Fully Synthetic TF-Based Self-Adjuvanting Vaccine Simultaneously Triggers iNKT Cells and Mincle and Protects Mice against Tumor Development.

The Thomsen-Friedenreich (TF) antigen has proven to be a promising target for developing novel therapeutic cancer vaccines. Here, a new strategy that TF antigen covalently coupled with KRN7000 and vizantin was developed. The resulting three-component vaccine KRN7000-TF-vizantin simultaneously triggers invariant natural killer T (iNKT) cells and macrophage-inducible C-type lectin (Mincle) signaling pathways, eliciting much stronger TF-specific immune responses than glycoprotein vaccine TF-KLH/alum and the corresponding two-component conjugate vaccines TF-KRN7000 and TF-vizantin. The analysis of IgG isotypes and the secretion of cytokines revealed that KRN7000-TF-vizantin induced Th1/Th2 mixed immune responses, where Th1 was dominant. In vivo experiments demonstrated that KRN7000-TF-vizantin increased the survival rate and survival time of tumor-challenged mice, and surviving mice rejected further tumor attacks without any additional treatment. This work demonstrates that covalently coupled KRN7000 and vizantin could serve as a promising TF-based vaccine carrier for antitumor immune therapy, and KRN7000-TF-vizantin features great potential to be a vaccine candidate.

The effect of prone-position ventilatory strategy among neurology patients with SARS-CoV-2: A cross-sectional survey.

Awake-prone position combined with noninvasive ventilation or high-flow nasal cannula ventilation has been shown to be safe in the treatment of patients with moderate to severe ARDS and COVID-19, and may avoid intubation and reduce patient mortality. We conducted a cross-sectional study in a hospital to observe the effect of prone position on neurological patients with SARS-CoV-2. A total of 52 neurological patients with SARS-CoV-2 participated in the survey. Most patients (76.92%) had cerebrovascular disease combined with SARS-CoV-2. After prone position, the oxygen saturation increased by 3.25% ± 3.02%. The number of patients with an oxygen saturation of 95% or more increased by 28.85%. Among the 3 types of neurological diseases, the oxygen saturation improvement values in patients with encephalitis or encephalopathy was the greatest, and cerebrovascular disease was the least. Oxygen saturation improvements did not differ among delivery modes. Prone position nursing can improve the effect of oxygen therapy on patients with neurological diseases combined with SARS-CoV-2 infection. Prone position nursing can slow the need for advanced equipment such as ventilators during the COVID-19 pandemic.

Molecular Epidemiology of mcr-1-Positive Polymyxin B-Resistant Escherichia coli Producing Extended-Spectrum ß-Lactamase (ESBL) in a Tertiary Hospital in Shandong, China.

Escherichia coli, a rod-shaped Gram-negative bacterium, is a significant causative agent of severe clinical bacterial infections. This study aimed to analyze the epidemiology of extended-spectrum ß-lactamase (ESBL)-producing mcr-1 -positive E. coli in Shandong, China. We collected 668 non-duplicate ESBL-producing E. coli strains from clinical samples at Shandong Provincial Hospital between January and December 2018, and estimated their minimum inhibitory concentrations (MICs) using a VITEK® 2 compact system and broth microdilution. Next-generation sequencing and bioinformatic analyses identified the mcr-1 gene and other resistance genes in the polymyxin B-resistant strains. The conjugation experiment assessed the horizontal transfer capacity of the mcr-1 gene. Of the strains collected, 24 polymyxin B-resistant strains were isolated with a positivity rate of 3.59% and among the 668 strains, 19 clinical strains carried the mobile colistin resistance gene mcr-1, with a positivity rate of approximately 2.8%. All 19 clinical strains were resistant to ampicillin, cefazolin, ceftriaxone, ciprofloxacin, levofloxacin, and polymyxin B. Seventeen strains successfully transferred the mcr-1 gene into E. coli J53. All transconjugants were resistant to polymyxin B, and carried the drug resistance gene mcr-1. The 19 clinical strains had 14 sequence types (STs), with ST155 (n = 4) being the most common. The whole-genome sequencing results of pECO-POL-29_mcr1 revealed that no ISApl1 insertion sequences were found on either side of the mcr-1 gene. Our study uncovered the molecular epidemiology of mcr-1-carrying ESBL-producing E. coli in the region and suggested horizontal transmission mediated by plasmids as the main mode of mcr-1 transmission.

