in zebrafish, in which KP1053 exposure significantly decreased the number of goblet cells, KP1195 caused epithelial dissolution and exfoliation. In addition, Klebsiella pneumoniae disturbed the composition of intestinal microbiota, and the Shannon index increased, which increased the number of harmful bacteria. Conclusions Klebsiella pneumoniae infection can lead to intestinal colonization, inflammation, pathological changes, and changes in microbial biodiversity. This study provides a reference for the intestinal pathology of clinical Klebsiella pneumoniae infection.

Abstract Background Venous thromboembolism (VTE) remains a priority challenge among orthopedic trauma patients. It is crucial to further improve the prophylaxis against VTE in routine orthopedic treatment. This study aims to compare the efficacy of two low molecular weight heparin (LMWH) regimens and additional intermittent pneumatic compression in preventing VTE among orthopedic trauma patients. Methods and analysis This is a cluster-randomized crossover clinical study conducted in four hospitals in Shanghai from December 2019 to December 2023. The unit of randomization is orthopedic wards, and each ward will define a cluster. All clusters will implement four diverse intervention measures and one control measure in a given random sequence. Perioperative orthopedic trauma patients aged ≥ 18 years with stable vital signs, Caprini score > 2, and no contraindication of anticoagulation or intermittent pneumatic compression (IPC) devices will be eligible. The sample size will be determined to be 2590, considering cluster effect, period effect, and interactions. We will generally use the intention-to-treat (ITT) at the subject level for each outcome. For the primary outcome of the study, the incidence of VTE will be presented as risk ratio and 95% CIs. Generalized estimating equation (GEE) will be deployed to compare differences and adjust cluster effect, period effect, and interaction among interventions and periods if applicable. Discussion VTE is a complication that cannot be underestimated after major orthopedic surgery. Early identification, early assessment, and early prevention can significantly reduce the incidence of VTE. Most guidelines recommend both medical and physical prevention, and we hope to demonstrate how they would affect the incidence among perioperative orthopedic patients. We want to explore if there is a difference between the two types of LWMH with or without an IPC device to provide more evidence for future guidelines and prevent more patients from the threat of VTE. Ethics and dissemination The study received approval from the IRB of the coordinating center and all participating hospitals. Findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration ChiCTR1900027659. Registered on 17 November 2019

Abstract Previous studies have reported significant decreases in the incidence of mental health problems following SARS-CoV-2 vaccination. However, less relevant studies are published in China. We conducted a cross-sectional study involving Chinese adults aged 18–75 years with no known psychiatric diseases. The study used data from mental health of SARS-CoV-2 vaccinated and unvaccinated participants from May 2020 to July 2021.Three standardized scales, namely, the Generalized Anxiety Disorder-7 (GAD-7) for anxious symptoms, Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms and Athens Insomnia Score-8 (AIS-8) for insomnia symptoms, as well as basic demographic questions were used. The hierarchical regression method was used for multivariate logistic regression analysis to explore the effects of SARS-CoV-2 vaccination on anxious, insomnia, and depressive symptoms. The results confirmed first that vaccinated participants experienced significantly lower anxious, insomnia, and depressive symptoms scores (P

