Despite substantial breakthroughs in the treatment of hepatocellular carcinoma (HCC) in recent years, many patients are diagnosed in the middle or late stages, denying them the option for surgical excision. Therefore, it is of great importance to find effective therapeutic targets of HCC. In this study, it is found that Gap junction protein beta-2 (GJB2) is highly enriched in malignant cells based on single-cell RNA sequencing and higher expression of GJB2 indicates a worse prognosis. The localization of GJB2 in HCC cancer cells is changed compared with normal liver tissue. In cancer cells, GJB2 tends to be located in the cytoplasm and nucleus, while in normal tissues, GJB2 is mainly located on the cell membrane. GJB2 is related to glycolysis, promoting NF-κB pathway via inducing the ubiquitination degradation of IκBa, and activating HIF-1α/GLUT-1/PD-L1 pathway. In addition, GJB2 knockdown reshapes tumor immune microenvironment and Salvianolic acid B inhibits the activity of GJB2. In conclusion, GJB2 promotes HCC progression by activating glycolysis through cytoplasmic translocation and generating a suppressive tumor microenvironment. Salvianolic acid B inhibits the expression of GJB2 and enhances the sensitivity of anti-PD1 therapy, which may provide insights into the development of novel combination therapeutic strategies for HCC.

OBJECTIVE: The aim of this study was to explore the functional consequences of two common variants, p.V37I and c.299-300delAT, in the hearing loss-associated gene GJB2.
METHODS: Connexin 26 expression and gap junctional permeability were studied in HEK 293T cells transfected with plasmids expressing GJB2 wild-type, p.V37I, or c.299-300delAT CX26 proteins tagged with fluorescent markers. Functional analyses of various GJB2 haplotypes were conducted to thoroughly evaluate alterations in ionic and small-molecule coupling.
RESULTS: The p.V37I protein was localized at the plasma membrane, but it failed to effectively transport intercellular propidium iodide or Ca2+ efficiently, indicating an impairment in both biochemical and ionic coupling. The presence of GJB2 p.V37I seemed to increase the cells\' sensitivity to H2O2 treatment. In contrast, the known variant c.299-300delAT protein was not transported to the cell membrane and was unable to form gap junctions, remaining confined to the cytoplasm. Both ionic and biochemical coupling were defective in cells transfected with c.299-300delAT.
CONCLUSIONS: The p.V37I and c.299-300delAT GJB2 mutations resulted in deficient gap junction-mediated coupling. Additionally, environmental factors could influence the functional outcomes of the GJB2 p.V37I mutation. These findings could pave the way for the development of molecular therapies targeting GJB2 mutations to treat hearing loss.

UNASSIGNED: Hearing loss is a common sensorineural dysfunction with a high incidence in China. Although genetic factors are important causes of hearing loss, hearing-related gene detection has not been widely adopted in China.
UNASSIGNED: Establishing a rapid and efficient method to simultaneously detect hotspot hearing loss gene mutations.
UNASSIGNED: A reverse dot blot assay combined with a flow-through hybridization technique was developed for the simultaneous detection of 13 hotspot mutations of 4 hearing loss-related genes including GJB2, GJB3, SLC26A4, and the mitochondrial gene MT-RNR1. This method involved PCR amplification systems and a hybridization platform.
UNASSIGNED: The technique can detect 13 hotspot mutations of 4 hearing loss-related genes. And a total of 213 blood samples were used to evaluate the availability of this method.
UNASSIGNED: Our reverse dot blot assay was a simple, rapid, accurate, and cost-effective method to identify hotspot mutations of 4 hearing loss-related genes in a Chinese population.

Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data（including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography）, imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
目的：探究GJB2基因与听神经病之间的关系，为此类患者及家庭的遗传咨询提供参考。 方法：对117例听神经病患者的基本信息、听力学资料（包括纯音测听、畸变耳声发射、听性脑干反应、耳蜗电图）、影像学资料、遗传学检测等数据进行收集，并筛选出携带GJB2基因变异的患者对其进行听神经病相关分析。 结果：共计16例患者检出GJB2基因变异，变异位点致病性均为致病的或可能致病的，其中1例为GJB2[c.427C>T][c.358_360del]复合杂合变异，听力学表现为全聋，1例为GJB2[c.299_300delAT][c.35_36insG]复合杂合变异，听力学表现为重度听力损失，其余14例携带GJB2基因变异患者听力学表型均为典型听神经病。 结论：本研究初步分析了GJB2基因与听神经病的相关性，并阐述了GJB2基因变异可能与听神经病表型相关的致病机制。.

Background: Preconception or prenatal carrier screening plays an important role in reproductive decision-making, but current research on hereditary deafness is limited. This study aimed to investigate the carrier frequencies of common deafness genes in the Chinese population who underwent carrier screening and to follow up on pregnancy outcomes in high-chance couples. Methods: Individual females or couples in preconception or early pregnancy were recruited from two hospitals in China. Carrier screening for common deafness genes in the Chinese population, including the GJB2 and SLC26A4 genes, was performed using next-generation sequencing technology. Genetic counseling was provided to subjects before and after testing. Results: Of the 9,993 subjects screened, the carrier rate was 2.86% for the GJB2 gene and 2.63% for the SLC26A4 gene. The variant with the highest carrier frequency in GJB2 was c.235delC (1.89%), and c.919-2A>G (1.08%) in SLC26A4. Of the six high-chance couples, four made alternative reproductive decisions (three with prenatal diagnosis and one with preimplantation genetic testing), with consequent termination of the birth of two affected fetuses. Conclusion: These findings confirmed the clinical utility of preconception or prenatal carrier screening for hereditary deafness.

UNASSIGNED: Cell death is a key regulatory process in organisms and its study has become increasingly important in the field of cancer. While prior research has primarily centered on the individual pathways of cell death in cancer, there has been a lack of comprehensive investigation into the synergistic effects of multiple cell death pathways.
UNASSIGNED: Genes related to autophagy, apoptosis, necroptosis, pyroptosis, and cuproptosis was selected, and patients\' data was collected from The Cancer Genome Atlas (TCGA)project. Cell death features were identified using principal component analysis and combined to create a composite score. A scalable prediction model was then created using LASSO regression after a thorough assessment of the composite scores. The model was subsequently validated across multiple external datasets to establish its robustness and reliability.
UNASSIGNED: The cell death features effectively represented the gene expression patterns in the samples. The composite score well predicted prognosis, clinical stage, mutation, tumor microenvironment, and immunotherapy effectiveness. The model built on composite scores accurately predicted prognosis and immunotherapy effectiveness across multiple datasets. GJB2 was identified as a potential biomarker.
UNASSIGNED: Models based on multiple cell death pathways have significant predictive power for prognosis and immunotherapy effectiveness in lung adenocarcinoma. This highlights the synergistic role of multiple cell death pathways in cancer development and offers a new perspective for cancer research.

OBJECTIVE: The molecular etiology of non-syndromic hearing loss (NSHL) in Southeastern China (Fujian) has not been precisely identified. our study selected patients with NSHL and analyzed their causative genes, which helped to improve the accuracy of the diagnosis of hereditary hearing loss (HHL) and its treatment.
METHODS: 251 unrelated patients who attended the otolaryngology clinic of Fujian Maternal and Child Health Hospital with hearing loss were enrolled to our study. All patients had genetic tests and listening tests, of which 251 were diagnosed with NSHL. In addition, we used whole-exome sequencing (WES) in a patient who has a significant family history of HHL but negative for gene chip testing, as well as in his family members.
RESULTS: Among of 251 patients, Nucleotide changes were found in 63 cases (25.09%), including 34 located in GJB2(13.5%, including 235delC and 299_300delAT), 13 located in SLC26A4(5.18%, including c.919-2G > A and 2168 A > G), 1 located in GJB3(0.4%,538C > T) and 16 located in mtDNA12SrRNA (6.37%,1555 A > G). In addition, we discuss the process of identifying novel PLS1 mutations from 251 patients.
CONCLUSIONS: Our results demonstrate the conventional deafness gene mutation in 251 NSHL patients in Fujian, China. Compared with the other area of China, we have a lower detection rate, but GJB2 235delC remains the most common mutation in Fujian. In addition, we discuss the process of discovering novel mutation locus for deafness, which provides an understanding for deafness diagnosis and genetic testing.

