The lectin Siglec-G inhibits dendritic cell cross-presentation by impairing MHC class I-peptide complex formation.

CD8α(+) dendritic cells (DCs) are specialized at cross-presenting extracellular antigens on major histocompatibility complex (MHC) class I molecules to initiate cytotoxic T lymphocyte (CTL) responses; however, details of the mechanisms that regulate cross-presentation remain unknown. We found lower expression of the lectin family member Siglec-G in CD8α(+) DCs, and Siglec-G deficient (Siglecg(-/-)) mice generated more antigen-specific CTLs to inhibit intracellular bacterial infection and tumor growth. MHC class I-peptide complexes were more abundant on Siglecg(-/-) CD8α(+) DCs than on Siglecg(+/+) CD8α(+) DCs. Mechanistically, phagosome-expressed Siglec-G recruited the phosphatase SHP-1, which dephosphorylated the NADPH oxidase component p47(phox) and inhibited the activation of NOX2 on phagosomes. This resulted in excessive hydrolysis of exogenous antigens, which led to diminished formation of MHC class I-peptide complexes for cross-presentation. Therefore, Siglec-G inhibited DC cross-presentation by impairing such complex formation, and our results add insight into the regulation of cross-presentation in adaptive immunity.

Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity.

The DNA methyltransferase Dnmt3a has high expression in terminally differentiated macrophages; however, its role in innate immunity remains unknown. Here we report that deficiency in Dnmt3a selectively impaired the production of type I interferons triggered by pattern-recognition receptors (PRRs), but not that of the proinflammatory cytokines TNF and IL-6. Dnmt3a-deficient mice exhibited enhanced susceptibility to viral challenge. Dnmt3a did not directly regulate the transcription of genes encoding type I interferons; instead, it increased the production of type I interferons through an epigenetic mechanism by maintaining high expression of the histone deacetylase HDAC9. In turn, HDAC9 directly maintained the deacetylation status of the key PRR signaling molecule TBK1 and enhanced its kinase activity. Our data add mechanistic insight into the crosstalk between epigenetic modifications and post-translational modifications in the regulation of PRR signaling and activation of antiviral innate immune responses.

The CsAP2-09-CsWRKY25-CsRBOH2 cascade confers resistance against citrus bacterial canker by regulating ROS homeostasis.

Citrus bacterial canker (CBC) is a serious bacterial disease caused by Xanthomonas citri subsp. citri (Xcc) that adversely impacts the global citrus industry. In a previous study, we demonstrated that overexpression of an Xcc-inducible apetala 2/ethylene response factor encoded by Citrus sinensis, CsAP2-09, enhances CBC resistance. The mechanism responsible for this effect, however, is not known. In the present study, we showed that CsAP2-09 targeted the promoter of the Xcc-inducible WRKY transcription factor coding gene CsWRKY25 directly, activating its transcription. CsWRKY25 was found to localize to the nucleus and to activate transcriptional activity. Plants overexpressing CsWRKY25 were more resistant to CBC and showed higher expression of the respiratory burst oxidase homolog (RBOH) CsRBOH2, in addition to exhibiting increased RBOH activity. Transient overexpression assays in citrus confirmed that CsWRKY25 and CsRBOH2 participated in the generation of reactive oxygen species (ROS) bursts, which were able to restore the ROS degradation caused by CsAP2-09 knockdown. Moreover, CsWRKY25 was found to bind directly to W-box elements within the CsRBOH2 promoter. Notably, CsRBOH2 knockdown had been reported previously to reduce the CBC resistance, while demonstrated in this study, CsRBOH2 transient overexpression can enhance the CBC resistance. Overall, our results outline a pathway through which CsAP2-09-CsWRKY25 transcriptionally reprograms CsRBOH2-mediated ROS homeostasis in a manner conducive to CBC resistance. These data offer new insight into the mechanisms and regulatory pathways through which CsAP2-09 regulates CBC resistance, highlighting its potential utility as a target for the breeding of CBC-resistant citrus varieties.

