LAPTM5 mediates immature B cell apoptosis and B cell tolerance by regulating the WWP2-PTEN-AKT pathway.

Elimination of autoreactive developing B cells is an important mechanism to prevent autoantibody production. However, how B cell receptor (BCR) signaling triggers apoptosis of immature B cells remains poorly understood. We show that BCR stimulation up-regulates the expression of the lysosomal-associated transmembrane protein 5 (LAPTM5), which in turn triggers apoptosis of immature B cells through two pathways. LAPTM5 causes BCR internalization, resulting in decreased phosphorylation of SYK and ERK. In addition, LAPTM5 targets the E3 ubiquitin ligase WWP2 for lysosomal degradation, resulting in the accumulation of its substrate PTEN. Elevated PTEN levels suppress AKT phosphorylation, leading to increased FOXO1 expression and up-regulation of the cell cycle inhibitor p27Kip1 and the proapoptotic molecule BIM. In vivo, LAPTM5 is involved in the elimination of autoreactive B cells and its deficiency exacerbates autoantibody production. Our results reveal a previously unidentified mechanism that contributes to immature B cell apoptosis and B cell tolerance.

A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

P2X4R promotes airway remodeling by acting on the phenotype switching of bronchial smooth muscle cells in rats.

The P2X4 receptor (P2X4R) contributes to airway inflammation and airway remodeling in mice with allergic asthma. However, the molecular mechanism by which P2X4R affects the airway remodeling in allergic asthma remains largely unknown. We established an allergic asthma model by ovalbumin (OVA) inhalation in BALB/c mice. Compared with the mice in the control group, the expression of proliferating cell nuclear antigen (PCNA) increased and that of alpha-smooth muscle actin (α-SMA) decreased in the OVA-challenged mice. 5-BDBD, a P2X4R antagonist, alleviated the OVA-induced changes. To clarify the role of P2X4R in the phenotype switching of the bronchial smooth muscle, bronchial smooth muscle contractility and p38MAPK expression were investigated. Platelet-derived growth factor-BB (PDGF-BB) was used to activate the proliferation of primary-cultured rat bronchial smooth muscle cells (BSMCs). P2X4R, p38MAPK, and phenotype markers were evaluated using Western blotting or immunofluorescence. PDGF-BB administration increased the P2X4R and phospho-p38MAPK expression in BSMCs, and the increased phospho-p38MAPK expression was downregulated by silencing of the P2X4R mRNA. PDGF-BB stimulated the proliferation and synthetic phenotype of BSMCs, which was aggravated by a P2X4R agonist and alleviated by a P2X4R antagonist or silencing the P2X4R mRNA. The decreased contractile phenotype induced by PDGF-BB was alleviated by a P2X4R antagonist or by silencing the P2X4R mRNA. SB203580, p38MAPK inhibitor, inhibited the PDGF-BB-induced increasing of synthetic phenotype and the proliferation of BSMCs. These findings indicate that P2X4R acts directly on the phenotype switching of BSMCs. Inhibiting P2X4R can promote the contractile differentiation of BSMCs via p38MAPK signaling. Thus, the effect of P2X4R on airway remodeling indicates that this receptor could be a target for future drug candidates.

SiO2-Ag-SiO2 core/shell structure with a high density of Ag nanoparticles for CO oxidation catalysis.

SiO2-Ag-SiO2, a sandwiched core/shell structure with a layer of Ag nanoparticles (∼4 nm) encapsulated between a shallow SiO2 surface layer and a SiO2 submicrosphere substrate (∼200 nm), has been synthesized from [Formula: see text] and SiO2 spheres by a facile one-pot hydrothermal method. The composite is proposed to result from the dynamic balance between the [Formula: see text] reduction and the dissolution-redeposition of SiO2 in mild basic media. The synthetic mechanism and the roles of the reaction time, temperature, and the amount of ammonia in the formation of this unique structure are investigated and discussed. The composite structure shows superior catalytic performance in CO oxidation to the control Ag/SiO2 structure prepared by impregnation. Pre-treatment by O2 at 600 °C significantly improves the catalytic performance of the composite structure and preserves the nanocomposite structure well.

Modulating fcc and hcp Ruthenium on the Surface of Palladium-Copper Alloy through Tunable Lattice Mismatch.

