m7GHub V2.0: an updated database for decoding the N7-methylguanosine (m7G) epitranscriptome.

With recent progress in mapping N7-methylguanosine (m7G) RNA methylation sites, tens of thousands of experimentally validated m7G sites have been discovered in various species, shedding light on the significant role of m7G modification in regulating numerous biological processes including disease pathogenesis. An integrated resource that enables the sharing, annotation and customized analysis of m7G data will greatly facilitate m7G studies under various physiological contexts. We previously developed the m7GHub database to host mRNA m7G sites identified in the human transcriptome. Here, we present m7GHub v.2.0, an updated resource for a comprehensive collection of m7G modifications in various types of RNA across multiple species: an m7GDB database containing 430 898 putative m7G sites identified in 23 species, collected from both widely applied next-generation sequencing (NGS) and the emerging Oxford Nanopore direct RNA sequencing (ONT) techniques; an m7GDiseaseDB hosting 156 206 m7G-associated variants (involving addition or removal of an m7G site), including 3238 disease-relevant m7G-SNPs that may function through epitranscriptome disturbance; and two enhanced analysis modules to perform interactive analyses on the collections of m7G sites (m7GFinder) and functional variants (m7GSNPer). We expect that m7Ghub v.2.0 should serve as a valuable centralized resource for studying m7G modification. It is freely accessible at: www.rnamd.org/m7GHub2.

m6A-TCPred: a web server to predict tissue-conserved human m6A sites using machine learning approach.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotic cells that plays a crucial role in regulating various biological processes, and dysregulation of m6A status is involved in multiple human diseases including cancer contexts. A number of prediction frameworks have been proposed for high-accuracy identification of putative m6A sites, however, none have targeted for direct prediction of tissue-conserved m6A modified residues from non-conserved ones at base-resolution level. RESULTS: We report here m6A-TCPred, a computational tool for predicting tissue-conserved m6A residues using m6A profiling data from 23 human tissues. By taking advantage of the traditional sequence-based characteristics and additional genome-derived information, m6A-TCPred successfully captured distinct patterns between potentially tissue-conserved m6A modifications and non-conserved ones, with an average AUROC of 0.871 and 0.879 tested on cross-validation and independent datasets, respectively. CONCLUSION: Our results have been integrated into an online platform: a database holding 268,115 high confidence m6A sites with their conserved information across 23 human tissues; and a web server to predict the conserved status of user-provided m6A collections. The web interface of m6A-TCPred is freely accessible at: www.rnamd.org/m6ATCPred .

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes.

INTRODUCTION: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD). METHODS: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC. RESULTS: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference. DISCUSSION: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

A single center retrospective study: Comparison between centrifugal separation plasma exchange with ACD-A and membrane separation plasma exchange with heparin on acute liver failure and acute on chronic liver failure.

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.

Underexplored viral auxiliary metabolic genes in soil: Diversity and eco-evolutionary significance.

Bacterial viruses are the most abundant biological entities in soil ecosystems. Owing to the advent of metagenomics and viromics approaches, an ever-increasing diversity of virus-encoded auxiliary metabolic genes (AMGs) have been identified in soils, including those involved in the transformation of carbon, phosphorus, and sulfur, degradation of organic pollutants, and antibiotic resistance, among other processes. These viral AMGs can alter soil biogeochemical processes and metabolic activities by interfering with bacterial host metabolism. It is recognized that viral AMGs compensate for host bacterial metabolism outputs by encoding accessory functional genes and are favourable for the hosts' adaptation to stressed soil environments. The eco-evolutionary mechanisms behind this fascinating diversity of viral AMGs in soil microbiomes have begun to emerge, such as horizontal gene transfer, lytic-lysogenic conversion, and single-nucleotide polymorphisms. In this mini-review, we summarize recent advances in the diversity and function of virus-encoded AMGs in the soil environment, especially focusing on the evolutionary significance of AMGs involved in virus-host interactions. This mini-review also sheds light on the existing gaps and future perspectives that could have major significance for viral AMGs research in soils.

Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies.

Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.

Adenoid cystic carcinoma in children and young adults: A clinicopathological study of 12 cases.