Structural brain characteristics of epilepsy patients with comorbid migraine without aura.

Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p < 0.001, false discovery rate correction [FDR]). Furthermore, the headache duration in the EM group was negatively correlated with the gray matter volume of the right temporal pole (p < 0.05). SBM analysis showed cortical atrophy in the left insula, left posterior cingulate gyrus, left postcentral gyrus, left middle temporal gyrus, and left fusiform gyrus in the EM compared with the HC group (p < 0.001, family wise error correction). We found a positive correlation between headache frequency and the cortical thickness of the left middle temporal gyrus (p < 0.05). SCN analysis revealed no differences in global parameters between the three groups. The area under the curve (AUC) of the nodal betweenness centrality in the right postcentral gyrus was lower in the EM group compared with the HC group (p < 0.001, FDR correction), and the AUC of the nodal degree in the right fusiform gyrus was lower in the EM group compared with the EC group (p < 0.001, FDR correction). We found clear differences in brain structure in the EM patients compared with the HC group. Accordingly, migraine episodes may influence brain structure in epilepsy patients. Conversely, abnormal brain structure may be an important factor in the development of epilepsy with comorbid migraine without aura. Further studies are needed to investigate the role of brain structure in individuals with epilepsy and comorbid migraine without aura.

Boosting supercapacitive performance of pristine covalent organic frameworks via phenolic hydroxyl groups: A two-in-one strategy.

Two-dimensional covalent organic frameworks (COFs) are ideal electrode materials for electrochemical energy storage devices due to their unique structures and properties, and the accessibility and utilization efficiency of the redox-active sites within COFs are critical determinants of their pseudocapacitive performance. Via introducing meticulously designed phenolic hydroxyl (Ar-OH) groups with hydrogen-bond forming ability onto the imine COF skeletons, DHBD-Sb-COF exhibited improved hydrophilicity and crystallinity than the parent BD-Sb-COF, the redox-active sites (SbPh3 moieties) in COF electrodes could thus be highly accessed by aqueous electrolyte with a high active-site utilization of 93%. DHBD-Sb-COF//AC provided an excellent supercapacitive performance with an energy density of 78 Wh Kg-1 at the power density of 2553 W Kg-1 and super cycling stability, exceeding most of the previously reported pristine COF electrode-based supercapacitors. The "two-in-one" strategy of introducing hydroxyl groups onto imine COF skeletons to enhance both hydrophilicity and crystallinity provides a new avenue to improve the electrochemical performance of COF-based electrodes for high-performance supercapacitors.

Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression.

In mammals, the transition from mitosis to meiosis facilitates the successful production of gametes. However, the regulatory mechanisms that control meiotic initiation remain unclear, particularly in the context of complex histone modifications. Herein, we show that KDM2A, acting as a lysine demethylase targeting H3K36me3 in male germ cells, plays an essential role in modulating meiotic entry and progression. Conditional deletion of Kdm2a in mouse pre-meiotic germ cells results in complete male sterility, with spermatogenesis ultimately arrested at the zygotene stage of meiosis. KDM2A deficiency disrupts H3K36me2/3 deposition in c-KIT+ germ cells, characterized by a reduction in H3K36me2 but a dramatic increase in H3K36me3. Furthermore, KDM2A recruits the transcription factor E2F1 and its co-factor HCFC1 to the promoters of key genes required for meiosis entry and progression, such as Stra8, Meiosin, Spo11, and Sycp1. Collectively, our study unveils an essential role for KDM2A in mediating H3K36me2/3 deposition and controlling the programmed gene expression necessary for the transition from mitosis to meiosis during spermatogenesis.

Analysis of Comprehensive Nursing in the Treatment of Elderly Patients with Thoracolumbar Vertebral Body Compression Fractures by Percutaneous Vertebroplasty.

