RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin.

The effect of Ryanodine receptor2 (RyR2) and its stabilizer on cardiac hypertrophy is not well known. C57/BL6 mice underwent transverse aortic contraction (TAC) or sham surgery were administered dantrolene, the RyR2 stabilizer, or control drug. Dantrolene significantly alleviated TAC-induced cardiac hypertrophy in mice, and RNA sequencing was performed implying calcineurin/NFAT3 and TNF-α/NF-κB/NLRP3 as critical signaling pathways. Further expression analysis and Western blot with heart tissue as well as neonatal rat cardiomyocyte (NRCM) model confirmed dantrolene decreases the activation of calcineurin/NFAT3 signaling pathway and TNF-α/NF-κB/NLRP3 signaling pathway, which was similar to FK506 and might be attenuated by calcineurin overexpression. The present study shows for the first time that RyR2 stabilizer dantrolene attenuates cardiac hypertrophy by inhibiting the calcineurin, therefore downregulating the TNF-α/NF-κB/NLRP3 pathway.

Risk factors and prediction model construction for peripherally inserted central catheter-related infections.

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312-3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119-3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677-4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019-2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012-4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133-3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172-3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

A new nomogram model for the individualized prediction of mild cognitive impairment in elderly patients with type 2 diabetes mellitus.

Background: A high risk of developing mild cognitive impairment (MCI) is faced by elderly patients with type 2 diabetes mellitus (T2DM). In this study, independent risk factors for MCI in elderly patients with T2DM were investigated, and an individualized nomogram model was developed. Methods: In this study, clinical data of elderly patients with T2DM admitted to the endocrine ward of the hospital from November 2021 to March 2023 were collected to evaluate cognitive function using the Montreal Cognitive Assessment scale. To screen the independent risk factors for MCI in elderly patients with T2DM, a logistic multifactorial regression model was employed. In addition, a nomogram to detect MCI was developed based on the findings of logistic multifactorial regression analysis. Furthermore, the accuracy of the prediction model was evaluated using calibration and receiver operating characteristic curves. Finally, decision curve analysis was used to evaluate the clinical utility of the nomogram. Results: In this study, 306 patients were included. Among them, 186 patients were identified as having MCI. The results of multivariate logistic regression analysis demonstrated that educational level, duration of diabetes, depression, glycated hemoglobin, walking speed, and sedentary duration were independently correlated with MCI, and correlation analyses showed which influencing factors were significantly correlated with cognitive function (p <0.05). The nomogram based on these factors had an area under the curve of 0.893 (95%CI:0.856-0.930)(p <0.05), and the sensitivity and specificity were 0.785 and 0.850, respectively. An adequate fit of the nomogram in the predictive value was demonstrated by the calibration plot. Conclusions: The nomogram developed in this study exhibits high accuracy in predicting the occurrence of cognitive dysfunction in elderly patients with T2DM, thereby offering a clinical basis for detecting MCI in patients with T2DM.

Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway.

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1ß. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

A panel of multivalent nanobodies broadly neutralizing Omicron subvariants and recombinant.

The emerging Omicron subvariants have a remarkable ability to spread and escape nearly all current monoclonal antibody (mAb) treatments. Although the virulence of SARS-CoV-2 has now diminished, it remains a significant threat to public health due to its high transmissibility and susceptibility to mutation. Therefore, it is urgent to develop broad-acting and potent therapeutics targeting current and emerging Omicron variants. Here, we identified a panel of Omicron BA.1 spike receptor-binding domain (RBD)-targeted nanobodies (Nbs) from a naive alpaca VHH library. This panel of Nbs exhibited high binding affinity to the spike RBD of wild-type, Alpha B.1.1.7, Beta B.1.351, Delta plus, Omicron BA.1, and BA.2. Through multivalent Nb construction, we obtained a subpanel of ultrapotent neutralizing Nbs against Omicron BA.1, BA.2, BF.7 and even emerging XBB.1.5, and XBB.1.16 pseudoviruses. Protein structure prediction and docking analysis showed that Nb trimer 2F2E5 targets two independent RBD epitopes, thus minimizing viral escape. Taken together, we obtained a panel of broad and ultrapotent neutralizing Nbs against Omicron BA.1, Omicron BA.2, BF.7, XBB.1.5, and XBB.1.16. These multivalent Nbs hold great promise for the treatment against SARS-CoV-2 infection and could possess a superwide neutralizing breadth against novel omicron mutants or recombinants.