OBJECTIVE: To investigate the clinicopathological characteristics, immunoprofile, and molecular alterations of adenoid cystic carcinoma (ACC) in children and young adults. MATERIALS AND METHODS: Twelve cases of ACC were included. MYB, MYBL1, Ki-67, type IV Collagen, Laminin, and LAMB1 expression were detected by immunohistochemistry. MYB and MYBL1 rearrangements were detected by fluorescence in situ hybridization. RESULTS: Among 12 patients, four were female and eight were male. Seven cases (58.3%) located in major salivary glands and eight cases (66.7%) were classified as Grade I. Ten tumors (83.3%) had collagenous and hyalinized stroma. MYB was positive in 83.3% cases, and the average Ki-67 labeling index (LI) was 8.3%. LAMB1, type IV Collagen, and Laminin were positive in 91.7%, 66.7%, and 58.3% cases, respectively. Besides, three out of eight tumors had MYB rearrangement. Cases without MYB rearrangement were negative for MYBL1 expression and MYBL1 rearrangement. The average follow-up time was 91.8 months. Four patients had recurrent diseases. CONCLUSIONS: ACC in children and young adults was seen more frequently in males and major salivary glands. Most cases had ECM and hyaline stroma. Grade III tumors, higher Ki-67 LI, negative expression of type IV Collagen, and Laminin showed a tendency of higher recurrence rate.

Adolescence is a sensitive period for acrylamide-induced sex hormone disruption: Evidence from NHANES populations and experimental mice.

Acrylamide (AA) is widely contaminated in environment and diet. However, the association of AA and sex hormones has rarely been investigated, especially in adolescents, a period of particular susceptibility to sex hormone disruption. In this study, survey-weighted multivariate linear regression models were conducted to determine the association between AA Hb biomarkers [HbAA and glycidamide (HbGA)] and sex hormones [total testosterone (TT) and estradiol (E2)] in a total of 3268 subjects from National Health and Nutrition Examination Survey (NHANES) 2013-2016 waves. Additionally, adult and pubertal mice were treated with AA to assess the effect of AA on sex hormones and to explore the potential mechanisms. Among all the subjects, significant negative patterns for HbGA and sex hormones were identified only in youths (6-19 years old), with the lowest ß being - 0.53 (95% CI: -0.80 to -0.26) for TT in males and - 0.58 (95% CI: -0.93 to -0.23) for E2 in females. Stratified analysis further revealed significant negative associations between HbGA and sex hormones in adolescents, with the lowest ß being - 0.58 (95% CI: -1.02 to -0.14) for TT in males and - 0.54 (95% CI: -1.03 to -0.04) for E2 in females, while there were no significant differences between children or late adolescents. In mice, the levels of TT and E2 were dramatically reduced in AA-treated pubertal mice but not in adult mice. AA disturbed the expression of genes in the hypothalamic-pituitary-gonadal (HPG) axis, induced apoptosis of hypothalamus-produced gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus and reduced serum and hypothalamic GnRH levels in pubertal mice. Our study indicates AA could reduce TT and E2 levels by injuring GnRH neurons and disrupting the HPG axis in puberty, which manifested as severe endocrine disruption on adolescents. Our findings reinforce the idea that adolescence is a vulnerable stage in AA-induced sex hormone disruption.

Oral epithelial dysplasia and aphthous ulceration in a patient with ulcerative colitis: a case report.

BACKGROUND: Ulcerative colitis is a chronic inflammatory disease with apparent extraintestinal manifestations, including in the oral cavity. Oral epithelial dysplasia, an exclusive histopathological diagnosis that is used to predict malignant transformation, has never been reported with ulcerative colitis. Herein, we report a case with ulcerative colitis that was diagnosed via extraintestinal manifestations of oral epithelial dysplasia and aphthous ulceration. CASE PRESENTATION: A 52-year-old male suffering from ulcerative colitis came to our hospital complaining of pain on his tongue with a history of 1 week. Clinical examination revealed multiple painful oval ulcers on the ventral surfaces of the tongue. Histopathological examination indicated ulcerative lesion and mild dysplasia in the adjacent epithelium. Direct immunofluorescence demonstrated negative staining along the junction of the epithelium and lamina propria. Immunohistochemical staining with Ki-67, p16, p53 and podoplanin was used to rule out the reactive cellular atypia to inflammation and ulceration of the mucosa. A diagnosis of aphthous ulceration and oral epithelial dysplasia was made. The patient was treated with mouthwash (composed of lidocaine, gentamicin and dexamethasone) and triamcinolone acetonide oral ointment. Oral ulceration healed after one week of treatment. At the 12-month follow-up, minor scarring was observed on the right ventral surface of the tongue, and the patient felt no discomfort in the oral mucosa. CONCLUSION: Oral epithelial dysplasia might also occur in patients with ulcerative colitis despite the low incidence, which should broaden the understanding of oral manifestations of ulcerative colitis.

