A self-supported porous NiMo electrocatalyst to boost the catalytic activity in the hydrogen evolution reaction.

To develop hydrogen energy production and address the issues of global warming, inexpensive, effective, and long-lasting transition metal-based electrocatalysts for the synthesis of hydrogen are crucial. Herein, a porous electrocatalyst NiMo/Ni/NF was successfully constructed by a two-step electrodeposition process, and was used in the hydrogen evolution reaction (HER) of electrocatalytic water decomposition. NiMo nanoparticles were coated on porous Ni/NF grown on nickel foam (NF), leading to a resilient porous structure with enhanced conductivity for efficient charge transfer, as well as distinctive three-dimensional channels for quick electrolyte diffusion and gas release. Notably, the low overpotential (42 mV) and fast kinetics (Tafel slope of 44 mV dec-1) at a current density of 10 mA cm-2 in 1.0 M KOH solution demonstrate the excellent HER activity of the electrode, which was superior to that of recently reported non-noble metal-based catalysts. Additionally, NiMo/Ni/NF showed extraordinary catalytic durability in stability tests at a current density of 10 mA cm-2 for 70 h. The porous structure catalyst and the electrodeposition-electrocatalysis technique examined in this study offer new approaches for the advancement of the electrocatalysis field because of these benefits.

Electrolyzing spent cupronickel to fabricate superhydrophilic electrocatalysts for enhanced water splitting.

Herein, novel and efficient IF-supported NiCu (NiCu/IF) and NiMn (NiMn/IF) electrocatalysts are successfully deposited on iron foam (IF) via electrolysis of spent cupronickel (SCN), with outstanding performance for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) in an alkaline solution, respectively. The physical and electrochemical characterization results demonstrate that the catalysts possess a large active surface area, remarkable performance, and excellent durability.

Transcriptome analysis reveals the impact of NETs activation on airway epithelial cell EMT and inflammation in bronchiolitis obliterans.

Bronchiolitis obliterans (BO) is a chronic airway disease that was often indicated by the pathological presentation of narrowed and irreversible airways. However, the molecular mechanisms of BO pathogenesis remain unknown. Although neutrophil extracellular traps (NETs) can contribute to inflammatory disorders, their involvement in BO is unclear. This study aims to identify potential signaling pathways in BO by exploring the correlations between NETs and BO. GSE52761 and GSE137169 datasets were downloaded from gene expression omnibus (GEO) database. A series of bioinformatics analyses such as differential expression analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were performed on GSE52761 and GSE137169 datasets to identify BO potential signaling pathways. Two different types of BO mouse models were constructed to verify NETs involvements in BO. Additional experiments and bioinformatics analysis using human small airway epithelial cells (SAECs) were also performed to further elucidate differential genes enrichment with their respective signaling pathways in BO. Our study identified 115 differentially expressed genes (DEGs) that were found up-regulated in BO. Pathway enrichment analysis revealed that these genes were primarily involved in inflammatory signaling processes. Besides, we found that neutrophil extracellular traps (NETs) were formed and activated during BO. Our western blot analysis on lung tissue from BO mice further confirmed NETs activation in BO, where neutrophil elastase (NE) and myeloperoxidase (MPO) expression were found significantly elevated. Transcriptomic and bioinformatics analysis of NETs treated-SAECs also revealed that NETs-DEGs were primarily associated through inflammatory and epithelial-to-mesenchymal transition (EMT) -related pathways. Our study provides novel clues towards the understanding of BO pathogenesis, in which NETs contribute to BO pathogenesis through the activation of inflammatory and EMT associated pathways. The completion of our study will provide the basis for potential novel therapeutic targets in BO treatment.

One-step electrodeposition of V-doped NiFe nanosheets for low-overpotential alkaline oxygen evolution.

