[Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases].

Objectives: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies.

Methods: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the gene.

Novel landscapes of N6-methyladenosine modification of mitochondrial oxidative stress in organ fibrosis.

Modern medicine increasingly focuses on the treatment and alleviation of diseases before they make substantial progress, and organ fibrosis has always been an important stage in the occurrence of substantial pathological changes in organs. The important characteristics of organ fibrosis are the excessive proliferation of myofibroblasts and the excessive deposition of extracellular matrix, which are regulated by a variety of complex signaling pathways and cytokines. The process of fibrosis cannot be separated from the functional support of mitochondria.

Molecular signatures of invasive and non-invasive pituitary adenomas: a comprehensive analysis of DNA methylation and gene expression.

Background: Pituitary adenomas (PAs) are benign tumors in the pituitary gland. However, 30-40% of these tumors are invasive, complicating diagnosis and treatment. Invasive pituitary adenomas (IPAs) often respond poorly to conventional therapies, emphasizing the need for better diagnostic and therapeutic strategies.

Pro-repair macrophages driven by CGRP rescue white matter integrity following intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) triggers a dynamic immune response involving macrophages, However, the functional heterogeneity of these cells and the mechanisms through which they promote repair remain unclear. Although the neuropeptide CGRP has been shown to modulate macrophage phenotypes in other pathological contexts, its role in ICH recovery and white matter repair remains unexplored.

Methods: Single-cell RNA sequencing (scRNA-seq) of CD45 + cells from ICH mice (GSE167593 and GSE230414 datasets) identified macrophage subsets.

The advancement of ubiquitination regulation in apoptosis, ferroptosis, autophagy, drug resistance and treatment of cancer.

Ubiquitination, a crucial post-translational modification, significantly influences cancer initiation and progression. This review emphasizes its roles in programmed cell death (including apoptosis, ferroptosis, and autophagy), drug resistance, and cancer therapy. In cell death pathways, ubiquitination through K48 and K63 linkages regulates proteins such as Bcl-2, ACSL4, and p62, thereby affecting cancer cell survival.

Phenotypic study of humanized mice carrying the PAH deep intronic variant c.1199+502A>T.

Background: The c.1199 + 502 A > T variant of the phenylalanine hydroxylase (PAH) gene, which is the most frequently reported deep intronic variant involved in phenylketonuria (PKU), is mainly observed in patients with classical or mild PKU. Prior to this study, no mouse models of PKU featuring deep intronic variants of PAH had been reported.

[Genetic analysis of a fetus pedigree affected with Thyroid dyshormonogenesis type 5 combined with familial Neurofibromatosis type 1].

Objective: To explore the genetic testing outcomes of a fetal family with Thyroid dyshormonogenesis type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.

Methods: One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method.

[Repellency of volatiles from bracts of banana flower bud to ].

infested a wide range of crops. However, no was found on banana flower bud. To investigate the effect of volatile of banana bud on the behavior of , we utilized Y-tube olfactometer to assess the behavioral responses of to different tissues of banana flower buds.

Epigenetic silencing of SOD2 exacerbates mitochondrial oxidative stress and promotes pulmonary fibrosis.

Mitochondrial oxidative damage-mediated dysfunction is implicated in pulmonary pathogenesis, yet the molecular mechanisms linking redox imbalance to pulmonary fibrosis remain elusive. In this study, we demonstrate that DNA methyltransferase 3 A (DNMT3A) drives fibroblast activation and pulmonary fibrosis by epigenetically repressing superoxide dismutase 2 (SOD2), a critical antioxidant enzyme. Using fibroblast-specific DNMT3A-deficient mice and bleomycin-induced pulmonary fibrosis models, we observed that DNMT3A ablation significantly attenuated mitochondrial oxidant overproduction, restored mitochondrial membrane potential (MMP), and reduced fibrotic progression.

Single cell multi-omics reveals re-dosing with CD3 bispecific antibody induces a TCF7 high central memory CD8 + T cell population associated with reduced cytokine production.

Background: T cell engaging therapies are commonly accompanied by excessive cytokine production and risk of cytokine release syndrome (CRS). Intriguingly, CRS risk with CD3-engaging bispecific antibody (BSP) is primarily limited to the first dose, termed the first-dose effect. Mechanisms underlying this effect remain unknown.

A Sugarcane Smut Fungus Effector Hijacks Plant Vacuolar Sorting Receptor-Mediated Trafficking to Evade Host Immune Detection.

