PTPσ-mediated PI3P regulation modulates neurodegeneration in C9ORF72-ALS/FTD.

The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the repeat expansion in C9ORF72. Dipeptide repeat (DPR) proteins translated from both sense and antisense repeats, especially arginine-rich DPRs (R-DPRs), contribute to neurodegeneration. Through CRISPR interference (CRISPRi) screening in human-derived neurons, we identified receptor-type tyrosine-protein phosphatase S (PTPσ) as a strong modifier of poly-GR-mediated toxicity.

Effects of acoustic stimulation on painful procedures in preterm and full-term infants: A systematic review and network meta-analysis.

Aim: This study aims to compare and rank the effects of acoustic stimulation on painful procedures in both preterm and full-term infants.

Methods: Six databases including Medline, Web of Science, the Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Embase, and SinoMed, were searched from inception to July, 2023. A Bayesian network meta-analysis with random effects models was performed using R software and Stata 15.

Correlation study on gut microbiota and myosteatosis in patients with liver cirrhosis.

Objective: To investigate the features of gut microbiota in cirrhotic patients with myosteatosis and identify specific bacterial species that may be involved in the pathogenesis of myosteatosis.

Methods: 80 patients with liver cirrhosis were categorized into the myosteatosis group ( = 44) and the non-myosteatosis group ( = 36). Metagenomic sequencing was used to analyze the differences in gut microbiota composition between the two groups.

Clinical characteristics and the role of IL-6 in acute-on-chronic liver failure patients with or without COVID-19: a multicenter paired cohort study.

Background And Aims: The impact of coronavirus disease 2019 (COVID-19) on patients with acute-on-chronic liver failure (ACLF) remains unclear. To investigate the clinical characteristics of patients with ACLF complicated with COVID-19 in order to provide evidence for the precise treatment of this patient population.

Methods: A total of 34 ACLF patients with COVID-19 admitted to these three hospitals from December 2022 to August 2023 were included as the ACLF+COVID-19 group.

Effects of nocturnal snacks on body composition in patients with liver cirrhosis.

Background: Patients with liver cirrhosis are universally malnourished and the nocturnal snacks intervention is the currently recommended nutritional intervention for patients with liver cirrhosis. Body composition is an important indicator for the assessment of nutritional conditions. We investigated the effects of nocturnal snacks (200 kcal/day) for 3 months on body composition in patients with liver cirrhosis.

Structural Elucidation and NMR Spectral Assignments of New Diphenyl Ether Derivatives From Liuweizhiji Gegen-Sangshen Oral Liquid.

Chemical investigation of the Liuweizhiji Gegen-Sangshen oral liquid afforded one new diphenyl ether derivative (1), together with one known compound (2). Their structures were established by 1D and 2D NMR, and HR-ESI-MS spectroscopic analysis and the absolute configuration of 1 was confirmed by ECD calculation. Compounds 1 and 2 were evaluated for the cytotoxic activities, and compounds 1 and 2 showed weak cytotoxic activities towards HepG2 human liver cancer cells, with IC values of 97.

Two New Alkaloids of the Endophytic Fungus Rhizopus oryzae From Atractylodes macrocephala Koidz.

Two new alkaloids, named migenomycin I (1) and II (2), along with nine known compounds (3-11), were isolated from the fungus Rhizopus oryzae from Atractylodes macrocephala Koidz. The structures of compounds 1 and 2 were determined by spectroscopic methods (MS, NMR, and CD). All compounds were isolated from Rhizopus oryzae for the first time.

In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia.

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate.

DDX3X overexpression decreases dipeptide repeat proteins in a mouse model of C9ORF72-ALS/FTD.

Hexanucleotide repeat expansion in C9ORF72 (C9) is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One of the proposed pathogenic mechanisms is the neurotoxicity arising from dipeptide repeat (DPR) proteins produced by repeat-associated non-AUG (RAN) translation. Therefore, reducing DPR levels emerges as a potential therapeutic strategy for C9ORF72-ALS/FTD.