Abstract Background Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease characterized by clinical and pathological diversity. Mitochondrial dysfunction has been identified as a critical pathogenetic factor in SLE. However, the specific molecular aspects and regulatory roles of this dysfunction in SLE are not fully understood. Our study aims to explore the molecular characteristics of mitochondria-related genes (MRGs) in SLE, with a focus on identifying reliable biomarkers for classification and therapeutic purposes. Methods We sourced six SLE-related microarray datasets (GSE61635, GSE50772, GSE30153, GSE99967, GSE81622, and GSE49454) from the Gene Expression Omnibus (GEO) database. Three of these datasets (GSE61635, GSE50772, GSE30153) were integrated into a training set for differential analysis. The intersection of differentially expressed genes with MRGs yielded a set of differentially expressed MRGs (DE-MRGs). We employed machine learning algorithms—random forest (RF), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) logistic regression—to select key hub genes. These genes’ classifying potential was validated in the training set and three other validation sets (GSE99967, GSE81622, and GSE49454). Further analyses included differential expression, co-expression, protein-protein interaction (PPI), gene set enrichment analysis (GSEA), and immune infiltration, centered on these hub genes. We also constructed TF-mRNA, miRNA-mRNA, and drug-target networks based on these hub genes using the ChEA3, miRcode, and PubChem databases. Results Our investigation identified 761 differentially expressed genes (DEGs), mainly related to viral infection, inflammatory, and immune-related signaling pathways. The interaction between these DEGs and MRGs led to the identification of 27 distinct DE-MRGs. Key among these were FAM210B, MSRB2, LYRM7, IFI27, and SCO2, designated as hub genes through machine learning analysis. Their significant role in SLE classification was confirmed in both the training and validation sets. Additional analyses included differential expression, co-expression, PPI, GSEA, immune infiltration, and the construction of TF-mRNA, miRNA-mRNA, and drug-target networks. Conclusions This research represents a novel exploration into the MRGs of SLE, identifying FAM210B, MSRB2, LYRM7, IFI27, and SCO2 as significant candidates for classifying and therapeutic targeting.

Abstract Background Influenza A virus (IAV) is the only influenza virus causing flu pandemics (i.e., global epidemics of flu disease). Influenza (the flu) is a highly contagious disease that can be deadly, especially in high-risk groups. Worldwide, these annual epidemics are estimated to result in about 3 to 5 million cases of severe illness and in about 290,000 to 650,000 respiratory deaths. We intend to reveal the effect of IAV infection on the host′s metabolism, immune response, and neurotoxicity by using a mouse IAV infection model. Methods 51 metabolites of murine blood plasma (33 amino acids/amino acid derivatives (AADs) and 18 metabolites of the tryptophan pathway) were analyzed by using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry with Electrospray Ionization at the acute (7 days post-infection (dpi)), resolution (14 dpi), and recovery (21 dpi) stages of the virus infection in comparison with controls. Results Among the 33 biogenic amino acids/AADs, the levels of five amino acids/AADs (1-methylhistidine, 5-oxoproline, α-aminobutyric acid, glutamine, and taurine) increased by 7 dpi, whereas the levels of ten amino acids/AADs (4-hydroxyproline, alanine, arginine, asparagine, cysteine, citrulline, glycine, methionine, proline, and tyrosine) decreased. By 14 dpi, the levels of one AAD (3-methylhistidine) increased, whereas the levels of five amino acids/AADs (α-aminobutyric acid, aminoadipic acid, methionine, threonine, valine) decreased. Among the 18 metabolites from the tryptophan pathway, the levels of kynurenine, quinolinic acid, hydroxykynurenine increased by 7 dpi, whereas the levels of indole-3-acetic acid and nicotinamide riboside decreased. Conclusions Our data may facilitate understanding the molecular mechanisms of host responses to IAV infection and provide a basis for discovering potential new mechanistic, diagnostic, and prognostic biomarkers and therapeutic targets for IAV infection.

Abstract Cutaneous melanoma is one of the most malignant types of skin cancer, with an extremely poor prognosis. Immune cells infiltrated in the tumor microenvironment (TME) affects melanoma initiation, progression, prognosis and immunotherapy strategies in melanoma. The potential utility of TME-related genes as a prognostic model for melanoma and as a predictor of immunotherapeutic response merits further exploration. In this study, we determined that an immune-related gene, protein tyrosine phosphatase receptor type C (PTPRC), was positively correlated with the positive prognosis of melanoma patients. Integration of this gene with TNM classification created a predictive model that showed better performance in determining overall survival than others. PTPRC expression was positively correlated with the levels of immune checkpoint molecules, and PTPRC knockdown significantly enhanced the migration, invasion, and proliferation of melanoma cells. Finally, immunohistochemical results from HPA and Real-time quantitative PCR of clinical tissues confirmed that PTPRC expression was higher in melanoma than in normal skin. In conclusion, PTPRC served as a potential predictor of survival and response to immunotherapy in melanoma patients. The risk model combining the PTPRC and TNM classifications holds the potential to be a promising tool for prognostic prediction of cutaneous melanoma. This will help in the effective clinical management of melanoma patients.

