Predictive Biophysical Neural Network Modeling of a Compendium of in vivo Transcription Factor DNA Binding Profiles for Escherichia coli.

The DNA binding of most Escherichia coli Transcription Factors (TFs) has not been comprehensively mapped, and few have models that can quantitatively predict binding affinity. We report the global mapping of in vivo DNA binding for 139 E. coli TFs using ChIP-Seq. We used these data to train BoltzNet, a novel neural network that predicts TF binding energy from DNA sequence. BoltzNet mirrors a quantitative biophysical model and provides directly interpretable predictions genome-wide at nucleotide resolution. We used BoltzNet to quantitatively design novel binding sites, which we validated with biophysical experiments on purified protein. We have generated models for 125 TFs that provide insight into global features of TF binding, including clustering of sites, the role of accessory bases, the relevance of weak sites, and the background affinity of the genome. Our paper provides new paradigms for studying TF-DNA binding and for the development of biophysically motivated neural networks.

High Stability and Corrosion-Resistant Gas of Recyclable and Versatile Manganese-Doped Lead-Free Double Perovskite Crystals toward Novel Functional Fabric and Photoelectric Device.

Lead-free halide perovskites possess excellent photoelectric properties, making them widely used in the photoelectric fields. Herein, lead-free double perovskite crystals (PCs) doped with manganese (Cs2NaInCl6:Mn2+) are successfully prepared by the more energy-efficient crystallization method. The crystals emit bright orange-red light under the ultraviolet (UV) lamp, showing unique optical properties. They have the highest photoluminescence quantum yield of 42.91%. The white light-emitting diodes (LEDs) are fabricated using these perovskite crystals, which show a color rendering index of 92 and external quantum efficiency (EQE) as high as 16.3%. Furtherly, perovskite-modified fiber paper made of aramid chopped fibers (ACFs) and polyphenylene sulfide (PPS) exhibited fluorescent properties under different conditions. This paper combines fiber composite technology with PPS fiber filter bags, which are widely used in environmental protection, for the first time and demonstrates functional fiber filter bags with fluorescent characteristics. This filter bag provides an idea for the automatic detection of industrial filtration. Meanwhile, after being exposed to industrial waste gas for 60 h, the filter bag can maintain superior fluorescence performance. In this study, lead-free double perovskites are synthesized using an efficient method for preparing high-performance LEDs and high-stability fluorescent fibers. Concurrently, the application of perovskites in environmental protection is expanded.

The dyadic associations among self-efficacy, dyadic coping, and health-related quality of life between high-risk pregnant women and spouses: a cross-sectional study.

AIM: Health-related quality of life(HRQoL) is essential for high-risk pregnant women and their spouses. This study aimed to explore the dyadic associations (including actor and partner effects) among self-efficacy, dyadic coping, and HRQoL of high-risk pregnant women and their spouses and examine the mediating effect of dyadic coping. METHODS: This cross-sectional study recruited participants from two Grade A tertiary hospitals in China from October 2022 to September 2023. A questionnaire including the Chinese version of the General Self-Efficacy Scale, Dyadic Coping Inventory, and 12 Short Form Health Survey Scales was used for the survey. The actor-partner interdependence mediation model was constructed to test dyadic associations and mediating effects. RESULTS: In the actor effects, self-efficacy was positively associated with dyadic coping and HRQoL (P < 0.05). Regarding partner effects, pregnant women's self-efficacy was positively associated with spouses' dyadic coping and physical health (P < 0.05). Dyadic coping partially mediated the relationship between self-efficacy and HRQoL for both groups(P < 0.05). CONCLUSION: The HRQoL of high-risk pregnant women and their spouses requires urgent attention. Enhancing self-efficacy and dyadic coping in these couples is related to their improved physical and mental health. Healthcare professionals should consider interactions between couples and include them together in perinatal care. Intervention programs for couples or families based on existing positive psychology and dyadic interventions may work together to improve the HRQoL of couples.

Dyadic coping and associated factors in women with high-risk pregnancy and their spouses: Do they interact?

