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With thermoplastic polyurethane (TPU) limit spring extruder head as the research object, the relevant material parameters of the constitutive equation of raw TPU were obtained by the rheological property test. Numerical simulation of the flow process of TPU in the extrusion runner was carried out based on the software Polyflow, and in the meanwhile, a second-order regression model of standard deviation of velocity (Sd) at the exit of the forming section was established by response surface method, and the influence law of extrusion runner structure on the melt flow uniformity of TPU was explored. The results showed that after optimization the structure parameters of extrusion runner were as follows: the length of the forming section of 165 mm, the expansion angle of 25°, and the number of diverter shuttles of 6. After optimization the predicted value of Sd at the exit of the forming section of extrusion runner was 0.531 m/s and was only 0.188% different from the actual value of Sd(0.532 m/s), which indicated that the model was more accurate, and the model could be used for the prediction and optimization of the structure parameters of extrusion runner.

Genetic algorithm (GA) and particle swarm optimization (PSO) were used to optimize the back propagation（BP） neural network to establish the prediction model of Mooney viscosity of ethylene-propylene-diene monomer (EPDM) compound, and the error of the prediction results was compared and analyzed. The results showed that the predicted va-lues of the BP neural network model optimized by the two algorithms all maintained a high degree of fit and correlation with the measured values. Compared with the single BP neural network, the accuracy of the GA-BP neural network prediction model increased by 58.9% and the accuracy of the PSO-BP model increased by 3.57%, which indicated that the prediction accuracy of the prediction model optimized by the two algorithms, especially the BP neural network prediction model optimized by GA, improved significantly Mooney viscosity of EPDM compound.

This study aimed to investigate the bactericidal effect and dynamics of slightly acidic electrolyzed water (SAEW) combined with ultrasonic (US) treatment on Escherichia coli on fresh-cut lettuce. Fresh-cut lettuce was treated with SAEW-US under different conditions of solid/liquid ratio (1:5, 1:10 and 1:15 (g/mL)) and temperature (25, 35 and 45 ℃). The colony number of E. coli on lettuce was determined by the plate counting method, and the synergistic effect of combined treatment with SAEW and US on reducing the colony number of E. coli was determined and kinetically analyzed. The sublethal damage of SAEW-US treated E. coli was detected by flow cytometry and the double-layer culture counting method. The results showed that the efficacy of SAEW-US treatment in killing E. coli was significantly better than that of SAEW treatment (p < 0.05), and increased with treatment time, solid/liquid ratio and temperature. SAEW-US treatment had a synergistic effect on killing E. coli, and the sterilization process followed a first-order kinetic model. Moreover, SAEW-US treatment reduced the rate of sublethal damage of E. coli. The results of this study will provide a theoretical basis for the sterilization of fresh agricultural products.

Abstract Background The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it’s necessary to clearly understand how S. cerevisiae cells respond to SA. Results In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA. Conclusions The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains’ potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains.

Background Urinary incontinence often occurs in women aged 40-60 years and contributes to a significant impact on women's physical health and quality of life. Objective To explore the prevalence and influencing factors of urinary incontinence and its impact on quality of life in women aged 40-60 years in Guizhou Province. Methods From June 2022 to January 2023, women aged 40-60 years who underwent health checkups in 10 hospitals in 7 regions of Guizhou Province were selected as the study subjects. A self-designed general data questionnaire was used to collect the basic data of the study subjects, and International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Incontinence Quality of Life Measure (I-QoL) were used to determine the severity of urinary incontinence and the level of quality of life of the study subjects, respectively. Different types of incontinence, including stress incontinence, urge incontinence, and mixed incontinence, were determined according to the diagnostic criteria established by the International Continence Society (ICS). Multivariate Logistic regression analysis was used to explore the influencing factors of urinary incontinence, and explore the effects of different types and severity levels of urinary incontinence on patients' quality of life. Results A total of 3 000 questionnaires were distributed, and 2 966 valid questionnaires were collected, with a valid recovery rate of 98.9%. The prevalence of urinary incontinence among the 2 966 study subjects was 33.4% (991/2 966), including 20.1% (596/2 966) for stress incontinence, 2.0% (58/2 966) for urge incontinence, and 11.4% (337/2 966) for mixed incontinence. Multivariate Logistic regression analysis showed that physical exercise, menstrual status, parity, history of pelvic organ prolapse, perineal laceration, and lateral episiotomy were the influencing factors of stress incontinence (P

Abstract Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor‐specific CD8+ T cells and their recruitment to tumor microenvironment. However, cDC1s are often underrepresented in the microenvironment. Systemic administration of Fms‐like tyrosine kinase 3 ligand, a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to cDC1 expansion in the periphery and recruitment into the microenvironment. FLT3 pathway stimulation using GS‐3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T‐cell mediated antitumor activity. This was a first‐in‐human, placebo‐controlled study of GS‐3583 in healthy participants to evaluate the safety, pharmacokinetics (PK), and pharmacodynamic (PD) of escalating single doses (75–2000 μg) of GS‐3583. Each dose cohort enrolled 8–12 healthy participants who received GS‐3583 or placebo as single IV infusion at 3:1 ratio. As part of the PD evaluation, the changes in the number of cDC1 cells were investigated. GS‐3583 was well‐tolerated in healthy participants up to the highest evaluated dose (2000 μg). There have been no serious or grade III or higher adverse events. PK analysis suggested a dose‐dependent increase in GS‐3583 exposure with target‐mediated disposition characteristics at low doses. PD analysis shows that administration of GS‐3583 resulted in transient, dose‐dependent increases in cDC1 cells that returned to baseline within 3 weeks of drug administration. The pharmacokinetics and pharmacodynamics of GS‐3583 following single dosing were characterized in this study which enabled subsequent phase Ib assessments in patients with advanced solid tumors.

Abstract Background To analyze the etiological distribution characteristics of drug-resistant epilepsy (DRE) in children, with the aim of providing valuable perspectives to enhance clinical practice. Methods In this retrospective study, clinical data were collected on 167 children with DRE who were hospitalized between January 2020 and December 2022, including gender, age of onset, seizure types, video electroencephalogram(VEEG) recordings, neuroimaging, and genetic testing results. Based on the etiology of epilepsy, the enrolled children were categorized into different groups. The rank-sum test was conducted to compare the age of onset for different etiologies. Results Of the 167 cases, 89 (53.3%) had a clear etiology. Among them, structural factors account for 23.4%, genetic factors for 19.2%, multiple factors for 7.2%, and immunological factors for 3.6%. The age of onset was significantly earlier in children with genetic causes than those with structural (P

Edible bird's nest (EBN) is considered a delicacy in Chinese cuisine. The nests are produced by male swiftlets (Aerodramus sp.). Due to their high price, the nutritional benefit from EBN can currently only be afforded by affluent consumers. Therefore, the ability to identify and produce recombinant, functional EBN mucins is highly desirable. Herein, we report the identification, bacterial expression, purification and glycosylation of the first recombinant mucin derived from the Edible-nest Swiftlet Aerodramus fuciphagus (AfMuc). Recombinant AfMuc was successfully expressed at high expression levels and purified to near homogeneity by nickel-chelation affinity chromatography. The in vitro glycosylation of the recombinant AfMuc protein backbone resulted in the addition of up to four GalNAc residues and could be achieved by using a human and a previously unstudied Aerodramus fuciphagus polypeptide N-acetylgalactosaminyltransferase (HsGalNT2 and AfGalNT2, respectively). A comparison of the biochemical properties of these enzymes revealed characteristics of these enzymes.

