Transforming an ATP-dependent enzyme into a dissipative, self-assembling system.

Nucleoside triphosphate (NTP)-dependent protein assemblies such as microtubules and actin filaments have inspired the development of diverse chemically fueled molecular machines and active materials but their functional sophistication has yet to be matched by design. Given this challenge, we asked whether it is possible to transform a natural adenosine 5'-triphosphate (ATP)-dependent enzyme into a dissipative self-assembling system, thereby altering the structural and functional mode in which chemical energy is used. Here we report that FtsH (filamentous temperature-sensitive protease H), a hexameric ATPase involved in membrane protein degradation, can be readily engineered to form one-dimensional helical nanotubes.

Loss-of-Function of CLMP Is Associated With Congenital Short Bowel Syndrome and Impaired Intestinal Development.

Coxsackie and adenovirus receptor-like membrane protein (CLMP) mutation is identified as a genetic risk factor of congenital short bowel syndrome (CSBS). However, the specific pathogenic mechanism remains unclear. This study aimed to explore the clinical manifestations, genetic characteristics, and molecular mechanisms underlying CSBS caused by CLMP mutations.

Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

Education Research: Has Video Killed the Interview Star?: A Survey of Current Neurology Residents on In-Person vs Virtual Residency Interviews.

Background And Objectives: The residency application process relies on interviews, which allow programs and applicants to assess one another. Historically, interviews were conducted in person at each program. With the advent of the coronavirus disease 2019 pandemic, residency interviews shifted to a virtual format.

A novel de novo GABRA2 gene missense variant causing developmental epileptic encephalopathy in a Chinese patient.

Background: Variants in the GABRA2 gene, which encodes the α2 subunit of the γ-aminobutyric acid A receptor, have been linked to a rare form of developmental and epileptic encephalopathy (DEE) referred to as DEE78. Only eight patients have been reported globally. This study presents the clinical presentation and genetic analysis of a Chinese family with a child diagnosed with DEE78, due to a novel GABRA2 variant.

Familial hypercholesterolemia in Chinese children and adolescents: a multicenter study.

Background: Familial hypercholesterolemia (FH) is an inherited disorder mainly marked by increased low-density lipoprotein cholesterol (LDL-C) concentrations and a heightened risk of early-onset arteriosclerotic cardiovascular disease (ASCVD). This study seeks to characterize the genetic spectrum and genotype‒phenotype correlations of FH in Chinese pediatric individuals.

Methods: Data were gathered from individuals diagnosed with FH either clinically or genetically at multiple hospitals across mainland China from January 2016 to June 2024.

Newborn Genetic Screening Improves the Screening Efficiency for Congenital Hypothyroidism: A Prospective Multicenter Study in China.

Newborn congenital hypothyroidism (CH) screening has been widely used worldwide. The objective of this study was to evaluate the effectiveness of applying biochemical and gene panel sequencing as screening tests for CH and to analyze the mutation spectrum of CH in China. Newborns were prospectively recruited from eight hospitals in China between February and December 2021.

Investigation of a hemophilia family with one female hemophilia A patient and 12 male hemophilia A patients.

Hemophilia A (HA) is an X-chromosome-linked recessive genetic disorder. Female carriers may have bleeding symptoms, but rarely have moderate or severe disease. We identified a female patient with moderate HA by pedigree tracking and genetic testing in a HA family involving consanguineous marriage.

The Association of PLA2G7 Gene Polymorphisms with Serum Lp-PLA2 Activity and Lipid Profile in Han Chinese Patients with Coronary Heart Disease.

Purpose: This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and lipid profiles.

Methods: A total of 93 han Chinese CHD patients were recruited. Serum Lp-PLA2 levels were determined using enzyme-linked immunosorbent assay (ELISA), while comprehensive analysis of PLA2G7 gene polymorphisms was conducted through whole-exome sequencing.

Employing splice-switching oligonucleotides and AAVrh74.U7 snRNA to target insulin receptor splicing and cancer hallmarks in osteosarcoma.

Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts to target IGF-1R signaling were mostly unsuccessful, likely due to compensatory signaling through alternative splicing of the insulin receptor () to the proliferative isoform.

Mandibular tongue-shaped flap reconstruction for lip defects following lip tumor surgery.

Lip defects due to lip tumor surgery need proper reconstruction to preserve their function. Traditional methods offer various options for lip repair, but each has limitations, and can lead to deformity, asymmetry, or functional impairment. This study aimed to investigate the clinical application of mandibular tongue-shaped flap reconstruction for postoperative defects following lip tumor surgery.

Late Gadolinium Enhancement of Nonischemic Cardiomyopathy at 5.0 T versus 3.0 T: A Crossover Design Study.

