Revealing the key role of cuproptosis in osteoporosis via the bioinformatic analysis and experimental validation of cuproptosis-related genes.

The incidence of osteoporosis has rapidly increased owing to the ageing population. Cuproptosis, a novel mechanism that regulates cell death, may be a new therapeutic approach. However, the relevance of cuproptosis in the immune microenvironment and osteoporosis immunotherapy is still unknown. We intersected the differentially expressed genes from osteoporotic samples with 75 cuproptosis-related genes to identify 16 significantly expressed cuproptosis genes. We further explored the connection between the cuproptosis pattern, immune microenvironment, and immunotherapy. The weighted gene co-expression network analysis algorithm was used to identify cuproptosis phenotype-associated genes, and we used quantitative real-time PCR and immunohistochemistry in mouse femur tissues to verify hub gene (MAP2K2, FDX1, COX19, VEGFA, CDKN2A, and NFE2L2) expression. Six hub genes and 59 cuproptosis phenotype-associated genes involved in immunisation were identified among the osteoporosis and control groups, and the majority of these 59 genes were enriched in the inflammatory response, as well as in signal transducers, Janus kinase, and transcription pathway activators. In addition, two different clusters of cuproptosis were found, and immune infiltration analysis showed that gene Cluster 1 had a greater immune score and immune infiltration level. Further analysis revealed that three key genes (COX19, MAP2K2, and FDX1) were highly correlated with immune cell infiltration, and external experiments validated the association of these three genes with the prognosis of osteoporosis. We used the three key mRNAs COX19, MAP2K2, and FDX1 as a classification model that may systematically elucidate the complex connection between cuproptosis and the immune microenvironment of osteoporosis. New insights into osteoporosis pathogenesis and immunotherapy prospects may be gained from this study.

Gut microbiota and oral cavity cancer: a two-sample bidirectional Mendelian randomization study.

This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral cavity cancer (OCC). Objective: To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis. Methods: Utilizing GWAS data from the MiBioGen consortium (18,340 individuals) and UK Biobank (n = 264,137), we selected instrumental variables and employed MR-Egger, weighted median, IVW, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test and MR-Egger intercept test. Results: Our findings indicate, at the order level, Bacteroidales (OR = 0.9990, 95% CI = 0.9980-1.0000, P = 0.046), Burkholderiales (OR = 1.0009, 95% CI = 1.0001-1.0018, P = 0.033), and Victivallales (OR = 0.9979, 95% CI = 0.9962-0.9995, P = 0.037) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, Alcaligenaceae (OR = 1.0012, 95% CI = 1.0004-1.0019, P = 0.002) and Clostridiaceae1 (OR = 0.9970, 95% CI = 0.9948-0.9992, P = 0.027) show causality on OCC in IVW and MR-Egger analyses. At the genus level, Clostridiumsensustricto1 (IVW, OR = 0.9987, 95% CI = 0.9980-0.9995, P = 0.001; MR-Egger, OR = 0.9978, 95% CI = 0.9962-0.9995, P = 0.035), Desulfovibrio (IVW, OR = 1.0008, 95% CI = 1.0001-1.0015, P = 0.016), Eggerthella (IVW, OR = 0.9995, 95% CI = 0.9990-1.0000, P = 0.048), Eubacterium fissicatena group (IVW, OR = 1.0005, 95% CI = 1.0000-1.0009, P = 0.032), and Holdemanella (IVW, OR = 0.9994, 95% CI = 0.9989-0.9999, P = 0.018) are implicated in causing OCC in related analyses. Conclusion: Our study identifies Burkholderiales order, Alcaligenaceae family, Desulfovibrio genus, and Eubacterium fissicatena group as causally increasing OCC risk. In contrast, Bacteroidales order, Victivallales order, Clostridiaceae1 family, Clostridiumsensustricto1 genus, Eggerthella genus, and Holdemanella genus are causally associated with a decreased OCC risk. However, further investigations are essential to delineate an optimal gut microbiota composition and unravel the underlying mechanisms of specific bacterial taxa in OCC pathophysiology.

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity.

Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family, represents a persistent menace to the global pig industry, causing reproductive failure and respiratory disease in pigs. In this study, we delved into the role of histone deacetylases (HDAC2) during PRRSV infection. Our findings revealed that HDAC2 expression is downregulated upon PRRSV infection. Notably, suppressing HDAC2 activity through specific small interfering RNA led to an increase in virus production, whereas overexpressing HDAC2 effectively inhibited PRRSV replication by boosting the expression of IFN-regulated antiviral molecules. Furthermore, we identified the virus's nonstructural protein 11 (nsp11) as a key player in reducing HDAC2 levels. Mutagenic analyses of PRRSV nsp11 revealed that its antagonistic effect on the antiviral activity of HDAC2 is dependent on its endonuclease activity. In summary, our research uncovered a novel immune evasion mechanism employed by PRRSV, providing crucial insights into the pathogenesis of this virus and guiding the development of innovative prevention strategies against PRRSV infection.

Meta-analysis of pulsed-field ablation versus cryoablation for atrial fibrillation.

PURPOSE: The available data on the treatment strategy of pulsed field ablation (PFA) for patients with atrial fibrillation (AF) is limited. This study aims to provide a comparative analysis of the efficacy, safety, and procedural efficiency between PFA and cryoballoon ablation (CBA) for AF. METHODS: We conducted a comprehensive search of the EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov databases to identify trials comparing PFA with CBA for AF from their inception until December 2023. The odds ratio (OR) and mean difference (MD), along with a 95% confidence interval (CI), were utilized as measures of treatment effect. RESULTS: The analysis included 15 eligible trials with a total enrollment of 1880 patients. No significant differences were found in recurrent atrial arrhythmia (OR 0.83, 95% CI 0.64, 1.07) or periprocedural complications (OR 0.78, 95% CI 0.46, 1.30) between the two ablation techniques examined in this study. However, the PFA technique demonstrated a significantly shorter procedure time (MD -7.17, 95% CI -13.60, -0.73), but a longer fluoroscopy time (MD 2.53, 95% CI 0.87, 4.19). Similarly, PFA was found to be significantly associated with a decreased incidence of phrenic nerve palsy (OR 0.20, 95% CI 0.07, 0.59), but an increased incidence of cardiac tamponade (OR 4.07, 95% CI 1.15, 14.39). Moreover, there was a significantly higher release of troponin with PFA compared to CBA (MD 470.28, 95% CI 18.89, 921.67), while the increase in S100 protein and heart rate was significantly lower with PFA than with CBA (MD -64.41, 95% CI -105.46, -17.36), (MD -8.76, 95% CI -15.12, -2.40). CONCLUSION: The utilization of PFA provides a safer, time-saving, and tissue-specific procedure compared to CBA, while maintaining comparable success rates. This has the potential to enhance procedural efficiency and optimize resource utilization in clinical practice. These findings underscore the feasibility and promise of PFA as an alternative technique for PVI in patients with AF.

Th17 Cell-Related Gene Biomarkers in Osteoporosis: Comprehensive Bioinformatics Analysis and In Vivo Validation.

The interaction between the bone and immune systems has a major role in osteoporosis regulation. However, the infiltration of T helper 17 (Th17) cells and their associated genes in osteoporosis remains unclear. The GSE35959 dataset was obtained from the Gene Expression Omnibus (GEO) database, and the Immune Cell Abundance Identifier (ImmuCellAI) program was used to evaluate the abundance of 24 immune cell types, including Th17 cells. Differential analysis and relevance analysis were performed to identify differentially expressed Th17 cell-related genes (DETh17RGs) in osteoporosis. The potential functions of DETh17RGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment. Hub DETh17RGs were obtained through comprehensive analysis using Weighted Gene Co-Expression Network Analysis (WGCNA) and the CytoHubba plug-in algorithm. The expression levels of hub genes were validated using additional osteoporosis datasets. Additionally, the transcript levels of Hub genes in a mice model of osteoporosis were examined using quantitative PCR (qPCR). 464 DETh17RGs were identified in this study, with 421 genes showing positive associations and 43 genes showing negative associations. Among these, seven genes (CD44, TGFB1, ACTN4, ARHGDIA, ESR1, TLN1, FLNA) were considered as Hub DETh17RGs. The qPCR transcript levels of hub DETh17RGs in a mice model of osteoporosis exhibited consistent expression trends with the bioinformatics analysis. This research enhances our understanding of the molecular mechanisms involving Th17 cells in the development of osteoporosis and contributes to the discovery of potential biomarkers.

Dural Puncture Epidural with 25-G Spinal Needles versus Conventional Epidural Technique in Conjunction with PIEB for Labor Analgesia: A Randomized Trial.