Translation and psychometric testing of the Chinese version of the Perinatal Missed Care Survey.

Objective: This study aimed to translate and evaluate the psychometric properties of the Perinatal Missed Care Survey in China.

Methods: The Perinatal Missed Care Survey was translated according to the guidelines of the cross-cultural debugging scale recommended by the American Academy of Orthopaedic Surgeons Evidence-Based Medicine Committee, including forward translation, back translation, cultural adaption, and content validation, and its Chinese version was used in a cross-sectional study conducted from February to April in 2023. A total of 491 midwives from 14 different level hospitals in southwest China were recruited through a convenience sampling method.

Identification of Novel -Glucosidase Inhibitors from Syzygium jambos (L.) Using Spectroscopy and Molecular Docking.

Fruits of Syzygium jambos (L.) are recognized as a "food", exhibiting significant antidiabetic activities. However, the α-glucosidase inhibition of the components from Syzygium jambos (L.

PAR2 deficiency tunes inflammatory microenvironment to magnify STING signalling for mitigating cancer metastasis via anionic CRISPR/Cas9 nanoparticles.

Metastasis is one of the most significant causes for deterioration of breast cancer, contributing to the clinical failure of anti-tumour drugs. Excessive inflammatory responses intensively promote the occurrence and development of tumour, while protease-activated receptor 2 (PAR2) as a cell membrane receptor actively participates in both tumour cell functions and inflammatory responses. However, rare investigations linked PAR2-mediated inflammatory environment to tumour progression.

Interplay between G protein-coupled receptors and nanotechnology.

G protein-coupled receptors (GPCRs), as the largest family of membrane receptors, actively modulate plasma membrane and endosomal signalling. Importantly, GPCRs are naturally nanosized, and spontaneously formed nanoaggregates of GPCRs (natural nano-GPCRs) may enhance GPCR-related signalling and functions. Although GPCRs are the molecular targets of the majority of marketed drugs, the poor pharmacokinetics and physicochemical properties of GPCR ligands greatly limit their clinical applicability.

Recent advances on Pestalotiopsis genus: chemistry, biological activities, structure-activity relationship, and biosynthesis.

Strains of the fungal genus Pestalotiopsis are reported as large promising sources of structurally varied biologically active metabolites. Many bioactive secondary metabolites with diverse structural features have been derived from Pestalotiopsis. Moreover, some of these compounds can potentially be developed into lead compounds.

Globally reduced N-methyladenosine (mA) in C9ORF72-ALS/FTD dysregulates RNA metabolism and contributes to neurodegeneration.

Repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we show that N-methyladenosine (mA), the most prevalent internal mRNA modification, is downregulated in C9ORF72-ALS/FTD patient-derived induced pluripotent stem cell (iPSC)-differentiated neurons and postmortem brain tissues. The global mA hypomethylation leads to transcriptome-wide mRNA stabilization and upregulated gene expression, particularly for genes involved in synaptic activity and neuronal function.

A double-layered gastric floating tablet for zero-order controlled release of dihydromyricetin: Design, development, and in vitro/in vivo evaluation.

Dihydromyricetin (DHM) is an important natural flavonoid. However, most of DHM preparations have shown shortcomings such as low drug loading, poor drug stability, and/or large fluctuations in blood concentration. This study aimed to develop a gastric floating tablet with a double-layered structure for zero-order controlled release of DHM (DHM@GF-DLT).

A conjoint analysis of bulk RNA-seq and single-nucleus RNA-seq for revealing the role of ferroptosis and iron metabolism in ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive and selective degeneration of motor neurons in the motor cortex of brain and spinal cord. Ferroptosis is a newly discovered form of cell death and reported to mediate selective motor neuron death in the mouse model of ALS. The growing awareness of ferroptosis and iron metabolism dysfunction in ALS prompted us to investigate the expression pattern of ferroptosis and iron metabolism-related genes (FIRGs) in ALS.