A large-cohort study of 2971 cases of epulis: focusing on risk factors associated with recurrence.

BACKGROUND: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence. MATERIALS AND METHODS: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information. RESULTS: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis. CONCLUSIONS: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis.

Plasma exchange versus intravenous immunoglobulin in AChR subtype myasthenic crisis: A prospective cohort study.

Myasthenic crisis (MC) is a life-threatening state with respiratory failure in patients with myasthenia gravis (MG). The fast-acting immunomodulatory therapies for treating MC included plasma exchange (PE) and intravenous immunoglobulin (IVIG). However, the efficacy and the impact on antibody changes remained unknown. We prospectively followed 40 anti-acetylcholine receptors (AChR) antibody-positive MC patients who received either PE (n = 12) or IVIG (n = 28) at crisis. PE was associated with a reduced ICU stay length (p = 0.018) and an early response by the average changes in MGFA-QMG (p = 0.003), MMT (p = 0.020), and ADL (p = 0.011) at one-week off-ventilation. However, the clinical efficacy was equally comparable in both groups after 1 month. Post-treatment hemoglobin drop was significant in both groups, while IVIG was associated with a significant reduction in anti-AChR antibody titers (p < 0.001). This analysis provides real-world evidence in supporting the use of PE as a fast-acting therapy for shortening the ICU stay in AChR-associated MC.

Study on the single-mode condition for x-cut LNOI rib waveguides based on leakage losses.

Lithium niobate-on-insulator (LNOI) has recently emerged as a promising material platform for high-density and advanced photonics integrated circuits (PICs). And single-mode waveguides (SMW) are the most basic building blocks for structuring various PICs. In this paper, single-mode conditions (SMCs) for shallowly etched LNOI rib waveguides in x-cut LNOI wafer are investigated with the finite element method (FEM) in consideration of the lateral leakage and the magic width for the first time, to our best knowledge. Our results indicate that due to the lateral leakage and the magic width these shallowly etched x-cut LNOI rib waveguides have unique and complex SMCs. Our method and results provide a guidance in designing low-loss LNOI SMW and high-performance PICs.

N6-methyladenosine-related lncRNAs identified as potential biomarkers for predicting the overall survival of Asian gastric cancer patients.

OBJECTIVE: Gastric cancer (GC) is one of the most prevalent malignant tumors in Asian countries. Studies have proposed that lncRNAs can be used as diagnostic and prognostic indicators of GC due to the high specificity of lncRNAs expression involvement in GC. Recently, N6-methyladenosine (m6A) has also emerged as an important modulator of the expression of lncRNAs in GC. This study aimed at establishing a novel m6A-related lncRNAs prognostic signature that can be used to construct accurate models for predicting the prognosis of GC in the Asian population. METHODS: First, the levels of m6A modification and m6A methyltransferases expression in GC samples were determined using dot blot and western blot analyses. Next, we evaluated the lncRNAs expression profiles and the corresponding clinical data of 88 Asian GC patients retrieved from The Cancer Genome Atlas (TCGA) database. Differential expression of m6A-related lncRNAs between GC and normal tissues was investigated. The relationship between these target lncRNAs and potential immunotherapeutic signatures was also analyzed. Gene set enrichment analysis (GSEA) was performed to identify the malignancy-associated pathways. Univariate Cox regression, LASSO regression, and multivariate Cox regression analyses were performed to establish a novel prognostic m6A-related lncRNAs prognostic signature. Moreover, we constructed a predictive nomogram and determined the expression levels of nine m6A-related lncRNAs in 12 pairs of clinical samples. RESULTS: We found that m6A methylation levels were significantly increased in GC tumor samples compared to adjacent normal tissues, and the increase was positively correlated with tumor stage. Patients were then divided into two clusters (cluster 1 and cluster 2) based on the differential expression of the m6A-related lncRNAs. Results showed that there was a significant difference in survival probability between the two clusters (p = 0.018). Notably, the low survival rate in cluster 2 may be associated with high expression of immune cells (resting memory CD4+ T cells, p = 0.027; regulatory T cells, p = 0.0018; monocytes, p = 0.00095; and resting dendritic cells, p = 0.015), and low expression of immune cells (resting NK cells, p = 0.033; and macrophages M1, p = 0.045). Enrichment analysis indicated that malignancy-associated biological processes were more common in the cluster 2 subgroup. Finally, the risk model comprising of six m6A-related lncRNAs was identified as an independent predictor of prognoses, which could divide patients into high- or low-risk groups. Time-dependent ROC analysis suggested that the risk score could accurately predict the prognosis of GC patients. Patients in the high-risk group had worse outcomes compared to patients in the low-risk group, and the risk score showed a positive correlation with immune cells (resting memory CD4+ T cells, R = 0.31, P = 0.038; regulatory T cells, R = 0.42, P = 0.0042; monocytes, R = 0.42, P = 0.0043). However, M1 macrophages (R = -0.37, P = 0.012) and resting NK cells (R = -0.31, P = 0.043) had a negative correlation with risk scores. Furthermore, analysis of clinical samples validated the weak positive correlation between the risk score and tumor stage. CONCLUSIONS: The risk model described here, based on the six m6A-related lncRNAs signature, and may predict the clinical prognoses and immunotherapeutic response in Asian GC patients.