As a non-noble metal electrocatalyst for the oxygen evolution reaction (OER), the binary NiFe layer double hydroxide (LDH) is expected to replace Ru-based and Ir-based anode materials for water decomposition. To attain threshold current density, nevertheless, a somewhat significant overpotential is still needed. In this work, layered double hydroxides of NiFe LDH are doped with V to form the terpolymer NiFeV LDH, which greatly increases the intrinsic activity of NiFe LDH and improves OER performance. This process is a straightforward and quick one-step electrodeposition process. Notably, NiFeV/NF has a low overpotential (218 mV at 10 mA cm-2) and faster kinetics (Tafel slope of 31 mV dec-1) as well as excellent durability and stability in 1 M KOH solution. In addition, the OER performance of the catalyst prepared in this work is better than that of a non-valuable metal catalyst that was recently reported. The V-doped NiFe LDH layered double hydroxides and the investigation of electrodeposition electrocatalytic methods in this work offer a fresh opportunity for the advancement of electrochemical technology.

Effect of Al2Cu constituent layer thickness discrepancy on the tensile mechanical behavior of Cu/Al2Cu/Al layered composites: a molecular dynamics simulation.

Nano-polycrystalline Cu/Al2Cu/Al layered composites with different layer thicknessesdof single-crystal Al2Cu constituent are constructed. The effects ofdon the strength and fracture modes of nano-polycrystalline Cu/Al2Cu/Al layered composites are systematically investigated by molecular dynamics simulations. The uniaxial tensile results show that the ultimate strength and fracture mode of the nano-polycrystalline Cu/Al2Cu/Al layered composites do not change monotonically with the change of single crystal Al2Cu constituent layer thicknessd, the ultimate strength peaking atd= 2.44 nm, and the toughness reaching the optimum atd= 4.88 nm. The improvement of deformation incompatibility between Cu, Al and Al2Cu components increases the ultimate strength of polycrystalline Cu/Al2Cu/Al laminated composites. Due to the high activity of Cu dislocation and the uniformity of strain distribution of single crystal Al2Cu, the fracture of nano-crystalline Cu/Al2Cu/Al layered composites changes from brittleness to toughness. This study is crucial to establish the organic connection between microstructure and macroscopic properties of Cu/Al layered composites. To provide theoretical basis and technical support for the application of Cu/Al layered composites in high-end fields, such as automotive and marine, aerospace and defense industries.

Identification of Hub Genes in the Pathogenesis of Bronchiolitis Obliterans via Bioinformatic Analysis and Experimental Verification.

Background: Bronchiolitis obliterans (BO) is a chronic disease that can arise as a complication of severe childhood pneumonia and can also impact the long-term survival of patients after lung transplantation. However, the precise molecular mechanism underlying BO remains unclear. We aimed to identify BO-associated hub genes and their molecular mechanisms. Methods: BO-associated transcriptome datasets (GSE52761, GSE137169, and GSE94557) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Additional bioinformatics analyses, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, were performed to determine functional roles and DEG-associated regulatory networks. Prediction of hub genes using the 12 algorithms available in the Cytohubba plugin of Cytoscape software was also performed. Verification was performed using the BO mouse model. Results: Our results revealed 57 DEGs associated with BO, of which 18 were down-regulated and 39 were up-regulated. The Cytohubba plugin data further narrowed down the 57 DEGs into 9 prominent hub genes (CCR2, CD1D, GM2A, TFEC, MPEG1, CTSS, GPNMB, BIRC2, and CTSZ). Genes such as CCR2, TFEC, MPEG1, CTSS, and CTSZ were dysregulated in 2,3-butanedione-induced BO mice, whereas TFEC, CTSS, and CTSZ were dysregulated in nitric acid-induced BO mouse models. Conclusion: Our study identified and validated four novel BO biomarkers, which may allow further investigation into the development of distinct BO diagnostic markers and novel therapeutic avenues.

Increased RNA editing sites revealed as potential novel biomarkers for diagnosis in primary Sjögren's syndrome.