The smut fungus Sporisorium scitamineum is a major pathogen in sugarcane, causing significant agricultural losses worldwide. However, the molecular mechanisms by which its effectors facilitate infection and evade host immunity remain largely unclear. In this study, we identified the sugarcane vacuolar sorting receptor 1 gene (ScVSR1), whose expression negatively correlate with several putative S.

Preparation and radon exhalation characteristics of fracture granite similar materials in Beishan underground research laboratory.

The mechanism of radon exhalation from surrounding rock fracture has important guiding significance for radon prevention and control in underground research laboratories. The optimal ratio scheme of similar materials in the granite surrounding rock of Beishan underground laboratory was obtained by orthogonal test. The radon exhalation characteristics of fractured rock samples under dry and saturated conditions were obtained by using 10 standard joint roughness coefficient (JRC) curves.

Alterations in Gut Microbiota Correlate With Hematological Injuries Induced by Radiation in Beagles.

Dynamics of gut microbiota and their associations with the corresponding hematological injuries postradiation remain to be elucidated. Using single whole-body exposure to Co- ray radiation at the sublethal dose of 2.5 Gy, we developed a beagle model of acute radiation syndrome (ARS) and then monitored the longitudinal changes of gut microbiome and hematology for 45 days.

Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept.

The success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies is still hampered by the lack of suitable and models recapitulating the complexity of the human immune system. Additionally, using cells derived from human healthy volunteers in such test systems may not adequately reflect the altered state of the patient's immune system thus potentially underestimating the risk of life-threatening conditions, such as cytokine release syndrome (CRS) following CAR T cell therapy.

Improving methylmalonic acidemia (MMA) screening and MMA genotype prediction using random forest classifier in two Chinese populations.

Background: Methylmalonic acidemia (MMA) is one of the most common hereditary organic acid metabolism disorders that endangers the lives and health of infants and children. Early detection and intervention before the appearance of a newborn's clinical symptoms can control disease progression and prevent or mitigate its serious consequences.

Methods: 42,004 newborns from two Chinese populations were included in the study.

Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.

BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD.

Noncoding RNA network crosstalk in organ fibrosis.

Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen.

Environmental risk evaluation for radionuclide transport through natural barriers of nuclear waste disposal with multi-scale streamline approaches.

Natural barriers, encompassing stable geological formations that serve as the final bastion against radionuclide transport, are paramount in mitigating the long-term contamination risks associated with the nuclear waste disposal. Therefore, it is important to simulate and predict the processes and spatial-temporal distributions of radionuclide transport within these barriers. However, accurately predicting radionuclide transport on the field scale is challenging due to uncertainties associated with parameter scaling.

Toxicity assessment of Cucurbita pepo cv Dayangua and its effects on gut microbiota in mice.

Background: Cucurbita pepo cv Dayangua (CPD) is an edible plant with diverse pharmacological properties. The current research on CPD has primarily focused on initial investigations of its chemical composition and pharmacological effects, and no comprehensive toxicity assessment has been conducted to date.

Methods: In the present study, the toxicity of CPD was evaluated through both acute and sub-chronic oral toxicity tests in mice.

The landscape of histone modification in organ fibrosis.

An increase in fibrous connective tissue and a decrease in parenchymal cells in organ tissues are the primary pathological alterations linked to organ fibrosis. If fibrosis is not treated, organ structure is destroyed, function can decline, or even fail, posing a serious risk to human life and health. Numerous organs develop fibrosis, and organ fibroproliferative illnesses account for almost 45% of patient deaths from various diseases in the industrialized world, as well as a major cause of disability and mortality in many other diseases.

Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.

Background: Hearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counselling for the patient's family.

Methods: We detected and analysed 362 Chinese non-syndromic HL patients by screening of variants in 15 hot spot mutations.

subsp. Alleviates Acute Injury in Hypoxic Mice.

Acute mountain sickness (AMS) is a common ailment in high-altitude areas caused by the body's inadequate adaptation to low-pressure, low-oxygen environments, leading to organ edema, oxidative stress, and impaired intestinal barrier function. The gastrointestinal tract, being the first to be affected by ischemia and hypoxia, is highly susceptible to injury. This study investigates the role of subsp.

[Clinical and molecular genetic analysis of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome].

Objective: To explore the genetic characteristics of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome (RTT).

Methods: A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject.