Loss of MALT1 Function in a Patient With Combined Immunodeficiency: a Novel Pathogenic Variant and Immunological Insights.

Background And Objectives: Germline pathogenic variants in the mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) encodes a caspase-like protease that plays a crucial role in the caspase recruitment domain (CARD)-B-cell lymphoma 10 (BCL10)-MALT1 (CBM) complex. This complex mediates the activation of nuclear factor-kB (NF-kB) pathway and are associated with diverse human diseases including combine immunodeficiency (CID), lymphoproliferation and others. This study aimed to determine the underlying cause of immune deficiency and immune dysregulation in a patient presented with recurrent respiratory infections, aphthous ulcers, dermatitis, chronic diarrhea, failure to thrive and early death.

Overcoming the blood-brain barrier challenge: nanotechnology-enhanced photodynamic therapy for glioblastoma treatment.

Glioblastoma (GBM), one of the most aggressive malignant tumors of the central nervous system, exhibits high recurrence rates and multiple pathological mechanisms, leading to an extremely poor prognosis for patients. Photodynamic therapy (PDT) has emerged as a significant research focus in solid tumor therapy due to its high efficacy and safety, inducing tumor cell-specific damage through a series of reactions mediated by photosensitizers. However, the blood-brain barrier (BBB) impedes drug delivery, and enhancing the penetration of photosensitizers across the BBB and targeting the lesion has become a critical challenge in the application of PDT for GBM.

Insights to enhanced coagulation based on the control of metal forms for treating acid mine drainage: Performance and mechanisms.

This study presents an enhanced oxidation-chelation-coagulation process for efficient acid mine drainage (AMD) treatment, addressing the limitations of conventional methods in terms of efficiency, cost, and environmental risks. Through systematic optimization, it was demonstrated that combined NaClO/KMnO₄ oxidation (3:1 molar ratio) at pH 8 effectively transformed Fe/Mn ions into insoluble Fe/Mn (hydr)oxides, while 0.40 g/L carboxymethyl cellulose (CMC) enabled effective chelation and removal of Pb/Ni.

Small extracellular vesicles from adipose derived stem cells alleviate microglia activation and improve motor deficit of Parkinson's disease via miR-100-5p/DTX3L/STAT1 signaling axis.

Dopaminergic neuron loss caused by microglia activation is an important pathological factor of Parkinson's disease (PD). Previously, we reported that small extracellular vesicle from adipose derived stem cells (ADSC-sEVs) could inhibit the activation of microglia and protect neuron apoptosis from microglia activation. However, whether ADSC-sEVs have protective effect on the motor deficit of PD mouse and the exact mechanism remains unknown.

Corrigendum: Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4 gain-of-function mutation.

[This corrects the article DOI: 10.3389/fimmu.2024.

Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4 gain-of-function mutation.

Background: WHIM syndrome is a rare, autosomal dominant inborn error of immunity characterized by warts, hypogammaglobulinemia, infection, and myelokathexis. It is caused mainly by heterozygous mutations at the C-terminus of the C-X-C chemokine receptor type 4 (CXCR4) gene.

Methods: We described the detailed clinical, genetic, immunological and treatment characteristic of four WHIM patients from a single Chinese family.

Controllable Design of Polyamide Composite Membrane Separation Layer Structures via Metal-Organic Frameworks: A Review.

Optimizing the structure of the polyamide (PA) layer to improve the separation performance of PA thin-film composite (TFC) membranes has always been a hot topic in the field of membrane preparation. As novel crystalline materials with high porosity, multi-functional groups, and good compatibility with membrane substrate, metal-organic frameworks (MOFs) have been introduced in the past decade for the modification of the PA structure in order to break through the separation trade-off between permeability and selectivity. This review begins by summarizing the recent progress in the control of MOF-based thin-film nanocomposite (TFN) membrane structures.

Neuroprotective effects of total phenolics from Baroni leaves through the PI3K/AKT pathway.

Neurological injury, as a major pathogenic mechanism in depression, holds significant importance in the research and development of antidepressant drugs. Baroni (), referred to as "Forgetting Sadness Grass," has been confirmed to possess remarkable neuroprotective effects. Studies have identified that the total phenolics in Baroni leaves (HLTP) consist of flavonoids and phenolic acids and numerous studies have substantiated the neuroprotective effects of them.

Cooperative effects of three preservatives on physiological quality, endophytic bacterial community and volatile organic compounds of postharvest Codonopsis pilosula var. modesta roots.

Background: Codonopsis pilosula var. modesta (CPVM) is a famous medicinal and edible plant of Campanulaceae. However, fresh CPVM roots (FCPVR) are prone to softening, browning and spoilage after concentrated harvesting in the main production area of Gansu Province, China in autumn, which poses great challenges to their large-scale storage and modern processing.

