Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections.

Up to 45% of patients surviving from transient global cerebral ischemia (GCI) after cardiac arrest develop post-global cerebral ischemia depression (PGCID), but how to treat PGCID is clinically unknown. Here we find that cannabinoid type-1 receptor (CBR) antagonists, CBR knockout and endocannabinoid (eCB) synthesis inhibition block acute stress-induced PGCID. Application of acute stress to GCI mice increases CBR activity from ventromedial prefrontal cortical (vmPFC) terminals synapsing with the basolateral amygdala (BLA) neurons, indicating the involvement of increased vmPFC-BLA synaptic eCB signaling in PGCID induction.

Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19.

The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CL), and papain-like protease (PL) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CL inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CL from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms.

Efflux of TolC protein to different antimicrobials can be replaced by other outer membrane proteins with similar β-barrel structures in extraintestinal pathogenic Escherichia coli.

Aim: As a major efflux pump system in Gram-negative bacteria, AcrAB-TolC plays a key role in the transport of multiple drug substrates and is considered a potential target for the development of novel antimicrobials. Our previous study found that TolC inactivation compromised the resistance to different antimicrobials in porcine extraintestinal pathogenic Escherichia coli (ExPEC) strain PPECC042 (WT). This study was designed to investigate the functional substitution of TolC by other outer membrane proteins (OMPs) with similar β-barrel structures in pumping out different antimicrobials.

Performance assessment of an artificial intelligence-based coronary artery calcium scoring algorithm in non-gated chest CT scans of different slice thickness.

Background: The coronary artery calcium score (CACS) has been shown to be an independent predictor of cardiovascular events. The traditional coronary artery calcium scoring algorithm has been optimized for electrocardiogram (ECG)-gated images, which are acquired with specific settings and timing. Therefore, if the artificial intelligence-based coronary artery calcium score (AI-CACS) could be calculated from a chest low-dose computed tomography (LDCT) examination, it could be valuable in assessing the risk of coronary artery disease (CAD) in advance, and it could potentially reduce the occurrence of cardiovascular events in patients.

Association of MAFLD and MASLD with all-cause and cause-specific dementia: a prospective cohort study.

Background: Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia.

Methods: We conducted a prospective study with 403,506 participants from the UK Biobank.

Constructing a prognostic model for colon cancer: insights from immunity-related genes.

Background: Colon cancer (CC) is a malignancy associated with significant morbidity and mortality within the gastrointestinal tract. Recurrence and metastasis are the main factors affecting the prognosis of CC patients undergoing radical surgery; consequently, we attempted to determine the impact of immunity-related genes.

Result: We constructed a CC risk model based on ZG16, MPC1, RBM47, SMOX, CPM and DNASE1L3.

Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein.

Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process.

Hyperexcitation of ovBNST CRF neurons during stress contributes to female-biased expression of anxiety-like avoidance behaviors.

Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei of the stria terminalis (ovBNST) is generally indicated in stress, but its role in female-biased susceptibility to anxiety is unknown. Here, we established a female-biased stress paradigm. We found that the CRF release in ovBNST during stress showed female-biased pattern, and ovBNST CRF neurons were more prone to be hyperexcited in female mice during stress in both in vitro and in vivo studies.

Association between the haemoglobin glycation index (HGI) and clinical outcomes in patients with acute decompensated heart failure.

Background: A growing number of studies show that people with similar blood glucose levels have different levels of glycosylated haemoglobin (HbA1c), and relying only on HbA1c may lead to clinical decision-making errors. The haemoglobin glycation index (HGI) quantifies the difference in HbA1c among individuals and is strongly linked to the risk of cardiovascular disease. However, the connection between this phenomenon and the poor outcomes of patients with acute decompensated heart failure (ADHF) is currently unknown.

MSC-Derived Exosomes Mitigate Myocardial Ischemia/Reperfusion Injury by Reducing Neutrophil Infiltration and the Formation of Neutrophil Extracellular Traps.

Introduction: Acute inflammatory storm is a major cause of myocardial ischemia/reperfusion (I/R) injury, with no effective treatment currently available. The excessive aggregation of neutrophils is correlated with an unfavorable prognosis in acute myocardial infarction (AMI) patients. Exosomes derived from mesenchymal stromal cells (MSC-Exo) have certain immunomodulatory potential and might be a therapeutic application.

Mechanisms and protective measures for radiation-induced brachial plexus nerve injury.

Radiation therapy is a common treatment modality for patients with malignant tumors of the head and neck, chest and axilla. However, radiotherapy inevitably causes damage to normal tissues at the irradiated site, among which damage to the brachial plexus nerve(BP) is a serious adverse effect in patients receiving radiation therapy in the scapular or axillary regions, with clinical manifestations including abnormal sensation, neuropathic pain, and dyskinesia, etc. These adverse effects seriously reduce the living quality of patients and pose obstacles to their prognosis.

Neutrophil and endothelial cell membranes coassembled roflumilast nanoparticles attenuate myocardial ischemia/reperfusion injury.