Targeting novel regulated cell death：Ferroptosis, pyroptosis, and autophagy in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is a heterogenous complex clinical syndrome caused by the dysfunctional response of a host to infection. This dysfunctional response leads to excess mortality and morbidity worldwide. Despite clinical relevance with high incidence, there is a lack of understanding for its both its acute/chronic pathogenesis and therapeutic management. A better understanding of the molecular mechanisms behind SAE may provide tools to better enhance therapeutic efficacy. Mounting evidence indicates that some types of non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, and autophagy, contribute to SAE. Targeting these types of RCD may provide meaningful targets for future treatments against SAE. This review summarizes the core mechanism by which non-apoptotic RCD leads to the pathogenesis of SAE. We focus on the emerging types of therapeutic compounds that can inhibit RCD and delineate their beneficial pharmacological effects against SAE. Within this review we suggest that pharmacological inhibition of non-apoptotic RCD may serve as a potential therapeutic strategy against SAE.

Discrimination of opium from Afghanistan and Myanmar by infrared spectroscopy coupled with machine learning methods.

Afghanistan and Myanmar are two overwhelming opium production places. In this study, rapid and efficient methods for distinguishing opium from Afghanistan and Myanmar were developed using infrared spectroscopy (IR) coupled with multiple machine learning (ML) methods for the first time. A total of 146 authentic opium samples were analyzed by mid-IR (MIR) and near-IR (NIR), within them 116 were used for model training and 30 were used for model validation. Six ML methods, including partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA), k-nearest neighbour (KNN), support vector machine (SVM), random forest (RF), and artificial neural networks (ANNs) were constructed and compared to get the best classification effect. For MIR data, the average of precision, recall and f1-score for all classification models were 1.0. For NIR data, the average of precision, recall and f1-score for different classification models ranged from 0.90 to 0.94. The comparison results of six ML models for MIR and NIR data showed that MIR was more suitable for opium geography classification. Compared with traditional chromatography and mass spectrometry profiling methods, the advantages of MIR are simple, rapid, cost-effective, and environmentally friendly. The developed IR chemical profiling methodology may find wide application in classification of opium from Afghanistan and Myanmar, and also to differentiate them from opium originating from other opium producing countries. This study presented new insights into the application of IR and ML to rapid drug profiling analysis.

A MgAl-LDH-CuS nanosheet-based thermo-responsive composite hydrogel with nir-responsive angiogenesis inhibitor releasing capability for multimode starvation therapy.

The rapid proliferation of tumors is highly dependent on the nutrition supply of blood vessels. Cutting off the nutrient supply to tumors is an effective strategy for cancer treatment, known as starvation therapy. Although various hydrogel-based biomaterials have been developed for starvation therapy through glucose consumption or intravascular embolization, the limitations of single-mode starvation therapy hinder their therapeutic effects. Herein, we propose a dual-function nutrition deprivation strategy that can block the nutrients delivery through extravascular gelation shrinkage and inhibit neovascularization through angiogenesis inhibitors based on a novel NIR-responsive nanocomposite hydrogel. CuS nanodots-modified MgAl-LDH nanosheets loaded with angiogenesis inhibitor (sorafenib, SOR) are incorporated into the poly(n-isopropylacrylamide) (PNIPAAm) hydrogel by radical polymerization to obtain the composite hydrogel (SOR@LDH-CuS/P). The SOR@LDH-CuS/P hydrogel can deliver hydrophobic SOR with a NIR-responsive release behavior, which could decrease the tumor vascular density and accelerate cancer cells apoptosis. Moreover, the SOR@LDH-CuS/P hydrogel exhibits higher (3.5 times) compressive strength than that of the PNIPAAm, which could squeeze blood vessels through extravascular gelation shrinkage. In vitro and in vivo assays demonstrate that the interruption of nutrient supply by gelation shrinkage and the prevention of angiogenesis by SOR is a promising strategy to inhibit tumor growth for multimode starvation therapy.