Autophagy is a cellular process in which proteins and organelles are engulfed in autophagosomal vesicles and transported to the lysosome/vacuole for degradation. Protein–protein interactions (PPIs) play a crucial role at many stages of autophagy, which present formidable but attainable targets for autophagy regulation. Moreover, selective regulation of PPIs tends to have a lower risk in causing undesired off-target effects in the context of a complicated biological network. Thus, small-molecule regulators, including peptides and peptidomimetics, targeting the critical PPIs involved in autophagy provide a new opportunity for innovative drug discovery. This article provides general background knowledge of the critical PPIs involved in autophagy and reviews a range of successful attempts on discovering regulators targeting those PPIs. Successful strategies and existing limitations in this field are also discussed.

The changing climate poses a growing challenge to the population health. The objective of this study was to assess the association between ambient temperature and cause-specific mortality in Suzhou. Based on the non-accidental mortality data collected during 2008–2022 in Suzhou, China, this study utilized an individual-level case-crossover design to evaluate the associations of temperature with cause-specific mortality. We applied a distributed lag nonlinear model with a maximum lag of 14 days to account for lag effects. Mortality risk due to extreme cold (97.5th percentile) was analyzed. A total of 634,530 non-accidental deaths were analyzed in this study. An inverse J-shaped exposure-response relationship was observed between ambient temperature and non-accidental mortality, with the minimum mortality temperature (MMT) at 29.1℃. The relative risk (RR) of mortality associated with extreme cold (2.5th percentile) was 1.37 [95 % confidence interval (CI): 1.30, 1.44], higher than estimate of 1.09 (95 %CI: 1.07, 1.11) for extreme heat (97.5th percentile) relative to the MMT. Heat effect lasted for 2–3 days, while cold effect could persist for almost 14 days. Higher mortality risk estimates were observed for cardiorespiratory deaths compared to total deaths, with statistically significant between-group differences. Consequently, this study provides first-hand evidence on the associations between ambient temperatures and mortality risks from various causes, which could help local government and policy-makers in designing targeted strategies and public health measures against the menace of climate change.

Previous studies on the co-evolving between vaccination strategies and epidemics mainly assumed that the vaccination strategies were made in the period between two spreading seasons. However, individual cognition during the spreading seasons might also alter the vaccination strategy and inversely influence the epidemic spreading. We propose a coupled disease–behavior model to describe the dynamic evolution of vaccination behavior during the spread of infectious diseases. The model integrates a susceptible–infected–vaccinated (SIV) model with the diffusion of vaccination behavior. We focus on the trade-off between perceptions of infection risk and the vaccination behaviors of neighbors, characterizing individual vaccination opinions. We introduce an opinion-critical value to map vaccination opinions into vaccination behavior. The vaccination coverage of the disease–behavior model is studied in network models and real-world networks. In addition, when societal costs are measured based on the degree of initial vaccinees, the cost of randomly selecting initial vaccinees is lower than selecting individuals with high or low degrees as vaccinees. Evaluating an individual’s ability to transmit vaccination behavior based on the neighbor’s number is inappropriate. We find that the impact of effective spreading rates on group vaccination is not one-sided and that reducing fear and highlighting the dangers of infectious diseases are crucial to increasing vaccination coverage.

