Novel Clinical Manifestation and Favorable Treatment Outcome of Cochlear Implant in a Chinese Family With Likely Pathogenic Variant of the P2RX2 Gene.

The rapid development and clinical application of sequencing technologies enable the genetic diagnosis of inherited deafness. P2RX2, as the gene responsible for autosomal dominant non-syndromic deafness-41 (DFNA41), has been proven to be essential for life-long normal hearing and for the protection of noise-induced hearing loss (NIHL). Our present study reports a missense variant in the P2RX2 gene (c.

Novel likely pathogenic variant in the EYA1 gene causing Branchio oto renal syndrome and the exploration of pathogenic mechanisms.

Objective: Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms.

Methods: The family spans 4 generations and consists of 9 individuals, including 4 affected by the BOR/BO syndrome.

Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs.

Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy has attracted increasing attention. Cancer stem cells (CSCs), a small subset of tumor cells with self-renewal and differentiation capacities, are resistant to traditional therapies such as radiotherapy and chemotherapy. Recently, CSCs have been proven to be the cells driving tumor relapse after immunotherapy.

Novel compound heterozygous pathogenic variants in the SLC3A1 gene in a Chinese family with cystinuria.

Background: Cystinuria is an autosomal recessive disorder characterized by a cystine transport deficiency in the renal tubules due to mutations in two genes: SLC3A1 and SLC7A9. Cystinuria can be classified into three forms based on the genotype: type A, due to mutations in the SLC3A1 gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to mutations in both genes.

Methods: We report a 12-year-old boy from central China with cystine stones.

Phenotypic variability in two female siblings with oocyte maturation arrest due to a TUBB8 variant.

Tubulin beta-8 (TUBB8) is expressed exclusively in the oocyte and early embryo, encoding a beta-tubulin polypeptide that participates in the assembly of microtubules. TUBB8 was first attributed to being responsible for oocyte MI arrest. Further studies have demonstrated that patients with different pathogenic variants have variable phenotypes.

Pretreatment with geniposide mitigates myocardial ischemia/reperfusion injury by modulating inflammatory response through TLR4/NF-κB pathway.

Geniposide (GEN), a medical herb, is known for its therapeutic applications in cardiovascular diseases, though its efficacy in treating myocardial ischemia/reperfusion injury (MI/RI) is yet to be fully elucidated. This study is an endeavor to explore the potential protective mechanism of GEN against MI/RI. To simulate the MI/RI condition, the left anterior descending artery was occluded for 30 min, followed by a reperfusion period of 120 min in a rat model.

Geniposide alleviates pressure overload in cardiac fibrosis with suppressed TGF-β1 pathway.

Background: Cardiac fibrosis is one of the main contributors to the pathogenesis of heart failure. Geniposide (GE), a major iridoid in gardenia fruit extract, has recently been reported to improve skeletal muscle fibrosis through the modulation of inflammation response. This investigation aimed to illuminate the cardio-protective effect and the potential mechanism of GE in cardiac fibrosis.

Molecular Mechanisms and Clinical Phenotypes of Missense Variants.

The gene is the most common gene responsible for hearing loss (HL) worldwide, and missense variants are the most abundant type. pathogenic missense variants cause nonsyndromic HL (autosomal recessive and dominant) and syndromic HL combined with skin diseases. However, the mechanism by which these different missense variants cause the different phenotypes is unknown.

Molecular diagnosis of hereditary deafness and application of stepwise testing strategy.

Hereditary deafness is one of the most common sensory disorders in humans, and exhibits high genetic heterogeneity. At present, the commonly used molecular diagnostic methods include gene chip, Sanger sequencing, targeted enrichment sequencing, and whole-exome sequencing, with diagnosis rates reaching 33.5%-56.

Increased diagnostic yield in a cohort of hearing loss families using a comprehensive stepwise strategy of molecular testing.

Hearing loss is one of the most common sensory disorders in humans. This study proposes a stepwise strategy of deafness gene detection using multiplex PCR combined with high-throughput sequencing, Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and whole-exome sequencing (WES) to explore its application in molecular diagnosis of hearing loss families. A total of 152 families with hearing loss were included in this study, the highest overall diagnosis rate was 73% (111/152).

Defining the sensitivity landscape of EGFR variants to tyrosine kinase inhibitors.

Tyrosine kinase inhibitor (TKI) is a standard treatment for patients with NSCLC harboring constitutively active epidermal growth factor receptor (EGFR) mutations. However, most rare EGFR mutations lack treatment regimens except for the well-studied ones. We constructed two EGFR variant libraries containing substitutions, deletions, or insertions using the saturation mutagenesis method.

A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient.

Background: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; OMIM# 615381) is a rare autosomal dominant disorder, with only a few reported cases worldwide. Herein, we describe the clinical features and underlying molecular etiology of MDPL syndrome in an 8-year-old Chinese patient.

Methods: We performed otological, endocrine, ultrasound, and radiological examinations, as well as genetic testing.

Cancer Cell Membrane Biomimetic Mesoporous Nanozyme System with Efficient ROS Generation for Antitumor Chemoresistance.