The prevalence of mild cognitive impairment and dementia among rural dwellers: A systematic review and meta-analysis.

The mild cognitive impairment (MCI) and dementia in rural areas are increasingly attracting public attention. However, their prevalence is still unclear. This study aims to reveal the distribution of MCI and dementia in rural areas. We systematically searched PubMed, Web of Science, Embase, and PsycINFO up to June 2023 for cohort and cross-sectional studies. Meta-analysis was conducted using random-effects models to evaluate the prevalence of MCI and dementia. Thirty-five studies with 16,936 participants met the inclusion criteria. The pooled prevalence of MCI and dementia was 27 % (n = 12, 95 %CI = 0.21-0.32, I2 = 99.5 %, P < 0.001) and 7 % (n = 27, 95 %CI = 0.05-0.08, I2 = 99.30 %, P < 0.001), respectively. Subgroup analyses revealed that aged 60 years or older [(MCI: 29 %, 95 %CI = 0.20-0.38, I2 = 99.7 %, P < 0.001), (dementia: 9 % (95 %CI = 0.06-0.12, I2 = 99 %, P < 0.001)], female [(MCI: 29 %, 95 %CI = 0.19-0.40, I2 = 99.3 %, P < 0.001), (dementia: 7 %, 95 % CI = 0.04-0.12, I2 = 98.66 %, P < 0.001)], a-MCI (19 %, 95 %CI = 0.12-0.26, I2 = 97.62 %, P < 0.001) and AD (4 %, 95 %CI = 0.02-0.05, I2 = 98.60 %, P < 0.001) showed higher prevalence. The prevalence of MCI and dementia in rural China was 23 % (95 %CI = 0.18-0.29, I2 = 99.5 %, P < 0.001) and 6 % (95 %CI = 0.04-0.08, I2 = 99.6 %, P < 0.001), respectively. Implementing cognitive impairment screening and intervention measures is necessary to improve the cognitive function of the rural population.

Global trends in research on MOG antibody-associated disease: bibliometrics and visualization analysis.

Objective: The purpose of this study was to investigate the current research status, focus areas, and developmental trends in the field of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) through an analysis of scientific literature. Methods: The relevant research articles on MOGAD published from 1947 to 2022 were retrieved from the Web of Science database. The quantitative output of MOGAD related research articles, their distribution by country/region, data on collaborative publishing, influential authors, high-yield institutions, keywords, hotspots, and development trends were analyzed. Additionally, visual knowledge maps were generated using VOSviewer and Citespace. Results: There has been a steady increase in the number of MOGAD related publications indicating that the subject has garnered increasing interest among researchers globally. The United States has been the leading contributor with 496 papers (19.25%), followed by China (244, 9.63%), Japan (183, 7.10%), the United Kingdom (154, 5.98%), and Germany (149, 5.78%). Among these countries, the United Kingdom boasts the highest citation frequency at the rate of 46.49 times per paper. Furthermore, active collaboration in MOGAD related research is observed primarily between the United States and countries such as Canada, Germany, Australia, Italy, the United Kingdom and Japan. Mayo Clinic ranks first in total articles published (109) and frequency of citations per article (77.79). Takahashi Toshiyuki from Tohoku University is the most prolific author, while Multiple Sclerosis and Related Disorders is the most widely read journal in this field. "Disease Phenotype", "Treatment", "Novel Coronavirus Infection and Vaccination", "Immunopathological Mechanisms", "Clinical characteristics of children" and "Prognosis" are the primary keywords clusters in this field. "Novel Coronavirus Infection and Vaccination" and "Immunopathological Mechanisms" are research hotspots and have great development potential. Conclusion: The past three decades have witnessed a significant expansion of research on MOGAD. The pathogenetic mechanism of MOGAD is poised to be the prominent research focus in this field in the foreseeable future.

Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.

OBJECTIVE: This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (MMA) with nervous system damage as the primary manifestation. METHODS: From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation, diagnosed with methylmalonic acidemia by metabolic and genetic testing, were enrolled and analyzed. Their clinical, imaging, and electroencephalogram data were analyzed. RESULTS: A total of 18 patients were enrolled, including 15 males and 3 females. The clinical symptoms were convulsions, poor feeding, growth retardation, disorder of consciousness, developmental delay, hypotonia, and blood system changes. There were 6 cases (33%) of hydrocephalus, 9 (50%) of extracerebral space widened, 5 (27%) of corpus callosum thinning, 3 (17%) of ventricular dilation, 3 (17%) of abnormal signals in the brain parenchyma (frontal lobe, basal ganglia region, and brain stem), and 3 (17%) of abnormal signals in the lateral paraventricular. In addition, there were 3 cases (17%) of cerebral white matter atrophy and 1 (5%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data displayed 2 cases (11%) of hypsarrhythmia, 3 (17%) of voltage reduction, 12(67%) of abnormal discharge, 13 (72%) of abnormal sleep physiological waves or abnormal sleep structure, 1 (5%) of immature (delayed) EEG development, and 8 (44%) of slow background. There were 2 cases (11%) of spasms, 1 (5%) of atonic seizures, and 1 (5%) of myoclonic seizures. There were 16 patients (89%) with hyperhomocysteinemia. During follow-up, 1 patient was lost to follow-up, and 1 died. In total, 87.5% (14/16) of the children had varying developmental delays. EEG was re-examined in 11 cases, of which 8 were normal, and 3 were abnormal. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral antiepileptic therapy. Acute treatment included anti-infective, blood transfusion, fluid replacement, and correcting acidosis. The other treatments included low-protein diets and special formula milk powder. CONCLUSION: Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals on brain MRI. Metabolic screening and genetic testing help clarify the diagnosis. EEG can reflect changes in brain waves during the acute phase.

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer's disease.

Butyrylcholinesterase (BuChE) and neuroinflammation have recently emerged as promising therapeutic directions for Alzheimer's disease (AD). Herein, we synthesised 19 novel pyranone-carbamate derivatives and evaluated their activities against cholinesterases and neuroinflammation. The optimal compound 7p exhibited balanced BuChE inhibitory activity (eqBuChE IC50 = 4.68 nM; huBuChE IC50 = 9.12 nM) and anti-neuroinflammatory activity (NO inhibition = 28.82% at 10 µM, comparable to hydrocortisone). Enzyme kinetic and docking studies confirmed compound 7p was a mix-type BuChE inhibitor. Additionally, compound 7p displayed favourable drug-likeness properties in silico prediction, and exhibited high BBB permeability in the PAMPA-BBB assay. Compound 7p had good safety in vivo as verified by an acute toxicity assay (LD50 > 1000 mg/kg). Most importantly, compound 7p effectively mitigated cognitive and memory impairments in the scopolamine-induced mouse model, showing comparable effects to Rivastigmine. Therefore, we envisioned that compound 7p could serve as a promising lead compound for treating AD.

Single-Cell Transcriptomics Reveals the Ameliorative Effect of Oridonin on Septic Liver Injury.