Abstract Reversible proton ceramic electrochemical cells are promising solid-state ion devices for efficient power generation and energy storage, but necessitate effective air electrodes to accelerate the commercial application. Here, we construct a triple-conducting hybrid electrode through a stoichiometry tuning strategy, composed of a cubic phase Ba0.5Sr0.5Co0.8Fe0.2O3−δ and a hexagonal phase Ba4Sr4(Co0.8Fe0.2)4O16−δ. Unlike the common method of creating self-assembled hybrids by breaking through material tolerance limits, the strategy of adjusting the stoichiometric ratio of the A-site/B-site not only achieves strong interactions between hybrid phases, but also can efficiently modifies the phase contents. When operate as an air electrode for reversible proton ceramic electrochemical cell, the hybrid electrode with unique dual-phase synergy shows excellent electrochemical performance with a current density of 3.73 A cm−2 @ 1.3 V in electrolysis mode and a peak power density of 1.99 W cm−2 in fuel cell mode at 650 °C.

The interaction between tumor fatty acid metabolism and immune microenvironment is a novel topic in oncology research, and the relationship of lipid-derived factors with immune editing in tumor is unclear. The breast cancer samples from the TCGA database were used as the training set, and samples from GSE42568 were employed as the validation set for constructing a model to identify a signature associated with fatty acid metabolism through Lasso Cox regression. And the changes in immune related signatures and risk score before and after anti-PD-1 monotherapy were caught by the differential analysis in GSE225078. A 14-gene prognostic risk scoring model identifying by fatty acid metabolism relevant signature was conducted, and the high risk group had shorter overall survival and progression free survival than low risk group. Many metabolism-related pathways were enriched in the high risk group, and many immune-related pathways were enriched in low risk group. The crucial differentially expressed genes between the high/low risk groups, CYP4F8 and CD52, were found to be strongly associated with SUCLA2 and ACOT4 of 14-gene model, and strongly related to immune infiltration. Immune related signatures, fatty acid metabolism-risk score and the expression level of ALDH1A1 (in 14-gene-model) changed after anti-PD-1 monotherapy. And the mice model results also showed anti-PD-1 mAb could significantly reduce the expression level of ALDH1A1 (p < 0.01). These results brought up the crosstalk between immune components and fatty acid metabolism in breast cancer microenvironment, which provided a new possibility of targeting fatty acid metabolism for combination therapy in breast cancer immunotherapy.

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014–2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China. Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014–2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases. Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014–2022, and the incidence rate of NRIDs was higher during 2017–2019 (153/100 000) than during 2014–2016 (930/100 000) and during 2020–2022 (371/100 000), respectively (both P

Summary: The co-culture of two adult human colorectal cancer cell lines, Caco-2 and HT29, on Transwell is commonly used as an in vitro gut mimic, yet the translatability of insights from such a system to adult human physiological contexts is not fully characterized. Here, we used single-cell RNA sequencing on the co-culture to obtain a detailed survey of cell type heterogeneity in the system and conducted a holistic comparison with human physiology. We identified the intestinal stem cell-, transit amplifying-, enterocyte-, goblet cell-, and enteroendocrine-like cells in the system. In general, the co-culture was fetal intestine-like, with less variety of gene expression compared to the adult human gut. Transporters for major types of nutrients were found in the majority of the enterocytes-like cells in the system. TLR 4 was not expressed in the sample, indicating that the co-culture model is incapable of mimicking the innate immune aspect of the human epithelium.

ABSTRACTThe purpose of this study was to determine the effect of different subjects from Lactiplantibacillus plantarum SCS5 (L. plantarum SCS5) on type 2 diabetes by modulating oxidative stress levels.The normal group (NG) and the model group (MG) of mice were fed normally, while the three test groups (LP1,LP2,LP3) received 10 ml/kg (body weight) of the L. plantarum SCS5 suspension, intracellular material, or heat-killed intracellular material daily for 10 weeks. The weight loss and the increase in blood glucose were alleviated in the LP2 and LP3 groups. Insulin, catalase, superoxide dismutase, and glutathione peroxidase significantly increased in the LP3 group of mice compared with the MG group. Additionally, the pathological sections showed that the lesions in the LP3 group were less severe than those in the MG group. These findings indicate that the heat-killed intracellular L. plantarum SCS5 material was most effective in alleviating oxidative stress in type 2 diabetic mice.

ABSTRACT: Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.

The intestinal bacteria of longhorn beetles would be ideal targets for pest control and lignocellulosic resources by destroying or exploiting their cellulose-degrading function. This article aims to investigate the diversity and community structure of intestinal bacteria the oligophagous longhorn beetle Glenea cantor. Additionally, it seeks to identify the presence of lignocellulose-degrading bacteria in the gut, and explore their role in consuming host kapok trees Bombax malabaricum. In this study, the bacterial community from G. cantor was examined by Illumina sequencing of 16S ribosomal RNA (rRNA) targeting the V3 and V4 regions. A total of 563,201 valid sequences and 814 OTUs were obtained. The dominant phyla were Proteobacteria, and the dominant genera were Acinetobacter and Lactococcus. The analysis of microbial diversity revealed a high bacterial diversity in the samples, with the gut bacteria playing a crucial role in the physiological activities of the host, particularly, 9 genera of intestinal bacteria with cellulose degradation function were found, highlighting their vital role in cellulose degradation. Five strains of cellulose-degrading bacteria, belonging to the genus Pseudomonas, were obtained from the intestinal tract of G. cantor larvae using traditional isolation and culture techniques as well as 16S rDNA sequencing. Among these strains, A4 exhibited a cellulase activity of 94.42 ± 0.42 U/mL, while A5 displayed the highest filter paper enzyme activity of 127.46 ± 3.54 U/mL. These results offered valuable insights into potential targets for pest control through internal attack digestion and cellulose-degrading bacteria in longhorn beetles.