OBJECTIVE: The objective of this study was to examine the present situation of dyadic coping in pregnant women with high-risk pregnancy and their spouses, as well as the relevant factors and the interactions between partners. METHODS: From October 2022 to September 2023, a cross-sectional survey was undertaken, involving 460 pairs of pregnant women with high-risk pregnancy who were hospitalized for childbirth and their accompanying spouses. These participants completed self-assessments on dyadic coping, marital satisfaction, perceived stress, and self-efficacy through the completion of paper questionnaires. The collected data was then subjected to analysis utilizing correlation analysis and multiple linear regression. The actor-partner interdependence model (APIM) was then developed using the structural equation modeling(SEM) to test the binary association. FINDINGS: Pregnant women preferred to utilize stressful communication, whereas their spouses employed supportive and delegated coping. Both external (such as education level, employment status, and medical insurance) and internal (such as marital satisfaction, perceived stress, and self-efficacy) factors were associated with pregnant women's dyadic coping. Education level and internal factors were also associated with the spouses' dyadic coping. In contrast to spouses, who can only have a partner effect on pregnant women through marriage satisfaction, all pregnant women's internal elements played the partner effect on the spouses' dyadic coping. IMPLICATIONS: The study's findings help identify populations with inadequate coping ability. Promoting marital satisfaction, self-efficacy, and reducing perceived stress are associated with enhancing the dyadic coping ability of pregnant women with high-risk pregnancy and their spouses. It also suggests that antenatal care should intervene with pregnant women with high-risk pregnancy and their spouses as a whole, and emphasize collaborative coping and effective mutual support between couples rather than spousal support alone.

Pressure-Insensitive Epidermal Thickness of Fingertip Skin for Optical Image Encryption.

In this study, an internal fingerprint-guided epidermal thickness of fingertip skin is proposed for optical image encryption based on optical coherence tomography (OCT) combined with U-Net architecture of a convolutional neural network (CNN). The epidermal thickness of fingertip skin is calculated by the distance between the upper and lower boundaries of the epidermal layer in cross-sectional optical coherence tomography (OCT) images, which is segmented using CNN, and the internal fingerprint at the epidermis-dermis junction (DEJ) is extracted based on the maximum intensity projection (MIP) algorithm. The experimental results indicate that the internal fingerprint-guided epidermal thickness is insensitive to pressure due to normal correlation coefficients and the encryption process between epidermal thickness maps of fingertip skin under different pressures. In addition, the result of the numerical simulation demonstrates the feasibility and security of the encryption scheme by structural similarity index matrix (SSIM) analysis between the original image and the recovered image with the correct and error keys decryption, respectively. The robustness is analyzed based on the SSIM value in three aspects: different pressures, noise attacks, and data loss. Key randomness is valid by the gray histograms, and the average correlation coefficients of adjacent pixelated values in three directions and the average entropy were calculated. This study suggests that the epidermal thickness of fingertip skin could be seen as important biometric information for information encryption.

PMC-LLaMA: toward building open-source language models for medicine.

OBJECTIVE: Recently, large language models (LLMs) have showcased remarkable capabilities in natural language understanding. While demonstrating proficiency in everyday conversations and question-answering (QA) situations, these models frequently struggle in domains that require precision, such as medical applications, due to their lack of domain-specific knowledge. In this article, we describe the procedure for building a powerful, open-source language model specifically designed for medicine applications, termed as PMC-LLaMA. MATERIALS AND METHODS: We adapt a general-purpose LLM toward the medical domain, involving data-centric knowledge injection through the integration of 4.8M biomedical academic papers and 30K medical textbooks, as well as comprehensive domain-specific instruction fine-tuning, encompassing medical QA, rationale for reasoning, and conversational dialogues with 202M tokens. RESULTS: While evaluating various public medical QA benchmarks and manual rating, our lightweight PMC-LLaMA, which consists of only 13B parameters, exhibits superior performance, even surpassing ChatGPT. All models, codes, and datasets for instruction tuning will be released to the research community. DISCUSSION: Our contributions are 3-fold: (1) we build up an open-source LLM toward the medical domain. We believe the proposed PMC-LLaMA model can promote further development of foundation models in medicine, serving as a medical trainable basic generative language backbone; (2) we conduct thorough ablation studies to demonstrate the effectiveness of each proposed component, demonstrating how different training data and model scales affect medical LLMs; (3) we contribute a large-scale, comprehensive dataset for instruction tuning. CONCLUSION: In this article, we systematically investigate the process of building up an open-source medical-specific LLM, PMC-LLaMA.