Purpose: To compare the effect of Dural puncture epidural (DPE) and conventional epidural (EP), in conjunction with programmed intermittent epidural bolus (PIEB) and low-concentration ropivacaine strategy. Methods: After written informed consent was obtained, healthy nulliparous women with singleton pregnancies, vertex presentation at 38-42 weeks' gestation, cervical dilation of 3-5 cm, and a desire for pain relief were randomly assigned to DPE or EP group. Dural matter was puncture with 25G Whitacre needle in DPE group. Analgesia was initiated with 15 mL of 0.1% ropivacaine over 5 minutes and was maintained by PIEB (8 mL of 0.08% ropivacaine with 2 µg/mL fentanyl every 40 min). Primary outcome was the percentage of adequate analgesia, defined as NRPS ≤1, at 30 minutes after the initiation of the epidural bolus. Results: Out of 130 enrolled parturients, 127 were included in final analysis (64 in DPE group, 63 in EP group). No significant difference was found in percentage of adequate analgesia at 30 minutes (risk ratio: 1.09; 95% confidence interval: 0.90-1.31; P = 0.366). At 8, 12, 14, and 16 minutes, percentage of adequate analgesia was higher in DPE group (P = 0.023, 0.027, 0.016 and 0.033, respectively). NPRS scores in DPE group decreased more dramatically within the first 30 min. The incidence of S2 sensory blocks at 20 and 30 min in DPE group was higher (P = 0.010 and 0.006, respectively). There were no differences in patient satisfaction, delivery mode, adverse effects, fetal bradycardia, and Apgar scores at 1 and 5 minutes. Conclusion: The combination of the use of DPE technique with 25G spinal needle and PIEB technique for labor analgesia appears to enhance the quality of labor analgesia by accelerating onset and providing improved sacral blockade, without increasing adverse effects.

Molecularly Imprinted Electrochemical Sensors Based on Ti3C2Tx-MXene and Graphene Composite Modifications for Ultrasensitive Cortisol Detection.

The increasing pressure and unhealthy lifestyle are gradually eroding the physical and mental health of modern people. As a key hormone responsible for maintaining the normal functioning of human systems, cortisol plays a vital role in regulating physiological activities. Moreover, cortisol can serve as a marker for monitoring psychological stress. The development of cortisol detection sensors carries immense potential, as they not only facilitate timely adjustments and treatments by detecting abnormal physiological indicators but also provide comprehensive data for conducting research on the correlation between cortisol and several potential diseases. Here, we report a molecularly imprinted polymer (MIP) electrochemical biosensor that utilizes a porous composite (MXG) modified electrode. MXG composite is prepared by combining Ti3C2Tx-MXene sheets and graphene (Gr). MXG composite material with high conductive properties and large electroactive surface area promotes the charge transfer capability of the electrode surface, expands the effective surface area of the sensor, and increases the content of cortisol-imprinted cavities on the electrode, thereby improving the sensing ability of the sensor. By optimizing the preparation process, the prepared sensor has an ultralow lower limit of detection of 0.4 fM, a wide detection range of 1 fM-10 µM, and good specificity for steroid hormones and interfering substances with similar cortisol structure. The ability of the sensor to detect cortisol in saliva was also confirmed experimentally. This highly sensitive and selective cortisol sensor is expected to be widely used in the fields of physiological and psychological care.

A Therapeutic DNA Vaccine Targeting HPV16 E7 in Combination with Anti-PD-1/PD-L1 Enhanced Tumor Regression and Cytotoxic Immune Responses.

Persistent infection of high-risk human papillomavirus (HPV) and the expression of E6 and E7 oncoproteins are the main causes of cervical cancer. Several prophylactic HPV vaccines are used in the clinic, but these vaccines have limited efficacy in patients already infected with HPV. Since HPV E7 is vital for tumor-specific immunity, developing a vaccine against HPV E7 is an attractive strategy for cervical cancer treatment. Here, we constructed an HPV16 E7 mutant that loses the ability to bind pRb while still eliciting a robust immune response. In order to build a therapeutic DNA vaccine, the E7 mutant was packaged in an adenovirus vector (Ad-E7) for efficient expression and enhanced immunogenicity of the vaccine. Our results showed that the Ad-E7 vaccine effectively inhibited tumor growth and increased the proportion of interferon-gamma (IFN-γ)-secreting CD8+ T cells in the spleen, and tumor-infiltrating lymphocytes in a mouse cervical cancer model was achieved by injecting with HPV16-E6/E7-expressing TC-1 cells subcutaneously. Combining the Ad-E7 vaccine with the PD-1/PD-L1 antibody blockade significantly improved the control of TC-1 tumors. Combination therapy elicited stronger cytotoxic T lymphocyte (CTL) responses, and IFN-γ secretion downregulated the proportion of Tregs and MDSCs significantly. The expressions of cancer-promoting factors, such as TNF-α, were also significantly down-regulated in the case of combination therapy. In addition, combination therapy inhibited the number of capillaries in tumor tissues and increased the thickness of the tumor capsule. Thus, Ad-E7 vaccination, in combination with an immune checkpoint blockade, may benefit patients with HPV16-associated cervical cancer.