The wall-associated receptor-like kinase CsWAKL01, positively regulated by the transcription factor CsWRKY53, confers resistance to citrus bacterial canker via regulation of phytohormone signaling.

Citrus bacterial canker (CBC) is a disease that poses a major threat to global citrus production and is caused by infection with Xanthomonas citri subsp. citri (Xcc). Wall-associated receptor-like kinase (WAKL) proteins play an important role in shaping plant resistance to various bacterial and fungal pathogens. In a prior report, CsWAKL01 was identified as a candidate Xcc-inducible gene found to be upregulated in CBC-resistant citrus plants. However, the functional role of CsWAKL01 and the mechanisms whereby it may influence resistance to CBC have yet to be clarified. Here, CsWAKL01 was found to localize to the plasma membrane, and the overexpression of the corresponding gene in transgenic sweet oranges resulted in the pronounced enhancement of CBC resistance, whereas its knockdown had the opposite effect. Mechanistically, the ability of CsWAKL01 was linked to its ability to reprogram jasmonic acid, salicylic acid, and abscisic acid signaling activity. CsWRKY53 was further identified as a transcription factor capable of directly binding the CsWAKL01 promoter and inducing its transcriptional upregulation. CsWRKY53 silencing conferred greater CBC susceptibility to infected plants. Overall, these data support a model wherein CsWRKY53 functions as a positive regulator of CsWAKL01 to enhance resistance to CBC via the reprogramming of phytohormone signaling. Together these results offer new insight into the mechanisms whereby WAKLs shape phytopathogen resistance while underscoring the potential value of targeting the CsWRKY53-CsWAKL01 axis when seeking to breed CBC-resistant citrus plant varieties.

EH domain-containing protein 2 (EHD2): Overview, biological function, and therapeutic potential.

EH domain-containing protein 2 (EHD2) is a member of the EHD protein family and is mainly located in the plasma membrane, but can also be found in the cytoplasm and endosomes. EHD2 is also a nuclear-cytoplasmic shuttle protein. After entering the cell nuclear, EHD2 acts as a corepressor of transcription to inhibit gene transcription. EHD2 regulates a series of biological processes. As a key regulator of endocytic transport, EHD2 is involved in the formation and maintenance of endosomal tubules and vesicles, which are critical for the intracellular transport of proteins and other substances. The N-terminal of EHD2 is attached to the cell membrane, while its C-terminal binds to the actin-binding protein. After binding, EHD2 connects with the actin cytoskeleton, forming the curvature of the membrane and promoting cell endocytosis. EHD2 is also associated with membrane protein trafficking and receptor signaling, as well as in glucose metabolism and lipid metabolism. In this review, we highlight the recent advances in the function of EHD2 in various cellular processes and its potential implications in human diseases such as cancer and metabolic disease. We also discussed the prospects for the future of EHD2. EHD2 has a broad prospect as a therapeutic target for a variety of diseases. Further research is needed to explore its mechanism, which could pave the way for the development of targeted treatments.

Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.

Which roads lead to access? A global landscape of six COVID-19 vaccine innovation models.

