Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process.

The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes.

Med1 controls thymic T-cell migration into lymph node through enhancer-based Foxo1-Klf2 transcription program.

The migration is the key step for thymic T cells to enter circulation and then lymph nodes (LNs), essential for future immune surveillance. Although promoter-based transcriptional regulation through Foxo1, Klf2, Ccr7, and Sell regulates T-cell migration, it remains largely unexplored whether and how enhancers are involved in this process. Here we found that the conditional deletion of Med1, a component of the mediator complex and a mediator between enhancers and RNA polymerase II, caused a reduction of both CD4 and CD8 T cells in LNs, as well as a decrease of CD8 T cells in the spleen.

[Effects of different exercise modes on neuromuscular junction and metabolism of skeletal muscle-related proteins in aging rats].

The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining.

Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8 T cell effector differentiation and anti-tumor immunity.

CD8 T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8 T cells.

Emerging Role of Sorting Nexin 17 in Human Health and Disease.

The distortion of the cellular membrane transport pathway has a profound impact on cell dynamics and can drive serious physiological consequences during the process of cell sorting. SNX17 is a member of the Sorting Nexin (SNX) family and plays a crucial role in protein sorting and transport in the endocytic pathway. SNX17, SNX27, and SNX31 belong to the SNX-FERM subfamily and possess the FERM domain, which can assist in endocytic transport and lysosomal degradation.

The compensatory role of T cells from lymph nodes in mice with splenectomy.

The spleen is a vital organ for the immune system, while splenectomy may be necessary for various reasons. However, there is limited research on the impact of splenectomy on T cell function in peripheral lymph nodes as a compensatory mechanism in preventing infections. This study aimed to investigate the characteristics and function of CD8 and CD4 T cells in different peripheral lymph nodes during viral infection using a well-established splenectomy model.

The Transcription Factor Zfp335 Promotes Differentiation and Survival of Effector Th1 Cells by Directly Regulating Lmna Expression.

Ag-specific effector CD4+ T cells play a crucial role in defending against exogenous pathogens. However, the mechanisms governing the differentiation and function of IFN-γ-producing effector CD4+ Th1 cells in immune responses remain largely unknown. In this study, we elucidated the pivotal role of zinc finger protein 335 (Zfp335) in regulating effector Th1 cell differentiation and survival during acute bacterial infection.

Effects of blood flow restriction training on muscle fitness and cardiovascular risk of obese college students.

The aim of this study was to investigate the effect of blood flow restriction (BFR) combined with low-intensity resistance training (RT) on cardiovascular risk factors in obese individuals. Twenty-six male obese college students were recruited and randomly assigned to a control group (CON, = 8), a low-intensity RT group (RT, = 9), and a combined BFR training and low-intensity RT group (BFRT, = 9). The subjects in BFRT group showed significant reductions in body fat percentage and waist-to-hip ratio and a significant increase in lean mass and muscle mass; the peak torque, peak power, and endurance ratio of knee extensors and elbow flexors were significantly upregulated; the root mean square (RMS) for the medial femoral muscle, lateral femoral muscle and biceps significantly increased; the diastolic blood pressure (DBP) showed a significant decrease.

Progress and Challenges in Tumor Ferroptosis Treatment Strategies: A Comprehensive Review of Metal Complexes and Nanomedicine.

Ferroptosis is a new form of regulated cell death featuring iron-dependent lipid peroxides accumulation to kill tumor cells. A growing body of evidence has shown the potential of ferroptosis-based cancer therapy in eradicating refractory malignancies that are resistant to apoptosis-based conventional therapies. In recent years, studies have reported a number of ferroptosis inducers that can increase the vulnerability of tumor cells to ferroptosis by regulating ferroptosis-related signaling pathways.

Nanoreactor-based catalytic systems for therapeutic applications: Principles, strategies, and challenges.

Inspired by natural catalytic compartments, various synthetic compartments that seclude catalytic reactions have been developed to understand complex multistep biosynthetic pathways, bestow therapeutic effects, or extend biosynthetic pathways in living cells. These emerging nanoreactors possessed many advantages over conventional biomedicine, such as good catalytic activity, specificity, and sustainability. In the past decade, a great number of efficient catalytic systems based on diverse nanoreactors (polymer vesicles, liposome, polymer micelles, inorganic-organic hybrid materials, MOFs, etc.

Zfp335 establishes eTreg lineage and neonatal immune tolerance by targeting Hadha-mediated fatty acid oxidation.

Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset.

Effects of ultrasound-guided stellate ganglion block on postoperative sore throat and postoperative sleep disturbance after lumbar spine surgery: a randomized controlled trial.

Background: Postoperative sore throat and sleep disturbance are prevalent among patients undergoing spinal surgery, and these conditions can substantially impact their postoperative satisfaction and quality of life. The present study aimed to examine the impact of ultrasound-guided stellate ganglion block (SGB) on the occurrence of postoperative sore throat (POST) and postoperative sleep disturbance (PSD) in patients who undergo lumbar spine surgery under general anesthesia.

Methods: Sixty patients were randomly assigned to either the experimental group (SGB group) or the control group (CG).

Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study.

Background: Emergency agitation is a common postoperative complication in patients under general anesthesia, which can lead to unpredictable damages such as shedding of drainage tube and bleeding from the wound. The purpose of the study is to investigate whether intraoperative infusion of Magnesium Sulfate reduces the incidence of emergency agitation (EA) in patients undergoing radical mastectomy, and to evaluate its safety and efficacy.