Integrated metabolomic and transcriptomic analysis of triterpenoid accumulation in the roots of Codonopsis pilosula var. modesta (Nannf.) L.T.Shen at different altitudes.

Introduction: Codonopsis Radix is a beneficial traditional Chinese medicine, and triterpenoid are the major bioactive constituents. Codonopsis pilosula var. modesta (Nannf.

Study on environmental factors affecting the quality of codonopsis radix based on MaxEnt model and all-in-one functional factor.

Owing to the increasing market demand of Codonopsis Radix, the cropper blindly cultivates to expand planting area for economic benefits, which seriously affects the quality of Codonopsis Radix. Therefore, this study synthesized 207 batches of Codonopsis Radix and 115 ecological factors, and analyzed the suitable planting areas of Codonopsis pilosula under current and future climate change based on Geographic Information System (GIS) and MaxEnt model. Secondly, we evaluated the quality of Codonopsis Radix based on the all-in-one functional factor including chromatographic fingerprint, the index components, the effective compounds groups, the nutritional components, and the nutritional elements, and the quality regionalization of Codonopsis Radix was analyzed.

Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma.

Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8 T subsets, as well as cytotoxic CD4 T subsets.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

Ethnopharmacological Relevance: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf.

TXNIP Exacerbates the Senescence and Aging-Related Dysfunction of β Cells by Inducing Cell Cycle Arrest Through p38-p16/p21-CDK-Rb Pathway.

Thioredoxin-interacting protein (TXNIP) is a crucial molecular promoter of oxidative stress and has been identified to be associated with cellular senescence. It is an important mediator of β cell insulin secretion and has effects on β cell mass. However, its role in β cell senescence is unclear.

Genetic and Functional Identifying of Novel STAT1 Loss-of-Function Mutations in Patients with Diverse Clinical Phenotypes.

Purpose: Mutations in signal transducer and activator of transcription 1 (STAT1) cause a broad spectrum of disease phenotypes. Heterozygous STAT1 loss-of-function (LOF) mutations cause Mendelian susceptibility to mycobacterial diseases (MSMD) infection, which is attributable to impaired IFN-γ signaling. The identification of novel mutations may extend the phenotypes associated with autosomal dominant (AD) STAT1 deficiency.

WASp Deficiency Selectively Affects the TCR Diversity of Different Memory T Cell Subsets in WAS Chimeric Mice.

Background: The T cell receptor (TCR) diversity is essential for effective T cell immunity. Previous studies showed that TCR diversity in Wiskott-Aldrich Syndrome (WAS) patients was severely impaired, especially in the memory T cell populations. Whether this defect was caused by intrinsic WASp deficiency or extrinsic reasons is still unclear.

Circulating Prokineticin 2 Levels Are Increased in Children with Obesity and Correlated with Insulin Resistance.

Objective: Prokineticin 2 (PK2) has been shown to regulate food intake, fat production, and the inflammation process, which play vital roles in the pathogenesis of obesity. The first aim of this study was to investigate serum PK2 levels in children with obesity and normal-weight children. The second aim was to compare the levels of PK2 between children with obesity, with and without nonalcoholic fatty liver disease (NAFLD).

A Novel Homozygous Mutation Destabilizes IKKβ and Leads to Human Combined Immunodeficiency.

Mutations in the gene cause severe immunodeficiency, characterized clinically by persistent respiratory or gastrointestinal infections. Targeted gene panel sequencing revealed a novel homozygous missense mutation in the gene of a patient with immune dysregulation and combined T and B cell functional defects. PBMCs from the patient, Y397H mice, and transfected cells were used to elucidate how the Y395H mutation triggers IKKβ deficiency and impairs immune function.

Thioredoxin-interacting protein: a critical link between autophagy disorders and pancreatic β-cell dysfunction.

Thioredoxin-interacting protein (TXNIP) is a known important regulatory protein of islet β-cell biology and function, but the detailed mechanism is not clear. Autophagy plays a pivotal role in maintaining cellular homoeostasis. This study aimed to elucidate the influence of TXNIP on the autophagy of β-cell.

Hyperactive PI3Kδ predisposes naive T cells to activation via aerobic glycolysis programs.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal-dominant combined immunodeficiency disorder resulting from pathogenic gain-of-function (GOF) mutations in the PIK3CD gene. Patients with APDS display abnormal T cell homeostasis. However, the mechanisms by which PIK3CD GOF contributes to this feature remain unknown.

Decreased Circulating MANF in Women with PCOS is Elevated by Metformin Therapy and is Inversely Correlated with Insulin Resistance and Hyperandrogenism.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel neurotrophic factor. Although recent studies have suggested that MANF appeared to be associated with insulin resistance, the results have been inconsistent. The aim of our study was to determine the serum MANF levels in women with PCOS and controls, to investigate their relationship to insulin resistance, and to evaluate circulating MANF changes with metformin intervention in PCOS women.