MORF4L2 induces immunosuppressive microenvironment and immunotherapy resistance through GRHL2/MORF4L2/H4K12Ac/CSF1 axis in triple-negative breast cancer.

Background: Although immunotherapy has achieved great progress in advanced triple-negative breast cancer (TNBC), there are still numerous patients who do not benefit from immunotherapy. Therefore, identification of the key molecule that induces immune escape and clarification of its specific mechanism in TNBC are urgently needed.

Methods: In this research, single cell sequencing and bulk sequencing were conducted for biomarker screening.

Inflammatory markers link triglyceride-glucose index and obesity indicators with adverse cardiovascular events in patients with hypertension: insights from three cohorts.

Background: Among hypertensive cohorts across different nations, the relationship between the triglyceride-glucose index (TyG) and its conjunction with obesity metrics in relation to cardiovascular disease (CVD) incidence and mortality remains to be elucidated.

Methods: This study enrolled 9,283, 164,357, and 5,334 hypertensives from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKBB), and Shanghai Pudong cohort. The related outcomes for CVD were defined by multivariate Cox proportional hazards models, Generalized Additive Models and Mendelian randomization analysis.

Cross-cultural adaptation of the simple Chinese version of the medication adherence reasons scale in patients undergoing adjuvant endocrine therapy for breast cancer.

Adjuvant endocrine therapy (AET) is essential for improving survival and reducing mortality and recurrence rates in breast cancer (BrCa) patients. However, the adherence to AET among BrCa patients is poor, and there is no scale to measure adherence to AET or the reasons for non-adherence among BrCa patients in mainland China. The aim of this study was to assess the psychometric properties of the simple Chinese version of the Medication Adherence Reasons (MAR) scale in BrCa patients undergoing AET.

Compound 38, a novel potent and selective antagonist of adenosine A receptor, enhances arousal in mice.

Adenosine A receptor (AR) plays a pivotal role in the regulation of sleep-wake behaviors. We previously reported an AR selective antagonist compound 38 with an IC value of 29.0 nM.

Low-density lipoprotein receptor-related protein 6 ameliorates cardiac hypertrophy by regulating CTSD/HSP90α signaling during pressure overload.

Pressure overload induces pathological cardiac remodeling, including cardiac hypertrophy and fibrosis, resulting in cardiac dysfunction or heart failure. Recently, we observed that the low-density lipoprotein receptor-related protein 6 (LRP6), has shown potential in enhancing cardiac function by mitigating cardiac fibrosis in a mouse model subjected to pressure overload. In this study, we investigated the role of LRP6 as a potential modulator of pressure overload-induced cardiac hypertrophy and elucidated the underlying molecular mechanisms.

Gallbladder-derived retinoic acid signalling drives reconstruction of the damaged intrahepatic biliary ducts.

Severe damage to the intrahepatic biliary duct (IHBD) network occurs in multiple human advanced cholangiopathies, such as primary sclerosing cholangitis, biliary atresia and end-stage primary biliary cholangitis. Whether and how a severely damaged IHBD network could reconstruct has remained unclear. Here we show that, although the gallbladder is not directly connected to the IHBD, there is a common hepatic duct (CHD) in between, and severe damage to the IHBD network induces migration of gallbladder smooth muscle cells (SMCs) to coat the CHD in mouse and zebrafish models.

Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration.

Traditional approaches to studying astrocyte heterogeneity have mostly focused on analyzing static properties, failing to identify whether subtypes represent intermediate or final states of reactive astrocytes. Here we show that previously proposed neuroprotective and neurotoxic astrocytes are transitional states rather than distinct subtypes, as revealed through time-series multiomic sequencing. Neuroprotective astrocytes are an intermediate state of the transition from a nonreactive to a neurotoxic state in response to neuroinflammation, a process regulated by the mTOR signaling pathway.

Privacy protection of sexually transmitted infections information from Chinese electronic medical records.