ObjectivePost-traumatic seizure (PTS) is a well-known complication of traumatic brain injury (TBI). The objective of this study was to identify risk factors associated with breakthrough early PTS in TBI patients receiving phenytoin prophylaxis.MethodsThis was a single-centered retrospective study including adult patients admitted to the intensive care unit (ICU), had a TBI, and started on phenytoin for seizure prophylaxis within 24 h of admission. The primary outcome was the incidence and factors associated with early PTS, defined as a confirmed seizure on a continuous electroencephalogram within 7 days of TBI. Secondary outcomes included the association between early post-traumatic seizures and ICU length of stay, hospital length of stay, and in-hospital mortality.ResultsA total of 105 patients were included in the final analysis. Patients with early PTS were older (65 vs. 48 years old, p = 0.01), had a higher Marshall score (5 vs. 2, p = 0.01), were more likely to have a Marshall score > 2 (73 vs. 37%, p = 0.01), and had more neurosurgeries for hematoma evacuation (57 vs. 19%, p = 0.01). In patients with early PTS, 57% had a level at the time of seizure, and of those, 87.5% had a therapeutic level (>10 mcg/mL). Patients with early PTS had a longer ICU length of stay (14.7 vs. 5.9 days, p = 0.04) and a greater proportion of hospital mortality (21 vs. 2%, p = 0.02).ConclusionPatients with higher age, Marshall score, and neurosurgical procedures for hematoma evacuation had higher incidences of breakthrough early PTS despite the use of phenytoin prophylaxis. The majority of patients with early PTS had therapeutic phenytoin levels at the time of seizure when a level was available; however, approximately half (43%) did not have a level.

IntroductionConsidering the role of bacteria in the onset of acute exacerbation of COPD (AECOPD), we hypothesized that the use of influenza-Streptococcus pneumoniae vaccination, oral probiotics or inhaled amikacin could prevent AECOPD.MethodsIn this pilot prospective, muti-central, randomized trial, moderate-to-very severe COPD subjects with a history of moderate-to-severe exacerbations in the previous year were enrolled and assigned in a ratio of 1:1:1:1 into 4 groups. All participants were managed based on the conventional treatment recommended by GOLD 2019 report for 3 months, with three groups receiving additional treatment of inhaled amikacin (0.4 g twice daily, 5–7 days monthly for 3 months), oral probiotic Lactobacillus rhamnosus GG (1 tablet daily for 3 months), or influenza-S. pneumoniae vaccination. The primary endpoint was time to the next onset of moderate-to-severe AECOPD from enrollment. Secondary endpoints included CAT score, mMRC score, adverse events, and survival in 12 months.ResultsAmong all 112 analyzed subjects (101 males, 96 smokers or ex-smokers, mean ± SD age 67.19 ± 7.39 years, FEV1 41.06 ± 16.09% predicted), those who were given dual vaccination (239.7 vs. 198.2 days, p = 0.044, 95%CI [0.85, 82.13]) and oral probiotics (248.8 vs. 198.2 days, p = 0.017, 95%CI [7.49, 93.59]) had significantly delayed onset of next moderate-to-severe AECOPD than those received conventional treatment only. For subjects with high symptom burden, the exacerbations were significantly delayed in inhaled amikacin group as compared to the conventional treatment group (237.3 vs. 179.1 days, p = 0.009, 95%CI [12.40,104.04]). The three interventions seemed to be safe and well tolerated for patient with stable COPD.ConclusionThe influenza-S. pneumoniae vaccine and long-term oral probiotic LGG can significantly delay the next moderate-to-severe AECOPD. Periodically amikacin inhalation seems to work in symptomatic patients. The findings in the current study warrants validation in future studies with microbiome investigation.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03449459.

Abstract Introduction Generative pretrained transformer-4 (GPT-4) has gained widespread attention from society, and its potential has been extensively evaluated in many areas. However, investigation of GPT-4’s use in medicine, especially in the ophthalmology field, is still limited. This study aims to evaluate GPT-4’s capability to identify rare ophthalmic diseases in three simulated scenarios for different end-users, including patients, family physicians, and junior ophthalmologists. Methods We selected ten treatable rare ophthalmic disease cases from the publicly available EyeRounds service. We gradually increased the amount of information fed into GPT-4 to simulate the scenarios of patient, family physician, and junior ophthalmologist using GPT-4. GPT-4’s responses were evaluated from two aspects: suitability (appropriate or inappropriate) and accuracy (right or wrong) by senior ophthalmologists (> 10 years’ experiences). Results Among the 30 responses, 83.3% were considered "appropriate" by senior ophthalmologists. In the scenarios of simulated patient, family physician, and junior ophthalmologist, seven (70%), ten (100%), and eight (80%) responses were graded as “appropriate” by senior ophthalmologists. However, compared to the ground truth, GPT-4 could only output several possible diseases generally without “right” responses in the simulated patient scenarios. In contrast, in the simulated family physician scenario, 50% of GPT-4's responses were “right,” and in the simulated junior ophthalmologist scenario, the model achieved a higher “right” rate of 90%. Conclusion To our knowledge, this is the first proof-of-concept study that evaluates GPT-4’s capacity to identify rare eye diseases in simulated scenarios involving patients, family physicians, and junior ophthalmologists. The results indicate that GPT-4 has the potential to serve as a consultation assisting tool for patients and family physicians to receive referral suggestions and an assisting tool for junior ophthalmologists to diagnose rare eye diseases. However, it is important to approach GPT-4 with caution and acknowledge the need for verification and careful referrals in clinical settings.

Abstract Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB−/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Abstract Background The present study aimed to investigate the function of miR‐3529‐3p in lung adenocarcinoma and MnO2‐SiO2‐APTES (MSA) as a promising multifunctional delivery agent for lung adenocarcinoma therapy. Methods Expression levels of miR‐3529‐3p were evaluated in lung carcinoma cells and tissues by qRT‐PCR. The effects of miR‐3529‐3p on apoptosis, proliferation, metastasis and neovascularization were assessed by CCK‐8, FACS, transwell and wound healing assays, tube formation and xenografts experiments. Luciferase reporter assays, western blot, qRT‐PCR and mitochondrial complex assay were used to determine the targeting relationship between miR‐3529‐3p and hypoxia‐inducible gene domain family member 1A (HIGD1A). MSA was fabricated using MnO2 nanoflowers, and its heating curves, temperature curves, IC50, and delivery efficiency were examined. The hypoxia and reactive oxygen species (ROS) production was investigated by nitro reductase probing, DCFH‐DA staining and FACS. Results MiR‐3529‐3p expression was reduced in lung carcinoma tissues and cells. Transfection of miR‐3529‐3p could promote apoptosis and suppress cell proliferation, migration and angiogenesis. As a target of miR‐3529‐3p, HIGD1A expression was downregulated, through which miR‐3529‐3p could disrupt the activities of complexes III and IV of the respiratory chain. The multifunctional nanoparticle MSA could not only efficiently deliver miR‐3529‐3p into cells, but also enhance the antitumor function of miR‐3529‐3p. The underlying mechanism may be that MSA alleviates hypoxia and has synergistic effects in cellular ROS promotion with miR‐3529‐3p. Conclusions Our results establish the antioncogenic role of miR‐3529‐3p, and demonstrate that miR‐3529‐3p delivered by MSA has enhanced tumor suppressive effects, probably through elevating ROS production and thermogenesis.