Determining the timing of fracturing is crucial for understanding reservoir evolution and hydrocarbon accumulation in foreland basins. Using fracturing data from cores, borehole images, and outcrops, combined with the clumped isotope (Δ47) and fluid inclusion analyses of carbonate minerals filled in pores and fractures, this study ascertained the fracturing timing of the Jurassic reservoirs in the Dibei-Tuziluoke Gas Field, Kuqa Foreland Basin. Data from outcrops and borehole images show two dominant fracture sets in the study area: W-E and NE-SW striking fractures. Some W-E striking fractures are carbonate-filled, while NE-SW striking fractures lack mineral fillings. Bitumen veins, not easy to be identified in borehole images, are prevalent in cores. The petrographic analysis reveals that these bitumen veins formed before the calcite cementation in pores and display high viscosity and low maturity. Homogenization temperatures (Th) from primary fluid inclusion assemblages in two representative calcite vein samples were notably lower than TΔ47 values from corresponding samples. This suggests the Δ47 signature underwent alteration due to partial reordering during burial. Thus, Δ47-derived temperatures (apparent temperatures) may not faithfully represent the mineral precipitation temperatures. When plotting these apparent temperatures vs. the burial history, only the possible latest ages of fracturing emerged. These ages were further refined by considering petroleum charging, tectonic evolution, and stress orientation. Bitumen-filled fractures likely resulted from the Late Cretaceous uplift, marking the migration of low-maturity hydrocarbons in the study area. Carbonate-filled E-W striking fractures emerged during the late Miocene (∼13–6.5 Ma) alongside fold development. NE-striking fractures that crosscut W-E ones possibly formed recently due to stress reorientation.

Background and aimGallstone disease (GSD) is a major public health problem worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) have been used to describe dietary inflammatory potential. The current study sought to investigate the pro-inflammatory role of diet on GSD among outpatients in the United States.MethodsCross-sectional data from 7,334 individuals older than 20 years who participated in the National Health and Nutrition Examination Survey (NHANES) from January 2017 to March 2020 were obtained. The relationship between GSD and DII was assessed using self-reported data. An association between DII and the risk of GSD was determined using sample-weighted logistic regression and restricted cubic splines (RCS). Subgroup analyzes were conducted to assess the interaction between DII and related factors. Sensitivity analysis was further used to confirm the stability of the relationship. To control for the effect of total energy intake, E-DII was calculated and analyzed.ResultsA total of 10.5% of the study participants had GSD. The DII ranged from −5.52 to 5.51, and the median DII was significantly higher for participants with GSD than those without (1.68 vs. 1.23, p

Lipopeptides (LPs) produced by Pseudomonas spp. are specialized metabolites with diverse structures and functions, including powerful biosurfactant and antimicrobial properties. Despite their enormous potential in environmental and industrial biotechnology, low yield and high production cost limit their practical use. While genome mining and functional genomics have identified a multitude of LP biosynthetic gene clusters, the regulatory mechanisms underlying their biosynthesis remain poorly understood. We propose that regulation holds the key to unlocking LP production in Pseudomonas for biotechnology. In this review, we summarize the structure and function of Pseudomonas-derived LPs and describe the molecular basis for their biosynthesis and regulation. We examine the global and specific regulator-driven mechanisms controlling LP synthesis including the influence of environmental signals. Understanding LP regulation is key to modulating production of these valuable compounds, both quantitatively and qualitatively, for industrial and environmental biotechnology.

Abstract As a new type of secondary ion battery, aqueous zinc‐ion battery has a broad application prospect in the field of large‐scale energy storage due to its characteristics of low cost, high safety, environmental friendliness, and high‐power density. In recent years, manganese dioxide (MnO2)‐based materials have been extensively explored as cathodes for Zn‐ion batteries. Based on the research experiences of our group in the field of aqueous zinc ion batteries and combining with the latest literature of system, we systematically summarize the research progress of Zn−MnO2 batteries. This article first reviews the current research progress and reaction mechanism of Zn−MnO2 batteries, and then respectively expounds the optimization of MnO2 cathode, Zn anodes, and diverse electrolytes and their effects on battery performance. Additionally, primary challenges related to different components and their respective strategies for mitigating them are discussed, with the ultimate objective of offering comprehensive guidance for the design and fabrication of high‐performance Zn−MnO2 batteries. Finally, the future research and development direction of aqueous Zn−MnO2 batteries with high energy density, high safety and long life is envisioned.