BACKGROUND: Unequal and inequitable access to Covid-19 vaccines in low- and middle-income countries (L&MICs) was a major political, ethical and public health failure in the pandemic. However, vaccine developers' practices were not monolithic, but rather, took diverse approaches to supplying different countries, with important implications for global access. RESULTS: Using data on R&D investments, regulatory approvals, manufacturing and purchase agreements, and vaccine deliveries, we identified six distinct innovation models that apply across the 14 COVID-19 vaccines with more international presence from 2020-2022. "Western Early Arrivers" Pfizer/BioNTech and Moderna supplied the largest volumes quickly and prioritized high-income countries (HICs) from registration to vaccine delivery. "Western Latecomers" Janssen and Novavax supplied intermediate volumes later, also prioritizing HICs but with a greater proportion to L&MICs. "Major Chinese Developers" Sinopharm and Sinovac supplied intermediate volumes early, primarily to middle-income countries (MICs). "Russian Developer" Gamaleya completed development early but ultimately supplied small volumes, primarily to middle-income countries (MICs). "Cosmopolitan Developer" Oxford/AstraZeneca supplied large volumes early to HICs and MICs at the lowest prices. Finally, "Small MIC Developers" CanSino, Bharat Biotech, Medigen, Finlay Institute and the Center for Genetic Engineering and Biotechnology (CGEB), exported relatively small volumes to a few MICs. Low-income countries (LICs) were not targeted by any developer, and received far fewer doses, later, than any other income group. Almost all developers received public funding and other forms of support, but we found little evidence that such support was leveraged to expand global access. CONCLUSIONS: Each of the six innovation models has different implications for which countries get access to which vaccines, how quickly, and at which prices. Each offers different strengths and weaknesses for achieving equitable access. Our findings also suggest that Western firms had the greatest capacity to develop and deliver vaccines quickly during the pandemic, but such capacity is rapidly becoming more globally distributed with MICs playing a significant role, especially in supplying other MICs. Given the critical role of public support in enabling pandemic vaccine development and supply, governments have both the capacity and responsibility to craft international rules that will make responses to future pandemics more equitable and effective.

Co2Mo6S8 Catalyzes Nearly Exclusive Electrochemical Nitrate Conversion to Ammonia with Enzyme-like Activity.

Electrocatalytic nitrate to ammonia conversion is a key reaction for energy and environmental sustainability. This reaction involves complex multi electron and proton transfer steps, and is impeded by the lack of catalyst for promoting both reactivity and ammonia selectivity. Here, we demonstrate active motifs based on the Chevrel phase Co2Mo6S8 exhibit an enzyme-like high turnover frequency of ∼95.1 s-1 for nitrate electroreduction to ammonia. We reveal strong synergy of multiple binding sites on this catalyst, such that the ligand effect of Co steers Had* toward hydrogenation other than hydrogen evolution, the ensemble effect of Co, and the spatial confinement effect that promote the full hydrogenation of NOx to ammonia without N-N coupling. The catalyst exhibits almost exclusive ammonia conversion with a Faradaic efficiency of 97.1% and ammonia yielding rate of 115.5 mmol·gcat-1·h-1 in neutral electrolytes. The high activity was also confirmed in electrolytes with dilute nitrate and high chloride concentrations.

Regulatory T cells: A suppressor arm in post-stroke immune homeostasis.

The activation of the immune system and the onset of pro- and anti-inflammatory responses play crucial roles in the pathophysiological processes of ischaemic stroke (IS). CD4+ regulatory T (Treg) cells is the main immunosuppressive cell population that is studied in the context of peripheral tolerance, autoimmunity, and the development of chronic inflammatory diseases. In recent years, more studies have focused on immune modulation after IS, and Treg cells have been demonstrated to be essential in the remission of inflammation, nerve regeneration, and behavioural recovery. However, the exact effects of Treg cells in the context of IS remain controversial, with some studies suggesting a negative correlation with stroke outcomes. In this review, we aim to provide a comprehensive overview of the current understanding of Treg cell involvement in post-stroke homeostasis. We summarized the literature focusing on the temporal changes in Treg cell populations after IS, the mechanisms of Treg cell-mediated immunomodulation in the brain, and the potential of Treg cell-based therapies for treatment. The purposes of the current article are to address the importance of Treg cells and inspire more studies to help physicians, as well as scientists, understand the whole map of immune responses during IS.

The engineered CRISPR-Mb2Cas12a variant enables sensitive and fast nucleic acid-based pathogens diagnostics in the field.