BACKGROUND: Transcriptome-wide aberrant RNA editing has been shown to contribute to autoimmune diseases, but its extent and significance in primary Sjögren's syndrome (pSS) are currently poorly understood. METHODS: We systematically characterized the global pattern and clinical relevance of RNA editing in pSS by performing large-scale RNA sequencing of minor salivary gland tissues obtained from 439 pSS patients and 130 non-pSS or healthy controls. FINDINGS: Compared with controls, pSS patients displayed increased global RNA-editing levels, which were significantly correlated and clinically relevant to various immune features in pSS. The elevated editing levels were likely explained by significantly increased expression of adenosine deaminase acting on RNA 1 (ADAR1) p150 in pSS, which was associated with disease features. In addition, genome-wide differential RNA editing (DRE) analysis between pSS and non-pSS showed that most (249/284) DRE sites were hyper-edited in pSS, especially the top 10 DRE sites dominated by hyper-edited sites and assigned to nine unique genes involved in the inflammatory response or immune system. Interestingly, among all DRE sites, six RNA editing sites were only detected in pSS and resided in three unique genes (NLRC5, IKZF3 and JAK3). Furthermore, these six specific DRE sites with significant clinical relevance in pSS showed a strong capacity to distinguish between pSS and non-pSS, reflecting powerful diagnostic efficacy and accuracy. CONCLUSION: These findings reveal the potential role of RNA editing in contributing to the risk of pSS and further highlight the important prognostic value and diagnostic potential of RNA editing in pSS.

Evaluation of waterlogging tolerance and responses of protective enzymes to waterlogging stress in pumpkin.

Waterlogging caused by short and severe, or prolonged precipitation can be attributed to global warming. Pumpkin plants are drought-tolerant but not tolerate to waterlogging stress. Under frequent rain and waterlogging conditions, the production of pumpkins is of lower quality, sometimes rotten, and harvest failure occurs in severe cases. Therefore, it is of great significance to assess the waterlogging tolerance mechanism of pumpkin plants. In this study, 10 novel pumpkin varieties from Baimi series were used. The waterlogging tolerance level of pumpkin plants was evaluated by measuring waterlogging tolerance coefficient of biomass and physiological indices using waterlogging stress simulation method. The criteria to evaluate the waterlogging tolerance capacities of pumpkin plants were also explored. Using principal component and membership function analysis, waterlogging tolerance levels of the pumpkin varieties were ranked as follows: Baimi No. 10>; Baimi No. 5>; Baimi No. 1>; Baimi No. 2>; Baimi No. 3>; Baimi No. 7>; Baimi No. 9>; Baimi No. 6>; Baimi No. 4>; Baimi No. 8. Based on the results, Baimi No. 10 was identified with strong waterlogging tolerance and Baimi No. 8 with weak waterlogging tolerance. The responses of malondialdehyde (MDA), proline, key enzymes responsible for anaerobic respiration, and antioxidant enzymes to waterlogging stress were studied in pumpkin plants. The relative expression levels of related genes were determined using real-time fluorescence quantitative PCR technique. The aim of our study was to assess the waterlogging tolerance mechanism of pumpkin plants, thus laying a theoretical foundation for breeding waterlogging-tolerant varieties in the future. After flooding stress treatment, the antioxidant enzyme activities, contents of proline and alcohol dehydrogenases of Baimi No. 10 and Baimi No. 8 displayed an increase followed by a decrease. All indices of Baimi No. 10 were higher than Baimi No. 8. MDA contents gradually increased, with the content being higher in Baimi No. 8 than Baimi No. 10. The activities of pyruvate decarboxylases (PDCs) in Baimi No. 8 and Baimi No. 10 exhibited a decrease initially, followed by an increase, and then a decrease again. The PDC activity in Baimi No. 8 was generally higher than Baimi No. 10. The relative expression levels of genes encoding superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase were consistent with their corresponding enzyme activities. During the early stage of flooding stress, pumpkin plants waterlogging tolerance was improved by enhancing the expression levels of antioxidant enzyme encoding genes and increasing the antioxidant enzyme activities.

An empirical study on the asset-light operation and corporate performance of China's tourism listed companies.

Transitioning to an asset-light strategy is a significant shift for tourism companies in light of the global COVID-19 outbreak. This study investigates the impact of asset-light strategy on corporate performance using a sample of 588 firm-year observations from China A-share publicly traded tourism companies from 2003 to 2021. Using two-way fixed effects models, our results indicate that adopting an asset-light strategy can significantly improve the performance of tourism enterprises. We further verify that this influence mechanism is supply chain management using path analysis. More interestingly, the positive impact of asset-light strategy on enterprise performance is particularly significant in non-state-owned enterprises. Robustness tests with the system GMM method, the variable substitution method and the two-stage instrumental variables method support our main findings. The findings have significant ramifications for assisting the tourism industry, managers, and investors to strategically cope with settings that are complex and dynamic.

