Association between red blood cell distribution width to serum calcium ratio and all-cause mortality in critically ill patients with diabetic nephropathy: a retrospective analysis of the MIMIC-IV database.

Background: Diabetic nephropathy (DN) is a critical diabetes complication that raises mortality risk, particularly in intensive care unit (ICU) settings where metabolic disturbances are more pronounced. The prevalence and economic burden of DN are growing globally, posing a major public health challenge. Red blood cell distribution width (RDW) and serum calcium (SC) levels, which frequently exhibit significant alterations in critically ill patients, are linked to DN progression.

Calycosin-7-O-β-D-glucoside alleviates nonalcoholic fatty liver disease by regulating short-chain fatty acids metabolism and metabolic regulators.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury disease caused by excessive fat deposition in hepatocytes. Astragalus memeranaceus Fisch., mainly consists of flavonoids, is considered to have good liver protection effects.

Design and synthesis of CDK9/EZH2 dual-target inhibitors to achieve synergistic antitumor effects.

Cyclin-dependent kinase 9 (CDK9) plays a pivotal role in regulating transcriptional elongation and has emerged as a promising target in cancer therapy. However, it is reported that CDK9 inhibitors cause abnormal upregulation of H3K27me3 in Diffuse Large B-cell Lymphoma (DLBCL) cell lines. Here, we designed a series of dual inhibitors targeting CDK9 and EZH2 by linking two distinct pharmacophores to achieve synergistic antitumor effects.

Clinical and electrophysiological features of pure sensory Guillain-Barré syndrome: retrospective analysis of 22 patients across 14 provinces in Southern China.

Objective: Currently, there are limited reports, both nationally and internationally, regarding Guillain-Barré Syndrome (GBS) that manifests solely with isolated sensory impairment. This study aims to explore the epidemiological and clinical features of GBS patients experiencing only paresthesia in southern China.

Methods: We conducted a retrospective analysis of the medical records of GBS patients admitted to 31 hospitals across 14 provinces in southern China from January 1, 2013, to September 30, 2016.

Identification of a circRNA-mediated immune-related ceRNA network and circRNAs as diagnostic biomarkers in acute ischemic stroke.

Background: Research has demonstrated that circular RNAs (circRNAs) play important roles in acute ischemic stroke (AIS). However, the functions of circRNA-mediated competitive endogenous RNA (ceRNA) in AIS-related immunological inflammation are not well understood. In our study, we aimed to construct a circRNA-mediated immune-related ceRNA network and identify diagnostic circRNAs for AIS.

Discovery of 2,4-quinazolinedione derivatives as LC3B recruiters in the facilitation of protein complex degradations.

Targeted protein degradation through autophagosome-tethering compounds (ATTECs) that bypasses the ubiquitination process has garnered increasing attention. LC3B, a key protein in autophagosome formation, recruits substrates into the autophagy-lysosome system for degradation. In this study, we systematically optimized 2,4-quinazolinedione derivatives as LC3B-recruiting fragments, utilizing the CDK9 indicator.

Transcriptomic Regulation by Astrocytic m6A Methylation in the mPFC.

Astrocytes, the most prevalent type of glial cells, have been found to play a crucial part in numerous physiological functions. By offering metabolic and structural support, astrocytes are vital for the proper functioning of the brain and regulating information processing and synaptic transmission. Astrocytes located in the medial prefrontal cortex (mPFC) are highly responsive to environmental changes and have been associated with the development of brain disorders.

Qingre Huoxue decoction attenuates myocardial ischemia‒reperfusion injury by regulating the autophagy‒endoplasmic reticulum stress axis via FAM134B-mediated ER-phagy.

Background: Autophagy‒endoplasmic reticulum (ER) stress axis dysregulation is linked to myocardial ischemia‒reperfusion injury (MIRI), which counteracts the benefits of acute myocardial infarction (AMI) reperfusion therapy. Qingre Huoxue decoction (QRHX) improves the short- and long-term prognosis of AMI after percutaneous coronary intervention and alleviates myocardial injury in AMI rats by stimulating autophagy via the PI3K/Akt pathway. We aimed to further explore the efficacy of QRHX in treating MIRI and its regulatory relationship with FAM134B-mediated ER-phagy.

Aberrant resting-state voxel-mirrored homotopic connectivity in major depressive disorder with and without anxiety.

Objective: Prior researchers have identified distinct differences in functional connectivity neuroimaging characteristics among MDD patients. However, the auxiliary diagnosis and subtype differentiation roles of VMHC values in MDD patients have yet to be fully understood. We aim to explore the separating ability of VMHC values in patients with anxious MDD or with non-anxious MDD and HCs.

Ginkgetin attenuates bone loss in OVX mice by inhibiting the NF-κB/IκBα signaling pathway.

Background: Osteoporosis is a disease associated with bone resorption, characterized primarily by the excessive activation of osteoclasts. Ginkgetin is a compound purified from natural ginkgo leaves which has various biological properties, including anti-inflammation, antioxidant, and anti-tumor effects. This study investigated the bone-protective effects of ginkgetin in ovariectomized (OVX) mice and explored their potential signaling pathway in inhibiting osteoclastogenesis in a mouse model of osteoporosis.

Feature selection and risk prediction for diabetic patients with ketoacidosis based on MIMIC-IV.

Background: Diabetic ketoacidosis (DKA) is a frequent acute complication of diabetes mellitus (DM). It develops quickly, produces severe symptoms, and greatly affects the lives and health of individuals with DM.This article utilizes machine learning methods to examine the baseline characteristics that significantly contribute to the development of DKA.

