Discovery of a potent anticancer agent against pancreatic ductal adenocarcinoma targeting FAK with DFG-out state and JAK/Aurora kinases.

Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer because of the difficulty in diagnosis and its resistance to chemotherapy. Focal adhesion kinase (FAK) is found overexpressed in PDAC, and targeting FAK has been proved to impede the progress of PDAC. However, most of FAK inhibitors were reported to bind with FAK in a DFG-in conformation, leading to a limited anti-tumor effect in clinical studies.

Cerebral Endothelial CXCR2 Promotes Neutrophil Transmigration into Central Nervous System in LPS-Induced Septic Encephalopathy.

Septic encephalopathy (SE) represents a severe inflammatory syndrome linked to elevated septic mortality rates, lacking specific therapeutic interventions, and often resulting in enduring neurological sequelae. The present investigation endeavors to elucidate the involvement of C-X-C Motif Chemokine Receptor 2 (CXCR2) in the pathogenesis of SE and to explore the potential of CXCR2 modulation as a therapeutic avenue for SE. Employing a murine SE model induced by lipopolysaccharide (LPS) administration, CXCR2 knockout mice and the CXCR2 inhibitor SB225002 were utilized to assess neutrophil recruitment, endothelial integrity, and transendothelial migration.

Smart seq2 revealed distinct molecular responses during in vitro porcine oocyte maturation before or after the addition of mogroside V.

Oocyte maturation involves both nuclear and cytoplasmic maturation. Mogroside V (MV) has been shown to enhance nuclear maturation, mitochondrial content, and developmental potential of porcine oocyte during in vitro maturation (IVM). However, the impact of MV on cytoplasmic maturation and its underlying mechanisms are not understood.

PTPRO inhibits LPS-induced apoptosis in alveolar epithelial cells.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), represent critical clinical syndromes with multifactorial origins, notably stemming from sepsis within intensive care units (ICUs). Despite their high mortality rates, no selective cure is available beside ventilation support. Apoptosis plays a complex and pivotal role in the pathophysiology of acute lung injury.

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors.

Integrase plays an important role in the life cycle of HIV-1, and integrase strand transfer inhibitors (INSTIs) can effectively impair the viral replication. However, drug resistance mutations have been confirmed to decrease the efficacy of INSTI during the antiviral therapy. Herein, indole-2-carboxylic acid (1) was found to inhibit the strand transfer of integrase, and the indole nucleus of compound 1 was observed to chelate with two Mg ions within the active site of integrase.

Self-Guided DMT: Exploring a Novel Paradigm of Dance Movement Therapy in Mixed Reality for Children with ASD.

Children diagnosed with Autism Spectrum Disorder (ASD) often exhibit motor disorders. Dance Movement Therapy (DMT) has shown great potential for improving the motor control ability of children with ASD. However, traditional DMT methods often lack vividness and are difficult to implement effectively.

The arsenic-lowering effect of inulin-type prebiotics in end-stage renal disease: a randomized crossover trial.

: Circulatory imbalance of trace elements is frequent in end-stage renal disease (ESRD), leading to a deficiency of essential elements and excess of toxic elements. The present study aimed to investigate whether inulin-type fructans (ITFs) could ameliorate the circulatory imbalance by modulating gut microbiota and regulating the absorption and elimination of trace elements. : Peritoneal dialysis patients were enrolled in a randomized crossover trial, undergoing interventions with ITFs (10 g d) and maltodextrin (placebo) over a 9-month period (with a 3-month washout).

Dietary Polyphenol Intake and Risk of Hypertension: An 18-y Nationwide Cohort Study in China.

Background: Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still lacking.

Objectives: This study aimed to investigate the association between dietary polyphenol and hypertension risk in the China Health and Nutrition Survey (N = 11,056).

Methods: Food intake was assessed using 3-d, 24-h dietary recalls and household weighing method; polyphenol intake was calculated by multiplying consumption of each food and its polyphenol content.

[CXCL1 induces the contraction of endothelial cytoskeleton and increases permeability in mouse cerebral endothelium bEND.3 cells by promoting protein kinase B phosphorylation].