UNASSIGNED: Hearing loss is found in more than 5 % of cases worldwide. Hearing loss is divided into three types: Sensorineural hearing loss, Combined hearing loss and Conductive hearing loss. Among them, no less than 50 % of pediatric cases of sensorineural hearing loss are genetic. In Henan, China, there are no statistics on the allele frequency of deafness gene variants.
UNASSIGNED: We divided 2178 subjects enrolled at the Third Affiliated Hospital of Zhengzhou College from January 2019 to March 2021 into a hearing loss group and a normal control group. We performed array and pathogenicity classification for screening the 15 deafness gene variants, calculated and compared the allele frequency of the deafness gene variants, and then compared the hearing loss diagnosis rate between the hearing loss group and the normal control group.
UNASSIGNED: We found that in the hearing loss group, the overall allele frequency of all detected variants was 16.6 %. Comparative analysis showed that the allele frequencies of GJB2 c.235delC variant, GJB3 c.538C > T variant and SLC26A4 c.919-2A > G variant were significantly higher than those of the East Asian population average in the gnomAD database. At the same time, our study confirmed that GJB3 c.538C > T variant may not be the disease-causing variant of hearing loss.
UNASSIGNED: These results support genetic counseling and rational prediction of risk for deafness.

UNASSIGNED: Firstly, observe the prognostic significance and the biological functional effects of gap junction protein beta 2 (GJB2 or Cx26) in lung adenocarcinoma (LUAD). Subsequently, explore the role played by GJB2 in intercellular communication by single-cell RNA sequencing.
UNASSIGNED: We made a differential analysis of GJB2 expression through public databases and investigated the clinical characteristics and prognostic significance. ESTIMATE analysis and Tumor Immune Estimation Resource (TIMER) database were utilized to illustrate the association of GJB2 with immune infiltration and components of the tumor microenvironment. Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSEA) were performed to study the biological function of GJB2. Cell-cell communication was analyzed using the CellChat R package through sc-RNA data.
UNASSIGNED: GJB2 has an outstanding prognosis value in LUAD and a close relationship was found between GJB2 and immune infiltration in LUAD. GJB2 could participate in several tumor biological processes, including extracellular matrix remodeling and upregulation of multiple cancer-related active pathways. GJB2 related hub-genes influence intercellular communication through the SPP1 signaling pathway.
UNASSIGNED: Our study illustrates one mechanism by which GJB2 exerts its cancer-specific relevant effects, that is, causing changes in intercellular communication through the SPP1 signaling pathway. Blockade of this pathway may limit the functional role of GJB2 and provide us with promising new perceptions for LUAD treatment.

The GJB2 gene is the most common gene responsible for hearing loss (HL) worldwide, and missense variants are the most abundant type. GJB2 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. Over 2/3 of the GJB2 missense variants have yet to be functionally studied and are currently classified as variants of uncertain significance (VUS). Based on these functionally determined missense variants, we reviewed the clinical phenotypes and investigated the molecular mechanisms that affected hemichannel and gap junction functions, including connexin biosynthesis, trafficking, oligomerization into connexons, permeability, and interactions between other coexpressed connexins. We predict that all possible GJB2 missense variants will be described in the future by deep mutational scanning technology and optimizing computational models. Therefore, the mechanisms by which different missense variants cause different phenotypes will be fully elucidated.