Objective: To explore and analyze the comprehensive nursing effect of percutaneous vertebroplasty (PVP) in the treatment of elderly patients with thoracolumbar vertebral compression fractures. Methods: This study recruited elderly patients with thoracolumbar vertebral compression fractures who were diagnosed in Lujiang County People's Hospital from January 2020 to December 2022 and underwent PVP. Finally, a total of 80 cases were included in this study. All patients were randomly divided into two treatment groups: the observation group and the control group. The patients in the control group were given routine nursing measures, and the patients in the observation group were given comprehensive nursing intervention. The baseline characteristics of the two groups of patients were recorded thoroughly, and relevant indicators such as clinical indicators, functional recovery, pain relief, and occurrence of complications were observed and compared between the two groups. Results: The recovery time of the patients in the observation group, including the time of getting out of bed and the time of hospitalization, was significantly shorter than that of the control group [OR = 0.61 (95%CI: 0.44 - 0.83); OR = 0.70 (95%CI: 0.51 - 0.96)] P < .05; the JOA score of the observation group was significantly higher than that of the control group after treatment (RR = 1.28 (95%CI: 1.16 - 1.42)); the vas scores of the patients at each time point were lower than those of the control group [OR = 0.60 (95%CI: 0.43 - 0.84); OR = 0.57 (95%CI: 0.41 - 0.80); OR = 0.61 (95%CI: 0.44 - 0.85); OR = 0.72 (95%CI: 0.52 - 0.99)]; the incidence of complications in the observation group was significantly lower than that of the control group OR = 0.27 (95%CI: 0.10 - 0.72). Conclusion: The implementation of comprehensive nursing has a clear application effect on PVP in the treatment of elderly patients with thoracolumbar vertebral compression fractures. It can effectively speed up patients' movement speeds, reduce the overall length of hospitalization, and promote the recovery of thoracolumbar spine function. It can also relieve the patient's pain faster, reduce the possibility of complications, and have a positive impact on the patient's prognosis, which is worthy of clinical application.

Genome-wide identification and characterization of the JAZ gene family in Gynostemma pentaphyllum reveals the COI1/JAZ/MYC2 complex potential involved in the regulation of the MeJA-induced gypenoside biosynthesis.

The Jasmonate ZIM domain (JAZ) proteins, functioning as critical suppressors for jasmonic acid (JA) signal transduction in plants, occupy crucial roles in multiple biological processes, particularly in the orchestration of secondary metabolic pathways. However, the mechanism underlying the JA-induced gypenosides accumulation in Gynostemma pentaphyllum remains poorly elucidated. Our research led to the identification of 11 distinct JAZ members in G. pentaphyllum (GpJAZs). According to the classification approach of AtJAZ, we allocated these members into five subgroups that shared similar conserved motif compositions. Subsequently, we identified the presence of various cis-acting elements associated with light stimuli, hormone responses, and stress signals within the promoter regions of the GpJAZ gene family. The expression levels of GpJAZ genes in different tissues were quite different, and the majority of GpJAZ genes exhibited varying degrees of response to methyl jasmonate (MeJA) induction. Yeast two-hybrid (Y2H) assays revealed interactions between GpJAZ1/2/4/5/7/9/10 and GpMYC2, whereas GpCOI1 protein was found to interact with GpJAZ1/2/4/5, thereby forming the COI1/JAZ/MYC2 complex. Furthermore, as an activator of gypenoside metabolic pathway, GpMYC2 could activate the promoter activity of the gypenoside metabolism-related genes to varying degrees by binding to their promoters, indicating that the COI1/JAZ/MYC2 module involved in the MeJA-induced regulation of gypenosides. In summary, our findings present an exhaustive examination of the JAZ gene family, furnishing a significant lead for delving deeper into the molecular mechanisms that drive the MeJA-induced enhancement of gypenosides accumulation in G. pentaphyllum.

Differentiation between viral and autoimmune limbic encephalitis: a prospective cohort study with development and validation of a diagnostic model.