Autoimmune hepatitis (AIH) is a progressive liver disease mediated by the immune system that involves an imbalance in pro-inflammatory and regulatory mechanisms including regulatory T cells (Tregs), T helper 17 (Th17) cells, Th1, macrophages, and many other immune cells. Current steroid therapy for AIH has significant systemic side effects and is poorly tolerated by some individuals. Therefore, there is an urgent need for alternative treatments. Maintaining homeostasis in macrophage differentiation and activation is crucial for regulating immune responses in hepatitis. In this study, we loaded small interfering RNA (siRNA) targeting receptor-interacting protein kinase 3 (RIPK3) into M2-type macrophage-derived exosomes (M2 Exos) to create functionalized exosomes called M2 Exos/siRIPK3. These exosomes demonstrated a natural ability to target the liver in mice, as they were efficiently taken up by hepatic macrophages and showed significant and stable accumulation. M2 Exos/siRIPK3 effectively mitigated immune-mediated hepatitis by suppressing the expression of RIPK3, resulting in a reduced release of pro-inflammatory cytokines and chemokines in both liver tissues and serum. Additionally, M2 Exos/siRIPK3 exhibited immunomodulatory effects, as its administration resulted in a decreased proportion of hepatic and splenic Th17 cells, along with an increased ratio of Tregs. Overall, this study suggests that loading small molecule drugs onto M2 Exos could be a promising approach for developing immunomodulators that specifically target liver macrophages to treat AIH. This strategy has the potential to provide a safer and more effective alternative to current therapy for AIH patients.

Abstract Background Children with congenital heart disease (CHD) are easily complicated by severe pneumonia and heart failure. We aimed to conduct a meta-analysis to evaluate the effects and safety of milrinone for the treatment of heart failure caused by severe pneumonia in children with CHD to provide evidence for the clinical CHD treatment. Methods Two authors searched MEDLINE, PubMed, Embase, Science Direct, Cochrane Central Register of Controlled Trials, the Cochrane Library, Wanfang database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI) for randomized controlled trials (RCTs) about the application of milrinone in the treatment of heart failure caused by severe pneumonia in children with CHD in children up to December 10, 2022. Two evaluators independently selected the literature, extracted data and evaluated the methodological quality, meta-analysis was carried out with RevMan 5.3 software. Results Eight RCTs involving 680 CHD children complicated by severe pneumonia and heart failure were included in this meta-analysis. Meta-analysis indicated that total effective rate of the milrinone group was higher than that of control group (RR = 1.25, 95%CI: 1.17 ~ 1.34, P 0.05). Conclusions Milrinone is beneficial to improve clinical symptoms and cardiac function and increase the therapeutic effect and safety in children with CHD complicated by severe pneumonia and heart failure. However, more RCTs with large samples and rigorous design are needed to verify this finding.

Abstract Background Chlamydia psittaci (C. psittaci) causes parrot fever in humans. Development of metagenomic next-generation sequencing (mNGS) enables the identification of C. psittaci. Methods This study aimed to determine the epidemiological and clinical characteristics of parrot fever cases in China. A multi-center observational study was conducted in 44 tertiary and secondary hospitals across 14 provinces and municipalities between April 2019 and October 2021. Results A total of 4545 patients with complicated or atypical pulmonary infection were included in the study, among which the prevalence of C. psittaci was determined to be 2.1% using mNGS. The prevalence of C. psittaci was further determined across demographic groups and types of specimens. It was significantly higher in patients with senior age (2.6% in those > 50 years), winter-spring (3.6%; particularly in December, January, and February), and southwestern (3.4%) and central and southern China (2.7%) (each P 0.05). Conclusion Parrot fever remains low in patients with complicated or atypical pulmonary infection. It is likely to occur in winter-spring and southwestern region in China. BALF may be the optimal specimen in the application of mNGS. Co-infection of multiple microorganisms should be further considered.