Abstract Aflatoxins are toxic secondary metabolites that often contaminate food and animal feed, causing huge economic losses and serious health hazards. Aflatoxin contamination has become a major concern worldwide. Biological methods have been used to reduce aflatoxins in food and feed by inhibiting toxin production and detoxification. Among biological methods, lactic acid bacteria are of significant interest because of their safety, efficiency, and environmental friendliness. This study aimed to review the mechanisms by which lactic acid bacteria degrade aflatoxins and the factors that influence their degradation efficiency, including the action of the lactic acid bacteria themselves (cell wall adsorption) and the antifungal metabolites produced by the lactic acid bacteria. The current applications of lactic acid bacteria to food and feed were also reviewed. This comprehensive analysis provided insight into the binding mechanisms between lactic acid bacteria and aflatoxins, facilitating the practical applications of lactic acid bacteria to food and agriculture.

The demand for flexibility and rechargeability in tandem with high energy density, reliability, and safety in energy‐storage devices to power wearable electronics has translated to significant advances in flexible solid‐state Zn–air batteries (FSZABs) technology. FSZABs using self‐supported bifunctional air electrodes are currently one of the most attractive alternatives to Li‐ion battery technology for next‐generation wearable electronics. Unlike the conventional powder‐based air electrodes, self‐supported bifunctional air electrodes offer higher electron‐transfer rate, larger specific surface area (and catalyst–reactant–product interfacial contact area), mechanical flexibility, and better operational robustness. To realize their potential nonetheless, self‐supported bifunctional air electrodes should have high and stable bifunctional catalytic activity, low cost, and environmental compatibility. This review first summarizes the three typical configurations and working principles of FSZABs. Then, significant development of self‐supported bifunctional air electrodes for FSZABs and efficient synthesis strategies are emphasized. The review concludes by providing perspectives on how to further improve the electrochemical performance of FSZABs and their suitability for next‐generation wearable electronic devices.

Abstract Background This study aimed to investigate the relationship between chronotypes and aggression in adolescents. Methods A cross-sectional study was conducted on 755 primary and secondary school students aged 11–16 years in rural areas of Ningxia Province, China. The Chinese version of the Buss-Perry Aggression Questionnaire (AQ-CV) and the Chinese version Morningness-Eveningness Questionnaire (MEQ-CV) were used to assess the aggressive behavior and chronotypes of the study subjects. The Kruskal-Wallis test was then used to compare the differences in aggression among adolescents with different chronotypes, and Spearman correlation analysis to determine the relationship between chronotypes and aggression. Further linear regression analysis was used to investigate the effects of chronotype, personality traits, family environment, and class environment on adolescent aggression. Results There were significant differences in chronotypes between different age groups and different sexes. Spearman correlation analysis showed that the MEQ-CV total score was negatively correlated with the AQ-CV total score (r = -0.263) and score of each AQ-CV subscale. In Model 1, chronotypes were negatively associated with aggression when controlling for age and sex, and evening-type adolescents might be more likely to exhibit aggressive behavior (b = -0.513, 95% CI: [-0.712, -0.315], P

Abstract Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.

Abstract Background The uniportal video-assisted thoracoscopic right upper lobectomy (UVATRUL), as a common procedure for thoracic surgeons, is difficult to manipulate and has some inherent challenges. To solve both of problems, we summarized a series of techniques as the three steps method and investigated its feasibility on the patients of right upper lung cancer. Methods Forty-eight patients with right upper lobe lung cancer who underwent the three steps method UVATRUL in our hospital from January 2020 to May 2022 were selected as the three steps method group. Forty-seven patients who underwent the traditional UVATRUL were selected as the traditional method group. The intraoperative condition and postoperative condition of the two groups were retrospectively analysed. Multiple linear regression analysis was carried out to analyze the relationship between positive results and surgical method. Results All patients had successfully completed their surgeries. There was no significant difference between the two groups in respect of intraoperative blood loss, rate of conversion, day one thoracic drainage volume, chest tube indwelling time, incidence of postoperative complications, number of lymph node, and postoperative hospital stay (P > 0.05). Operative time of the three steps method group was significantly shorter than the traditional method group (P

Hydrogen (H2) is regarded as a promising and renewable energy carrier to achieve a sustainable future. Among the various H2 production routes, photocatalytic water splitting has received particular interest; it strongly relies on the optical and structural properties of photocatalysts such as their sunlight absorption capabilities, carrier transport properties, and amount of oxygen vacancy. Perovskite oxides have been widely investigated as photocatalysts for photocatalytic water splitting to produce H2 because of their distinct optical properties, tunable band gaps and excellent compositional/structural flexibility. Herein, an aluminum cation (Al3+) doping strategy is developed to enhance the photocatalytic performance of Ruddlesden-Popper (RP) Sr2TiO4 perovskite oxides for photocatalytic H2 production. After optimizing the Al3+ substitution concentration, Sr2Ti0.9Al0.1O4 exhibits a superior H2 evolution rate of 331 μmol h−1 g−1, which is ~3 times better than that of Sr2TiO4 under full-range light illumination, due to its enhanced light harvesting capabilities, facilitated charge transfer, and tailored band structure. This work presents a simple and useful Al3+ cation doping strategy to boost the photocatalytic performance of RP-phase perovskites for solar water splitting.

Abstract Breast cancer (BC) is the most common malignant tumor in women worldwide. Metastasis is the main cause of BC-related death. The specific mechanism underlying BC metastasis remains obscure. Recently, PRSS22 was discovered to be involved in tumor development, however, its detailed biological function and regulatory mechanism in BC are unclear. Here, we characterized that PRSS22 expression is upregulated in BC tissues compared with non-tumorous breast tissues. Dual luciferase assays, bioinformatics analyses and chromatin immunoprecipitation (ChIP) assays indicated that transcription factor E2F1 directly binds to the PRSS22 promoter region and activates its transcription. Functionally, upregulation of PRSS22 promoted invasion and metastasis of BC cells in vitro and in vivo, whereas knockdown of PRSS22 inhibited its function. Mechanistically, the combination of PRSS22 and ANXA1 protein in BC cells was first screened by protein mass spectrometry analysis, and then confirmed by co-immunoprecipitation (Co-IP) and western blot assays. Co-overexpression of PRSS22 and ANXA1 could promote BC cell migration and invasion. We further demonstrated that PRSS22 promotes the cleavage of ANXA1 and in turn generates an N-terminal peptide, which initiates the FPR2/ERK signaling axis to increase BC aggressiveness.