Existing CRISPR/Cas12a-based diagnostic platforms offer accurate and vigorous monitoring of nucleic acid targets, but have the potential to be further optimized for more efficient detection. Here, we profiled 16 Cas12a orthologs, focusing on their trans-cleavage activity and their potential as diagnostic enzymes. We observed the Mb2Cas12a has more robust trans-cleavage activity than other orthologs, especially at lower temperatures. An engineered Mb2Cas12a-RRVRR variant presented robust trans-cleavage activity and looser PAM constraints. Moreover, we found the existing one-pot assay, which simultaneously performed Recombinase Polymerase Amplification (RPA) and Cas12a reaction in one system, resulted in the loss of single-base discrimination during diagnosis. Therefore, we designed a reaction vessel that physically separated the RPA and Cas12a steps while maintaining a closed system. This isolated but closed system made diagnostics more sensitive and specific and effectively prevented contamination. This shelved Mb2Cas12a-RRVRR variant-mediated assay detected various targets in less than 15 min and exhibited equal or greater sensitivity than qPCR when detecting bacterial pathogens, plant RNA viruses and genetically modified crops. Overall, our findings further improved the efficiency of the current CRISPR-based diagnostic system and undoubtedly have great potential for highly sensitive and specific detection of multiple sample types.

Effect of COVID-19 vaccination on semen parameters: A systematic review and meta-analysis.

The aim of this study was to investigate the effect of coronavirus disease 2019 (COVID-19) vaccination on semen parameters through systematic review and meta-analysis. PubMed, EMBASE, Web of Science, and Cochrane Library were comprehensively searched by June 2022. Studies were considered eligible if they compared semen parameters before and after COVID-19 vaccination or between vaccinated and unvaccinated men, with no restrictions on vaccine types or doses. The effect size was calculated as mean difference (MD) with 95% confidence interval (CI) using a random-effects model. Subgroup and sensitivity analyses were conducted to assess the sources of heterogeneity measured by the I2 statistic, with publication bias evaluated by Egger's test. Twelve cohort studies involving 914 participants fulfilled the inclusion criteria. In a comparison of vaccinated versus unvaccinated group, the pooled data revealed no significant differences in semen volume (MD = 0.18 ml, 95% CI -0.02 to 0.38), sperm concentration (MD = 1.16 million/ml, 95% CI -1.34 to 3.66), total sperm motility (MD = -0.14%, 95% CI -2.84 to 2.56), progressive sperm motility (MD = -1.06%, 95% CI -2.88 to 0.77), total sperm count (MD = 5.92 million, 95% CI -10.22 to 22.05), total motile sperm count (MD = 2.18 million, 95% CI -1.28 to 5.63), total progressively motile sperm count (MD = -3.87 million, 95% CI -13.16 to 5.43), and sperm morphology (MD = 0.07%, 95% CI -0.84 to 0.97). The results also remained similar across messenger ribonucleic acid, viral-vector, and inactivated COVID-19 vaccines. Sensitivity analysis identified two individual studies that contributed to heterogeneity, while the effect size was not materially altered. No obvious publication bias was detected among included studies. Our finding suggested that COVID-19 vaccination had no detrimental impact on semen quality, which could be potentially helpful to reduce male vaccine hesitancy and increase vaccination coverage.

Mining electronic health records using artificial intelligence: Bibliometric and content analyses for current research status and product conversion.

BACKGROUND: The use of Electronic Health Records is the most important milestone in the digitization and intelligence of the entire medical industry. AI can effectively mine the immense medical information contained in EHRs, potentially assist doctors in reducing many medical errors. OBJECTIVE: This article aims to summarize the research status and trends in using AI to mine medical information from EHRs for the past thirteen years and investigate its information application. METHODS: A systematic search was carried out in 5 databases, including Web of Science Core Collection and PubMed, to identify research using AI to mine medical information from EHRs for the past thirteen years. Furthermore, bibliometric and content analysis were used to explore the research hotspots and trends, and systematically analyze the conversion rate of research resources in this field. RESULTS: A total of 631 articles were included and analyzed. The number of published articles has increased rapidly after 2017, with an average annual growth rate of 55.73%. The US (41.68%) and China (19.65%) publish the most articles, but there is a lack of international cooperation. The extraction of disease lesions is a hot topic at present, and the research topic is gradually shifting from disease risk grading to disease risk prediction. Classification (66%), and regress (15%) are the main implemented AI tasks. For AI algorithms, deep learning (31.70%), decision tree algorithms family (26.47%), and regression algorithms family (17.43%) are used most frequently. The funding rate for publications is 69.26%, and the input-output conversion rate is 21.05%. CONCLUSIONS: Over the past decade, the use of AI to mine medical information from EHRs has been developing rapidly. However, it is necessary to strengthen international cooperation, improve EHRs data availability, focus on interpretable AI algorithms, and improve the resource conversion rate in future research.

Case Analysis of Water Gushing in a Deep Foundation Pit Caused by Local Defects.

Water gushing is a common engineering geological disaster in the process of foundation pit construction. Its successful judgment directly affects the safety of engineering construction. Taking the case of water gushing at the bottom of the foundation pitas as a research object, the mechanism and treatment of water gushing in foundation pits, the stability against water gushing, and its influencing factors are analyzed with a field investigation, field testing, and theoretical calculation. The calculation formula for the safety factor and critical thickness of the foundation pit against surges, considering the influence of multiple factors, is deduced. The influence of the height of the confined water level, the thickness of the water-resisting layer, the shear strength of the soil mass, the reinforcement depth of the soil mass in the pit, and the diameter of the bearing pile in the pit on the safety factor of the foundation pit surge are expounded. In addition, measures such as the reinforcement of the soil mass in the passive area in the pit, the increase in the thickness of the water-resisting layer, and the reduction in the confined water level are proposed to improve the anti-surge stability of the foundation pit. A new monitoring method is proposed for characterizing uplift deformation at the bottom of the pit without affecting normal construction. The research results show that: (1) the minimum safety factor against surges, considering multiple factors, is 1.455, and the critical thickness is 5.87 m, which is in line with specifications. (2) Measures such as reinforcing the soil in the passive zone of the pit, increasing the thickness of the water-insulating layer, and lowering the bearing pressure level are used to improve the stability of the pit against surges. (3) The pit, obtained by the pit bottom counter-pressure, pumping water out of the pit, and the timely construction of the pit bottom bedding to block the program, exhibits a measured maximum bottom plate pressure of 115.189 kPa, and the deformation corresponding to the method proposed in this paper is 1.406 mm, which is better disposed in the field. The research results provide a reference basis for the judgment of anti-surge stability of foundation pits and similar engineering applications.

Progress in research on the safety of silicone rubber products in food processing.

Silicone rubber (SR) is widely used in the food processing industry due to its excellent physical and chemical properties. However, due to the differences in SR product production formulas and processes, the quality of commercially available SR products varies greatly, with chemical and biological hazard potentials. Residual chemicals in SR, such as siloxane oligomers and 2,4-dichlorobenzoic acid, are non-intentionally added substances, which may migrate into food during processing so the safe use of SR must be guaranteed. Simultaneously, SR in contact with food is susceptible to pathogenic bacteria growing and biofilm formation, like Cronobacter sakazakii, Staphylococcus aureus, Salmonella enteritidis, and Listeria monocytogenes, posing a food safety risk. Under severe usage scenarios such as high-temperature, high-pressure, microwave, and freezing environments with long-term use, SR products are more prone to aging, and their degradation products may pose potential food safety hazards. Based on the goal of ensuring food quality and safety to the greatest extent possible, this review suggests that enterprises need to prepare high-quality food-contact SR products by optimizing the manufacturing formula and production process, and developing products with antibacterial and antiaging properties. The government departments should establish quality standards for food-contact SR products and conduct effective supervision. Besides, the reusable SR products should be cleaned by consumers immediately after use, and the deteriorated products should be replaced as soon as possible.

Single-Site Carbon-Supported Metal-Oxo Complexes in Heterogeneous Catalysis: Structure, Reactivity, and Mechanism.

When early transition metal complexes are molecularly grafted onto catalyst supports, well-defined, surface-bound species are created, which are highly active and selective single-site heterogeneous catalysts (SSHCs) for diverse chemical transformations. In this minireview, we analyze and summarize a less conventional type of SSHC in which molybdenum dioxo species are grafted onto unusual carbon-unsaturated scaffolds, such as activated carbon, reduced graphene oxide, and carbon nanohorns. The choice of earth-abundant, low-toxicity, versatile metal constituents, and various carbon supports illustrates "catalyst by design" principles and yields insights into new catalytic systems of both academic and technological interest. Here, we summarize experimental and computational investigations of the bonding, electronic structure, reaction scope, and mechanistic pathways of these unusual catalysts.

The role of diet in renal cell carcinoma incidence: an umbrella review of meta-analyses of observational studies.

BACKGROUND: Evidence associating diet with the incidence of renal cell carcinoma (RCC) is inconclusive. We aimed to summarize evidence associating dietary factors with RCC incidence and assess the strength and validity of this evidence. METHODS: We conducted an umbrella review of systematic reviews or meta-analyses (SRoMAs) that assessed the association between diet and RCC incidence. Through April 2021, PubMed, Web of Science, Embase, The Cochrane Library, Scopus, and WCRF were searched. Two independent reviewers selected studies, extracted data, and appraised the quality of SRoMAs. According to credibility assessment criteria, evidence can be divided into five categories: convincing (class I), highly suggestive (class II), suggestive (class III), weak (class IV), and nonsignificant (class V). RESULTS: Twenty-nine meta-analyses were obtained after screening. After excluding 7 overlapping meta-analyses, 22 meta-analyses including 502 individual studies and 64 summary hazard ratios for RCC incidence were included: dietary patterns or dietary quality indices (n = 6), foods (n = 13), beverages (n = 4), alcohol (n = 7), macronutrients (n =15), and micronutrients (n =19). No meta-analyses had high methodological quality. Five meta-analyses exhibited small study effects; one meta-analysis showed evidence of excess significance bias. No dietary factors showed convincing or highly suggestive evidence of association with RCC in the overall analysis. Two protective factors had suggestive evidence (vegetables (0.74, 95% confidence interval 0.63 to 0.86) and vitamin C (0.77, 0.66 to 0.90)) in overall analysis. One protective factor had convincing evidence (moderate drinking (0.77, 0.70 to 0.84)) in Europe and North America and one protective factor had highly suggestive evidence (cruciferous vegetables (0.78, 0.70 to 0.86)) in North America. CONCLUSIONS: Although many meta-analyses have assessed associations between dietary factors and RCC, no high-quality evidence exists (classes I and II) in the overall analysis. Increased intake of vegetables and vitamin C is negatively associated with RCC risk. Moderate drinking might be beneficial for Europeans and North Americans, and cruciferous vegetables might be beneficial to North Americans, but the results should be interpreted with caution. More researches are needed in the future. TRIAL REGISTRATION: PROSPERO CRD42021246619.

Dose-response relationship between qAnti-HBc and liver inflammation in chronic hepatitis B with normal or mildly elevated alanine transaminase based on liver biopsy.

