A cohort of allogeneic hematopoietic stem cell transplantation for pediatric rare diseases (allo-HSCT-PRD): design and preliminary results.

Rare diseases in children have attracted widespread attention worldwide due to their rarity and difficulty in diagnosis and treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is emerging as a promising and curable therapy for multiple rare diseases. However, rare disease research in China is relatively backward, prompting us to construct the first cohort of allo-HSCT for pediatric rare diseases (allo-HSCT-PRD) involving those who underwent allo-HSCT at the Children's Hospital of Fudan University from 1 January 2014 to 31 October 2024.

Trophic transfer of CeO nanoparticles from clamworm to juvenile turbot and related changes in fish flesh quality.

Engineered nanoparticles (ENPs) accumulate in marine sediments and exhibit adverse effects on benthic organisms. However, the effect of ENPs on marine benthic food chains is largely unknown. Herein, we investigated the trophic transfer and transformation of CeO ENPs within a simulated marine benthic food chain from clamworm () to turbot (), as well as their effects on fish flesh quality.

Molecular mechanisms of mitochondrial quality control.

Mitochondria produce adenosine triphosphate (ATP), the main source of cellular energy. To maintain normal function, cells rely on a complex mitochondrial quality control (MQC) system that regulates mitochondrial homeostasis, including mitochondrial dynamics, mitochondrial dynamic localization, mitochondrial biogenesis, clearance of damaged mitochondria, oxygen radical scavenging, and mitochondrial protein quality control. The MQC system also involves coordination of other organelles, such as the endoplasmic reticulum, lysosomes, and peroxisomes.

A Peripheral Mechanism of Depression: Disturbed Intestinal Epithelial Per2 Gene Expression Causes Depressive Behaviors in Mice with Circadian Rhythm Disruption via Gut Barrier Damage and Microbiota Dysbiosis.

Circadian rhythm disruption (CRD) is a potential risk factor for the development of depression. However, the underlying mechanisms remain unclarified. Here, it is found that in CRD model mice showing significant depressive-like behaviors, the expression rhythm of Period 2 (Per2), an important rhythm gene, is disrupted in intestinal epithelium, which results in defect of gut barrier integrity and gut microbiota disturbance, accompanied by peripheral and neuroinflammation, deficit in hippocampal neurogenesis, and impairment of excitatory neurotransmission.

Dimer-Specific FokT-seq Reveals DNA-Binding Dimerization and Novel Genomic Targets of TDP-43.

In postmortem brain tissues of patients with sporadic amyotrophic lateral sclerosis (ALS), the dimerization ability of TAR DNA-binding protein 43 (TDP-43) is impaired, accompanied by an accumulation of insoluble TDP-43. Thus, the loss of TDP-43 dimerization may play a critical driving role in ALS pathogenesis, although its underlying mechanism remains unclear. In this study, the FokT (FokI-TDP-43) system is developed, which fuses TDP-43 protein with FokI nuclease.

Whole Exome Sequencing in Chinese Pediatric Patients With Nephrolithiasis.

Introduction: The incidence of pediatric nephrolithiasis has been increasing, and the role of genetic factors has garnered attention in recent years. This study aimed to explore the genetic basis underlying pediatric nephrolithiasis in Chinese population.

Methods: Whole exome sequencing (WES) was conducted in a consecutive cohort of 456 children over a 11-year period.

Fano-resonant electric field sensor based on the thin film lithium niobate micro-ring with enhanced sensitivity.

Electric field sensing is vital for applications ranging from telecommunications to biomedical diagnostics, where high sensitivity and compact form factors are increasingly demanded. Traditional photonic integrated electric field sensors, despite leveraging electro-optic effects, often enhance sensitivity by enlarging interaction regions or complex optoelectronic circuits, compromising device scalability and footprint. Here, we demonstrate an electric field sensor on a lithium niobate on insulator (LNOI) platform that enhances sensitivity by leveraging Fano resonance.

A Novel R140S γc Variant Alters Cellular Distribution, Reduces Surface Expression, and Impairs Cytokine Signaling in Atypical X-SCID.