Abstract Reversible proton ceramic electrochemical cell (R-PCEC) is regarded as the most promising energy conversion device, which can realize efficient mutual conversion of electrical and chemical energy and to solve the problem of large-scale energy storage. However, the development of robust electrodes with high catalytic activity is the main bottleneck for the commercialization of R-PCECs. Here, a novel type of high-entropy perovskite oxide consisting of six equimolar metals in the A-site, Pr1/6La1/6Nd1/6Ba1/6Sr1/6Ca1/6CoO3−δ (PLNBSCC), is reported as a high-performance bifunctional air electrode for R-PCEC. By harnessing the unique functionalities of multiple elements, high-entropy perovskite oxide can be anticipated to accelerate reaction rates in both fuel cell and electrolysis modes. Especially, an R-PCEC utilizing the PLNBSCC air electrode achieves exceptional electrochemical performances, demonstrating a peak power density of 1.21 W cm−2 for the fuel cell, while simultaneously obtaining an astonishing current density of − 1.95 A cm−2 at an electrolysis voltage of 1.3 V and a temperature of 600 °C. The significantly enhanced electrochemical performance and durability of the PLNBSCC air electrode is attributed mainly to the high electrons/ions conductivity, fast hydration reactivity and high configurational entropy. This research explores to a new avenue to develop optimally active and stable air electrodes for R-PCECs.

This study aimed to examine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and other clinicopathological features in HER2+ MBC patients who received first-line anti-HER2 therapy. A total of 129 patients were assigned to NLR-low and NLR-high groups based on a cutoff value of 3.0 at baseline. Peripheral blood lymphocyte subsets and gene mutations in circulating tumor DNA were analyzed by flow cytometry and Next-generation sequencing, respectively. Survival was evaluated by the Kaplan–Meier method and Cox regression analysis. Of the 129 patients, 77 and 52 were assigned to the NLR-low (≤3) and NLR-high (>3) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median progression-free survival (PFS) (11.7 vs. 7.7 months) (p = 0.001, HR = 2.703 95% CI 1.543–4.736 and overall survival (OS) (37.4 vs. 28.7 months) (p = 0.044, HR = 2.254 95% CI 1.024–4.924). Furthermore, this association was independent of metastatic sites or estrogen receptor status. Peripheral blood CD3+ (p = 0.034) and CD4+ (p = 0.010) T cell numbers were significantly higher in the NLR-low group than the NLR-high group. The mutational profile of MBC was generally similar between the two groups. Baseline NLR was a prognostic factor of PFS and OS for patients with HER2+ MBC in the first-line setting. These results may facilitate the selection of patients who will benefit most from anti-HER2 treatment.

Objective To investigate the protective effect of idebenone (IDBN) on hippocampal neuron injury in epileptic rats and its mechanism. Methods Forty-eight Wistar rats were randomly divided into normal control group, IDBN prevention group (prevention group), epilepsy group, IDBN 25, 50 and 100 mg groups. Behavioral changes of rats in different treatment groups before and after treatment with IDBN were observed. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in hippocampal were detected. The ultrastructural changes of hippocampal neurons and mitochondria were observed. Results The expression levels of SOD, GSH-Px and MDA in different treatment groups were significantly different (P = 0.000, for all). The activity of SOD and GSH-Px was the highest and the content of MDA was the lowest in IDBN 100 mg group. The activity of SOD and GSH-Px in IDBN 100 mg group were higher than those in epilepsy group (P = 0.000, 0.000), IDBN 25 mg group (P = 0.000, 0.000) and 50 mg group (P = 0.004, 0.005), while the content of MDA was lower than that in epilepsy group (P = 0.000), IDBN 25 mg group (P = 0.000) and 50 mg group (P = 0.002). Compared with normal control group and prevention group, hippocampal neurons in epilepsy group showed different degrees of damage, which was relieved after treatment with IDBN and gradually decreased with the increase of dose. In epilepsy group, the mitochondrial structure of hippocampal neurons was damaged obviously, with deformation and swelling, and some mitochondria were vacuolated. After treatment with IDBN, the damage was relieved, and the 100 mg group had the least damage. Conclusions IDBN can protect hippocampal neuron structure and function by inhibiting oxidative stress injury in epileptic rats.

Abstract PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a “pseudokinase”, has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2−/− mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.

IntroductionPyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomic profile of this subpopulation is almost undefined.Methods and materialsPatients with BM of HER2-positive MBC (n = 35) treated with pyrotinib-containing therapy were enrolled in this analysis. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease progression were estimated using the Cox proportional hazards models. Targeted next-generation sequencing of 618 cancer-relevant genes was performed on plasma and primary breast tumors from patients with BM and without BM.ResultsThe median PFS time was 8.00 (95% CI, 5.98–10.017) months, and the median OS time was 23 (95% CI, 10.412–35.588) months. The ORR was 45.7%, and the DCR was 74.3%. In the Cox multivariate analysis, prior exposure to brain radiotherapy (HR = 3.268), received pyrotinib as third- or higher-line treatment (HR = 4.949), subtentorial brain metastasis (HR = 6.222), and both supratentorial and subtentorial brain metastases (HR = 5.863) were independently associated with increased risk of progression. The frequent grade 3–4 adverse event was increased direct bilirubin (14.3%), and two patients suffered from grade 3–4 diarrhea. In the exploratory genomic analysis, altered frequencies of FGFR3, CD276, CDC73, and EPHX1 were higher in the BM group. The consistency of mutated profiles of plasma and primary lesion in the BM group was significantly lower (30.4% vs. 65.5%; p = 0.0038).ConclusionsPyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in a population that is brain radiotherapy-naïve, received pyrotinib as first- or second-line treatment, and developed supratentorial brain metastasis. In the exploratory genomic analysis, patients with BM showed distinct genomic features from patients without BM.

Background: To meet the growing global demand for rehabilitation services, the World Health Organization (WHO) launched Rehabilitation 2030. This study was commissioned by the WHO to investigate the integration degree of traditional Chinese medicine (TCM) in Chinese health system rehabilitation services and the demand for TCM rehabilitation in China. Methods: Twenty TCM rehabilitation experts and relevant government administrators were invited to complete the questionnaire between September 2019 and January 2022. The development of traditional, complementary, and integrative medicine (TCI) rehabilitation in China was assessed primarily based on six different health system components. Results: 26 policies, regulations, and national strategic plans related to TCI rehabilitation were issued by relevant government departments since 2002; notably, 14 policies related to TCI rehabilitation development were intensively introduced from 2016 to 2021. These policies cover the three main areas of financing, infrastructure development, and service delivery. The National Administration of Traditional Chinese Medicine's investment in TCM clinical capacity infrastructure and scientific research in 2019–2021 increased by 66% compared to 2010–2012, and the average number of TCM hospitals with rehabilitation departments in 2020 increased by 6.5% compared to 2018. The proportion of community health service centers providing TCM services in primary medical and health institutions has increased by 30.8% over the past 10 years. Conclusion: Long-term continuous policies, substantial financial investment, and expansion of the scope of TCI rehabilitation services in primary care institutions have effectively contributed to the rapid development of TCI rehabilitation. However, human resources and financing mechanisms for TCI rehabilitation need further improvement.

Abstract Electrochemical carbon dioxide (CO2) reduction (ECR) is a promising technology to produce valuable fuels and feedstocks from CO2. Despite large efforts to develop ECR catalysts, the investigation of the catalytic performance and electrochemical behavior of complex metal oxides, especially perovskite oxides, is rarely reported. Here, the inorganic perovskite oxide Ag‐doped (La0.8Sr0.2)0.95Ag0.05MnO3–δ (LSA0.05M) is reported as an efficient electrocatalyst for ECR to CO for the first time, which exhibits a Faradaic efficiency (FE) of 84.3%, a remarkable mass activity of 75 A g−1 (normalized to the mass of Ag), and stability of 130 h at a moderate overpotential of 0.79 V. The LSA0.05M catalyst experiences structure reconstruction during ECR, creating the in operando‐formed interface between the perovskite and the evolved Ag phase. The evolved Ag is uniformly distributed with a small particle size on the perovskite surface. Theoretical calculations indicate the reconstruction of LSA0.05M during ECR and reveal that the perovskite–Ag interface provides adsorption sites for CO2 and accelerates the desorption of the *CO intermediate to enhance ECR. This study presents a novel high‐performance perovskite catalyst for ECR and may inspire the future design of electrocatalysts via the in operando formation of metal–metal oxide interfaces.

This article reports a case of spontaneous spinal subdural hematoma (SSDH) after brain surgery in a patient with immune thrombocytopenic purpura (ITP), reviews the relevant literature, and discusses the etiology, pathogenesis, and clinical features of SSDH in patients with ITP. A male patient in his early 50 s with an 8-year history of ITP and suffering from coexistent hemifacial spasm and trigeminal neuralgia underwent microvascular decompression in our department. His preoperative corrected platelet count was within the normal range. On postoperative day 2, the patient complained of acute low back pain and sciatica. Lumbar magnetic resonance imaging demonstrated an SSDH extending from L3 to L4 with a significantly decreased platelet count (30.0 × 10 9 /L). The pain was gradually relieved after 2 weeks of conservative treatment, and no neurological deficit occurred during the 1-year follow-up. Brain surgery may increase the risk of postoperative SSDH in patients with ITP. Clinicians planning brain surgery must conduct a rigorous assessment through detailed physical examination, laboratory tests, and medical history records and maintain perioperative platelet counts within the normal range to prevent various risks associated with spinal cord compression.

Salvianolic acid A (SAA) is a traditional Chinese medicine that has a good therapeutic effect on cardiovascular disease. However, the underlying mechanisms by which SAA improves mitochondrial respiration and cardiac function in diabetic cardiomyopathy (DCM) remain unknown. This study aims to elucidate whether SAA had any cardiovascular protection on the pathophysiology of DCM and explored the potential mechanisms. Diabetes was induced in rats by 30 mg/kg of streptozotocin (STZ) treatment. After a week of stability, 5 mg/kg isoprenaline (ISO) was injected into the rats subcutaneously. 3 mg/kg SAA was orally administered for six weeks and 150 mg/kg Metformin was selected as a positive group. At the end of this period, cardiac function was assessed by ultrasound, electrocardiogram, and relevant cardiac injury biomarkers testing. Treatment with SAA improved cardiac function, glucose, and lipid levels, mitochondrial respiration, and suppressed myocardial inflammation and apoptosis. Furthermore, SAA treatment inhibits the apoptosis pathway through CRYAB in diabetic cardiomyopathy rats. As a result, this study not only provides new insights into the mechanism of SAA against DCM but also provides new therapeutic ideas for the discovery of anti-DCM compounds in the clinic.

Abstract Neuropeptides and neuropeptide receptors are crucial regulators to insect physiological processes. The 21.0 Gb bases were obtained from Illumina sequencing of two libraries representing the female and male heads of Phauda flammans (Walker) (Lepidoptera: Phaudidae), which is a diurnal defoliator of ficus plants and usually outbreaks in the south and south-east Asia, to identify differentially expressed genes, neuropeptides and neuropeptide receptor whose tissue expressions were also evaluated. In total, 99,386 unigenes were obtained, in which 156 up-regulated and 61 down-regulated genes were detected. Fifteen neuropeptides (i.e., F1b, Ast, NP1, IMF, Y, BbA1, CAP2b, NPLP1, SIF, CCH2, NP28, NP3, PDP3, ARF2 and SNPF) and 66 neuropeptide receptor genes (e.g., A2-1, FRL2, A32-1, A32-2, FRL3, etc.) were identified and well-clustered with other lepidopteron. This is the first sequencing, identification neuropeptides and neuropeptide receptor genes from P. flammans which provides valuable information regarding the molecular basis of P. flammans.

OBJECTIVES:. Tracheal intubation (TI) is a common procedure in critical care, often performed with a Macintosh curved blade used for direct laryngoscopy (DL). Minimal evidence informs the choice between Macintosh blade sizes during TI. We hypothesized that Macintosh 4 blade would have higher first-attempt success than Macintosh 3 blade during DL. DESIGN:. Retrospective analysis using a propensity score and inverse probability weighting of data from six prior multicenter randomized trials. SETTING AND PARTICIPANTS:. Adult patients who underwent nonelective TI at participating emergency departments and ICUs. We compared the first-pass success of TI with DL in subjects intubated with a size 4 Macintosh blade on the first TI attempt to subjects with a size 3 Macintosh blade on the first TI attempt. MAIN RESULTS:. Among 979 subjects, 592 (60.5%) had TI using DL with a Macintosh blade, of whom 362 (37%) were intubated with a size 4 blade and 222 (22.7%) with a size 3 blade. We used inverse probability weighting with a propensity score for analyzing data. We found that patients intubated with a size 4 blade had a worse (higher) Cormack-Lehane grade of glottic view than patients intubated with a size 3 blade (adjusted odds ratio [aOR], 1.458; 95% CI, 1.064–2.003; p = 0.02). Patients intubated with a size 4 blade had a lower first pass success than those with a size 3 blade (71.1% vs 81.2%; aOR, 0.566; 95% CI, 0.372–0.850; p = 0.01). CONCLUSIONS AND RELEVANCE:. In critically ill adults undergoing TI using DL with a Macintosh blade, patients intubated using a size 4 blade on first attempt had a worse glottic view and a lower first pass success than patients intubated with a size 3 Macintosh blade. Further prospective studies are needed to examine the optimal approach to selecting laryngoscope blade size during TI of critically ill adults.

Abstract Before the practical application of rechargeable Zn–air batteries (ZABs), a critical issue regarding the inherent slow reaction kinetics of the oxygen reduction (ORR) and oxygen evolution (OER) must be addressed. Here, we fabricate a cost‐effective bifunctional oxygen electrocatalyst with a self‐antistacking structure, where three‐dimensional (3D) Fe–Co bimetallic oxide particles (FeCoOx) are directly grown on 2D N‐doped graphene (NG). The in situ grown FeCoOx particles can alleviate the NG interlaminar restacking, ensuring abundant channels for diffusion of O2/OH− species, while the NG allows rapid electron flow. Benefiting from this self‐antistacking 3D‐on‐2D structure and synergetic electrocatalysis, FeCoOx@NG demonstrated excellent activity for both ORR and OER (ΔE = 0.78 V), which is superior to that of the binary mixtures of Pt/C and RuO2 (ΔE = 0.83 V). A homemade ZAB with 20%‐FeCoOx@NG delivers a specific capacity of 758.9 mAh g−1, a peak power density of 215 mW cm−2, and long‐term cyclability for over 400 h. These research results suggest that designing a bimetallic oxide/N‐doped carbon 3D‐on‐2D nanoarchitecture using an in situ growth strategy is an attractive and feasible solution to overcome electrocatalytic problems in ZABs.

BackgroundBrucellosis is a zoonotic disease that threatens public health and creates an economic burden. Unfortunately, it is often overlooked in developing countries, with misdiagnosis causing negative impacts on those with low income. Although the symptoms of brucellosis are commonly reported as fever and fatigue, rare pulmonary, and psychiatric involvements should also be considered. We present the first brucellosis patient in China with multiple pulmonary nodules and depression. Furthermore, this report highlights the importance of collecting patient history in epidemic areas of brucellosis.Case presentationWe report the case of a 40-year-old woman with intermittent fever for 2 months and gradually accompanied by chills, dry cough, arthralgia, and fatigue. The patient was also diagnosed with depression after fever. She received symptomatic treatment at a regional hospital; however, there was no significant symptom relief. She suddenly developed hemoptysis 1 day prior to arrival at our hospital, where we discovered that her liver, spleen, neck, and axillary lymph nodes were enlarged, and there were multiple nodules in both lungs. The patient was eventually diagnosed with brucellosis after the serum agglutination test and received antibiotic therapy, which provided symptom relief.ConclusionThis report describes a case of brucellosis with uncommon multipulmonary nodules and depression in China. This study has widened the evidence of respiratory involvement due to brucellosis. Second, it demonstrates the importance of collecting a comprehensive medical history, especially in epidemic areas. In conclusion, for febrile patients with pulmonary nodules and depression, especially in endemic areas, brucellosis should be considered.

ABSTRACT: Poultry is susceptible to fatty liver which lead to decrease egg production and increase mortality. But the potential molecular mechanisms remain largely unclear. In the current study, in combination with transcriptome sequencing and miRNA sequencing data analysis from F1 generation of the normal liver and fatty liver tissues, the differentially expressed miR-375 and its target gene RBPJ were screened and verified. The expression levels of miR-375 and RBPJ gene in the liver between control and fatty liver groups of F0-F3 generation for Jingxing-Huang (JXH) chicken are different significantly (P < 0.05 or P < 0.01). And downregulated RBPJ expression can promote TG content and lipid droplets in primary hepatocytes cultured in vitro (P < 0.01). Cell proliferation-related genes, including PMP22, IGF-1, IGF-2, and IGFBP-5, increased or decreased significantly after overexpression or knock-down RBPJ (P < 0.05 or P < 0.01), respectively. This study uniquely revealed that miR-375 induced lipid synthesis and inhibited cell proliferation may partly due to regulation of RBPJ expression, thereby involving in fatty liver formation and inheritance in chicken. The results could be useful in identifying candidate genes and revealing the pathogenesis of fatty liver that may be used for disease-resistance selective breeding in chicken.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

Paracoccus marginatus is a highly polyphagous invasive pest that poses a significant quarantine threat to tropical and subtropical countries. Infested commodities in international trade should undergo phytosanitary treatment, and irradiation is recommended as a viable alternative to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-day-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15–105 Gy with an interval of 15 Gy. Radiotolerance was compared using ANOVA, fiducial overlapping and lethal dose ratio (LDR) test, resulting in no significant difference among treatments, except for the overall mortality and LDR at LD90 (a dose causing 90% mortality at 95% confidence level). The estimated dose for LD99.9968 was 176.5–185.2 Gy, which was validated in the confirmatory tests. No nymphs emerged from a total of 60,386 gravid females exposed to a gamma radiation dose range of 146.8–185.0 Gy in the confirmatory tests. The largest dose in confirmatory tests should be the minimum threshold for phytosanitary treatment, consequently, a minimum dose of 185 Gy is recommended for the phytosanitary irradiation treatment of papaya mealybug-infested commodities, ensuring a treatment efficacy of ≥99.9950% at 95% confidence level.