Purpose To compare the acquisition time, image quality, and late gadolinium enhancement (LGE) visualization and quantification on phase-sensitive inversion recovery (PSIR) images using 5.0-T versus 3.0-T cardiac MRI.

Sirolimus alleviated intractable diarrhea of IPEX syndrome: a case report and literature review.

Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare single-gene X-linked immunodeficiency disease caused by mutations in the forkhead box protein 3 (FOXP3) gene. The typical clinical manifestations of IPEX mainly include severe atopic dermatitis, insulin-dependent type 1 diabetes mellitus, and intractable diarrhea.

Case Presentation: Here, we report a boy with intractable diarrhea diagnosed with early-onset IPEX syndrome due to the c.

Congenital isolated adrenocorticotropic hormone deficiency in a newborn caused by mutation: a case report and literature review.

Background: To investigate the clinical phenotype, genetic characteristics, and prognosis of isolated adrenocorticotropic hormone deficiency in a newborn (IAD, OMIM 201400) caused by mutation of the gene.

Case Presentation: The clinical features, diagnosis, treatment, and prognosis of a newborn with IAD admitted to our hospital were retrospectively analyzed. The patient and his parents were also examined by whole exome sequencing.

Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.

A dual-nucleophilic ester-induced supramacromolecular fire-proof hydrogel coating for protecting polymers.

Polymer materials are highly vulnerable to fire disaster. However, current research focuses on flame retardancy rather than protection. In this work, two natural extracts of phytic acid (PA) and tannic acid (TA), were successfully compounded via dual-nucleophilic esterification, which facilitated the formation supramolecular hydrogel (T-P-PAA).

Novel variants in PADI6 genes cause female infertility due to early embryo arrest.

Purpose: Early embryo arrest is characterized by premature termination of development in preimplantation embryos. Human subcortical maternal complex (SCMC) is a protein complex that is specifically expressed in mammalian oocytes and early embryos and is essential for embryonic cell division. Peptidyl arginine deiminase 6 (PADI6) is proven to be a member of SCMC.

Case Report: Allelic and biallelic variants in cause factor XI deficiency.

Factor XI deficiency is a rare inherited coagulation disorder with an estimated prevalence of affecting 1 in 1 million. It is characterized by mild and variable bleeding phenotypes, including bruises, nosebleeds, hematuria, and postpartum hemorrhage. It can be caused by either allelic or biallelic variants in ().

Transcriptome analyses reveal molecular mechanisms of novel compound heterozygous variants causing infantile cerebellar retinal degeneration.

Background And Purpose: Infantile cerebellar retinal degeneration (ICRD) (OMIM #614559) is a rare autosomal recessive inherited disease associated with mutations in the aconitase 2 (ACO2) gene. We report a Chinese girl with novel compound heterozygous variants in , who presented at 7 months of age with psychomotor retardation, truncal hypotonia, and ophthalmologic abnormalities. This study aims to investigate the potential molecular mechanisms underlying deficiency-induced neuropathy.

Pathogenicity of the LDLR c.97C>T (p.Gln33Ter) Mutation in Familial Hypercholesterolemia.

Background: Familial hypercholesterolemia (FH) is a hereditary disease caused mainly by mutations in the gene encoding the low-density lipoprotein receptor (LDLR). This study aimed to confirm the pathogenicity of the LDLR c.97C>T (p.

Short-Term Frequently Relapsing Ischemic Strokes Followed by Rapidly Progressive Dementia in CADASIL: A Case Report and Literature Review.

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease with slow natural progression. Ischemic stroke and cognitive impairment are its most common clinical symptoms. Here, we report a rare 50-year-old woman who had rapid disease progression with c.

Novel biallelic variants in IREB2 cause an early-onset neurodegenerative disorder in a Chinese pedigree.

Background: Cellular iron metabolism is essential for maintaining various biological processes in organisms, and this is influenced by the function of iron-responsive element-binding protein 2 (IRP2), encoded by the IREB2 gene. Since 2019, three cases of a genetic neurodegenerative syndrome resulting from compound heterozygous mutations in IREB2 have been documented, highlighting the crucial role of IRP2 in regulating iron metabolism homeostasis. This study aims to investigate the molecular basis in a single proband born to non-consanguineous healthy parents, presenting with severe psychomotor developmental abnormalities and microcytic anemia.

Clinical characteristics of patients with variant-associated epilepsy and therapeutic exploration: a case report and literature review.

The gene encodes a transmembrane prolyl 4-hydroxylase, which is responsible for the degradation of hypoxia-inducible transcription factors (HIF) under normoxia. Clinically, biallelic variants have been identified in patients with hypotonia, hypoventilation, intellectual disabilities, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome). Seizure was one of the most prominent symptoms.