Path Analysis Between Family Functioning and Mental Health in People With Neuropathic Pain: Roles of Pain Intensity, Self-Perceived Burden, Pain Catastrophizing, and Functional Status.

PURPOSE: This study aimed to explore the pathways between family functioning and mental health in people with neuropathic pain, as well as to discuss the mediating role of pain intensity, self-perceived burden, pain catastrophizing, and functional status. DESIGN: Cross-sectional design reported using the STROBE guidelines. METHODS: A total of 277 people with neuropathic pain completed face-to-face questionnaires to evaluate family functioning, pain intensity, pain catastrophizing, self-perceived burden, functional status, and mental health. Structural equation modeling (SEM) was constructed to analyze the pathways between these variables. RESULTS: The positive total effect between family functioning and mental health was significant and partially mediated by self-perceived burden, pain catastrophizing, and functional status. In addition, better family functioning was associated with higher pain intensity, which worsens self-perceived burden, pain catastrophizing, and functional status, masking 23.68% of the positive effects between family functioning and mental health. CONCLUSIONS: Better family functioning was associated with better mental health, as explained by reduced self-perceived burden, reduced pain catastrophizing, and improved functional status. However, this benefit may be partially masked by the relationship that better family functioning explains higher pain intensity. CLINICAL IMPLICATIONS: Nurses' comprehensive assessment and management of neuropathic pain from both the family and individual levels, such as family functioning, pain intensity, self-perceived burden, pain catastrophizing, and functional status, may be beneficial in promoting patients' mental health. In addition, it is necessary to identify why good family functioning is associated with higher pain intensity and intervene in this regard.

Investigation and analysis of magnetic resonance imaging experience and psychological status of patients.

OBJECTIVE: To analyze factors influencing the service experience of magnetic resonance imaging (MRI) examination and psychological status of patients admitted to a hospital and propose targeted solutions, and optimize the examination process and nursing by analyzing the MRI examination experience and psychological effect on patients. METHODS: The MRI examination rooms of two tertiary general hospitals in Haikou City were sampled at random, and 206 patients who met the study criteria were surveyed on site. RESULTS: (1) The item with the lowest mean score for patient examination services was whether earplugs were provided to the patient during the examination (B8 = 0.47). (2) Environmental logistics experience (16.83 ± 3.036) received the lowest score among the three service experience dimensions. (3) The average anxiety score of the patients was 5.38. (4) There was a positive correlation between the examination experience and the examination service experience of the patients. (5) Patients with higher monthly income had decreased anxiety (coefficient = -2.334), and MRI examination of the extremities relieved the anxiety (coefficient = -4.782). CONCLUSION: The environmental logistics factors, poor service attitude, examination site, and income were the most significant factors affecting the MRI examination experience and psychological status of patients, which can be improved by providing information, enhancing the waiting environment, providing targeted patient education, and evaluating the experience immediately.

Pain intensity and self-perceived burden mediate the relationship between family functioning and pain catastrophizing in patients with neuropathic pain.

This cross-sectional study aimed to investigate the relationship between family functioning, pain intensity, self-perceived burden, and pain catastrophizing. Moreover, we also wanted to explore the multiple mediating roles of pain intensity and self-perceived burden. From October 2022 to March 2023, 252 Chinese people with neuropathic pain completed face-to-face questionnaires to assess family functioning, pain intensity, self-perceived burden, and pain catastrophizing. Data analysis was done using descriptive statistics and a structural equation model. The results showed better family functioning was significantly associated with more intense pain, less self-perceived burden, and less pain catastrophizing. Mediation analysis showed that family functioning could indirectly affect pain catastrophizing through pain intensity and self-perceived burden in addition to a direct effect on pain catastrophizing. Moreover, the mediating variable of pain intensity played a masking role. These findings suggest that good family functioning can effectively reduce the self-perceived burden and pain catastrophizing in patients with neuropathic pain. However, family functioning cannot show its maximum effectiveness, and it may be necessary to construct a model of family functioning suitable for patients with neuropathic pain in the future.