BACKGROUND: Distinguishing between viral encephalitis (VE) and autoimmune limbic encephalitis (ALE) presents a clinical challenge due to the overlap in symptoms. We aimed to develop and validate a diagnostic prediction model to differentiate VE and ALE. METHODS: A prospective observational multicentre cohort study, which continuously enrolled patients diagnosed with either ALE or VE from October 2011 to April 2023. The demographic data, clinical features, and laboratory test results were collected and subjected to logistic regression analyses. The model was displayed as a web-based nomogram and then modified into a scored prediction tool. Model performance was assessed in both derivation and external validation cohorts. RESULTS: A total of 2423 individuals were recruited, and 1001 (496 VE, 505 ALE) patients were included. Based on the derivation cohort (389 VE, 388 ALE), the model was developed with eight variables including age at onset, acuity, fever, headache, nausea/vomiting, psychiatric or memory complaints, status epilepticus, and CSF white blood cell count. The model showed good discrimination and calibration in both derivation (AUC 0.890; 0.868-0.913) and external validation (107 VE, 117 ALE, AUC 0.872; 0.827-0.917) cohorts. The scored prediction tool had a total point that ranged from - 4 to 10 also showing good discrimination and calibration in both derivation (AUC 0.885, 0.863-0.908) and external validation (AUC 0.868, 0.823-0.913) cohorts. CONCLUSIONS: The prediction model provides a reliable and user-friendly tool for differentiating between the VE and ALE, which would benefit early diagnosis and appropriate treatment and alleviate economic burdens on both patients and society.

Dietary supplementation with non-digestible isomaltooligosaccharide and Lactiplantibacillus plantarum ZDY2013 ameliorates DSS-induced colitis via modulating intestinal barrier integrity and the gut microbiota.

Non-digestible oligosaccharides have attracted attention due to their critical role in maintaining the balance of a host's gut microbiota. Lactiplantibacillus plantarum ZDY2013 was isolated from traditional fermented acid beans, which could metabolize many complex carbohydrates and had intestinal immunomodulatory effects. In our study, the ameliorative effect of a combination of non-digestible isomaltooligosaccharide (IMO) and L. plantarum ZDY2013 was investigated in dextran sulfate sodium (DSS)-induced colitis mice. The results showed that IMO could specifically promote L. plantarum ZDY2013 intestinal colonization after five days of gavage and ameliorate the symptoms of colitis (survival rate, DAI score, colon length, etc.) as well as colon tissue integrity. IMO combined with L. plantarum ZDY2013 increased the levels of intestinal tight junction proteins (ZO-1 and claudin) and mucin (MUC-2), followed by alleviation of inflammatory responses (decreased the expression of IL-1ß, TNF-α, and IL-6 and increased the expression of IL-10 and IL-22) and the level of oxidative stress (decreased the level of COX-2 and iNOS and increased the expression of T-AOC and SOD). Furthermore, the combination increased the diversity of the gut microbiota and modulated the microbial structural component (decreased the abundance of Escherichia and Helicobacter and increased the abundance of Lactobacillus and SCFA-producing related species). Taken together, our results suggested that the consumption of IMO and L. plantarum ZDY2013 could improve the symptoms of colitis in mice by improving the intestinal barrier along with regulating the composition and metabolites of the gut microbiota.

A cross-sectional, multicenter survey of the prevalence and influencing factors for migraine in epilepsy.

OBJECTIVES: Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy. METHODS: Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine. RESULTS: A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068-1.975; p = 0.018), focal and focal to bilateral tonic-clonic seizures (OR = 1.583, 95% CI: 1.090-2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282-3.063; p = 0.002) were the influencing factors for migraine. However, <10% of patients with epilepsy received analgesics for migraine. SIGNIFICANCE: Approximately 20% of patients with epilepsy screened positive for migraine. Being female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were the influencing factors for migraine. Neurologists should pay more attention to the screening and management of the migraine among patients with epilepsy in China. PLAIN LANGUAGE SUMMARY: Epilepsy and migraine are common chronic neurological disease with shared pathophysiological mechanisms and therapeutic options. However, migraine is often underestimated among patients with epilepsy. This multicenter study aimed to evaluate the prevalence of migraine and current status of treatment. In this study, approximately 20% of patients with epilepsy screened positive for migraine. Female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were identified as independent influencing factors for migraine. Despite the high prevalence, the treatment for migraine was not optimistic, neurologists should pay more attention to the screening and management of migraine.

Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

ML241 Antagonizes ERK 1/2 Activation and Inhibits Rotavirus Proliferation.

Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.

Social support and the burden of physical and psychiatric comorbidities in the patients with late-onset epilepsy in China: A cross-sectional study.

INTRODUCTION: Epilepsy is the third most common neurological disorder in elderly people. Patients with epilepsy (PWEs) are more likely to have comorbidities. Social support is very important for PWEs. However, there are many gaps in the research on social support in older PWEs, especially the correlation between social support and comorbidities. METHODS: A cross-sectional study was conducted in three hospitals in China. Social support was assessed using the Social Support Rate Scale. The burden of physical comorbidities was assessed using the CCI, and global disability was assessed using the mRS. The NDDIE was used to assess depression, the GAD7 was used for anxiety, the CDR was used for cognitive status, and the NPI was used for psychotic symptoms. RESULTS: A total of 154 older PWEs participated in the study. There were 97 patients with at least one physical comorbidities. The burden of physical comorbidities was negatively correlated with overall social support (Adj. r = -0.35, P < 0.001) and global disability (Adj. r = -0.45, P < 0.001). In terms of psychiatric comorbidities, anxiety, depression, and cognitive status were not correlated with overall social support (Adj. r = -0.03, -0.02, and -0.11, P > 0.05). Psychotic symptoms were correlated with overall social support (Adj. r = -0.20, P < 0.05). The overall burden of psychiatric comorbidities was associated with overall social support (r = 0.30, P < 0.01). DISCUSSION: Neurologists and social workers should consider more personalized biopsychosocial care to improve the quality of life of older PWEs.

Controllable fabrication of CoNi bimetallic alloy for high-performance electromagnetic wave absorption.

With the coming era of artificial intelligence (AI) dominated by high-tech electronics, developing high-performance microwave absorption materials (MAMs) is imperative to solve the problem of increasing electromagnetic inference and pollution. Herein, a metal-organic framework (MOF)-derived CoNi bimetallic alloy (CoNi/C) with an irregular rod-like structure is prepared by a thermal reduction method. Introducing the CoNi alloy facilitates the balance between conduction loss and polarization loss and forms good impedance matching, leading to excellent microwave absorption performance. Interestingly, the optimization of absorption performance can be further achieved by controllably modulating the molar ratio of Co and Ni (Co2+/Ni2+). As expected, the obtained CoNi/C delivers excellent microwave absorption performance with a minimum reflection loss (RLmin) of -50.80 dB at 10.40 GHz and an effective absorption bandwidth (EAB) of 3.28 GHz (8.91-12.19 GHz) with a filler loading of 50 wt% at 2.0 mm. In addition, the CoNi/C can reach a maximum EAB of 4.77 GHz (12.99-17.76 GHz) at a low thickness of 1.5 mm, spanning nearly the entire Ku band. The CoNi3/C also exhibits an impressive RLmin of -44.84 dB at 3.28 GHz in the S band. This work offers a novel strategy to modulate the magnetic/electric properties of MOF-derived MAMs.

Blood and CSF findings of cellular immunity in anti-NMDAR encephalitis.

OBJECTIVES: To investigate the immunopathogenic mechanisms of anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) by characterizing the changes of immune cells in both peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with NMDAR-E. METHODS: Cytology and flow cytometry were used to explore and compare different immunological parameters in PB and CSF of patients with NMDAR-E, viral encephalitis (VE) and healthy volunteers. Moreover, different models were established to assess the possibility of identifying NMDAR-E patients based on PB and CSF parameters. RESULTS: The neutrophil counts and monocyte-to-lymphocyte ratios (MLR) in PB are higher in NMDAR-E patients than in both VEs and controls (P < 0.001, respectively), while the percentages of CD3 + T, CD4 + T lymphocytes, and the leukocytes count in CSF were lower in NMDAR-Es than in VEs (P < 0.01, respectively). The higher percentages of CD8 + T cells in blood and CSF were both correlated with more severe NMDAR-E (P < 0.05, respectively). The poor neurological status group had significantly higher PB leukocytes but lower CSF leukocyte count (P < 0.05). Longitudinal observations in patients with NMDAR-E showed a decreasing trend of leukocyte count, neutrophils count, neutrophil-to-monocyte ratios (NMR), and neutrophil-to-lymphocyte ratios (NLR) with the gradual recovery of neurological function. CONCLUSIONS: The expression patterns of T lymphocyte subsets were different in patients with NMDAR-E and viral encephalitis. The changing trends of leukocyte and lymphocyte populations in peripheral blood and cerebrospinal fluid may provide clues for the diagnosis of different types of encephalitides, including NMDARE, and can be used as immunological markers to assess and predict the prognosis.