Objective To investigate the effects of C-X-C motif chemokine ligand 1 (CXCL1) and its receptor CXCR2 on the cerebral endothelial cytoskeleton rearrangement and permeability in the inflammation of septic encephalopathy. Methods The murine model of septic encephalopathy was established by intraperitoneal injection of LPS (10 mg/kg). The levels of TNF-α and CXCL1 in the whole brain tissue were detected by ELISA.

The Effect of Inulin-Type Fructans on Plasma Trimethylamine N-Oxide Levels in Peritoneal Dialysis Patients: A Randomized Crossover Trial.

Scope: Trimethylamine N-oxide (TMAO), an important proatherogenic uremic toxin, is oxidized by hepatic-flavin monooxygenases from gut microbiome-generated trimethylamine (TMA). The present study aims to explore whether manipulating the gut microbiota by inulin-type fructans (ITFs) can reduce circulating TMAO levels in peritoneal dialysis patients.

Methods And Results: This is a randomized, double-blind, placebo-controlled, crossover trial with 10 g day ITFs intervention for 3 months in continuous ambulatory peritoneal dialysis patients.

[Protein tyrosine phosphatase receptor type O (PTPRO) promotes phagocytic activity of alveolar epithelial cells via activating AKT signal pathway in LPS induced acute lung injury].

Objective To investigate the effect of protein tyrosine phosphatase receptor type O (PTPRO) on the phagocytic activity of alveolar epithelial cells in LPS-induced acute lung injury. Methods Mice were randomly divided into the normal control group and LPS stimulation group. The infiltration of inflammatory cells was detected by HE staining.

Sal synthase induced cytotoxicity of PC12 cells through production of the dopamine metabolites salsolinol and N-methyl-salsolinol.

As a catechol isoquinoline, salsolinol (Sal) is widely distributed in mammalian brains, and is increased in the cerebrospinal fluid (CSF) and urine of Parkinsonian patients. Sal can be metabolized to N-methyl-salsolinol (NM-Sal), an MPP+-like neurotoxin, and impairs the function of dopaminergic neurons, causing the clinical symptoms of Parkinson's disease (PD). Sal synthase, which catalyzes the production of Sal from dopamine and acetaldehyde, may be the important enzyme in the metabolism of catechol isoquinolines (CTIQs).

Increased risk of modality failure with higher serum uric acid level in continuous ambulatory peritoneal dialysis patients: a prospective cohort study.

Background: Peritoneal dialysis (PD) is one of the most important kidney replacement therapies for patients with end-stage kidney disease (ESKD). PD technique failure can lead to an escalated cost and increased infectious and cardiovascular risk, up and including to death. The accumulation of uric acid (UA) was associated with adverse outcomes in ESKD patients.

The Accumulation of Gut Microbiome-derived Indoxyl Sulfate and P-Cresyl Sulfate in Patients With End-stage Renal Disease.

Objectives: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two important gut microbiota-generated protein-bound uremic toxins. The present study aims to explore the alterations of serum IS and pCS concentrations, their production, and daily removal in end-stage renal disease (ESRD).

Methods: A case-controlled study was conducted based on 11 patients with ESRD and 11 healthy volunteers.

Nutritional predictors associated with malnutrition in continuous ambulatory peritoneal dialysis patients.

Background: Currently in China, out of the total dialysis population, approximately 20% represents continuous ambulatory peritoneal dialysis (CAPD) and almost half of CAPD patients was affected by malnutrition. This study aimed to investigate the association between nutritional predictors and malnutrition with 5.1 years of dialysis according to the subjective global assessment (SGA) in continuous ambulatory peritoneal dialysis (CAPD) patients.

Inulin-type prebiotics reduce serum uric acid levels via gut microbiota modulation: a randomized, controlled crossover trial in peritoneal dialysis patients.

Purpose: Increased levels of uric acid (UA), which is mainly excreted through the kidneys, are independently associated with higher mortality in end-stage renal disease (ESRD) patients. The uricolysis of gut microbiota plays an important role in extrarenal excretion of UA. This study aimed to examine the effect of inulin-type prebiotics (a type of fermentable dietary fiber) on intestinal microbiota modulation and serum UA levels in ESRD patients.