CD276 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma through the TGF-ß/SMAD signaling.

OBJECTIVE: Aberrant expression of CD276 has been reported in malignant tumors. However, the exact role and mechanisms of CD276 influence the progression of esophageal squamous cell carcinoma (ESCC) still need to be understood. METHODS: Bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemistry staining, was used to explore the expression patterns of CD276 in ESCC. Cell counting kit-8 and Transwell assays were employed to evaluate the effects of CD276 expression on tumor cell proliferation and motility. Western blotting and Transwell assays were used to explore the potential pathways through which CD276 mediates the progression of ESCC. Moreover, the in vivo role of CD276 in tumor progression was investigated by establishing a lung metastasis mouse model. RESULTS: A significant upregulation of CD276 was observed in ESCC tissues compared to adjacent tissues. The inhibition of CD276 had no evident impact on ESCC cell proliferation but notably hindered their migratory and invasive properties and the expression of epithelial-mesenchymal transition (EMT) markers. Inversely, overexpressing CD276 led to an upregulation of EMT markers, underscoring the capacity of CD276 to amplify the motility of ESCC cells. Furthermore, CD276 was found to enhance the migratory and invasive abilities of ESCC cells by activating the TGF-ß/SMAD signaling but not the PI3K/AKT pathway. In vivo studies demonstrated that CD276 facilitates pulmonary metastasis. CONCLUSION: CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-ß/SMAD signaling, thus promoting the progression of ESCC.

Federated machine learning in healthcare: A systematic review on clinical applications and technical architecture.

Federated learning (FL) is a distributed machine learning framework that is gaining traction in view of increasing health data privacy protection needs. By conducting a systematic review of FL applications in healthcare, we identify relevant articles in scientific, engineering, and medical journals in English up to August 31st, 2023. Out of a total of 22,693 articles under review, 612 articles are included in the final analysis. The majority of articles are proof-of-concepts studies, and only 5.2% are studies with real-life application of FL. Radiology and internal medicine are the most common specialties involved in FL. FL is robust to a variety of machine learning models and data types, with neural networks and medical imaging being the most common, respectively. We highlight the need to address the barriers to clinical translation and to assess its real-world impact in this new digital data-driven healthcare scene.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Mediating effects of social support and presenteeism on turnover intention and post-traumatic stress disorder among Chinese nurses in the post-pandemic era: a cross-sectional study.

Background: The shift in national policies for epidemic prevention and control in the post-pandemic era is undoubtedly a challenge for health care professionals. Nurses, as an important part of the health care professional population, have an even greater impact on their mental health and occupational safety. This may expose nurses to post-traumatic stress disorder (PTSD) and presenteeism, and ultimately lead to their turnover. Objective: This study aimed to investigate the relationship between turnover intention and post-traumatic stress disorder among Chinese nurses during post-pandemic era, and the mediating role of social support and presenteeism. Methods: In this study, a multicentre cross-sectional survey was conducted in April 2023 among nursing staff in several tertiary general hospitals in northern China, with online data collection using the Turnover intention Scale (PTSD), the Impact of Events Scale (IES), the Social Support Scale (SSS), and the Stanford presenteeism Scale (STAS) and the relationship between variables was analyzed using hierarchical multivariate regression, and Structural Equation Modeling (SEM) was used to analyze the relationship between post-traumatic stress disorder and the Turnover intention from the pathway between. Results: Data were collected from 2,513 nurses who met the inclusion criteria, in which general information such as age, department, specific department, Professional title, history of alcohol consumption, form of employment, Years of working, and Average working hours per day were statistically significant with the difference in the turnover intention. The results of the study showed a 32% high turnover intention among nurses in the post-pandemic era, which was lower than the turnover intention during the pandemic. The results of hierarchical multiple regression analysis showed that post-traumatic stress disorder, social support, and presenteeism were significant predictors of turnover intention. The total effect of post-traumatic stress disorder on turnover intention to work was 0.472 [bias modified 95% confidence interval (0.415-0.483), p < 0.001]. Social support and attendance played a partially intermediate role in post-traumatic stress disorder and propensity to leave (an indirect effect of 26% of the total effect). Conclusion: Turnover intention and post-traumatic stress disorder levels are high and social support plays an important role in the tendency to leave the job and post-traumatic stress disorder, healthcare institution can be achieved by strengthening social support for nurses in the post-epidemic era and preventing the occurrence of presenteeism.