Risk prediction model of polypharmacy for community-dwelling elderly patients: An assessment tool for early detection.

Background: Polypharmacy has become a major and growing public health issue, with significant implications for health outcomes and expenditure on healthcare resources. In this study, a risk prediction model of polypharmacy represented by a nomogram for community-dwelling elderly patients based on the Chinese population was constructed. Methods: A cross-sectional study was conducted in Shanghai, China. The variables data affecting polypharmacy were fetched from the information system database of health government departments in Shanghai. The Least Absolute Shrinkage Selection Operator (LASSO) regression analysis was used to select the predictor variables, and multivariate logistic regression was used to establish the prediction model. A visual tool of the nomogram was established for predicting the risk of polypharmacy in the elderly population. In addition, the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to estimate the performance of the model. Results: A total of 80,012 elderly patients were included in this study. Eight variables, containing age, residential area, preferred medical institutions, number of visits to tertiary hospitals, number of visits to secondary hospitals, number of visits to community health centers, number of diagnoses, and main types of disease, were included in the risk prediction model of nomogram. The area under the curve (AUC) of the nomogram was 0.782 in both sets, demonstrating that the model has a good discriminant ability. The calibration chart shows that the prediction model fits well with the validation set. DCA results displayed that the threshold probabilities of the two sets in the prediction model reached up to 90%, implying that the model had a preferable application value. Conclusion: This study explored the risk factors for polypharmacy among the elderly in Shanghai, China, and applied the nomogram to establish a predictive model via eight variables, which provided an effective tool for early screening and timely prevention of polypharmacy. Family physicians or pharmacists could scientifically use the tool to closely observe community-dwelling elderly patients, decreasing the adverse health effects caused by medication for the elderly.

Microbiota dysbiosis in primary Sjögren's syndrome and the ameliorative effect of hydroxychloroquine.

The human microbiome plays an important role in autoimmune diseases. However, there is limited knowledge regarding the microbiota in individuals with primary Sjögren's syndrome (pSS). Here, we perform 16S ribosomal RNA gene sequencing of fecal, oral, and vaginal samples from a cohort of 133 individuals with pSS, 56 with non-pSS, and 40 healthy control (HC) individuals. Dysbiosis in the gut, oral, and vaginal microbiome is evident in patients with pSS, and oral samples demonstrate the greatest extent of microbial variation. Multiple key indicator bacteria and clinical characteristics are identified across different body sites, implying that microbial dysbiosis has important roles in the pathogenesis of pSS. Furthermore, we observe pSS-like dysbiosis in individuals with pre-clinical pSS or non-pSS-related disease, revealing that microbial shifts could appear prior to pSS. After hydroxychloroquine (HCQ) treatment, microbial dysbiosis in individuals with pSS is partially resolved, although the microbiota composition remain disordered. These results contribute to the overall understanding of the relationship between the microbiome and pSS.

Rational medication management mode and its implementation effect for the elderly with multimorbidity: A prospective cohort study in China.