The interleukin-2 receptor γ (IL-2Rγ, or γc) is a crucial component of several cytokine receptor complexes. Deficiencies in γc lead to X-linked severe combined immunodeficiency (X-SCID), characterized by recurrent infections due to the absence or dysfunction of T and NK cells, and nonfunctional B cells. Missense variants in the γc extracellular region are linked to atypical X-SCID with normal counts of T, B, and NK cells and less severe symptoms, yet the underlying cellular and molecular mechanisms are not well understood.

Mevalonate kinase deficiency: genetic and clinical characteristics of a Chinese pediatric cohort.

Background: Mevalonate kinase deficiency (MKD) is a rare autoinflammatory disease, and mevalonic aciduria (MA) is a severe phenotype of MKD. The present study reports the characteristics of MKD and four novel mutations in the mevalonate kinase (MVK) gene in a Chinese cohort.

Method: A retrospective study was conducted on patients diagnosed with MKD from July 2013 to December 2024.

Factors associated with and kinetics of anti-IFN-α autoantibodies in deficiency.

Background: Autoantibodies against IFN-α (anti-IFN-α) have been reported in recombinase activating gene (RAG) deficiency, attributed to impaired central and peripheral T-cell/B-cell tolerance. However, the clinical features, especially viral infections, associated with these autoantibodies at baseline, their kinetics over time, and their response to hematopoietic cell transplantation are not well defined.

Objective: We described the clinical and immunologic findings linked to anti-IFN-α IgG in RAG deficiency and tracked its kinetics longitudinally, including in those who underwent hematopoietic cell transplantation.

Gut microbiota dysbiosis and disturbed tryptophan metabolism mediate cognitive impairment in mice with circadian rhythm disruption.

Circadian rhythm disorder (CRD) is a risk factor for cognitive deficits, yet its mechanisms remain unclear. We previously found CRD model mice developed cognitive impairment mediated through gut microbiota disturbance, intestinal barrier damage, and microglia activation, but the signaling pathway was undefined. Here, we show CRD induces cognitive deficits and gut microbiota disturbance in mice.

High-risk factors for urinary calculus recurrence in Chinese preschool children: findings from a medium-term follow-up survey.

Background: To date, most literature has focused on factors contributing to the initial occurrence of pediatric urinary stones. However, there is scant literature on the risk factors for recurrence following the initial episode. Effective treatment strategies for the initial episode and measures to reduce the risk of stone recurrence are crucial.

Enhanced uncertainty sampling with category information for improved active learning.

Traditional uncertainty sampling methods in active learning often neglect category information, leading to imbalanced sample selection in multi-class computer vision tasks. Our approach integrates category information with uncertainty sampling through a novel active learning framework to address this limitation. Our method employs a pre-trained VGG16 architecture and cosine similarity metrics to efficiently extract category features without requiring additional model training.

Clusterin facilitates glioma progression via BCL2L1-dependent regulation of apoptotic resistance.

Background: Clusterin (CLU) is a multifunctional protein involved in various pathophysiological processes and diseases. Glioma, the most common aggressive primary brain tumor, is characterized by high morbidity, mortality, and extremely poor prognosis. Our research has found that CLU is upregulated in glioma and contributes to increased tumor malignancy.

Astrocyte-Derived CXCL10 Induces Neuronal Tau Hyperphosphorylation and Cognitive Impairments in Sepsis.

Sepsis-associated encephalopathy (SAE) is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis, yet the underlying mechanisms remain elusive. The current study, using a Lipopolysaccharide (LPS)-induced septic rat model, revealed the hyperphosphorylation of tau and cognitive impairments, accompanied by the release of inflammatory cytokines and activation of glial cells in the hippocampal dentate gyrus region of septic rats. Proteomic and bioinformatic analyses identified C-X-C motif chemokine ligand 10(CXCL10) as a central regulator of neuroinflammation.

Cryptic Splicing of GAP43 mRNA is a Novel Hallmark of TDP-43-Associated ALS and AD.

Cytoplasmic aggregation of transactive response DNA-binding protein 43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and occurs in 57% of Alzheimer's disease (AD) cases. TDP-43 regulates RNA processing, including cryptic exon splicing. Here, we demonstrate that TDP-43 directly controls growth-associated protein (GAP43) expression by binding to its pre-mRNA.

Long Term High-Salt Diet Induces Cognitive Impairments via Down-Regulating SHANK1.

High-salt (HS) diet is an established risk factor for cognitive impairment, but the underlying mechanisms remain unclear. This study reveals that HS diet reduces SHANK1, a key postsynaptic scaffolding protein, via downregulation of the PKA/CREB pathway, leading to synaptic dysfunction and cognitive deficits in rats. RNA sequencing of HS-fed rat hippocampi showed downregulation of cAMP signaling and SHANK1 expression.

Platelet-Rich Plasma Combined with a Low-Frequency Pulsed Electromagnetic Field Alleviates Sciatic Nerve Injury by Regulating the AMPK/mTOR Signaling Pathway.

Sciatic nerve injury (SNI) is a complex neurological disease, and its occurrence and development are closely related to the apoptosis signaling pathway. The mechanism of platelet-rich plasma (PRP) combined with a low-frequency pulsed electromagnetic field (LFPEMF) regulating apoptosis has not been fully elucidated. The SNI gene chip dataset GSE172064 and data from sham ( = 3) and SNI ( = 3) rats were downloaded from the Gene Expression Omnibus.

Efficacy and safety of negative pressure wound therapy for the treatment of diabetic foot ulcers: A meta-analysis.

Background: Diabetic foot ulcers (DFUs) are a significant challenge in diabetic care, and the efficacy of negative pressure wound therapy (NPWT) in treating them remains a subject of continuous investigation.

Aim: To provide a comprehensive meta-analysis of the role of NPWT in the management of DFUs.

Methods: A systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching databases like PubMed, Embase, Web of Science, and the Cochrane Library.

Age-dependent elevation of Nr4a1 attenuates PI3K/AKT/GSK3β pathway and mediates tau hyperphosphorylation and cognitive impairments.

Introduction: Tau hyperphosphorylation exhibited in Alzheimer's brains is also commonly observed in aging process, however, the molecular mechanism underlying tau hyperphosphorylation in aging is largely unknown. The nuclear receptor subfamily 4 group A (Nr4a1) has been implicated in various pathophysiological processes including neurodegeneration, and was found to be increased in Alzheimer's brains.

Objectives: Our study aims to investigate whether and how Nr4a1 promotes age-related tau hyperphosphorylation and cognitive decline.

Distinct molecular characteristics and virulence profiles of carbapenem-resistant , , and isolated from patients with inborn errors of immunity.

Unlabelled: Bacterial infections, especially multidrug-resistant Gram-negative bacterial infections, pose a great threat to patients with inborn errors of immunity (IEIs). This study investigates the molecular and virulence profiles of carbapenem-resistant (CR-AB), carbapenem-resistant (CR-ECO), and carbapenem-resistant (CR-ECL) strains from patients with IEI. Strains from IEI and non-IEI groups underwent antimicrobial susceptibility testing and whole-genome sequencing (NovaSeq 6000 PE150), with statistical analysis of differences.

H3K27me3 modulates trained immunity of monocytes in HDM-allergic diseases.

Background: Monocytes have been confirmed to increase in persistently food-allergic children. A phenomenon of innate immune memory, called trained immunity, has also been observed in monocytes from allergic children. However, the underlying mechanism remains poorly understood.

M2 macrophages promote PKM2 production in fibroblasts to alleviate UVB-induced photoaging.

Ultraviolet radiation is a major factor in causing skin aging. Compared to younger individuals, older adults exhibit a significant imbalance in the M1/M2 macrophage ratio, with an elevated proportion of M1 macrophages, but little is known about the role of macrophages in skin aging. Here, we report the critical role of M2 macrophages and PKM2 in preventing fibroblast photoaging.