Bifidobacterium longum promotes postoperative liver function recovery in patients with hepatocellular carcinoma.

Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B. longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients.

[Clinical characteristics and genetic analysis of two children with Tuberous sclerosis complex].

OBJECTIVE: To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). METHODS: Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. RESULTS: Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.

Fluoride-Rich, Organic-Inorganic Gradient Interphase Enabled by Sacrificial Solvation Shells for Reversible Zinc Metal Batteries.

Zinc metal batteries are strongly hindered by water corrosion, as solvated zinc ions would bring the active water molecules to the electrode/electrolyte interface constantly. Herein, we report a sacrificial solvation shell to repel active water molecules from the electrode/electrolyte interface and assist in forming a fluoride-rich, organic-inorganic gradient solid electrolyte interface (SEI) layer. The simultaneous sacrificial process of methanol and Zn(CF3SO3)2 results in the gradient SEI layer with an organic-rich surface (CH2OC- and C5 product) and an inorganic-rich (ZnF2) bottom, which combines the merits of fast ion diffusion and high flexibility. As a result, the methanol additive enables corrosion-free zinc stripping/plating on copper foils for 300 cycles with an average coulombic efficiency of 99.5%, a record high cumulative plating capacity of 10 A h/cm2 at 40 mA/cm2 in Zn/Zn symmetrical batteries. More importantly, at an ultralow N/P ratio of 2, the practical VO2//20 µm thick Zn plate full batteries with a high areal capacity of 4.7 mAh/cm2 stably operate for over 250 cycles, establishing their promising application for grid-scale energy storage devices. Furthermore, directly utilizing the 20 µm thick Zn for the commercial-level areal capacity (4.7 mAh/cm2) full zinc battery in our work would simplify the manufacturing process and boost the development of the commercial zinc battery for stationary storage.

The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry.

Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the IBV and PEDV life cycles was investigated. When the UPS was suppressed by pharmacological inhibition at the early infection stage, IBV and PEDV infectivity were severely impaired. Further study showed that inhibition of UPS did not change the internalization of virus particles; however, by using R18 and DiOC-labeled virus particles, we found that inhibition of UPS prevented the IBV and PEDV membrane fusion with late endosomes or lysosomes. In addition, proteasome inhibitors blocked the degradation of the incoming viral protein N, suggesting the uncoating process and genomic RNA release were suppressed. Subsequently, the initial translation of genomic RNA was blocked. Thus, UPS may target the virus-cellular membrane fusion to facilitate the release of incoming viruses from late endosomes or lysosomes, subsequently blocking the following virus uncoating, initial translation, and replication events. Similar to the observation of proteasome inhibitors, ubiquitin-activating enzyme E1 inhibitor PYR-41 also impaired the entry of IBV, enhanced the accumulation of ubiquitinated proteins, and depleted mono-ubiquitin. In all, this study reveals an important role of UPS in coronavirus entry by preventing membrane fusion and identifies UPS as a potential target for developing antiviral therapies for coronavirus.

Melatonin attenuates chronic intermittent hypoxia-induced intestinal barrier dysfunction in mice.

BACKGROUND AND PURPOSE: Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear. EXPERIMENTAL APPROACH: C57BL/6 J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16 S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation. KEY RESULTS: We found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and decrease the expression of intestinal tight junction proteins. CIH could decrease the abundance of the beneficial genera Clostridium, Akkermansia, and Bacteroides, while increasing the abundance of the pathogenic genera Desulfovibrio and Bifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in vitro and elevated the circulating pro-inflammatory cytokine in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above. CONCLUSION AND IMPLICATIONS: Melatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling.

[Analysis of CLCN4 gene variant in a child with Raynaud-Claes syndrome].

OBJECTIVE: To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS). METHODS: A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed. RESULTS: The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.