Sepsis is a life-threatening syndrome leading to hemodynamic instability and potential organ dysfunction. Oridonin, commonly used in Traditional Chinese Medicine (TCM), exhibits significant anti-inflammation activity. To explore the protective mechanisms of oridonin against the pathophysiological changes, the authors conducted single-cell transcriptome (scRNA-seq) analysis on septic liver models induced by cecal ligation and puncture (CLP). They obtained a total of 63,486 cells, distributed across 11 major cell clusters, and concentrated their analysis on four specific clusters (hepatocytes/Heps, macrophages, endothelial/Endos and T/NK) based on their changes in proportion during sepsis and under oridonin treatment. Firstly, biological changes in Hep, which are related to metabolic dysregulation and pro-inflammatory signaling, are observed during sepsis. Secondly, they uncovered the dynamic profiles of macrophage's phenotype, indicating that a substantial number of macrophages exhibited a M1-skewed phenotype associated with pro-inflammatory characteristics in septic model. Thirdly, they detected an upregulation of both inflammatory cytokines and transcriptomic factor Nfkb1 expression within Endo, along with slight capillarization during sepsis. Moreover, excessive accumulation of cytotoxic NK led to an immune imbalance. Though, oridonin ameliorated inflammatory-related responses and improved the liver dysfunction in septic mice. This study provides fundamental evidence of the protective effects of oridonin against sepsis-induced cytokine storm.

Association between Body-Image Satisfaction and Anxiety, Depressive Symptoms among Women with PCOS: The Mediating Role of Emotion Regulation Strategies.

Anxiety and depressive symptoms are prevalent in women with polycystic ovary syndrome (PCOS), and there is a great need for culturally relevant interventions to improve anxiety and depressive symptoms in women with PCOS. The current study aimed to analyze the factors influencing body-image satisfaction, anxiety, and depressive symptoms in Chinese women with PCOS. It also aimed to clarify the association between body-image satisfaction and anxiety and depressive symptoms in women with PCOS, and whether this association was mediated by cognitive reappraisal and expressive suppression. A total of 477 women with PCOS were recruited from the Department of Gynecology and Reproductive Medicine Center of one university-affiliated tertiary hospital in China. They completed the Generalized Anxiety Disorder-7 scale, the Patient Health Questionnaire-9, the Body Image States Scale, and the Emotion Regulation Questionnaire. The study found body-image satisfaction showed significant associations with anxiety and depressive symptoms. This association was mediated by cognitive reappraisal and expressive suppression. The findings of this study offer new insights into the relationship between body image and anxiety and depressive symptoms in women with PCOS. They also emphasize the potential value of promoting body-image satisfaction and enhancing cognitive reappraisal abilities to improve the mental health of women with PCOS.

Recapitulating primary immunodeficiencies with expanded potential stem cells: Proof of concept with STAT1 gain of function.

BACKGROUND: Inborn errors of immunity (IEI) often lack specific disease models and personalized management. Signal transducer and activator of transcription (STAT)-1 gain of function (GoF) is such example of an IEI with diverse clinical phenotype with unclear pathomechanisms and unpredictable response to therapy. Limitations in obtaining fresh samples for functional testing and research further highlights the need for patient-specific ex vivo platforms. OBJECTIVE: Using STAT1-GoF as an example IEI, we investigated the potential of patient-derived expanded potential stem cells (EPSC) as an ex vivo platform for disease modeling and personalized treatment. METHODS: We generated EPSC derived from individual STAT1-GoF patients. STAT1 mutations were confirmed with Sanger sequencing. Functional testing including STAT1 phosphorylation/dephosphorylation and gene expression with or without Janus activating kinase inhibitors were performed. Functional tests were repeated on EPSC lines with GoF mutations repaired by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) editing. RESULTS: EPSC were successfully reprogrammed from STAT1-GoF patients and expressed the same pluripotent makers as controls, with distinct morphologic differences. Patient-derived EPSC recapitulated the functional abnormalities of index STAT1-GoF patients with STAT1 hyperphosphorylation and increased expression of STAT1 and its downstream genes (IRF1, APOL6, and OAS1) after IFN-γ stimulation. Addition of ruxolitinib and baricitinib inhibited STAT1 hyperactivation in STAT1-GoF EPSC in a dose-dependent manner, which was not observed with tofacitinib. Corrected STAT1 phosphorylation and downstream gene expression were observed among repaired STAT1-GoF EPSC cell lines. CONCLUSION: This proof-of-concept study demonstrates the potential of our patient-derived EPSC platform to model STAT1-GoF. We propose this platform when researching, recapitulating, and repairing other IEI in the future.