Herein, we report an epitaxial-growth-mediated method to grow face-centered cubic (fcc) Ru, which is thermodynamically unfavorable in the bulk form, on the surface of Pd-Cu alloy. Induced by the galvanic replacement between Ru and Pd-Cu alloy, a shape transformation from a Pd-Cu@Ru core-shell to a yolk-shell structure was observed during the epitaxial growth. The successful coating of the unconventional crystallographic structure is critically dependent on the moderate lattice mismatch between the fcc Ru overlayer and PdCu3 alloy substrate. Further, both fcc and hexagonal close packed (hcp) Ru can be selectively grown through varying the lattice spacing of the Pd-Cu substrate. The presented findings provide a new synthetic pathway to control the crystallographic structure of metal nanomaterials.

The Probiotic Kluyveromyces lactis JSA 18 Alleviates Obesity and Hyperlipidemia in High-Fat Diet C57BL/6J Mice.

Obesity poses a significant threat to various health conditions such as heart diseases, diabetes, high blood pressure, and heart attack, with the gut microbiota playing a crucial role in maintaining the body's energy balance. We identified a novel probiotic fungal strain, Kluyveromyces lactis JSA 18 (K. lactis), which was isolated from yak milk and was found to possess anti-obesity properties. Additionally, Lactobacillus plantarum CGMCC 8198 (LP8198) from our previous study was also included to evaluate its anti-obesity properties. The findings indicated that K. lactis caused a notable reduction in weight gain, liver and fat indexes, and hyperlipidemia in mice fed a high-fat diet (HFD). Administering K. lactis and LP8198 to mice on a high-fat diet resulted in a reduction of serum triglyceride levels. Furthermore, the supplements reduced ALT and AST activity, and inhibited the production of inflammatory cytokines such as TNF-α and IL-1ß. In addition, lipid metabolism was enhanced by the downregulation of ACC1, PPAR-γ, SREBP-1, and Fasn. Moreover, this study found that K. lactis and LP8198 have little effect on gut bacteria. Additionally, K. lactis partially influenced intestinal fungi, while LP8198 had a minor influence on gut mycobiota. The main goal of this research was to show how effective K. lactis can be as a probiotic in combating obesity.

Micro(nano)plastics in human urine: A surprising contrast between Chongqing's urban and rural regions.

Microplastics (100 nm-5 mm) and nanoplastics (<100 nm) collectively referred to as micro(nano)plastics (MNPs), which are emerging pollutants all over the world. Environmental differences affect its distribution. The content of MNPs differs between urban and rural environments, according to previous studies. To understand the actual situation of human exposure to MNPs in various environments, this study collected 12 urine samples from volunteers in urban and rural regions of Chongqing and used pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and laser direct infrared spectroscopy (LDIR) to detect and analyze MNPs in urine. With an average abundance of 1.50 (2.31) mg/kg, MNPs were found in 9 samples by Py-GC/MS. Polyethylene (PE), polyvinyl chloride (PVC) and polyamide 66 (PA66), three different types of MNPs were found, with PE content being the highest among them. By using LDIR, MNPs were found in 7 samples, with an average abundance of 15.17 (23.13) particles/kg. Five different types of MNPs were found, with acrylates (ACR) being the main type, followed by polymethylmethacrylate (PMMA), polyurethane (PU), polypropylene (PP), polyethylene terephthalate (PET). The findings demonstrated that urban region had much greater levels and more types of MNPs in human urine than rural. Additionally, regular contact with plastic toys and the use of personal care products are linked to the presence of MNPs. The influence of environmental factors on the actual exposure of the human body to MNPs was preliminary explored in this study, and two different methods were used for the first time to simultaneously detect and analyze MNPs in human urine. This allowed for the feasibility of comprehensively and effectively quantitatively analyzing the actual exposure of the human body to MNPs, and also provided the theoretical foundation for further research on the harm of MNPs to human health in different environments.

MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation.

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell-specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced dextran sulfate sodium salt (DSS)-induced colitis. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in Mzb1-/- mice compared with Mzb1+/+ mice. The increase in CRC development and progression in Mzb1-/- mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing Mzb1+/+ and Mzb1-/- mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.

Characterization of glomerular basement membrane components within pediatric glomerular diseases.

