Discovery of Potent and Selective Pyrrolo[2,3-]pyrimidine Derivatives as Fourth-Generation EGFR Inhibitors Targeting Triple Mutations.

Three generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs) have shown clinical efficacy in nonsmall cell lung cancer (NSCLC), but acquired resistance mutations─especially the -EGFR─remain a major challenge. Here, we report the identification of a series of pyrrolo[2,3-]pyrimidine derivatives that inhibit C797S-mediated EGFR triple mutants. Among them, compound shows subnanomolar IC values against Ba/F3 EGFR and Ba/F3 EGFR, while sparing wild-type EGFR.

Transition Shock Among Nursing Interns: Roles of Achievement Motivation and Clinical Practice Environment-A Cross-Sectional Study.

Aims: To examine the relationships between achievement motivation, clinical practice environment and nursing interns' transition shock.

Design: A descriptive cross-sectional study with an online survey.

Methods: This study included 343 nursing interns from practice hospitals across six Chinese provinces.

Single-dose GC101 gene therapy for spinal muscular atrophy types II and III: an open-label single-arm study.

QUICK TAKE.

Size-dependent effects of the intestinal microbiota in juvenile Chinese alligators: implications for species protection.

Increasing the quality of offspring to optimize population reproductive efficiency represents a viable approach for increasing population size. The population of Chinese alligators has a growing age structure, but the high mortality rate of juveniles is a serious problem that needs to be solved. We investigated the relationship between the weight of juvenile Chinese alligators and the microbiota to improve the survival rate and provide better protection for Chinese alligators.

Impact of early-life deprivation and threat on physical, psychological, and cognitive multimorbidity: Evidence from multinational prospective cohorts.

Background: The impact of early-life stressful events on physical-psychological-cognitive multimorbidity needs to be better understood. This study aimed to examine both the prevalence patterns of physical-psychological-cognitive multimorbidity and the associations between specific adverse childhood experiences (ACEs) and multimorbidity among middle-aged and older adults in China, Europe, the US, and the UK.

Methods: Data came from the China Health and Retirement Longitudinal Study (CHARLS) and its partner studies: the US Health and Retirement Study (HRS), the Survey of Health, Ageing and Retirement in Europe (SHARE), and the English Longitudinal Study on Ageing (ELSA).

Aneurysm Wall Enhancement and Systemic Inflammation Jointly Contribute to Cognitive Dysfunction in Untreated Unruptured Intracranial Aneurysm Patients.

Background And Purpose: Peripheral inflammatory markers and aneurysm wall enhancement (AWE) on high-resolution vessel wall MRI (HR-VWI) may reflect inflammation in unruptured intracranial aneurysms (UIAs). We assessed cognitive function and its association with inflammatory markers in UIA patients.

Methods: The study included 120 consecutive patients with UIAs diagnosed between September 2018 and December 2023 and a control group of 27 healthy adults at our institution.

Brominated Flame Retardants Exposure Promotes the Formation of Atherosclerotic Plaque in Aortic Roots of Mice by Increasing Macrophage Recruitment and Foam Cell Formation.

Brominated flame retardants (BFRs) are persistent organic pollutants worldwide. However, the effect of BFRs on the development of atherosclerosis is currently unknown. Here we aimed to investigate the effects of three typical BFRs (BDE-47, BDE-209, and DBDPE) on the development of atherosclerosis and explored the underlying mechanisms using an cell model and mice.

AAV9-Mediated Gene Therapy for Infantile-Onset Pompe's Disease.

Four patients with infantile-onset Pompe's disease received a single intravenous injection of an adeno-associated virus serotype 9 vector carrying codon-optimized complementary DNA encoding human acid α-glucosidase (GAA) (dose, 1.2 × 10 vector genomes per kilogram of body weight). One patient was withdrawn from the study and subsequently died.

Latent profile analysis and influence factor study of well-being among nurses in China: a cross-sectional study.

Objective: The present study employed latent profile analysis (LPA) to identify three distinct profiles of subjective well-being (SWB) among Chinese nurses. It further examined the factors influencing these profiles and aimed to provide a foundation for targeted interventions to enhance nurses'SWB.

Design: A cross-sectional study was conducted between November 2023 and March 2024.

Physical, Mental, and Health Empowerment Disparities Across Chronic Obstructive Pulmonary Disease, Asthma, and Combined Groups and the Moderating Role of eHealth Literacy: Cross-Sectional Study.

Background: Nonpharmacological management plays a key role in enhancing the quality of life for individuals with chronic obstructive pulmonary disease (COPD), asthma, or both. However, disparities in their physical, mental, and health empowerment outcomes have not been fully explored, particularly in relation to the moderating effect of eHealth literacy.

Objective: This study aims to assess these disparities and examine how eHealth literacy moderates them to guide the development of tailored nonpharmacological strategies.

Preclinical evaluation of AAV9-coSMN1 gene therapy for spinal muscular atrophy: efficacy and safety in mouse models and non-human primates.

Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by the loss of motor neurons in the spinal cord. Our team has initiated clinical trials using adeno-associated virus serotype 9 (AAV9) vectors carrying a codon-optimized human SMN1 (coSMN1) gene, delivered via intrathecal (IT) injection. Here, we present the preclinical research that laid the groundwork for these trials, offering comprehensive data on the efficacy and safety of AAV9-coSMN1 in both murine models and non-human primates.

Multi-Omics Analysis of Gut Microbiome and Host Metabolism in Different Populations of Chinese Alligators () During Various Reintroduction Phases.