Epithelioid sarcoma: A clinicopathological study of 12 head and neck cases.

OBJECTIVES: To determine the clinicopathological features of epithelioid sarcoma presenting in head and neck region (HNES) and elucidate diagnostic key points and treatment options for HNES. MATERIALS AND METHODS: A total of 12 HNES cases were collected in our department from 2010 to 2020. Their clinical information and pathological features were documented, and relevant follow-up was performed. Immunohistochemistry was carried to analyze the protein markers of HNES. RESULTS: Of the 12 HNES cases, 10 were primary tumors and 2 were metastasized from foot and shoulder, respectively. The patients with primary tumors were significantly younger than those with metastasized ones (22.7 vs 41.5, p = .0157), and male patients outnumbered female patients (3:1). Of all HNES cases, 9 were classic subtype, and 3 were proximal subtype. HNES patients had a poor prognosis, with 5-year overall survival of 41.5% and 5-year relapse-free survival of 22.5%. A loss of INI1 was identified as the hallmark of HNES with 83.3% (10/12) of HNES cases presenting as EZH2 positive. CONCLUSIONS: HNES is more prevalent at younger ages and in males, has a poor prognosis, and exhibits a greater proportion of classic subtype than proximal subtype. EZH2 inhibitor has therapeutic potential in HNES.

Follicular dendritic cell sarcoma of the cervical lymph node diagnosed on fine needle aspiration cytology.

Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations. We report herein a case of a 57-year-old female who presented with a right neck mass of 5 months duration. Computed Tomography (CT) imaging of the neck reported a necrotic right level IIb lymph node and asymmetric fullness of the right palatine tonsil. Fine needle aspiration (FNA) biopsy revealed numerous spindle, oval and stellate neoplastic cells, arranged singly and in syncytia with moderate nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli, sprinkled with small lymphocytes. The tumour cells were strongly diffusely positive for CD21, CD23, and D2-40 immunostaining on cell bock sections, but were negative for CD1a and CD34, supporting the diagnosis of FDCS. Follow-up surgical pathology on the resection showed histopathological features and an immunohistochemical profile consistent with FDCS.

CO2 Reduction: From Homogeneous to Heterogeneous Electrocatalysis.