Antioxidant and anti-inflammatory activity of constituents isolated from (Lindl.).

(Lindl.) have long been used as herbal tea and a traditional herbal medicine to treat Alzheimer's disease (AD). In the current study, nineteen compounds (), including two new vitamin E homologues (), one new sesquiterpene (), and two new dendrobines (, ), were isolated and identified from stems of .

The Yin-Yang roles of protease-activated receptors in inflammatory signalling and diseases.

Inflammatory diseases have become increasingly prevalent throughout the world. Coronavirus disease 2019 (COVID-19), which has recently become pandemic, also exhibits hyperinflammation and cytokine release syndrome. To address inflammation-related diseases, numerous molecular targets have been explored in preclinical studies and clinical trials.

The value of diffusion weighted imaging-alberta stroke program early CT score in predicting stroke-associated pneumonia in patients with acute cerebral infarction: a retrospective study.

Background: In this study, we aimed to investigate the value of Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS) in predicting stroke-associated pneumonia (SAP) in patients with acute ischemic stroke.

Methods: A total of 291 patients who suffered acute cerebral infarction for the first time were included in this retrospective study. DWI-ASPECTS was assessed and clinical data were collected in order to find the risk factors of SAP, and a logistic regression model was used to investigate the effect of predicting SAP.

Cyclic RGD-Decorated Liposomal Gossypol AT-101 Targeting for Enhanced Antitumor Effect.

Introduction: (-)-Gossypol (AT-101), the (-)-enantiomer of the natural compound gossypol, has shown significant inhibitory effects on various types of cancers such as osteosarcoma, myeloma, glioma, lung cancer, and prostate cancer. However, the clinical application of (-)-gossypol was often hindered by its evident side effects and the low bioavailability via oral administration, which necessitated the development of suitable (-)-gossypol preparations to settle the problems. In this study, injectable cyclic RGD (cRGD)-decorated liposome (cRGD-LP) was prepared for tumor-targeted delivery of (-)-gossypol.

PAR2 blockade reverses osimertinib resistance in non-small-cell lung cancer cells via attenuating ERK-mediated EMT and PD-L1 expression.

Osimertinib, as the third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), is a first-line molecularly targeted drug for non-small cell lung cancer (NSCLC). However, the emergence of therapeutic resistance to osimertinib markedly impairs its efficiency and efficacy, leading to the failure of clinical applications. Novel molecular targets and drugs are urgently needed for reversing osimertinib resistance in NSCLC.

Elevated blood and cerebrospinal fluid glucose levels affect the severity and short-term prognosis of Guillain-Barré syndrome.

Objective: This study aimed to explore the correlation of elevated glucose levels in the blood and cerebrospinal fluid with the progression and short-term prognosis of Guillain-Barré syndrome (GBS).

Methods: The medical records of 982 patients who were diagnosed with GBS in 31 representative tertiary hospitals, located in 14 provinces in southern China, were collected and retrospectively reviewed. Patients were grouped according to the levels of fasting plasma glucose (FPG) and cerebrospinal fluid (CSF) glucose, as well as the concentration of blood hemoglobinAlc (HbA1c).

Targeting PAR2 Overcomes Gefitinib Resistance in Non-Small-Cell Lung Cancer Cells Through Inhibition of EGFR Transactivation.

Drug resistance can notably restrict clinical applications of gefitinib that is a commonly used EGFR-tyrosine kinase inhibitors (EGFR-TKIs) for non-small cell lung cancer (NSCLC). The attempts in exploring novel drug targets and reversal strategies are still needed, since gefitinib resistance has not been fully addressed. Protease-activated receptor 2 (PAR2), a G protein-coupled receptor, possesses a transactivation with EGFR to initiate a variety of intracellular signal transductions, but there is a lack of investigations on the role of PAR2 in gefitinib resistance.