Reintroduction plays a significant role in the self-maintenance and reconstruction of wild animal populations, serving as a communication bridge between captive and wild animals. The Chinese alligator () is a distinct and endangered reptile species found in China. The mechanisms by which artificially bred Chinese alligators adapt following their release into the wild remain poorly understood.

Genomic insights and the conservation potential of captive breeding: The case of Chinese alligator.

Despite 40 years of conservation of the critically endangered Chinese alligator (), the genomic underpinnings of its status remained uncharted. Genome sequencing data of 244 individuals uncovered relatively low overall genomic diversity/heterozygosity and long runs of homozygosity, with captive populations exhibiting higher heterozygosity and smaller inbreeding coefficients compared to wild individuals. The decreased level of inbreeding in the captive population demonstrates the contribution of the large captive breeding population.

Community-Based Peer Support for Diabetes Management: 24-Month Changes Relative to Comparison Communities.

Objective: To evaluate the effectiveness of community-based peer support for diabetes self-management with HbA1c and other clinical and psychosocial outcomes over 24 months.

Research Design And Methods: This study used an intervention comparison design with 12 intervention communities and 4 comparison communities matched according to location in urban or suburban areas. A community organization approach was used to integrate standardization of key messages and patient education protocols, along with adaptation and innovation among multiple community partners.

Effect of Positive Mental Health on Elderly Patients with Chronic Diseases: The Chain-Mediated Effects of Gratitude and Forgiveness Tendencies at a Tertiary Hospital in Guangzhou.

This study aims to elucidate the mediating roles of gratitude and forgiveness tendency between mature happiness and positive mental health, seeking to reveal the significance of enhancing these psychological traits to enhance the well-being of this population, so as to provide a theoretical foundation for strategies aimed at promoting healthy aging and enhancing the happiness of elderly patients with chronic illness. From April to October 2024, elderly patients with chronic diseases in the geriatric department of a tertiary hospital in Guangzhou China were selected as subjects through convenience sampling. The study utilized the general information questionnaire, the Chinese Version of Mature Happiness Scale-Revised, the Positive Mental Health Scale, the Gratitude Questionnaire-6, and the Tendency to Forgive Scale for data collection.

Habitat Integrity Challenges for the Chinese Alligator Amid Land Occupation by Human: Pathways for Protection.

Effective conservation of endangered species necessitates not only the preservation of core habitats but also the enhancement of landscape connectivity. As a critically endangered Crocodylia, the Chinese alligator () strongly relies on the fragmented wetland habitat of the lower area of the Yangtze River. The integrity of its habitat needs evaluating, and the connectivity restoring plan needs designing.

Dimeric natural product panepocyclinol A inhibits STAT3 di-covalent modification.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity.

Pre-existing Anti-AAV9 antibodies in the Chinese healthy and rare disease populations: Implications for gene therapy.

The adeno-associated virus 9 (AAV9) vector was particularly notable for its broad tissue tropism, making it a preferred vector for gene therapy. Goals: The study aimed to investigate the patterns of pre-existing immunity against AAV9 in the Chinese population. In this study, we conducted a serological research from November 2022 to June 2024.

Association between normal weight obesity and comorbidities and events of cardiovascular diseases among adults in South China.

Background: The increased risks for cardiovascular comorbidities and cardiovascular diseases (CVD) in populations with normal weight obesity (NWO) have not been well-identified. We aimed to study their associations in an adult population in South China.

Methods: Based on the CVD prevalence of 4% in Shenzhen and a calculated sample size of 6,000, a cross-sectional study with a multi-stage stratified cluster sampling method was conducted in Shenzhen City.

Analyzing lipid profiles and dyslipidemia prevalence in hypertensive patients: a cross-sectional study from primary community health institutions.

Background: A significant proportion of hypertensive patients also suffer from comorbid dyslipidemia, which critically influences their treatment outcomes and overall prognosis. Given its implications, the lipid profiles of hypertensive individuals warrant increased attention for more effective clinical management.

Methods: We analyzed data from 92,443 hypertensive patients registered at primary community health institutions in 2021.

Tackling activity-stability paradox of reconstructed NiIrO electrocatalysts by bridged W-O moiety.

One challenge remaining in the development of Ir-based electrocatalyst is the activity-stability paradox during acidic oxygen evolution reaction (OER), especially for the surface reconstructed IrO catalyst with high efficiency. To address this, a phase selective Ir-based electrocatalyst is constructed by forming bridged W-O moiety in NiIrO electrocatalyst. Through an electrochemical dealloying process, an nano-porous structure with surface-hydroxylated rutile NiWIrO electrocatalyst is engineered via Ni as a sacrificial element.

Novel metabolic indicators and the risk of cardiovascular disease in patients with hypertension: A primary-care cohort study.

Background And Aims: Data are limited on whether several easily measured indices serve as effective tools for Cardiovascular disease (CVD) risk assessment in hypertensive patients. This study aimed to assess the associations of metabolic score for insulin resistance (METS-IR), lipid accumulation product (LAP), and visceral adiposity index (VAI) with CVD risk in hypertensive patients.

Methods And Results: Our data were drawn from the medical records of primary-care institutions in China.

Genome-Wide Identification and Expression Analysis of the Gene Superfamily Provides Insight into Sex Determination and Early Gonadal Development of .

The gene superfamily is widely distributed among higher eukaryotes and plays a significant role in numerous biological processes. However, there is limited knowledge about the structure and function of genes in the critically endangered species , which is endemic to China. A total of 170 genes were identified from the genome, classified into 13 families, and unevenly distributed across 16 chromosomes.