Due to increasing worldwide fossil fuel consumption, carbon dioxide levels have increased in the atmosphere with increasingly important impacts on the environment. Renewable and clean sources of energy have been proposed, including wind and solar, but they are intermittent and require efficient and scalable energy storage technologies. Electrochemical CO2 reduction reaction (CO2RR) provides a valuable approach in this area. It combines solar- or wind-generated electrical production with energy storage in the chemical bonds of carbon-based fuels. It can provide ways to integrate carbon capture, utilization, and storage in energy cycles while maintaining controlled levels of atmospheric CO2. Electrochemistry allows for the utilization of an electrical input to drive chemical reactions. Because CO2 is kinetically inert, highly active catalysts are required to decrease reaction barriers sufficiently so that reaction rates can be achieved that are sufficient for electrochemical CO2 reduction. Given the reaction barriers associated with multiple electron-proton reduction of CO2 to CO, formaldehyde (HC(O)H), formic acid, or formate (HC(O)OH, HC(O)O-), or more highly reduced forms of carbon, there is also a demand for high selectivity in catalysis. Catalysts that have been explored include homogeneous catalysts in solution, catalysts immobilized on surfaces, and heterogeneous catalysts. In homogeneous catalysis, reduction occurs following diffusion of the catalyst to an electrode where multiple proton coupled electron transfer reduction occurs. Useful catalysts in this area are typically transition-metal complexes with organic ligands and electron transfer properties that utilize combinations of metal and ligand redox levels. As a way to limit the amount of catalyst, in device-like configurations, catalysts are added to the surfaces of conductive substrates by surface binding, in polymeric films, or on carbon electrode surfaces with molecular structures and electronic configurations related to catalysts in solution. Immobilized, homogeneous catalysts can suffer from performance losses and even decomposition during long-term CO2 reduction cycles, but they are amenable to detailed mechanistic investigations. In parallel efforts, heterogeneous nanocatalysts have been explored in detail with the development of facile synthetic procedures that can offer highly active catalytic surface areas. Their high activity and stability have attracted a significant level of investigation, including possible exploitation for large-scale applications. However, translation of catalytic reactivity to the surface creates a new reactivity environment and complicates the elucidation of mechanistic details and identification of the active site in exploring reaction pathways. Here, the results of previous studies based on transition-metal complex catalysts for CO2 electroreduction are summarized. Early studies showed that transition-metal complexes of Ru, Ir, Rh, and Os, with well-defined structures, are all capable of catalyzing CO2 reduction to CO or formate. Derivatives of the complexes were surface attached to conducting electrodes by chemical bonding, noncovalent bonding, or polymerization. The concept of surface binding has also been extended to the preparation of surface area electrodes by the chemically controlled deposition of nanostructured catalysts such as nano tin, nano copper, and nano carbon, all of which have been shown to have high selectivities and activities toward CO2 reduction. In our presentation, we end this Account with recent advances and a perspective about the application of electrocatalysis in carbon dioxide reduction.

Gynaecological perivascular epithelioid cell tumour (PEComa): comparative analysis of proposed algorithms for prediction of clinical outcome.

AIMS: Perivascular epithelioid cell tumours (PEComas) are rare mesenchymal tumours that coexpress smooth muscle and melanocytic markers. They have a predilection for gynaecological organs, where they present a unique diagnostic challenge, because of morphological and immunohistochemical overlap with more common smooth muscle and stromal tumours. Limited information regarding the natural history, owing to the rarity of this tumour, makes accurate risk stratification difficult. We aimed to review clinicopathological features of gynaecological PEComa and compare accuracy of five different classification systems for prediction of prognosis. METHODS AND RESULTS: We have described the clinicopathological features of 13 new cases and tested five prognostic algorithms in a total of 67 cases of gynaecological PEComa. Receiver operating characteristic curves were constructed and areas under the curve (AUCs) were calculated to evaluate predictive accuracy. The modified gynaecological-specific algorithm showed high sensitivity and specificity and yielded the highest AUC (0.864). It's earlier version, the gynaecological-specific algorithm, suffered from lower specificity (AUC = 0.843). The post-hoc McNemar test confirmed significant differences between the performances of the modified gynaecological-specific algorithm and the gynaecological-specific algorithm (P = 0.008). The original Folpe algorithm for PEComas of all sites showed low specificity, had a lower AUC (0.591), and was inapplicable in 18% of cases. Its two later versions (the revised Folpe algorithm and the modified Folpe algorithm) also yielded lower AUCs (0.690 and 0.591, respectively). CONCLUSION: We have shown that the modified gynaecological-specific algorithm predicts the clinical outcome of gynaecological PEComa with high accuracy, and have validated its use for prognostic stratification of gynaecological PEComa.

Prognostic value of a novel glycolysis-related gene expression signature for gastrointestinal cancer in the Asian population.

