Discovery of a novel exceptionally potent and orally active Nur77 ligand NB1 with a distinct binding mode for cancer therapy.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands.

A microfluidic coculture model for mapping signaling perturbations and precise drug screening against macrophage-mediated dynamic myocardial injury.

Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury.

Joint association of physical activity and the geriatric nutritional risk index with survival outcomes among cancer survivors in the United States: a population-based cohort study.

Introduction: The relationship between physical activity (PA) and nutritional status on the prognosis of cancer survivors remains underexplored. We aimed to investigate the combined effects of PA and Geriatric Nutritional Risk Index (GNRI) on prognostic assessment of survival outcomes in US cancer survivors.

Methods: 2,619 subjects were screened from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018.

Causal Association between Arm Fat, Left Leg Fat, and Trunk Fat Masses and Risk of Polycystic Ovarian Syndrome: A Mendelian Randomization Study.

Background: Observational studies have reported that arm fat, left leg fat, and trunk fat masses have different effects on polycystic ovarian syndrome (PCOS). However, the causal relationship between them remains unknown.

Materials And Methods: A two-sample Mendelian randomization (MR) study was conducted by utilizing pooled data from the largest Genome-Wide Association Study (GWAS).

[Focus on the outbreaks of invasive group A streptococcal disease].

In recent years, particularly since the outbreaks of scarlet fever and invasive group A streptococcal diseases/infections (iGAS) in several European countries in 2022, iGAS has garnered widespread attention. Recently, Japan experienced an outbreak of a specific type of iGAS, streptococcal toxic shock syndrome (STSS). The outbreak was reported under the label"flesh-eating bacteria,"emphasizing the pathogenic potential of group A streptococcus (GAS).

Twisted Cucurbit[14]uril-Based Supramolecular Self-Assembly Induces Fluorescence Emission of Dye Molecules for Multi-Channel Cell Imaging.

In this study, a supramolecular fluorescent material was constructed by using double-cavity twisted cucurbit[14]uril (tQ[14]) and positively charged Astrazon Pink FG (APFG) based on the non-covalent host-guest interaction for the first time. The thermodynamic parameters of the APFG@tQ[14] in aqueous solution were determined by isothermal titration calorimetry (ITC), the results indicated that the spontaneous assembly of APFG@tQ[14] is mainly driven by enthalpy. The intramolecular charge transfer (ICT) effect induced the APFG@tQ[14] probe to emit a strong orange-red fluorescence.

Association between forced expiratory volume in 1 s and relapse-free survival in operable non-small cell lung cancer: a prospective cohort study with propensity score overlap weighting.

Objectives: Investigate the correlation between the percentage of predicted forced expiratory volume in 1 s (FEV1%pred) and survival outcomes, namely relapse-free survival (RFS) and overall survival (OS), in patients diagnosed with operable early-stage non-small cell lung cancer (NSCLC).

Design: Prospective observational study.

Setting: Clinical settings in Xiangya Hospital, Central South University, Hunan, China.

Risk factors and prediction model of breast cancer-related lymphoedema in a Chinese cancer centre: a prospective cohort study protocol.

Introduction: Lymphoedema is a distressing and long-term complication for breast cancer survivors. However, the reported incidence of lymphoedema varies, and its risk factors remain underexplored. Currently, a well-established risk prediction model is still lacking.

Effect of insulin sensitivity, insulin secretion, and beta cell function on the remission of type 2 diabetes: A post hoc analysis of the IDEATE trial.

Aims: To compare the probability of achieving diabetes remission in individuals with different phenotypes of insulin sensitivity, insulin secretion, and beta cell function and further detect the effects of diet, exercise, and lifestyle education intervention on these indexes.

Methods: Three-hundred and one participants who had glycated haemoglobin (HbA1c) data at baseline and after intervention were included for this post hoc analysis. We used the multi-way analysis of variance to assess the differences between the diabetes remission and non-remission groups or between intervention groups in changes of the indexes of insulin sensitivity, insulin secretion, and beta cell function.

Diagnostic Accuracy of a Point-Of-Care aMMP-8 Test for Discriminating Periodontal Health Status in Adults: Validation Trials and Updated Meta-Analysis.

Aim: To evaluate the diagnostic accuracy of an active matrix metalloproteinase-8 (aMMP-8) point-of-care oral rinse test (POC-ORT) for predicting periodontitis in treatment-naïve subjects in two independent studies and update a recent meta-analysis.

Methods: The aMMP-8 POC-ORT index test was performed in a representative population in Hong Kong, China, and a consecutive convenience sample in Shanghai, China. The reference standard was the 2017 World Workshop classification of periodontal diseases.

Potential drug targets for asthma identified through mendelian randomization analysis.

Background: The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS).

Signal integrator function of CXXC5 in Cancer.

CXXC type zinc finger protein 5 (CXXC5) is a member of the ZF-CXXC family and plays a pivotal role in signal integration and information transfer within cell signaling network. CXXC5 acts as a regulator in various physiological processes, and abnormalities in its protein structure or function have been linked to multiple pathological processes. In this article, we correspondingly describe the composition of the ZF-CXXC family, emphatically introducing the features of the CXXC5 gene and protein, review the role of CXXC5 in cellular signaling networks, the physiological and pathological processes associated with CXXC5 dysregulation, and particularly focus on the correlation between CXXC5 and cancers.

Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.

Background: Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).

Objective: We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).

Patients And Methods: Eligible patients had pathologically confirmed advanced ccRCC.

Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT.

The vesicular acetylcholine transporter (VAChT) has a pivotal role in packaging and transporting acetylcholine for exocytotic release, serving as a vital component of cholinergic neurotransmission. Dysregulation of its function can result in neurological disorders. It also serves as a target for developing radiotracers to quantify cholinergic neuron deficits in neurodegenerative conditions.

Clinical characteristics and management of reoperation for high jejunal atresia: a retrospective study.

Objective: To analyze the clinical characteristics and available treatment strategies for reoperation of neonatal high jejunal atresia, and recommend preventive measures to reduce the reoperation rate of high jejunal atresia.

Methods: The clinical data of 16 children with high jejunal atresia who underwent reoperation in the Neonatal Surgery Department at Children's Hospital of Zhejiang University School of Medicine from January 2018 to January 2023 were retrospectively analyzed.

Results: Among the 16 unplanned reoperations, 7 (43.

Radiotherapy combined with chemoimmunotherapy improves survival compared to chemoimmunotherapy alone as first-line treatment for oligometastatic esophageal squamous cell carcinoma.

Purpose: To evaluate the safety and efficacy of radiotherapy combined with chemoimmunotherapy (RCIT) versus chemoimmunotherapy (CIT) alone as first-line treatment for oligometastatic esophageal squamous cell carcinoma (OESCC) at initial diagnosis.

Methods: We retrospectively evaluated 140 patients newly diagnosed with OESCC who received RCIT or CIT as first-line treatment between June 2018 and December 2021. Among them, 76 patients were in the RCIT cohort and 64 patients in the CIT cohort.

Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia.

Acute myeloid leukemia (AML) featuring retinoic acid receptor-gamma (RARG) rearrangements exhibits morphological features resembling those of acute promyelocytic leukemia but is associated with drug resistance and poor clinical outcomes. However, the mechanisms underlying the role of RARG fusions in leukemogenesis remain elusive. Here, we show that RARG fusions disrupt myeloid differentiation and promote proliferation and self-renewal of hematopoietic stem and progenitor cells (HSPCs) by upregulating BCL2 and ATF3.

CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.

Acute myeloid leukemia (AML) with retinoic acid receptor gamma (RARG) fusions, which exhibits clinical features resembling acute promyelocytic leukemia (APL), has been identified as a new subtype with poor clinical outcomes. The underlying mechanism of RARG-fusion leukemia remains poorly understood, and needs to be explored urgently to instruct developing effective therapeutic strategies. Here, using the most prevalent RARG fusion, CPSF6-RARG (CR), as a representative, we reveal that the CR fusion, enhances the expansion of myeloid progenitors, impairs their maturation and synergizes with RAS mutations to drive more aggressive myeloid malignancies.

[Mechanism of Tanyu Tongzhi Formula in treatment of atherosclerosis by maintaining vascular homeostasis based on TGF-β signaling pathway].

This study aimed to investigate the potential mechanism and the compatibility significance of Tanyu Tongzhi Formula in treating atherosclerosis(AS) in mice based on the transforming growth factor-β(TGF-β)/Smad2/3 signaling pathway. Eight C57BL/6J mice were as assigned to a normal control group and fed a regular diet, while 35 ApoE~(-/-) mice of the same strain were fed a high-fat diet for 8 weeks to establish an AS model. The model mice were randomly divided into a model group, a Tanyu Tongzhi group(18.

[Mechanism of traditional Chinese medicine in treating vascular calcification in chronic kidney disease based on BMP and SIRT signaling pathways].

Vascular calcification significantly increases the incidence of cardiovascular disease and all-cause mortality patients with chronic kidney disease(CKD), severely affecting their health and lifespan. However, the mechanisms underlying vascular calcification in CKD remain incompletely understood, and the available therapeutic agents are limited. Research has found that the transformation of vascular smooth muscle cells(VSMCs) from a contractile phenotype to an osteoblast-like phenotype is a key step in CKD-related vascular calcification.

Application of machine learning algorithms in predicting new onset hypertension: a study based on the China Health and Nutrition Survey.

Background: Hypertension is a serious chronic disease that can significantly lead to various cardiovascular diseases, affecting vital organs such as the heart, brain, and kidneys. Our goal is to predict the risk of new onset hypertension using machine learning algorithms and identify the characteristics of patients with new onset hypertension.

Methods: We analyzed data from the 2011 China Health and Nutrition Survey cohort of individuals who were not hypertensive at baseline and had follow-up results available for prediction by 2015.