NeuroD1 administration ameliorated neuroinflammation and boosted neurogenesis in a mouse model of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) causes significant long-term neurocognitive dysfunction, which is associated with hippocampal neuroinflammation. Growing evidences have shown that astrocytes played a significant role in mediating neuroinflammation. Recently, in vivo reprogramming of astrocytes to neurons by NeuroD1 or PTBP1 administration has generated a lot of interests and controversies. While the debates centered on the source of neurogenesis, no attention has been paid to the changes of the astrocytes-mediated neuroinflammation and its impact on endogenous neurogenesis after NeuroD1 administration. METHODS: 80 adult male C57BL/6 mice were used in this study. SAH was established by pre-chiasmatic injection of 100 µl blood. AAV-NeuroD1-GFP virus was injected to the hippocampus 3 day post-SAH. Neurocognitive function, brain water content, in vivo electrophysiology, Golgi staining, western blot and immunofluorescent staining were assessed at day 14 post-virus injection. RESULTS: NeuroD1 administration markedly attenuated reactive astrocytes-mediated neuroinflammation by reversing neurotoxic A1 astrocytes transformation, decreasing the secretion of neuroinflammatory cytokines, and reducing the activation of harmful microglia. NeuroD1 treatment significantly reversed the brain-blood barrier impairment and promoted the release of neurotrophic factors pleiotrophin (PTN), all of which contributed to the improvement of cellular microenvironment and made it more suitable for neurogenesis. Interestingly, besides neurogenesis in the hippocampus from cells transfected with NeuroD1 at the early phase of SAH, NeuroD1 administration significantly boosted the endogenous neurogenesis at the late phase of SAH, which likely benefited from the improvement of the neuroinflammatory microenvironment. Functionally, NeuroD1 treatment significantly alleviated neurocognitive dysfunction impaired by SAH. CONCLUSIONS: NeuroD1 significantly promoted neurofunctional recovery by attenuating reactive astrocytes-mediated neuroinflammation and boosting neurogenesis decimated by SAH. Specifically, NeuroD1 efficiently converted transfected cells, most likely astrocytes, to neurons at the early phase of SAH, suppressed astrocytes-mediated neuroinflammation and boosted endogenous neurogenesis at the late phase of SAH.

A sensitive and simple RT-LAMP assay for sarbecovirus screening in bats.

IMPORTANCE: We report the application of a colorimetric and fluorescent reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to facilitate mass screening for sarbecoviruses in bats. The assay was evaluated using a total of 838 oral and alimentary samples from bats and demonstrated comparable sensitivity and specificity to quantitative reverse transcription PCR (qRT-PCR), with a simple setup. The addition of SYTO9, a fluorescent nucleic acid stain, also allows for quantitative analysis. The scalability and simplicity of the assay are believed to contribute to improving preparedness for detecting emerging coronaviruses by applying it to field studies and surveillance.

Geographical classification of opium samples from Myanmar and Afghanistan by NMR profiling and chemometrics.