Abstract Aim To identify the measures assessing the nursing image, and to analyse, evaluate and synthesize the psychometric properties of these available instruments. Design A systematic review of the psychometric properties of instruments assessing the nursing image. The system review has been registered in the PROSPERO database with the registration number CRD42020221511. Methods The systematic review was conducted according to COSMIN guidelines. Search strategies were run in CINAHL, MEDLINE, APA PsycINFO, Web of Science, Scopus, COSMIN systematic review database, Cochrane Library and China National Knowledge Infrastructure (CNKI). Two reviewers independently screened the studies, extracting the psychometric properties of the included study characteristics and instruments. The methodological quality of the studies, instrument measurement performance, risk of bias and grade of evidence were evaluated and disagreements were resolved via discussion. Results The search strategy yielded a total of 24 studies and 11 instruments assessing nursing image. None of the measures fulfilled all criteria in the COSMIN Risk of Bias checklist. The Nurses Self‐Concept Instrument (NSCI) and the Nurses Self‐Concept Questionnaire (NSCQ) were recommended for measuring the professional image of nursing, and the Nursing Brand Image Scale (NBIS) have the potential to be recommended for measuring a more comprehensive image of nursing. Every instrument evaluated in this review had different characteristics in the nursing image (e.g. the traditional image, the professional image, and the brand image). Therefore, the selection of the most appropriate instrument depends on the psychometrics, the context and the aim of the assessment.

Crytosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are important diarrheal pathogens with a global distribution that threatens the health of humans and animals. Despite cattle being potential transmission hosts of these protozoans, the associated risks to public health have been neglected. In the present study, a total of 1155 cattle fecal samples were collected from 13 administrative regions of Heilongjiang Province. The prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 5.5% (64/1155; 95% CI: 4.2–6.9), 3.8% (44/1155; 95% CI: 2.7–4.9), and 6.5% (75/1155; 95% CI: 5.1–7.9), respectively. Among these positive fecal samples, five Cryptosporidium species (C. andersoni, C. bovis, C. ryanae, C. parvum, and C. occultus), two G. duodenalis assemblages (E and A), and eight E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, CHS7, CHS8, and COS-I) were identified. Phylogenetic analysis showed that all eight genotypes of E. bieneusi identified in the present study belonged to group 2. It is worth noting that some species/genotypes of these intestinal protozoans are zoonotic, suggesting a risk of zoonotic disease transmission in endemic areas. The findings expanded our understanding of the genetic composition and zoonotic potential of Cryptosporidium spp., G. duodenalis, and E. bieneusi in cattle in Heilongjiang Province.

Background & Aims: Association studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients. Methods: We performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls. Results: A total of 588 HLA variants were significantly associated with AIH, with HLA-B∗35:01 (p = 8.17 × 10−304; odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B∗08:01 (p = 1.35 × 10−33; OR = 4.26) and rs7765379 (p = 5.08 × 10−18; OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B∗35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels. Conclusions: Our study reveals three novel and independent variants at HLA-B∗35:01, HLA-B∗08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH. Impact and implications: This study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.

ABSTRACT Picocyanobacteria can synthesize a distinctive class of lanthipeptides referred to as prochlorosins. They are classified within the Nif11 family and are subject to post-translational modifications by a solitary promiscuous enzyme from the ProcM group. Their biological function is unknown but highly speculated upon. In this study, we conducted a comprehensive genome mining investigation of the Synechococcus and Prochlorococcus genomes to elucidate the genomic landscape associated with the biosynthetic gene clusters (BGCs) harboring prochlorosin genes. Our mining study led to a substantial expansion of the known prochlorosin repertoire identified in 15 picocyanobacterial genomes. We also identified a range of tailoring enzymes and gene families proximal to the procA/syncA genes. The recombination-related proteins we detected were of particular interest, as they may have a critical role in generating the diversity observed within this peptide family. Interestingly, we identified novel LAP/YcaO BGCs in Synechococcus that had not been previously described. These BGCs hold the potential to generate prochlorosins with secondary modifications and introduce new putative azol(in)e-containing ribosomally synthesized and post-translationally modified peptides precursors. Our investigation offers an in-depth analysis of the vast prochlorosin family. IMPORTANCE Genome mining studies have revealed the remarkable combinatorial diversity of ribosomally synthesized and post-translationally modified peptides (RiPPs) in marine bacteria, including prochlorosins. However, mining strategies also prove valuable in investigating the genomic landscape of associated genes within biosynthetic gene cluster (BGC) specific to targeted RiPPs of interest. Our study contributes to the enrichment of knowledge regarding prochlorosin diversity. It offers insights into potential mechanisms involved in their biosynthesis and modification, such as hyper-modification, which may give rise to active lantibiotics. Additionally, our study uncovers putative novel promiscuous post-translational enzymes, thereby expanding the chemical space explored within the Synechococcus genus. Moreover, this research extends the applications of mining techniques beyond the discovery of new RiPP-like clusters, allowing for a deeper understanding of genomics and diversity. Furthermore, it holds the potential to reveal previously unknown functions within the intriguing RiPP families, particularly in the case of prochlorosins.

BackgroundRadiomics have been increasingly used in the clinical management of hepatocellular carcinoma (HCC), such as markers prediction. Ki-67 and cytokeratin 19 (CK-19) are important prognostic markers of HCC. Radiomics has been introduced by many researchers in the prediction of these markers expression, but its diagnostic value remains controversial. Therefore, this review aims to assess the diagnostic value of radiomics in predicting Ki-67 and CK-19 expression in HCC.MethodsOriginal studies were systematically searched in PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 2023. All included studies were evaluated by the radiomics quality score. The C-index was used as the effect size of the performance of radiomics in predicting Ki-67and CK-19 expression, and the positive cutoff values of Ki-67 label index (LI) were determined by subgroup analysis and meta-regression.ResultsWe identified 34 eligible studies for Ki-67 (18 studies) and CK-19 (16 studies). The most common radiomics source was magnetic resonance imaging (MRI; 25/34). The pooled C-index of MRI-based models in predicting Ki-67 was 0.89 (95% CI:0.86–0.92) in the training set, and 0.87 (95% CI: 0.82–0.92) in the validation set. The pooled C-index of MRI-based models in predicting CK-19 was 0.86 (95% CI:0.81–0.90) in the training set, and 0.79 (95% CI: 0.73–0.84) in the validation set. Subgroup analysis suggested Ki-67 LI cutoff was a significant source of heterogeneity (I2 = 0.0% P>0.05), and meta-regression showed that the C-index increased as Ki-67 LI increased.ConclusionRadiomics shows promising diagnostic value in predicting positive Ki-67 or CK-19 expression. But lacks standardized guidelines, which makes the model and variables selection dependent on researcher experience, leading to study heterogeneity. Therefore, standardized guidelines are warranted for future research.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023427953.

IntroductionThe under representation of women in STEM fields is a persistent issue worldwide. In China, although women have made significant progress in pursuing STEM degrees in recent years, they continue to face challenges in the workforce. Given the importance of the self-perceived employability (SPE) of female STEM students in China, the research questions are: How do curriculum experience, extracurricular experience, and faculty supportive activities affect the SPE of female STEM students in Chinese universities? To what extent does university stratification affect the relationship between college experience and female STEM students’ SPE?MethodsWe analyzed the 2018 data of the Chinese College Student Survey (CCSS) consisting of a sample of 59,066 students, and six focus group interviews.ResultsThe findings suggest that curriculum experience, extracurricular experience and faculty supportive activities have a positive impact on the SPE of female students, but the gender gap in SPE is still valid as reflected by the fact that women have lower SPE than men in each tier of universities and that men benefit more in terms of the increase in SPE from most types of college activities and support except academic ones.DiscussionThis study reveals that the different tiers of universities in China affect female students’ SPE in different ways, and provides valuable evidence for academic as well as university administrators and policymakers regarding how college experience affect women and how university stratification can affect female students’ college experience and their career expectations and paths.

ABSTRACTObjectives POEMS syndrome is a rare disorder which has been increasingly recognized. The clonal origin is controversial. Some people argue that POEMS syndrome originates from abnormal plasma cell clones. So, treatment frequently targets the plasma cell clone. Nevertheless, others believe that both plasma cells and B cells can be the potential culprit in POEMS syndrome.Methods A 65-year-old male came to the emergency department of our hospital with the complaints of bilateral soles numbness and weight loss for half a year, abdominal distension for half a month, and chest tightness and shortness of breath for one day. He was then diagnosed as POEMS syndrome complicated with monoclonal B-cell lymphocytosis (non-CLL type). A standard bendamustine plus rituximab (BR) regimen combined with low dose of lenalidomide was administered.Results After four cycles of treatment, the ascites of the patient was absent and the neurological symptom disappeared. The renal function, the IgA level, and the VEGF level all returned to normal.Discussion POEMS syndrome, a multi-system disorder, is easily misdiagnosed. The clonal origin of POEMS syndrome is controversial and needs further study. For now, there are no approved treatment regimens. Treatments mainly target the plasma cell clone. This case suggested that other therapy besides anti-plasma cell treatment may also be effective in POEMS syndrome.Conclusion We report a patient with POEMS syndrome who achieved complete response after treatment with the combination of a standard BR regimen and low dose of lenalidomide. POEMS syndrome's pathological mechanisms and therapies warrant further studies.