The comprehensive adoption of Electronic Medical Records (EMRs) offers numerous benefits but also introduces risks of privacy leakage, particularly for patients with Sexually Transmitted Infections (STI) who need protection from social secondary harm. Despite advancements in privacy protection research, the effectiveness of these strategies in real-world data remains debatable. The objective is to develop effective information extraction and privacy protection strategies to safeguard STI patients in the Chinese healthcare environment and prevent unnecessary privacy leakage during the data-sharing process of EMRs.

Prodromal Parkinson's disease and subsequent risk of Parkinson's disease and mortality.

Association of prodromal Parkinson's disease (PD) with risk of PD and risk of mortality in individuals with PD warrant investigation through large-scale prospective study. We included 501,475 participants without PD at baseline. Eight prodromal features were measured.

AFM observation of protein translocation mediated by one unit of SecYEG-SecA complex.

Protein translocation across cellular membranes is an essential and nano-scale dynamic process. In the bacterial cytoplasmic membrane, the core proteins in this process are a membrane protein complex, SecYEG, corresponding to the eukaryotic Sec61 complex, and a cytoplasmic protein, SecA ATPase. Despite more than three decades of extensive research on Sec proteins, from genetic experiments to cutting-edge single-molecule analyses, no study has visually demonstrated protein translocation.

Astemizole Exacerbates 5-Fluorouracil-Triggered Cardiotoxicity by Enhancing Ptgs2.

5-fluorouracil (5-FU), a commonly utilized antitumor agent for the treatment of colon cancer, is linked to an increased risk of cardiovascular diseases. Antihistamines including astemizole (AST) have been reported to present cardiovascular toxicity; however, it remains unclear how 5-FU-mediated cardiotoxicity is affected by AST during the treatment of colon cancer. This study explored the role of AST in 5-FU-induced cardiotoxicity in colon cancer.

Exploring the relationship between professional roles and behavioural intentions in chronic kidney disease management: a cross-sectional study among primary and specialist health professionals in Shanghai, China.

Objectives: General practitioners, nephrologists and renal nurses play key roles in professional integration in chronic kidney disease (CKD) management. Professional roles may influence professionals' behavioural intentions, namely, the degree to which individuals formulate behavioural plans to attain a behavioural goal. However, little is known about the relationship between professional roles and their behavioural intentions in CKD management.

Cost-effectiveness of toripalimab plus chemotherapy versus chemotherapy as first-line treatment for advanced non-small cell lung cancer in China: a societal perspective.

Background: To investigate the cost-effectiveness of toripalimab plus chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer (NSCLC) patients from a societal perspective.

Methods: A partitioned-survival model estimated the costs and cost-effectiveness of toripalimab plus chemotherapy versus standard chemotherapy for advanced NSCLC over 20 years. Clinical data were derived from the CHOICE-01 trial, and cost and utility inputs were gathered from Yaozh.

Nanomedicine-unlocked radiofrequency dynamic therapy dampens incomplete radiofrequency ablation-arised immunosuppression to suppress cancer relapse.

Incomplete radiofrequency ablation (iRFA) not only leaves residual tumor, but also render the residual tumor highly self-adaptable and immunosuppressive, consequently expediting residual tumor progression including relapse. To address it, radiofrequency dynamic therapy (RFDT) with identical trigger (namely radiofrequency) has been established and enabled by polyethylene glycol (PEG)-modified Fe-based single atom nanozyme (P@Fe SAZ). P@Fe SAZ can respond to radiofrequency field to produce reactive oxygen species (ROS), attaining the nanomedicine-unlocked low-temperature RFDT.

Conductive Hydrogel Systems Enabling Rapid and Controllable Release of Guests at Low-Voltage Region.

Smart delivery materials that respond to electric fields attract interest across various fields, whereas systems enabling rapid, controllable, and safe delivery capabilities remain essential. Based on the hypothesis of utilizing electric field to manipulate inter-component noncovalent bonds in delivery materials, a hydrogel system is hereby reported that is capable of achieving rapid guest release at low-voltage region. This system harnesses the synergistic regulation of electric field-induced host-guest electrostatic repulsion, alongside the dynamic modulation of H-bond interactions within the conductive hydrogel.

Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.

Vaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such as insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, likely due to their short in vivo exposure. Recent advances in extending the half-life of protein therapeutics have shown promise in improving drug efficacy, yet whether increasing in vivo persistence can enhance the efficacy of subunit vaccines remains underexplored.

The association of parental age at delivery with childhood allergic disease and the modified effect of breastfeeding.

Background: Childhood allergic diseases are a global concern; quite limited studies have examined the impacts of parental age at delivery. This study aimed to explore the association between separate and combined parental age at delivery and childhood allergic diseases and whether adequate breastfeeding could modify this association.

Methods: This cross-sectional study sampled 15,976 children from Shanghai, China.

Cortical direction selectivity increases from the input to the output layers of visual cortex.

Sensitivity to motion direction is a feature of visual neurons that is essential for motion perception. Recent studies have suggested that direction selectivity is re-established at multiple stages throughout the visual hierarchy, which contradicts the traditional assumption that direction selectivity in later stages largely derives from that in earlier stages. By recording laminar responses in areas 17 and 18 of anesthetized cats of both sexes, we aimed to understand how direction selectivity is processed and relayed across 2 successive stages: the input layers and the output layers within the early visual cortices.

Exploring genetic mapping and co-expression patterns to illuminate significance of Tbx20 in cardiac biology.

The transcription factor Tbx20 is integral to heart development and plays a significant role in various cardiac diseases. Despite its established importance, the regulatory mechanisms and functional significance of Tbx20 remain incompletely understood. To elucidate these mechanisms, we initially conducted eQTL mapping to identify genetic loci associated with Tbx20 expression in heart tissue from BXD mice.

Predictive, preventive and personalized project of vascular cognitive impairment in China (P3): Study design and interim baseline patient characteristics of a Nationwide multicenter prospective registry.

Objectives: To outline the design of the P3 study and serve as a summary of the interim baseline patient characteristics.

Methods: P3 study is a multicenter, prospective cohort study targeting 1000 acute ischemic stroke (AIS) and cerebral small vessel disease (CSVD) patients with a 2-year follow-up from 80 participating hospitals across China. Comprehensive multimodal imaging, neuropsychological tests, and biological samples were collected prospectively on admission and follow-up visits.

Denture use and a slower rate of cognitive decline among older adults with partial tooth loss in China: A 10-year prospective cohort study.

Objective: Denture use has been shown to improve nutritional intake and diet quality in people with tooth loss. Despite evidence linking tooth loss and dementia, few studies have examined the association between denture use and cognitive decline. We investigated the relationship between denture use and cognitive decline among Chinese older adults with tooth loss.

Exploring causal relationships between immune cells and age-related macular degeneration through univariable, bidirectional, and multivariable Mendelian analysis.

Objective: This study systematically investigates the causal relationships between 731 immune cell phenotypes and age-related macular degeneration (AMD) using comprehensive Mendelian randomization (MR) analyses. The goal is to identify immune cell factors that contribute to or protect against AMD, thereby clarifying the immunological mechanisms underlying AMD pathophysiology and informing prevention and treatment strategies.

Methods: Univariable, bidirectional, and multivariable MR analyses were conducted to evaluate the associations between immune cells and AMD.

Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.

The tumor microenvironment (TME) is involved in cancer initiation and progression. With advances in the TME field, numerous therapeutic approaches, such as antiangiogenic treatment and immune checkpoint inhibitors, have been inspired and developed. Nevertheless, the sophisticated regulatory effects on the biological balance of the TME remain unclear.

Drug-phospholipid conjugate nano-assembly for drug delivery.

Phospholipid-based liposomes are among the most successful nanodrug delivery systems in clinical use. However, these conventional liposomes present significant challenges including low drug-loading capacity and issues with drug leakage. Drug-phospholipid conjugates (DPCs) and their assemblies offer a promising strategy for addressing these limitations.