Background: Disruptions in gene expression associated with the glomerular basement membrane (GBM) could precipitate glomerular dysfunction. Nevertheless, a comprehensive understanding of the characterization of GBM components within pediatric glomerular diseases and their potential association with glomerular function necessitates further systematic investigation. Methods: We conducted a systematic analysis focusing on the pathological transformations and molecular attributes of key constituents within the GBM, specifically Collagen IV α3α4α5, Laminin α5ß2γ1, and Integrin α3ß1, across prevalent pediatric glomerular diseases. Results: We observed upregulation of linear expression levels of COL4A3/4/5 and Laminin 5α proteins, along with a partial reduction in the linear structural expression of Podocin in idiopathic nephrotic syndrome (INS), encompassing minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), but showing a reduction in IgA nephropathy (IgAN), IgA vasculitis nephritis (IgAVN) and lupus nephritis (LN). Furthermore, our study revealed reductions in Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases. Conclusion: In INS, notably MCD and FSGS, there is a notable increase in the linear expression levels of COL4A3/4/5 and Laminin 5α proteins. In contrast, in IgAN, IgAVN, and LN, there is a consistent reduction in the expression of these markers. Furthermore, the persistent reduction of Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases suggests a shared characteristic of structural alterations within the GBM across these conditions.

Unraveling the mysteries of spiral artery remodeling.

Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to the placenta to nourish the developing fetus. Failure of this process is associated with the pathophysiology of most of the major obstetric complications, including late miscarriage, fetal growth restriction and pre-eclampsia. However, the point at which remodeling 'fails' in these pathological pregnancies is not yet clear. Spiral artery remodeling has predominantly been described in terms of its morphological features, however we are starting to understand more about the cellular and molecular triggers of the different aspects of this process. This review will discuss the current state of knowledge of spiral artery remodeling, in particular the processes involved in loss of the vascular smooth muscle cells, and consider where in the process defects would lead to a pathological pregnancy.

A mini review on recent progress of steam reforming of ethanol.

H2 is one of the promising renewable energy sources, but its production and transportation remain challenging. Distributed H2 production using liquid H2 carriers is one of the ideal ways of H2 utilization. Among common H2 carriers, ethanol is promising as it has high H2 content and can be derived from renewable bio-energy sources such as sucrose, starch compounds, and cellulosic biomass. To generate H2 from ethanol, steam reforming of ethanol (SRE) is the most common way, while appropriate catalysts, usually supported metal catalysts, are indispensable. However, the SRE process is quite complicated and always accompanied by various undesirable by-products, causing low H2 yield. Moreover, the catalysts for SRE are easy to deactivate due to sintering and carbon deposition under high reaction temperatures. In recent years, lots of efforts have been made to reveal SRE mechanisms and synthesize catalysts with high H2 yield and excellent stability. Both active metals and supports play an important role in the reaction. This mini-review summarizes the recent progress of SRE catalysts from the view of the impacts of active metals and supports and draws an outlook for future research directions.

Simultaneous removing algal and its extracellular organic matters by Mg/Al-layered double hydroxide /La-montmorillonite.

Rapid and effective simultaneous removal of algal and extracellular organic matter (EOM) is essential for algal blooms water emergency treatment. In this study, a composite material was prepared by physical and chemical interaction between La-montmorillonite (La-MMT) and Mg/Al-layered double hydroxide (LDHs), and its removal effect of algal and extracellular organic matters (EOM) was investigated. The results showed that the removal rate of chlorophyll a (chl-a) was 96.8% within 2 h when the LDHs/La-MMT2:1 dosage was 1.0 g/L. Three-dimensional fluorescence characteristic spectra and parallel factor analysis showed that the removal of EOM by composite material mainly reflected in the removal of humus-like substances. The reaction heat of composite material for the algal solution was -32.7 J/g. Zeta potential changed from -25.7 mV to -16.9 mV, the main treatment mechanisms of composite material were surface adsorption, complexation precipitation, charge neutralisation, and ion exchange. These findings herein proposed that composite material was a potential and proper treating agent for removing algal cells and EOM from algal blooms water.

Molecular characteristics of circulating B cells and kidney cells at the single-cell level in special types of primary membranous nephropathy.

Background: Although primary membranous nephropathy (pMN) associated with podocyte autoantibodies (POS) is becoming well-known, the molecular characteristics of the specific type of pMN that is negative for podocyte autoantibodies (NEG) is still unclear. Methods: We performed single-cell transcriptome sequencing and single-cell B cell receptor sequencing on circulating CD19+ cells and kidney cells of a NEG paediatric patient with pMN. The single-cell datasets of POS patients and healthy control individuals were included for integrative analysis. Results: The gene expression characteristics and clonal expansion of naïve and memory B cells in the NEG patient changed significantly. We found that a group of CD38+ naïve B cells expanded in the NEG patient, which had the functional characteristics of cell activation. In addition, the conversion between immunoglobulin M (IgM)/IgD and IgG1 in the NEG patient was increased. Parietal epithelial cells (PECs) and podocytes shared similar signature genes (WT1, CLIC5), and new candidate marker genes for PECs, such as NID2, CAV1 and THY1, might contribute to the definition of cell subsets. PECs might have undergone significant changes in the disease, mainly manifested by changes in the expression of CCN2, PLAAT4 and SEPTIN2. The scores of gene sets related to extracellular matrix, cell adhesion and calcium channel in podocytes of the NEG patient was significantly increased. The gene expression of sodium transporter in a group of proximal tubule cells in the disease was significantly increased, especially SLC5A12, which might be related to the oedema of patients. Conclusions: Our research demonstrated the cell type-specific molecular features in the circulation and kidney of the NEG pMN patient.

Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome.

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7 high, TCF7 high, and HLA-DR low) and Treg2 (CCR7 low, TCF7 low, and HLA-DR high). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency.

Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function. We report a recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families. The patients exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii, and presented with agammaglobulinemia. Patients' B cells showed impaired maturation, decreased immunoglobulin isotype switching, and defective plasma cell differentiation, whereas their T cells contained reduced TH17 and TFH populations and exhibited decreased cytokine production. A knock-in mouse model of heterozygous T95R showed a severe defect in antibody production both at the steady state and after immunization with different types of antigens, consistent with the CID observed in these patients. The IRF4T95R variant maps to the TF's DNA binding domain, alters its canonical DNA binding specificities, and results in a simultaneous multimorphic combination of loss, gain, and new functions for IRF4. IRF4T95R behaved as a gain-of-function hypermorph by binding to DNA with higher affinity than IRF4WT. Despite this increased affinity for DNA, the transcriptional activity on IRF4 canonical genes was reduced, showcasing a hypomorphic activity of IRF4T95R. Simultaneously, IRF4T95R functions as a neomorph by binding to noncanonical DNA sites to alter the gene expression profile, including the transcription of genes exclusively induced by IRF4T95R but not by IRF4WT. This previously undescribed multimorphic IRF4 pathophysiology disrupts normal lymphocyte biology, causing human disease.

Advances in PSMA-targeted therapy for prostate cancer.

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein located on the cell membrane, is specifically and highly expressed in prostate cancer (PCa). Besides, its expression level is related to tumor invasiveness. As a molecular target of PCa, PSMA has been extensively studied in the past two decades. Currently, a great deal of evidence suggests that significant progresses have been made in the PSMA-targeted therapy of PCa. Herein, different PSMA-targeted therapies for PCa are reviewed, including radioligand therapy (177Lu-PSMA-RLT, 225Ac-PSMA-RLT), antibody-drug conjugates (MLN2704, PSMA-MMAE, MEDI3726), cellular immunotherapy (CAR-T, CAR/NK-92, PSMA-targeted BiTE), photodynamic therapy, imaging-guided surgery (radionuclide-guided surgery, fluorescence-guided surgery, multimodal imaging-guided surgery), and ultrasound-mediated nanobubble destruction.

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy.

Ferroptosis therapy by catalyzing the Fenton reaction has emerged as a promising tumor elimination strategy for lung adenocarcinoma (ADC). However, the unsatisfactory Fenton reaction efficiency, strong intracellular antioxidant system, and insufficient lung drug accumulation limits the ferroptosis therapeutic effect. To address these issues, an inhalable nanoreactor was proposed by spontaneously adsorbing biomimetic protein corona (PC) composed of matrix metalloproteinase 2 responsive gelatin and glutamate (Glu) on the surface of cationic nanostructured lipid carriers (NLC) core loaded with ferrocene (Fc) and fluvastatin. The prepared Fc-NLC(F)@PC could be nebulized into lung lesions with 2.6 times higher drug accumulation and boost lipid peroxide production by 3.2 times to enhance ferroptosis therapy. Mechanically, fluvastatin was proved to inhibit monocarboxylic acid transporter 4 mediated lactate efflux, inducing tumor acidosis to boost Fc-catalyzing reactive oxygen species production, while the extracellular elevating Glu concentration was found to inhibit xCT (system Xc-) functions and further collapse the tumor antioxidant system by glutathione synthesis suppression. Mitochondrial dysfunction and cell membrane damage were involved in the nanoreactor-driven ferroptotic cell death process. The enhanced antitumor effects by combination of tumor acidosis and antioxidant system collapse were confirmed in an orthotopic lung ADC tumor model. Overall, the proposed nanoreactor highlights the pulmonary delivery approach for local lung ADC treatment and underscores the great potential of ferroptosis therapy.