The Association of Feeding Practices and Sociodemographic Factors on Underweight and Wasting in Children in Ethiopia: A Secondary Analysis of Four Health Surveys from 2000 to 2016.

Background: Feeding practices highly influence the nutritional status of children between 6 and 23 months of age in developing countries, including Ethiopia. Therefore, this study was conducted to investigate the association of feeding practices and sociodemographic factors on underweight and wasting of children aged 6-23 months in Ethiopia.

Methods: Data on 8003 children 6-23 months of age from four Ethiopia demographic and health surveys (EDHS) from 2000 to 2016 were analyzed using complex sample crosstabs for multivariate analysis.

Casein Kinase 1 Family Member CK1δ/Hrr25 Is Required for Autophagosome Completion.

Autophagy starts with the initiation and nucleation of isolation membranes, which further expand and seal to form autophagosomes. The regulation of isolation membrane closure remains poorly understood. CK1δ is a member of the casein kinase I family of serine/threonine specific kinases.

Erratum: Analysis of Tau Protein Expression in Predicting Pathological Complete Response to Neoadjuvant Chemotherapy in Different Molecular Subtypes of Breast Cancer.

[This corrects the article on p. 47 in vol. 23, PMID: 32140269.

Analysis of Tau Protein Expression in Predicting Pathological Complete Response to Neoadjuvant Chemotherapy in Different Molecular Subtypes of Breast Cancer.

Purpose: Tau is a microtubule-associated protein that can be found in both normal and abnormal breast cells. Whether the expression of Tau protein can predict the response to neoadjuvant chemotherapy (NACT) is still unclear. In this study, we assessed the role of Tau protein expression in predicting a pathological complete response (pCR) to NACT for different subtypes of breast cancer.

Fatigue in Peritoneal Dialysis Patients and an Exploration of Contributing Factors: A Cross-Sectional Study.

Context: Fatigue is a common and detrimental symptom in dialysis patients; however, our understanding of it and investigation of its contributing factors is still very limited, especially in peritoneal dialysis (PD) patients.

Objectives: To assess fatigue in PD patients and identify contributing factors.

Methods: One hundred eight PD patients in a comprehensive hospital in China were recruited.

Mammography-based radiomic analysis for predicting benign BI-RADS category 4 calcifications.

Purpose: We developed and validated a radiomic model based on mammography and assessed its value for predicting the pathological diagnosis of Breast Imaging Reporting and Data System (BI-RADS) category 4 calcifications.

Materials And Methods: Patients with a total of 212 eligible calcifications were recruited (159 cases in the primary cohort and 53 cases in the validation cohort). In total, 8286 radiomic features were extracted from the craniocaudal (CC) and mediolateral oblique (MLO) images.

Multiparametric MRI-based radiomics analysis for prediction of breast cancers insensitive to neoadjuvant chemotherapy.

Purpose: To evaluate the value of multiparametric magnetic resonance imaging (MRI) in pretreatment prediction of breast cancers insensitive to neoadjuvant chemotherapy (NAC).

Methods: A total of 125 breast cancer patients (63 in the primary cohort and 62 in the validation cohort) who underwent MRI before receiving NAC were enrolled. All patients received surgical resection, and Miller-Payne grading system was applied to assess the response to NAC.

Radiomics of Multiparametric MRI for Pretreatment Prediction of Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer: A Multicenter Study.

Purpose: We evaluated the performance of the newly proposed radiomics of multiparametric MRI (RMM), developed and validated based on a multicenter dataset adopting a radiomic strategy, for pretreatment prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer.

Experimental Design: A total of 586 potentially eligible patients were retrospectively enrolled from four hospitals (primary cohort and external validation cohort 1-3). Quantitative imaging features were extracted from T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging before NAC for each patient.

Chronic inflammatory demyelinating polyradiculoneuropathy: A case report.

Rationale: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disorder characterized by a symmetrical, sensorimotor involvement and slowly progressive onset peripheral neuropathy. Peripheral neuropathies have been reported in some central demyelination patients. However, the central nervous system focus in the CIDP patient can mimic neuromyelitis optica have not been recognized by most of us.