This study presents a new strategy to discriminate between opium samples obtained from different geographical regions. Nuclear magnetic resonance (NMR) profiling and chemometrics were applied to geographical classification of opium originating from Myanmar and Afghanistan, which are two major opium producing countries in the world. A total of 50 Myanmar and 46 Afghanistan authentic opium samples were analyzed by 1 H-NMR, and the chemical profiles were characterized. Different sample preparation procedures, data processing methods, and chemometrics were compared to obtain the best classification effect. It was found that drying and the addition of buffer solutions were unnecessary for classification purposes; thus, the gum opium samples were extracted directly with CD3 OD, which shortened sample preparation time. A full discrimination between the two geographical origins was achieved by 1 H-NMR profiling and orthogonal partial least squares discriminant analysis. All 30 opium samples were classified correctly by the developed orthogonal partial least squares discriminant analysis model. Compared with traditional chromatography and mass spectrometry profiling methods, the 1 H-NMR profiling method was faster (with instrument analysis time of less than 3 min) and reproducible. This study provides new insights into the applying of NMR profiling and chemometrics to rapid drug profiling analysis.

Comparison of customized vacuum sealing drainage and vacuum sealing drainage in the treatment of diabetic foot ulcers: a retrospective analysis.

BACKGROUND: The prevalence of diabetic foot ulcers, a common, more serious chronic diabetes-related complication, is increasing. Vacuum sealing drainage (VSD) constitutes an effective adjunctive treatment for diabetic foot ulcers. Factors, such as poor glycemic control, ischemia, and infection prolong wound healing time, and VSD products are expensive and unaffordable for many patients. OBJECTIVE: To compare the use of customized VSD and customized VSD in the treatment of diabetic foot ulcer. METHOD: This retrospective study included 83 patients with diabetic foot ulcers in customized VSD (n = 44) and VSD (n = 39) groups. Baseline data, efficacy after 14 days, total treatment efficiency, final outcome (28 days after treatment, healing rate), average treatment cost, and hospitalization (days) of the two groups were compared. Factors affecting wound healing were analyzed. RESULTS: No significant intergroup differences in the baseline data were detected (VSD vs. customized VAD, p > 0.05). Treatment efficacy was higher in the customized VSD group than in the VSD group after 14 days (p < 0.05), although total treatment efficiency in both groups reached 100%. The final outcome in the customized VSD group was better (vs. VSD group, p < 0.05), and the wound healing rate was higher than in the VSD group (66.7% vs. 33.3%). The mean treatment cost and hospital days were greater in the VSD group (vs. customized VSD group; p < 0.05). Factors affecting wound healing include age, Wagner classification, HDL-C, and fasting C-peptide. Younger age, low Wagner classification grade, low HDL-C level, and high fasting C-peptide contribute to higher healing rate, CONCLUSION: Efficacy and final outcome of customized VSD were better than that of VSD; the customized VSD device is simple and convenient to operate, and enables cost-effective treatment.

The surgical treatment of female primary pelvic retroperitoneal tumours: A retrospective study of 99 patients from a single centre in China.

BACKGROUND: To summarise the application of minimally invasive surgery for female primary pelvic retroperitoneal tumours (PPRTs). METHODS: The clinical data of PPRT in a hospital between January 2017 and August 2022 were retrospectively collected. Surgical outcomes for cystic and solid tumours and two minimally invasive techniques were compared. RESULTS: 99 patients were included. Cystic tumours had fewer intraoperative injuries (4.0% vs. 28.0%, p < 0.001) than solid tumours. Robot-assisted laparoscopy (RALS) seemed to have fewer intraoperative complications (8.3% vs. 35.1%, p = 0.156) than conventional laparoscopy (CLS) in solid tumours. For cystic tumours, RALS included larger tumour sizes and longer operative times (p < 0.05), but intraoperative injury was comparable to CLS. RALS exhibited a higher cost than CLS in all tumours. CONCLUSIONS: Minimally invasive surgery for solid PPRTs tends to be more difficult than for cystic tumours, and RALS has a slight advantage over CLS with respect to short-term PPRT outcomes.