A Perfect Pair: Stabilized Black Phosphorous Nanosheets Engineering with Antimicrobial Peptides for Robust Multidrug Resistant Bacteria Eradication.

Black phosphorus (BP) nanosheets emerged as promising 2D nanomaterial that have been applied to eradicate antibiotic-resistant bacteria. However, their applications are limited by intrinsic ambient instability. Here, the ε-poly-l-lysine (ε-PL)-engineered BP nanosheets are constructed via simple electrostatic interaction to cater the demand for passivating BP with amplified antibacterial activity. The dual drug-delivery complex named BP@ε-PL can closely anchor onto the surface of bacteria, leading to membrane disintegration. Subsequently, in situ hyperthermia generated by BP under near-infrared (NIR) irradiation can precisely eradicate pathogenic bacteria. In vitro antibacterial studies verify the rapid disinfection ability of BP@ε-PL against Methicillin-resistant Staphylococcus aureus (MRSA) within 15 min. Moreover, ε-PL can serve as an effective protector to avoid chemical degradation of bare BP. The in vivo antibacterial study shows that a 99.4% antibacterial rate in a MRSA skin infection model is achieved, which is accompanied by negligible toxicity. In conclusion, this work not merely provides a new conjecture for protecting the BP, but also opens a novel window for synergistic antibiotic-resistant bacteria therapy based on antimicrobial peptides and 2D photothermal nanomaterial.

Single-cell RNA sequencing reveals the molecular features of peripheral blood immune cells in children, adults and centenarians.

Peripheral blood immune cells have different molecular characteristics at different stages of the whole lifespan. Knowledge of circulating immune cell types and states from children to centenarians remains incomplete. We profiled peripheral blood mononuclear cells (PBMCs) of multiple age groups with single-cell RNA sequencing (scRNA-seq), involving the age ranges of 1-12 (G1), 20-30(G2), 30-60(G3), 60-80(G4), and >110 years (G5). The proportion and states of myeloid cells change significantly from G1 to G2. We identified a novel CD8+CCR7+GZMB+ cytotoxic T cell subtype specific in G1, expressing naive and cytotoxic genes, and validated by flow cytometry. CD8+ T cells showed significant changes in the early stage (G1 to G2), while CD4+ T cells changed in the late stage (G4 to G5). Moreover, the intercellular crosstalk among PBMCs in G1 is very dynamic. Susceptibility genes for a variety of autoimmune diseases (AIDs) have different cell-specific expression localization, and the expression of susceptibility genes for AIDs changes with age. Notably, the CD3+ undefined T cells clearly expressed susceptibility genes for multiple AIDs, especially in G3. ETS1 and FLI1, susceptibility genes associated with systemic lupus erythematosus, were differentially expressed in CD4+ and CD8+ effector cells in G1 and G3. These results provided a valuable basis for future research on the unique immune system of the whole lifespan and AIDs.

Klotho gene improves oxidative stress injury after myocardial infarction.

The aim of the present study was to investigate the effects and mechanisms of the Klotho gene in oxidative stress injury after myocardial infarction. Sprague-Dawley rats were divided into five groups (sham, model, pDC316, LY294002, and pDC316-Klotho). Subsequently, the superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) concentrations were measured in myocardial tissues. Additionally, pathological differences among the groups were evaluated using hematoxylin and eosin and Masson's trichrome staining. Apoptosis was assayed by terminal deoxynucleotidyl transferase 2'-deoxyuridine-5'-triphosphate nick end-labeling assay, evaluated Klotho protein expression by immunohistochemical assay, and assessed Nrf 2 and ARE protein expressions using western blotting assay. As compared with in the sham group, the SOD, MDA, and GSH concentrations were significantly deteriorated (P<0.001, respectively); cardiomyocyte apoptosis index values were significantly increased (P<0.001); Klotho protein expression was significantly depressed; and Nrf-2 and ARE protein expressions were significantly (P<0.001, respectively) in the model and pDC316 groups. However, with Klotho supplementation by pDC316 transfection, as compared with in the model group, the SOD, MDA, and GSH concentrations were significantly improved (P<0.001, respectively); the cardiomyocyte apoptosis index values were significantly suppressed (P<0.001); and the pathology was improved. Further, the Klotho protein expression of the pDC316-Klotho group was significantly upregulated and the Nrf-2 and ARE proteins expressions of the LY294002 and pDC316-Klotho groups were significantly suppressed. Klotho overexpression improved findings of oxidative stress injury after myocardial infarction.