Background: As one of the countries with the most serious degree of aging, the incidence of potentially inappropriate drug use among the elderly is as high as 30. 4% in Chinese communities, and the lack of effective medication management and poor medication compliance at home are the main factors. Given these situations, we constructed a Rational Medication Management Mode based on family physician service, carried out an empirical research and evaluated the implementation effect. Methods: A prospective cohort study was conducted from September to December 2021 to analyze the implementation effect of the Rational Medication Management Mode by comparing the outcome indicators between the intervention group and control group. The primary outcome of this study was medication number and polypharmacy (taking 5 or more medications) at 90 days. The secondary outcomes included the situation for behavioral self-management and knowledge-belief-behavior of rational medication use. Results: A total of 618 elderly patients (309 in the intervention group and 309 in the control group) with multimorbidity were included in this study, those were all available at follow-up at 90 days. At 90 days, the number of medications was achieved by 3.88 (1.48), and patients with polypharmacy were reduced by 59.55% in the intervention group, having a significant difference compared with the control group (P < 0.001). Patients with medication reminders, intermittent medication and adverse drug reactions were achieved in 294 (95.15%), 47 (15.21%), and 51 (16.51%) respectively in the intervention group (P < 0.001). The knowledge, belief, behavior security and behavior compliance of rational medication use of elderly patients were all greatly improved in the intervention group at 90 days (P < 0.0001). Conclusion: The Rational Medication Management Mode based family physician service, which provides the support of manuals and pillboxes, can decrease the elderly patients' number of drugs with multimorbidity, reduce the incidence of polypharmacy, enhance behavioral self-management, increase the knowledge and belief of rational medication use, and improve the security and compliance of medication usage behavior. In order to provide a practical basis for rational medication management of elderly patients with multimorbidity under the background of long-term prescriptions in China.

A juvenile murine model with chronic lung inflammation induced by repeated intratracheal instillation of lipopolysaccharides: a versatile and replicable model.

Background: Recurrent lower respiratory tract infection or chronic pulmonary infection often occur in children with chronic lung diseases (CLDs). By continuous lung inflammation, recurrent and chronic infection could cause irreversible airway structural and lung function damage, which eventually leads to respiratory failure and death. Methods: In purpose of recapitulating persistent high-intensity lung inflammation caused by recurrent lower respiratory tract infection or chronic infection, we established a juvenile murine model with chronic lung inflammation induced by repeated intratracheal instillations of lipopolysaccharides (LPS) from Pseudomonas aeruginosa once a week for 4 weeks. Four-week-old C57BL/6N mice were divided into 4 groups, including LPS0.5 group (n=15), LPS1.0 group (n=15), Control group (n=15) and Normal group (n=15). Mice in LPS0.5 group and LPS1.0 group were instilled intratracheally with 0.5 mg/kg LPS and 1.0 mg/kg LPS respectively. Mice in control group were instilled intratracheally with LPS-free sterile 0.9% NaCl, whereas normal group received no treatment. The successful chronic lung inflammation murine model was validated via (I) pathological manifestations of chronic inflammatory mononuclear-cell infiltration and lung parenchyma damage; (II) decreased lung function. Results: All mice in LPS1.0 group died before the third instillation. No death after instillation was observed in Control and LPS0.5 group. Histological analysis revealed that in LPS0.5 group, 7 days after the third instillation, most bronchus and parabronchial vessels were wrapped by infiltrating monocytes and lymphocyte and alveolar cavities were compressed, which were not observed in control and normal group. Also, ratio of forced expiratory volume in 0.1 second (FEV0.1) and forced vital capacity (FVC) in LPS0.5 group was significantly lower (P<0.0001) than both control group and normal group, suggesting ventilatory dysfunction developed after repeatedly intratracheal instillation once a week for 4 weeks. Conclusions: Intratracheal instillation of 0.5 mg/kg LPS once a week for 4 weeks can cause chronic lung inflammation in young mice.

Human coronaviruses: Origin, host and receptor.

Coronavirus is a type of RNA-positive single-stranded virus with an envelope, and the spines on its surface derived its official name. Seven human coronaviruses 229E, OC43, SARS, NL63, HKU1, MERS, SARS-CoV-2 can cause both a mild cold and an epidemic of large-scale deaths and injuries. Although their clinical manifestations and many other pathogens that cause human colds are similar, studying the relationship between their evolutionary history and the receptors that infect the host can provide important insights into the natural history of human epidemics in the past and future. In this review, we describe the basic virology of these seven coronaviruses, their partial genome characteristics, and emphasize the function of receptors. We summarize the current understanding of these viruses and discuss the potential host of wild animals of these coronaviruses and the origin of zoonotic diseases.

Seroprevalence of neutralizing antibodies against the respiratory syncytial virus in healthy adults in Guangzhou, southern China.