Single-atom nanozymes (SAZs) with reaction specificity and optimized catalytic properties have great application prospects in tumor therapy. But the complex tumor microenvironment (low content of HO) limits its therapeutic effect. In this study, we developed a bionic mesoporous Fe SAZs/DDP nanosystem (CSD) for enhanced nanocatalytic therapy (NCT)/chemotherapy by simultaneously encapsulating the chemotherapeutic drugs cisplatin (DDP) and Fe SAZs with high peroxidase (POD) activity into the cancer cell membrane.

Hydrogel co-loading SO prodrug and FeGA nanoparticles for enhancing chemodynamic therapy by photothermal-triggered SO gas therapy.

Chemodynamic therapy (CDT) is an effective anti-tumor method, while CDT alone cannot achieve a good therapeutic effect. Moreover, the overexpression of glutathione (GSH) in tumor cells dramatically limits the efficiency of CDT. Here, we proposed a hydrogel co-loading SO prodrug and FeGA nanoparticles (NPs) for enhancing CDT by photothermal-triggered SO gas therapy (FBH) system by mixing benzothiazolyl sulfonates (BTS) and FeGA NPs in a certain ratio and encapsulating them in a heat-sensitive hydrogel.

CuS nanoparticles and camptothecin co-loaded thermosensitive injectable hydrogel with self-supplied HO for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) is a kind of anti-tumor strategy emerging in recent years, but the concentration of hydrogen peroxide (HO) in the tumor microenvironment is insufficient, and it is difficult for a single CDT to completely inhibit tumor growth. Here, we designed a CuS nanoparticles (NPs) and camptothecin (CPT) co-loaded thermosensitive injectable hydrogel (SCH) with self-supplied HO for enhanced CDT. SCH is composed of CuS NPs and CPT loaded into agarose hydrogel according to a certain ratio.

Superoxide dismutase@zeolite Imidazolate Framework-8 Attenuates Noise-Induced Hearing Loss in Rats.

Reactive oxygen species (ROS) and inflammation have been considered major contributors to noise-induced hearing loss (NIHL) that constituted a public health threat worldwide. Nanoantioxidants, with high antioxidant activity and good stability, have been extensively used in the study of ROS-related diseases. In this study, we constructed a superoxide dismutase (SOD)@zeolite imidazolate framework-8 (ZIF-8) nanoparticle based on biomimetic mineralization and applied it to a rat model of NIHL.

Application of Nanomedicine in Inner Ear Diseases.

The treatment of inner ear disorders always remains a challenge for researchers. The presence of various physiological barriers, primarily the blood-labyrinth barrier (BLB), limits the accessibility of the inner ear and hinders the efficacy of various drug therapies. Yet despite recent advances in the cochlea for repair and regeneration, there are currently no pharmacological or biological interventions for hearing loss.

Lighting up Individual Organelles With Fluorescent Carbon Dots.

Cell organelles play crucial roles in the normal functioning of an organism, therefore the disruption of their operation is associated with diseases and in some cases death. Thus, the detection and monitoring of the activities within these organelles are of great importance. Several probes based on graphene oxide, small molecules, and other nanomaterials have been developed for targeting specific organelles.

Genetic and Phenotypic Variability in Chinese Patients With Branchio-Oto-Renal or Branchio-Oto Syndrome.

Branchio-oto-renal syndrome (BOR) and branchio-oto syndrome (BOS) are rare autosomal dominant disorders defined by varying combinations of branchial, otic, and renal anomalies. Here, we characterized the clinical features and genetic etiology of BOR/BOS in several Chinese families and then explored the genotypes and phenotypes of BOR/BOS-related genes, as well as the outcomes of auditory rehabilitation in different modalities. Probands and all affected family members underwent detailed clinical examinations.

Establishment of an induced pluripotent stem cell line (ZZUPMCi001-A) derived from peripheral blood mononuclear cells in a patient with type 1 Waardenburg syndrome.

Waardenburg syndrome type I (WS1) is a human autosomal dominant genetic disease characterized by sensorineural hearing loss, pigmentary abnormalities, and dystopia canthorum. In this study, we generated an induced pluripotent stem cell (iPSC) line using non-integrative Sendai viral reprogramming technology from the peripheral blood mononuclear cells (PBMCs) of a 29-year-old woman affected with WS1, caused by a heterozygous frameshift mutation in the PAX3 (NM_181459.4:c.

Detection and clinical significance of circulating tumor cells in colorectal cancer.

Histopathological examination (biopsy) is the "gold standard" for the diagnosis of colorectal cancer (CRC). However, biopsy is an invasive method, and due to the temporal and spatial heterogeneity of the tumor, a single biopsy cannot reveal the comprehensive biological characteristics and dynamic changes of the tumor. Therefore, there is a need for new biomarkers to improve CRC diagnosis and to monitor and treat CRC patients.

Missense Variant of Endoplasmic Reticulum Region of Gene Causes Autosomal Dominant Hearing Loss without Syndromic Phenotype.

Objective: Genetic variants in the gene can cause Wolfram syndrome (WS) or autosomal dominant nonsyndromic low-frequency hearing loss (HL). This study is aimed at investigating the molecular basis of HL in an affected Chinese family and the genotype-phenotype correlation of variants.

Methods: The clinical phenotype of the five-generation Chinese family was characterized using audiological examinations and pedigree analysis.

An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease.

Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019.

Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next-generation sequencing of the SLC26A4 gene.

Background: The enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening can only diagnose a small number of patients.