Objectives: Norovirus is associated with one-fifth of all gastroenteritis cases, but basic epidemiological data is lacking, especially in developing countries. As long-term surveillance on norovirus gastroenteritis is scarce in western China, this study aims to update the epidemiological knowledge of norovirus gastroenteritis and to characterize the genotypes of norovirus strains. Methods: Stool samples were collected from hospitalized children under 5 years old with gastroenteritis in Chengdu, China. All samples were tested for norovirus as well as rotavirus, sapovirus, enteric adenovirus, and astrovirus by real-time RT-PCR. RdRp and VP1 genes were sequenced in norovirus-positive samples to investigate viral phylogenies. Results: Of the 1181 samples collected from 2015 to 2019, 242 (20.5%) were positive for norovirus.Among norovirus-positive cases, 65 cases had co-infection with another virus; norovirus/enteric adenovirus was most frequently detected (50.8%, 33/65). The highest positive rate was observed in children aged 13–18 months (23.7%, 68/287). Norovirus infection peaked in autumn (36.6%, 91/249), followed by summer (20.3%, 70/345). Pearson correlation analysis showed significant correlation between the norovirus-positive rate and humidity (r = 0.773, P

Hormone receptor-positive HER2-positive (HR+/HER2+) metastatic breast cancer (MBC) is a unique subtype of breast cancer. Most current guidelines recommend that combination regimens based on anti-HER2 therapy should be used as first-line treatment for HER2+ MBC, irrespective of HR status. Endocrine therapy can be applied as maintenance therapy for patients who are intolerant to chemotherapy or post-chemotherapy. Increasing evidence suggests that complex molecular crosstalk between HR and HER2 pathways may affect the sensitivity to both HER2-targeted and endocrine therapy in patients with HR+/HER2+ breast cancer. Recent research and clinical trials have revealed that a combination of endocrine therapy and anti-HER2 approaches without chemotherapy provides along-term disease control for some patients, but the challenge lies in how to accurately identify the subsets of patients who can benefit from such a de-chemotherapy treatment strategy. In this review, we aim to summarize the results of preclinical and clinical studies in HR+/HER2+ MBC and discuss the possibility of sparing chemotherapy in this subgroup of patients.

Early-stage temporomandibular joint osteoarthritis (TMJOA) is characterized by excessive subchondral bone loss. Emerging evidence suggests that TMJ disc displacement is involved, but the pathogenic mechanism remains unclear. Here, we established a rat model of TMJOA that simulated disc displacement with a capacitance-based force-sensing system to directly measure articular surface pressure in vivo. Micro-CT, histological staining, immunofluorescence staining, IHC staining, and Western blot were used to assess pathological changes and underlying mechanisms of TMJOA in the rat model in vivo as well as in RAW264.7 cells in vitro. We found that disc displacement led to significantly higher pressure on the articular surface, which caused rapid subchondral bone loss via activation of the RANTES–chemokine receptors–Akt2 (RANTES-CCRs-Akt2) axis. Inhibition of RANTES or Akt2 attenuated subchondral bone loss and resulted in improved subchondral bone microstructure. Cytological studies substantiated that RANTES regulated osteoclast formation by binding to its receptor CCRs and activating the Akt2 pathway. The clinical evidence further supported that RANTES was a potential biomarker for predicting subchondral bone loss in early-stage TMJOA. Taken together, this study demonstrates important functions of the RANTES-CCRs-Akt2 axis in the regulation of subchondral bone remodeling and provides further knowledge of how disc displacement causes TMJOA.

BackgroundZoster-associated pain (ZAP) is notoriously difficult to treat. Pulsed radiofrequency (PRF) and short-term nerve electrical stimulation (st-NES) have been proven effective treatments for ZAP. However, it is still unclear which technique provides improved analgesia in ZAP. This study is based on a large-scale, long-term follow-up to evaluate the efficacy and safety between st-NES and PRF.Materials and methodsAll eligible ZAP patients treated with st-NES or PRF in our department were enrolled. Cohorts were divided into the st-NES group and the PRF group. A 1:1 ratio propensity score matching (PSM) was used to balance the baseline characteristics. The PS-matched cohort was adopted to investigate the efficacy and safety of the two treatments. The ordinal regression analysis was performed to determine the variables affecting the treatment effect of ZAP.ResultsA total of 226 patients were included after PSM. The numerical rating scale (NRS) scores in st-NES and PRF groups considerably reduced compared to baseline levels after treatment. The NRS scores in the st-NES group were obviously lower than those in the PRF group at discharge, 1, 3, 6, 12, and 24 months. During the follow-up period, the NRS reduction rate remained higher in the st-NES group than in the PRF group (P < 0.01). The dosage of medication, Pittsburgh Sleep Quality Index (PSQI) score, and the number of patients with aggravated pain after discharge in the st-NES group were significantly less than in the PRF group after treatment.ConclusionShort-term nerve electrical stimulation has been shown to be more advantageous than PRF for pain relief and quality of life improvement for ZAP patients.

OBJECTIVES:. Describe the efficacy and safety of guanfacine for dexmedetomidine weaning in critically ill patients. DESIGN:. Retrospective descriptive analysis. SETTING:. Six hundred thirteen–bed academic medical center from October 2020 to October 2021. PATIENT/SUBJECTS:. All Adult patients on IV dexmedetomidine who received at least one dose of guanfacine for sedation or agitation were included. INTERVENTIONS:. Enteral guanfacine. MEASUREMENTS AND MAIN RESULTS:. The primary outcome was discontinuation of dexmedetomidine therapy within 48 hours after guanfacine initiation. Secondary outcomes assessed included adjunctive medication use, rate of dexmedetomidine reinitiation, and safety outcomes. One hundred five patients were included in the analysis. Median age was 59 years old, 66% were male, and median daily dose of guanfacine was 1.5 mg. Dexmedetomidine was discontinued within 48 hours in 58% of patients (n = 61) and within 72 hours in 71% of patients (n = 75). Fifty-five percent of patients (n = 58) required rescue medications for poorly controlled agitation, sedation, or pain while on guanfacine. Dexmedetomidine withdrawal occurred in 2% of patients (n = 2) while on guanfacine. Adverse effects attributed to guanfacine occurred in 8% of patients (n = 8), all experiencing hypotension leading to medication discontinuation. CONCLUSION:. Dexmedetomidine was successfully weaned within 48 hours of guanfacine initiation in 58% of patients with minimal withdrawal or adverse effects. Guanfacine may be an effective and safe enteral option for dexmedetomidine weaning in critically ill patients.

Long non-coding RNAs (lncRNAs) modulate cell proliferation, cycle, and apoptosis. However, the role of lncRNA-WFDC21P in the tumorigenesis of triple-negative breast cancer (TNBC) remains unclear. Results of this study demonstrated that WFDC21P levels significantly increased in TNBC, which was associated with the poor survival of patients. WFDC21P overexpression significantly promoted TNBC cell proliferation and metastasis. WFDC21P interacted with miR-628-5p, which further suppressed cell proliferation and metastasis by negatively regulating Smad3-related gene expression. Recovery of miR-628-5p weakened the roles of WFDC21P in promoting the growth and metastasis of TNBC cells. Moreover,N6-methyladenosine (m6A) modification upregulated WFDC21P expression in the TNBC cells. WFDC21P and its m6A levels were increased after methyltransferase like 3 (METTL3) overexpression but reduced after METTL3 silencing. The proliferation and metastasis of TNBC cells were promoted by METTL3 overexpression but suppressed by METTL3 silencing. This study demonstrated the vital roles of WFDC21P and its m6A in regulating the proliferation and metastasis of TNBC cells via the WFDC21P/miR-628/SMAD3 axis.