Respiratory syncytial virus (RSV) is the major cause of pneumonia and bronchiolitis in infants and young children and mediates substantial morbidity and mortality in the elderly and immunocompromised globally. The development of a safe and effective RSV vaccine and an optimized neutralizing antibody (NAb) with strong virus-neutralizing activity is appealing. To gain some detailed knowledge of the humoral immune response to RSV subgroup A (RSV-A) and RSV-B, we investigated the seroprevalence of pre-existing NAbs by using the microneutralization assay in healthy adult from Guangzhou, southern China. We found that the overall seropositive rate was 84.86% for anti-RSV NAbs. Furthermore, the seropositive rates were 68.47% and 73.61% for anti-RSV-A NAbs and anti-RSV-B NAbs, respectively. In addition, although the seropositive rates and NAb levels were not associated with the blood type, type AB individuals displayed higher seropositive rates for anti-RSV-A NAbs with high titer (≥ 288) and anti-RSV-B NAbs, especially those with moderate titer (≥ 72 to < 288). The seropositive rates and titers were comparable between anti-RSV-A NAbs and anti-RSV-B NAbs in the AB blood type group. Interestingly, only when the NAb titer of the serum to RSV-A was not less than 288, was it not less than 18 to RSV-B, and vice versa. These results would be helpful for a better understanding of the human serum NAb responses to RSV-A and RSV-B.

Elderly patients with comorbid hypertension who prefer primary care have a lower rate of polypharmacy: A cross-sectional study in Shanghai, China.

In 2017, the World Health Organization highlighted polypharmacy as one of the key focus areas of the Global Patient Safety Challenge on Medication Safety. According to the experience of developed countries, the provision of primary pharmaceutical care plays a very important role in the intervention of polypharmacy in the elderly. It is necessary to assess the associations between elderly polypharmacy status and primary care in developing countries. The findings of this paper provide the prevalence of polypharmacy in patients with comorbid hypertension, and the factors associated with it. A total of 19,332 elderly patients with hypertension were completed, among which the mean (SD) number of diseases was 4.83 (1.99), the mean (SD) daily maximum number of drugs was 5.13 (2.89), and the rate of polypharmacy was 50.5%. Age, living areas, total number of visits, preference for medical institutions and the number of diseases were associated with polypharmacy. Among them, advanced age, greater number of visits and diseases are the risk factors of polypharmacy for elderly patients with comorbid hypertension. The rate of polypharmacy in patients who intend to seek treatment in community healthcare centers is low. A total of 9,603 pharmaceutical workers worked in Shanghai public hospitals in 2020, among them 52.0% worked in the central city area, and more than 70% worked in secondary and tertiary hospitals. There was a large mismatch between patients' medical preference and the number of pharmaceutical personnel. As a consequence, it is necessary to strengthen the development of community pharmaceutical care in primary medical institutions for elderly polypharmacy management.

Metagenomic Analysis Reveals A Possible Association Between Respiratory Infection and Periodontitis.

Periodontitis is an inflammatory disease that is characterized by progressive destruction of the periodontium and causes tooth loss in adults. Periodontitis is known to be associated with dysbiosis of the oral microflora, which is often linked to various diseases. However, the complexity of plaque microbial communities of periodontitis, antibiotic resistance, and enhanced virulence make this disease difficult to treat. In this study, using metagenomic shotgun sequencing, we investigated the etiology, antibiotic resistance genes (ARGs), and virulence genes (VirGs) of periodontitis. We revealed a significant shift in the composition of oral microbiota as well as several functional pathways that were represented significantly more abundantly in periodontitis patients than in controls. In addition, we observed several positively selected ARGs and VirGs with the Ka/Ks ratio > 1 by analyzing our data and a previous periodontitis dataset, indicating that ARGs and VirGs in oral microbiota may be subjected to positive selection. Moreover, 5 of 12 positively selected ARGs and VirGs in periodontitis patients were found in the genomes of respiratory tract pathogens. Of note, 91.8% of the background VirGs with at least one non-synonymous single-nucleotide polymorphism for natural selection were also from respiratory tract pathogens. These observations suggest a potential association between periodontitis and respiratory infection at the gene level. Our study enriches the knowledge of pathogens and functional pathways as well as the positive selection of antibiotic resistance and pathogen virulence in periodontitis patients, and provides evidence at the gene level for an association between periodontitis and respiratory infection.