Medicarpin suppresses lung cancer cell growth in vitro and in vivo by inducing cell apoptosis.

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

Genome-wide characterization of the bHLH gene family in Gynostemma pentaphyllum reveals its potential role in the regulation of gypenoside biosynthesis.

BACKGROUND: Gynostemma pentaphyllum, an ancient Chinese herbal medicine, serves as a natural source of gypenosides with significant medicinal properties. Basic helix-loop-helix (bHLH) transcription factors play pivotal roles in numerous biological processes, especially in the regulation of secondary metabolism in plants. However, the characteristics and functions of the bHLH genes in G. pentaphyllum remain unexplored, and their regulatory role in gypenoside biosynthesis remains poorly elucidated. RESULTS: This study identified a total of 111 bHLH members in G. pentaphyllum (GpbHLHs), categorizing them into 26 subgroups based on shared conserved motif compositions and gene structures. Collinearity analysis illustrated that segmental duplications predominately lead to the evolution of GpbHLHs, with most duplicated GpbHLH gene pairs undergoing purifying selection. Among the nine gypenoside-related GpbHLH genes, two GpbHLHs (GpbHLH15 and GpbHLH58) were selected for further investigation based on co-expression analysis and functional prediction. The expression of these two selected GpbHLHs was dramatically induced by methyl jasmonate, and their nuclear localization was confirmed. Furthermore, yeast one-hybrid and dual-luciferase assays demonstrated that GpbHLH15 and GpbHLH58 could bind to the promoters of the gypenoside biosynthesis pathway genes, such as GpFPS1, GpSS1, and GpOSC1, and activate their promoter activity to varying degrees. CONCLUSIONS: In conclusion, our findings provide a detailed analysis of the bHLH family and valuable insights into the potential use of GpbHLHs to enhance the accumulation of gypenosides in G. pentaphyllum.

Exploring the Experiences and Support of Nurses as Second Victims After Patient Safety Events in China: A Mixed-Method Approach.

Aim: To investigate the current status of experience and support of nurses as second victims and explore its related factors in nurses. Design: A sequential, explanatory, mixed-method study was applied. Methods: A total of 406 nurses from seven tertiary hospitals in China were chosen as participants between September to October 2023. The Chinese version of the Second Victim Experience and Support Questionnaire (SVEST), Somatic Complaints of Sub-health Status Questionnaire (SCSSQ) and Generalized Anxiety Disorder (GAD-7) were applied to collect quantitative data. Eight nurses were selected for a qualitative study through in-depth interviews. Through interpretive phenomenological analysis, the interview data were analysed to explore the experience and support of nurses as second victims. Results: Practice distress (15.74 ± 4.97) and psychological distress (15.48 ± 3.74) were the highest dimensions, indicating Chinese nurses experienced second victim-related practice and psychological distress. Nurses with different gender, age, education, marital status, income, working hours, professional titles, and unit types have different levels of second victim-related experience and support (p < 0.05). In addition, the score of SVEST was positively associated with SCSSQ (r = 0.444) and GAD-7 (r = 0.490) (p < 0.05). This qualitative study found that the experience and support of nurses as second victims included nurses' perceptions and needs for patient safety events; psychological, physical and practice distress of nurses; and nurses and hospitals coping style after patient safety events. Discussion: Our findings suggest that nurses who are second victims of patient safety events experience severe practice and psychological distress, indicating that nursing managers should pay attention to psychological and practice distress of nurses after patient safety events and provide effective preventive measures.