The proportion of chronic hepatitis B (CHB) patients with normal or mildly elevated alanine transaminase (NMALT) levels who have moderate to severe inflammation was not rare. However, we lacked appropriate biomarkers to evaluate liver inflammation in these populations. We aimed to explore the relationship between quantitative hepatitis B core antibody (qAnti-HBc) and hepatic histological inflammation. This multicenter cohort study enrolled participants from 34 Chinese hospitals including 1376 treatment-naive CHB patients with liver biopsy (934 with NMALT entered treatment-naive cohort; 423 with secondary liver biopsy entered treatment cohort). Using unadjusted and multivariate-adjusted generalized linear models, generalized additive models with smooth curve fitting, we evaluated the associations between qAnti-HBc and liver inflammation in these patients. In the treatment-naive patients, qAnti-HBc was positively associated with liver inflammation (histology activity index [HAI] evaluated by Ishak scoring system; fully adjusted model: ß = 0.48, 95% confidence interval [CI] [0.30-0.66], p < 0.001). For per-SD increase in qAnti-HBc, the risk of moderate to severe inflammation (HAI ≥ 5) increased by 56% (odds ratio [OR] = 1.56, 95% CI [1.28-1.91], p < 0.001). The curve fitting indicated a significant "threshold effect" (inflection point was 4.5 log10  IU/ml, p < 0.001). Subgroup analyses and interactions were not significant (all p > 0.05). In the treatment patients, there was no significant correlation between qAnti-HBc and liver inflammation, whether based on unadjusted, minimally adjusted, or fully adjusted models (all p > 0.100). Paired analyses showed a significant correlation between decreasing in qAnti-HBc and alleviation of liver inflammation. qAnti-HBc was positively correlated with liver inflammation in treatment-naive CHB patients with NMALT. The cutoff value of qAnti-HBc for the diagnosis of moderate to severe inflammation was 4.5 log10  IU/ml. Decreasing in qAnti-HBc was positively correlated with liver inflammation relieving.

5' UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy.

Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A recent report suggested a non-coding trinucleotide repeat expansion in LRP12 to be associated with the disease. Here we report a genetic study in a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). In a large family with 12 affected individuals, combined haplotype and linkage analysis revealed a maximum two-point logarithm of the odds (LOD) score of 3.3 in chromosomal region chr19p13.11-p13.2 and narrowed the candidate region to an interval of 4.5 Mb. Using a comprehensive strategy combining whole-exome sequencing, long-read sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal CGG repeat expansion in the 5' UTR of the GIPC1 gene that co-segregated with disease. Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases), while the repeat expansion in LRP12 was only identified in one sporadic case (3.7%) in our cohort. The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident. These results further support that non-coding CGG repeat expansion plays an essential role in the pathogenesis of oculopharyngodistal myopathy.

Synthesis and Structure-Activity Characterization of a Single-Site MoO2 Catalytic Center Anchored on Reduced Graphene Oxide.

Molecularly derived single-site heterogeneous catalysts can bridge the understanding and performance gaps between conventional homogeneous and heterogeneous catalysis, guiding the rational design of next-generation catalysts. While impressive advances have been made with well-defined oxide supports, the structural complexity of other supports and the nature of the grafted surface species present an intriguing challenge. In this study, single-site Mo(═O)2 species grafted onto reduced graphene oxide (rGO/MoO2) are characterized by XPS, DRIFTS, powder XRD, N2 physisorption, NH3-TPD, aqueous contact angle, active site poisoning assay, Mo EXAFS, model compound single-crystal XRD, DFT, and catalytic performance. NH3-TPD reveals that the anchored MoO2 moiety is not strongly acidic, while Mo 3d5/2 XPS assigns the oxidation state as Mo(VI), and XRD shows little rGO periodicity change on MoO2 grafting. Contact angle analysis shows that MoO2 grafting consumes rGO surface polar groups, yielding a more hydrophobic surface. The rGO/MoO2 DRIFTS assigns features at 959 and 927 cm-1 to the symmetric and antisymmetric Mo═O stretching modes, respectively, of an isolated cis-(O═Mo═O) moiety, in agreement with DFT computation. Moreover, the Mo EXAFS rGO/MoO2 structural data are consistent with isolated (C-O)2-Mo(═O)2 species having two Mo═O bonds and two Mo-O bonds at distances of 1.69(3) and 1.90(3) Å, respectively. rGO/MoO2 is also more active than the previously reported AC/MoO2 catalyst, with reductive carbonyl coupling TOFs approaching 1.81 × 103 h-1. rGO/MoO2 is environmentally robust and multiply recyclable with 69 ± 2% of the Mo sites catalytically significant. Overall, rGO/MoO2 is a structurally well-defined and versatile single-site Mo(VI) dioxo heterogeneous catalytic system.