Biological role of heparan sulfate in osteogenesis: A review.

Heparan sulfate (HS) is extensively expressed in cells, for example, cell membrane and extracellular matrix of most mammalian cells and tissues, playing a key role in the growth and development of life by maintaining homeostasis and implicating in the etiology and diseases. Recent studies have revealed that HS is involved in osteogenesis via coordinating multiple signaling pathways. The potential effect of HS on osteogenesis is a complicated and delicate biological process, which involves the participation of osteocytes, chondrocytes, osteoblasts, osteoclasts and a variety of cytokines. In this review, we summarized the structural and functional characteristics of HS and highlighted the molecular mechanism of HS in bone metabolism to provide novel research perspectives for the further medical research.

Low Innate Immunity and Lagged Adaptive Immune Response in the Re-Tested Viral RNA Positivity of a COVID-19 Patient.

Recent studies have highlighted observations regarding re-tested positivity (RP) of SARS-CoV-2 RNA in discharged COVID-19 patients, however, the immune mechanisms underlying SARS-CoV-2 RNA RP in immunocompetent patients remain elusive. Herein, we describe the case of an immunocompetent COVID-19 patient with moderate symptoms who was twice re-tested as positive for SARS-CoV-2 RNA, and the period between first and third viral RNA positivity was 95 days, longer than previously reported (18-25 days). The chest computed tomography findings, plasma anti-SARS-CoV-2 antibody, neutralizing antibodies (NAbs) titer, and whole blood transcriptic characteristics in the viral RNA RP patient and other COVID-19 patients were analyzed. During the SARS-CoV-2 RNA RP period, new lung lesions were observed. The COVID-19 patient with viral RNA RP had delayed seroconversion of anti-spike/receptor-binding domain (RBD) IgA antibody and NAbs and were accompanied with disappearance of the lung lesions. Further experimental data validated that NAbs titer was significantly associated with anti-RBD IgA and IgG, and anti-spike IgG. The RP patient had lower interferon-, T cells- and B cell-related genes expression than non-RP patients with mild-to-moderate symptoms, and displayed lower cytokines and chemokines gene expression than severe patients. Interestingly, the RP patient had low expression of antigen presentation-related genes and low B cell counts which might have contributed to the delayed anti-RBD specific antibody and low CD8+ cell response. Collectively, delayed antigen presentation-related gene expression was found related to delayed adaptive immune response and contributed to the SARS-CoV-2 RNA RP in this described immunocompetent patient.

PRRT2 variants and effectiveness of various antiepileptic drugs in self-limited familial infantile epilepsy.

PURPOSE: Self-limited familial infantile epilepsy (SFIE) is largely associated with variants in proline-rich transmembrane protein 2 (PRRT2). However, the detailed phenotype-genotype correlations are unclear, along with the efficacy of various antiepileptic drugs in the treatment of this epilepsy syndrome. In this study, we analysed the PRRT2 variants associated with SFIE in Chinese patients, and the efficacy of different antiepileptic drugs prescribed during follow-up. METHODS: We retrospectively included 20 patients diagnosed with SFIE and reviewed their clinical characteristics, genetic variants, and treatment responses. RESULTS: Eighteen of the 20 (90%) patients harboured the common heterozygous variant of PRRT2 c.649dupC p.(Arg217fs). One patient had two heterozygous variants of PRRT2, c.640G>C p.(Ala214Pro) and c.955G>T p.(Val319Leu), and the other patient harboured a novel c.606delA (p.Pro203Hisfs) variant. Nine patients who had first-line treatment of oxcarbazepine (OXC) became seizure-free. However, initial treatment with levetiracetam (LEV) or sodium valproate (VPA) in eight and three patients, respectively, was not effective even after increasing the dosage, and seizure-free status was only achieved after changing the treatment to OXC. The treatment responses suggested a significant difference (P < 0.001) between OXC and other anti-epileptic drugs. CONCLUSION: OXC as a sodium channel blocker may have a better effect than LEV and VPA in the treatment of PRRT2-associated SFIE. PRRT2 variants may be used as a biomarker to help select antiepileptic drugs for SFIE.