BACKGROUND: Globally, gastrointestinal (GI) cancer is one of the most prevalent malignant tumors. However, studies have not established glycolysis-related gene signatures that can be used to construct accurate prognostic models for GI cancers in the Asian population. Herein, we aimed at establishing a novel glycolysis-related gene expression signature to predict the prognosis of GI cancers. METHODS: First, we evaluated the mRNA expression profiles and the corresponding clinical data of 296 Asian GI cancer patients in The Cancer Genome Atlas (TCGA) database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL and TCGA-READ). Differentially expressed mRNAs between GI tumors and normal tissues were investigated. Gene Set Enrichment Analysis (GSEA) was performed to identify glycolysis-related genes. Then, univariate, LASSO regression and multivariate Cox regression analyses were performed to establish a key prognostic glycolysis-related gene expression signature. The Kaplan-Meier and receiver operating characteristic (ROC) curves were used to evaluate the efficiency and accuracy of survival prediction. Finally, a risk score to predict the prognosis of GI cancers was calculated and validated using the TCGA data sets. Furthermore, this risk score was verified in two Gene Expression Omnibus (GEO) data sets (GSE116174 and GSE84433) and in 28 pairs of tissue samples. RESULTS: Prognosis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1) among the differentially expressed glycolysis-related genes were screened and identified. The five-gene expression signature was used to assign patients into high- and low-risk groups (p < 0.05) and it showed a satisfactory prognostic value for overall survival (OS, p = 6.383 × 10-6). The ROC curve analysis revealed that this model has a high sensitivity and specificity (0.757 at 5 years). Besides, stratification analysis showed that the prognostic value of the five-gene signature was independent of other clinical characteristics, and it could markedly discriminate between GI tumor tissues and normal tissues. Finally, the expression levels of the five prognosis-related genes in the clinical tissue samples were consistent with the results from the TCGA data sets. CONCLUSIONS: Based on the five glycolysis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1), and in combination with clinical characteristics, this model can independently predict the OS of GI cancers in Asian patients.

Fenvalerate induces oxidative hepatic lesions through an overload of intracellular calcium triggered by the ERK/IKK/NF-κB pathway.

Fenvalerate (FEN), a mainstream pyrethroid pesticide, was initially recommended as a low-toxicity agent for controlling agricultural and domestic pests. Despite the widespread use of FEN worldwide, little data are available on FEN-induced hepatic lesions and molecular mechanisms. In the present study, we first performed an occupational cross-sectional study on FEN factory workers and found that the levels of serum alanine aminotransferase (ALT) and total antioxidant capacity increased, whereas malondialdehyde decreased in laborers in the working areas where the levels of airborne FEN were much higher compared with the office area. The results were then confirmed by animal experiments that abnormal hepatic histology, increased ALT level, and compromised hepatic oxidative capability were observed in rats exposed to a high concentration of FEN. Furthermore, the bioinformatics analysis of gene microarray in rat liver tissue showed that FEN significantly changed the expressions of genes related to the regulation of intracellular calcium ion homeostasis and the calcium signal pathway. Finally, the functional experiments in Buffalo rat liver (BRL) cells demonstrated that FEN first activated ERK MAPK, followed by IKK and NF-κB, which triggered the transcription of genes responsible for accelerating an overload of intracellular calcium ions, prompted reactive oxygen species generation in the mitochondria, and finally, induced hepatic cellular apoptosis. The calcium signaling pathway and in particular, an overload of intracellular calcium play a critical role in this pathophysiological process via the ERK/IKK/NF-κB pathway. Our study furthers the understanding of the mechanism of FEN-induced hepatic injuries and may have implications in the prevention and control of liver diseases induced by environmental pesticides.-Qiu, L.-L., Wang, C., Yao, S., Li, N., Hu, Y., Yu, Y., Xia, R., Zhu, J., Ji, M., Zhang, Z., Wang S.-L. Fenvalerate induces oxidative hepatic lesions through an overload of intracellular calcium triggered by the ERK/IKK/NF-κB pathway.

Early experience with convalescent plasma as immunotherapy for COVID-19 in China: Knowns and unknowns.

BACKGROUND AND OBJECTIVES: In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID-19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID-19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of 5 May 2020 on CCP therapy according to the Clinical Treatment Guideline of COVID-19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti-epidemic strategy. MATERIALS AND METHODS: As of 5 May 2020, when the epidemic was well-controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified. RESULTS: As of 5 May 2020, up to 2000 samples of CCP had been collected across China and administered to 700 COVID-19 patients. From donors, 200-400 ml of plasma was collected at each donation, with antibody titres > 1:160. We identified three clinical studies for COVID-19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P < 0.001). No adverse effects were reported. CONCLUSION: From initial studies, convalescent plasma therapy appears effective and safe for COVID-19. However, there is clearly a need for well-designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.