This study aimed to develop biomimetic nanoparticles (NPs) of roflumilast (ROF) for attenuating myocardial ischemia/reperfusion (MI/R) injury. We synthesized biomimetic ROF NPs and assembled ROF NPs in neutrophil and endothelial cell membranes (NE/ROF NPs). The physical properties of NE/ROF NPs were characterized and biological functions of NE/ROF NPs were tested .

Ferroptosis: a potential target for the treatment of atherosclerosis.

Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation.

A Review of Screeners to Identify Risk of Developmental Language Disorder.

Purpose: This review aims to comprehensively summarize, compare, and evaluate screeners used to identify risk for developmental language disorder (DLD), a common learning disability that is underidentified. Screening for DLD is a cost-effective way to identify children in need of further assessment and, in turn, provides much needed supports.

Method: We identified 15 commercially available English language DLD screeners in North America.

Colchicine Attenuates Microvascular Obstruction after Myocardial Ischemia-Reperfusion Injury by Inhibiting the Proliferation of Neutrophil in Bone Marrow.

Purpose: Complete and rapid recanalization of blood flow by percutaneous coronary intervention (PCI) is the most effective intervention for patients with ST-segment elevation myocardial infarction (STEMI). However, myocardial ischemia/reperfusion (I/R) injury leads to microvascular obstruction (MVO), limiting its efficacy. Colchicine can reduce myocardial I/R injury, but its effect on MVO is unclear.

Platelet mitochondrial DNA methylation: A novel biomarker for myocardial infarction - A preliminary study.

Background: Platelet activation and thrombus formation play critical roles in the pathogenesis of myocardial infarction (MI). In addition to their role in energy production, platelet mitochondria also regulate cellular functions related to apoptosis, oxidative stress, and inflammation. Epigenetic modifications of platelet mitochondrial DNA (mtDNA) may influence platelet function and are believed to be an important factor in MI.

Hypertension-Driven Regulatory T-Cell Perturbations Accelerate Myocardial Ischemia-Reperfusion Injury.

Background: Patients with a history of hypertension have elevated inflammation and a worse prognosis after acute myocardial infarction (AMI). Regulatory T cells (Tregs) are reported to lose their immunosuppressive capacity under pathological conditions. However, whether hypertension leads to Treg dysfunction, thus accelerating myocardial ischemia-reperfusion injury, is still unknown.

The predictive value of relative wall thickness on the prognosis of the patients with ST-segment elevation myocardial infarction.

Objective: The study aimed to evaluate the prognostic value of relative wall thickness (RWT) in the patients with ST-segment elevation myocardial infarction (STEMI).

Methods: A total of 866 patients with STEMI admitted in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from November 2010 to December 2018 were enrolled in the current study retrospectively. Three methods were used to calculate RWT: RWT, RWT and RWT.

Development of a novel virus-like particle-based vaccine for preventing tick-borne encephalitis virus infection.

Tick-borne encephalitis virus (TBEV) is an important tick-borne pathogen that poses as a serious public health concern. The coverage and immunogenicity of the currently available vaccines against TBEV are relatively low; therefore, it is crucial to develop novel and effective vaccines against TBEV. The present study describes a novel strategy for the assembly of virus-like particles (VLPs) by co-expressing the structural (core/prM/E) and non-structural (NS2B/NS3Pro) proteins of TBEV.

Carotid ultrasound and systematic coronary risk assessment 2 in the prediction of cardiovascular events.

Aims: Subclinical carotid atherosclerosis adds predictive value to traditional risk factors for cardiovascular diseases (CVDs). Systematic Coronary Risk Assessment 2 (SCORE2), an algorithm composed of traditional risk factors, is a state-of-the-art to estimate the 10-year risk of first-onset CVDs. We aim to investigate whether and how subclinical carotid atherosclerosis affects the performance of SCORE2.

Penicillin-binding protein 1b encoded by mrcB gene mediates the enhancement of biofilm formation by subinhibitory concentrations of cefotaxime in monophasic Salmonella Typhimurium strain SH16SP46.

Development of cefotaxime-resistance and biofilm formation increase the difficulty to prevent and control the infection and contamination of Salmonella, one of the most important foodborne and zoonotic bacterial pathogen. Our previous study observed that 1/8 minimum inhibitory concentration (MIC) of cefotaxime induced the enhancement of biofilm formation and filamentous morphological change by a monophasic Salmonella Typhimurium strain SH16SP46. This study was designed to explore the role of three penicillin-binding proteins (PBPs) in mediating the induction effect of cefotaxime.

Heart-gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia/reperfusion.

Aims: Recent studies have suggested a key role of intestinal microbiota in pathological progress of multiple organs via immune modulation. However, the interactions between heart and gut microbiota remain to be fully elucidated. The aim of the study is to investigate the role of gut microbiota in the post-ischaemia/reperfusion (I/R) inflammatory microenvironment.