A comparison of invasive arterial blood pressure measurement with oscillometric non-invasive blood pressure measurement in patients with sepsis.

Purpose: This study aimed to compare non-invasive oscillometric blood pressure (NIBP) measurement with invasive arterial blood pressure (IBP) measurement in patients with sepsis.

Methods: We conducted a retrospective study to evaluate the agreement between IBP and NIBP using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Paired blood pressure measurements of mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were compared using Bland-Altman analysis and paired Student's t test.

Excess PrP inhibits muscle cell differentiation via miRNA-enhanced liquid-liquid phase separation implicated in myopathy.

The cellular prion protein (PrP) is required for skeletal muscle function. Here, we report that a higher level of PrP accumulates in the cytoplasm of the skeletal muscle of six myopathy patients compared to controls. PrP inhibits skeletal muscle cell autophagy, and blocks myoblast differentiation.

SPIDE: A single cell potency inference method based on the local cell-specific network entropy.

For a given single cell RNA-seq data, it is critical to pinpoint key cellular stages and quantify cells' differentiation potency along a differentiation pathway in a time course manner. Currently, several methods based on the entropy of gene functions or PPI network have been proposed to solve the problem. Nevertheless, these methods still suffer from the inaccurate interactions and noises originating from scRNA-seq profile.

Inferring single-cell gene regulatory network by non-redundant mutual information.

Gene regulatory network plays a crucial role in controlling the biological processes of living creatures. Deciphering the complex gene regulatory networks from experimental data remains a major challenge in system biology. Recent advances in single-cell RNA sequencing technology bring massive high-resolution data, enabling computational inference of cell-specific gene regulatory networks (GRNs).

Degradation of Cyclin-Dependent Kinase 9/Cyclin T1 by Optimized Microtubule-Associated Protein 1 Light Chain 3 Beta-Recruiting Coumarin Analogs.

Autophagy is an efficient and attractive protein degradation pathway in addition to the ubiquitin-proteasome system. Herein, systematic optimization of coumarin analogs linked with the CDK9 inhibitor SNS-032 is reported that may bind to cyclin-dependent kinase 9 (CDK9) and microtubule-associated protein 1 light chain 3 beta (LC3B) simultaneously, which leads to the selective autophagic degradation of targeted CDK9/cyclin T1 and is different from the PROTAC degrader THAL-SNS-032. Further mechanism studies revealed an autophagy-lysosome pathway, where the degraders possibly formed a ternary complex with CDK9 and LC3B.

Calycosin-7-glucoside promotes mitochondria-mediated apoptosis in hepatocellular carcinoma by targeting thioredoxin 1 to regulate oxidative stress.

Thioredoxin1 (TRX1) is a key protein that regulates redox and is considered to be a key target for cancer therapy. Flavonoids have been proven to have good antioxidant and anticancer activities. This study aimed to investigate whether the flavonoid calycosin-7-glucoside (CG) exerts an anti-hepatocellular carcinoma (HCC) role by targeting TRX1.

Olanzapine induces weight gain in offspring of prenatally exposed poly I:C rats by reducing brown fat thermogenic activity.

Olanzapine (OLZ) is an antipsychotic with a high risk of metabolic syndrome, and its induced metabolic disturbance may be related to the thermogenic function of brown adipose tissue (BAT). Of note is that schizophrenia itself appears to be associated with a higher incidence of metabolic syndrome. However, whether OLZ affects metabolic disorders by regulating BAT function and its mechanism in animal models of schizophrenia have not been reported.

Recent advances in natural phthalides: Distribution, chemistry, and biological activities.

Phthalides, an important class of bioactive natural products, are widely distributed in plants, fungi, lichens, and liverworts. Amon them, n-butylphthalide, a phthalide monomer, has been approved to cure ischemic stroke. Owing to their good bioactivities in anti-microbial, anti-inflammatory, anti-tumor, anti-diabetic, and other aspects, a large number of researches have been conducted on phthalides from nature materials.

Inhibition of TXNDC5 attenuates lipopolysaccharide-induced septic shock by altering inflammatory responses.

Sepsis and its severe form, septic shock, represent the leading cause of death among hospitalized patients. Thioredoxin is a ubiquitous protein essential for cellular redox balance and its aberrant expression is associated with a wide spectrum of inflammation-related pathological conditions. The current study aimed to compare the expression of thioredoxin domain containing 5 (TXNDC5) in septic patients with or without septic shock and to explore the potential regulatory effects of TXNDC5 in sepsis.

Multiple neurological manifestations in a patient with systemic lupus erythematosus and anti-NXP2-positive myositis: A case report.

Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease that frequently affects various organs. Neuropsychiatric manifestations in SLE patients, known as neuropsychiatric SLE, are clinically common. However, the principal manifestation of cranial neuropathy in patients with SLE and comorbidities is relatively rare.

Targeted Proteomics Combined with Affinity Mass Spectrometry Analysis Reveals Antagonist E7 Acts As an Intracellular Covalent Ligand of Orphan Receptor GPR52.

The GPR52, a class A orphan G protein-coupled receptor (GPCR), is regarded as a promising therapeutic target for the treatment of Huntington's disease and multiple psychiatric disorders. Although the recently solved structure of GPR52 has revealed a binding mechanism likely shared by all reported agonists, the small molecule antagonist E7 cannot fit into this agonist-binding pocket, and its interaction mode with the receptor remains unknown. Here, we employed targeted proteomics and affinity mass spectrometry approaches to uncover a unique binding mode of E7 which acts as a covalent and allosteric ligand of GPR52.