Methods: A total of 70 patients were randomly assigned to two groups: the Magnesium group (M group) and the control group (C group).

Immunogenic PANoptosis-Initiated Cancer Sono-Immune Reediting Nanotherapy by Iteratively Boosting Cancer Immunity Cycle.

The cancer-immune cycle conceptualized the mechanisms of driving T cell responses to tumors, but w as limited by immunological ignorance elicited by tumor inherent immunoediting, which failed to initiate and maintain adaptive immunity. Targeting specific vulnerabilities of cell death patterns may provide unique opportunities to boost T cell antitumor immunological effects. Here an ultrasound nanomedicine-triggered tumor immuno-reediting therapeutic strategy using nano/genetically engineered extracellular vesicles, which can induce tumor highly immunogenic PANoptosis and iteratively start-up the energization of cancer innate immunity cycle by repeatedly liberating damage-associated molecular patterns, thereby priming sufficient antigen-specific T cells and shaping protective immune response through activating cGAS-STING signaling pathways, is reported.

Questionnaire-based analysis of autism spectrum disorders and gastrointestinal symptoms in children and adolescents: a systematic review and meta-analysis.

Background: Gastrointestinal (GI) symptoms are frequently experienced by children with autism spectrum disorder (ASD), and these symptoms cause difficulties for these children and their families. However, studies of GI symptom prevalence differ significantly. This meta-analysis aimed to analyze the prevalence of GI symptoms in children with ASD.

Evolutionary overview of sarcopenia - bibliometric study on the Web of science: A review.

Sarcopenia is an age-related degenerative disease associated with adverse outcomes such as falls, functional decline, weakness, and mortality. Exploring the dynamic evolutionary path and patterns of sarcopenia research topics within a temporal framework from the perspective of strategic coordinate maps and data flow can help identify the development rules of sarcopenia themes. After searching, a total of 16,326 articles were obtained.

T cells in health and disease.

T cells are crucial for immune functions to maintain health and prevent disease. T cell development occurs in a stepwise process in the thymus and mainly generates CD4 and CD8 T cell subsets. Upon antigen stimulation, naïve T cells differentiate into CD4 helper and CD8 cytotoxic effector and memory cells, mediating direct killing, diverse immune regulatory function, and long-term protection.

Injectable nano-composite hydrogels based on hyaluronic acid-chitosan derivatives for simultaneous photothermal-chemo therapy of cancer with anti-inflammatory capacity.

Nowadays, the photothermal therapy (PTT) has received widespread attention and research by rapidly killing tumors with local high temperature. However, due to the irregular edges of tumor and the blurred boundary between normal and necrotic tissues, the desirable treatment cannot be achieved by the single PTT, and excessive heat will cause serious inflammation in local tissues. Herein, an injectable composite hydrogel is prepared by the oxidized hyaluronic acid (OHA) and hydroxypropyl chitosan (HPCS) via the imine bonds, which is employed as the delivery substrate for functional substances.

Single-cell sequencing reveals the evolution of immune molecules across multiple vertebrate species.

Introduction: Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates.

Objectives: Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species.

Amphiphilic Dendrimer Doping Enhanced pH-Sensitivity of Liposomal Vesicle for Effective Co-delivery toward Synergistic Ferroptosis-Apoptosis Therapy of Hepatocellular Carcinoma.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is the ferroptosis-apoptosis combination therapy for cancer treatment. Herein, a nanoplatform is reported for effective co-delivery of the anticancer drug sorafenib (S) and the ferroptosis inducer hemin (H), toward synergistic ferroptosis-apoptosis therapy of advanced hepatocellular carcinoma (HCC) as a proof-of-concept study.

Effects of Peripherally Inserted Central Catheter (PICC) Catheterization Nursing on Bloodstream Infection in Peripheral Central Venous Catheters in Lung Cancer: A Single-Center, Retrospective Study.

Background: Peripherally inserted central catheter (PICC), as one of the important intravenous routes for the rescue and treatment of critically ill patients, has been widely used in the fluid resuscitation of critically ill patients in intensive care. In particular, PICC can be widely used in the treatment of cancer patients. With the wide application of peripheral central venous catheterization, the clinical findings of bloodstream infection complications caused by PICC have gradually attracted the attention of doctors and patients.

Med1 Controls Effector CD8 T Cell Differentiation and Survival through C/EBPβ-Mediated Transcriptional Control of T-bet.

Effector CD8 T cells are crucial players in adaptive immunity for effective protection against invading pathogens. The regulatory mechanisms underlying CD8 T cell effector differentiation are incompletely understood. In this study, we defined a critical role of mediator complex subunit 1 (Med1) in controlling effector CD8 T cell differentiation and survival during acute bacterial infection.

Self-Splittable Transcytosis Nanoraspberry for NIR-II Photo-Immunometabolic Cancer Therapy in Deep Tumor Tissue.

Cancer photo-immunotherapy (CPIT) as an ideal strategy can rapidly release hostile signals by appropriate dosage of focal laser irradiation to unmask primary tumor immunogenicity and can activate adaptive immunity to control distant metastases. However, many factors, including disordered immunometabolism, poor penetration of photothermal agents and immuno-regulators, inadequate laser penetration into the deep tumor region, restrict the therapeutic outcomes of CPIT. Here, a second near-infrared window (NIR-II) photo-immunometabolic cancer therapy (PICT) by a programmed raspberry-structured nanoadjuvant (PRN ) is presented that can potentiates efficient immunogenic cell death (ICD) in deep tumor tissue and alleviates immunometabolic disorder.