ABSTRACTHow much the vaccine contributes to the induction and development of neutralizing antibodies (NAbs) of breakthrough cases relative to those unvaccinated-infected cases is not fully understood. We conducted a prospective cohort study and collected serum samples from 576 individuals who were diagnosed with SARS-CoV-2 Delta strain infection, including 245 breakthrough cases and 331 unvaccinated-infected cases. NAbs were analysed by live virus microneutralization test and transformation of NAb titre. NAbs titres against SARS-CoV-2 ancestral and Delta variant in breakthrough cases were 7.8-fold and 4.0-fold higher than in unvaccinated-infected cases, respectively. NAbs titres in breakthrough cases peaked at the second week after onset/infection. However, the NAbs titres in the unvaccinated-infected cases reached their highest levels during the third week. Compared to those with higher levels of NAbs, those with lower levels of NAbs had no difference in viral clearance duration time (P>0.05), did exhibit higher viral load at the beginning of infection/maximum viral load of infection. NAb levels were statistically higher in the moderate cases than in the mild cases (P

Abstract Background Psychological well-being (PWB) plays a vital role in successful adaptation to the Bachelor of Nursing journey and affects career development. However, there is little known about the functional and social processes associated with enhancing well-being specific to the subjective perspective of nursing students. Aim To investigate how nursing students promote their psychological well-being to conceptualize thriving psychological well-being. Method This qualitative study analyzed and reviewed a life grid and semi-structured in-depth interviews of 20 Chinese Nursing graduates by investigators and participants, following Charmaz's constructivist grounded theory. The constant comparative method was used to analyze data. This study took place between 2020 and 2022. Results All participants experienced fluctuations in psychological well-being. This study identified a new understanding of how nursing students enhance their psychological well-being. Thriving awareness was co-constructed as the core category and based on the relationship with a supportive environment, the thriving psychological well-being of nursing students is conceptualized. Conclusions It is imperative to enhance the psychological counseling and support for nursing students during their clinical placements, during the period just entering university as well as after repeated outbreaks of COVID-19. Nursing educators and administrators could develop appropriate educational programs and interventions based on the theoretical model—Thriving psychological well-being.

Objective To investigate the effect of isoprene cysteine carboxymethyltransferase (ICMT) gene on the migration and invasion of salivary adenoid cystic cancer cells (SACC) and the related mechanism, to provide experimental evidence for molecular targeted therapy of SACC. Methods Adenoid cystic cancer cells SACC-LM and SACC-83 were cultured in vitro, and siRNA was transfected into human SACC-LM and SACC-83 cells (experimental group) by transient transfection of a liposome vector. A blank control group and negative control group were set up respectively (transfected NC-siRNA). qRT-PCR was peformed to measure the mRNA expression of ICMT and RhoA in each group after transfection and to determine the silencing efficiency. The expression of ICMT, membrane RhoA, total RhoA, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and Rho associated with coiled helical binding protein kinase 1 (ROCK1) in each group was detected by Western blot. The proliferation abilityies of SACC cells was detected by CCK-8 assay. The migration and invasion ability of SACC cells were detected by comparing the relative healing area of cell scratch assay and the number of Transwell assay cells. Results After transfection of ICMT-siRNA into SACC-LM and SACC-83 cells, the expression of ICMT gene and protein in the experimental group was significantly decreased compared with the negative control group and blank control group (P0.05). The expression of RhoA membrane proteins, ROCK1, MMP-2, MMP-9 in the experimental group was significantly decreased compared with that in the negative control group and blank control group (P