CKM intron: an appropriate marker for the determination of the genetic relationships among horse populations and breeds.

To date, the origins, domestication, and genetic structure of Chinese Mongolian horses (CMH) are poorly understood. Furthermore, there have been sparse reports on the genetic differences between CMH and Thoroughbred. In order to determine their genetic structure, understand their genetic relationships, and explore their domestication processes, we performed an extensive survey of creatine kinase (muscle isoenzyme; CKM) variations among six populations of indigenous CMH, cultivated Sanhe horses, and imported Thoroughbred. Twenty-three single-nucleotide polymorphisms were found among the 343 horse sequences. From these, 40 haplotypes were inferred. Haplotype diversity (H) values differed from 0.6424 to 0.7881 and nucleotide diversity (π) values ranged from 0.00150 to 0.00211. The differences between Thoroughbred population and other Chinese horse populations were large, but only small differences were observed among Chinese horse populations with respect to CKM intron sequences suggesting that the domestication history, breeding measures, and origins of these horse populations are completely different. Results suggest that Sanhe and CMH are very closely related and the introgression (interbreeding) between them is serious. Our results suggest that Sanhe and Wushen require prompt and powerful protection. Overall, CKM intron was an appropriate marker for the determination of genetic relationships among horse populations and breeds.

Current Progress and Outlook for Agrimonolide: A Promising Bioactive Compound from Agrimonia pilosa Ledeb.

Agrimonolide (AM), which is a derivative of isocoumarins, is found mainly in the herb Agrimonia pilosa Ledeb. This compound is highly lipophilic and readily crosses the blood-brain barrier. In recent years, interest has grown in the use of AM as a multitarget natural treatment for various diseases, such as cancer, inflammation, hepatic injury, myocardial damage, and diabetes mellitus. The potential mechanisms of these pharmacological effects have been clarified at cellular and molecular levels. AM shows no cytotoxicity over a range of concentrations in different types of cells, providing evidence for its good safety profile in vitro. These findings indicate that AM is a promising medicinal agent. However, most studies on AM's pharmacological activities, mechanisms of action, and safety lack substantial animal or human data. Additionally, the pharmacokinetics, metabolism, and disposition of this compound have received little attention. This review highlights the status of current information regarding the sources, properties, pharmacological effects, and safety of AM. Furthermore, potential strategies to resolve problematic issues identified in previous studies are fully discussed. This summary and analysis of the research progress of AM may inspire deeper investigations and more extensive applications of AM in the future.

Comparison of the Effect of Chemoradiotherapy and Chemotherapy on the Survival of Patients with Primary Diffuse Large B-Cell Lymphoma of the Spine: A SEER-Based Study.

OBJECTIVE: The role of radiotherapy in primary spinal diffuse large B-cell lymphoma (PB-DLBCL) remains controversial. This study explored the effects of chemoradiotherapy and chemotherapy alone on the survival of patients with PB-DLBCL and established an instructive nomogram. METHODS: Survival analysis using the Kaplan-Meier method and log-rank test was performed for patients diagnosed with PB-DLBCL from 1983 to 2016, identified in the Surveillance Epidemiology and End Results database. The Cox regression model was used to analyze the effects of each variable on the overall survival (OS) and construct a nomogram for predicting OS in patients. RESULTS: Overall, 873 patients with PB-DLBCL were included. The patients were divided into the 1983-2001 (227 [26%]) and 2002-2016 (646 [74%]) groups. The 5-and 10-year OS rates of patients with PB-DLBCL in the 2002-2016 group were 62.8% and 49.9%, respectively. The results of the multivariate Cox regression analysis in the 2002-2016 group showed that age, stage, marriage, and treatment strategy were independent prognostic factors. Kaplan-Meier analysis showed that the OS of patients who underwent chemoradiotherapy from 2002 to 2016 was significantly better than that of patients treated with chemotherapy alone. Further subgroup analysis of patients with different stages of DLBCL and at different ages showed that chemoradiotherapy had a better prognosis than chemotherapy alone in stages I-II and age >60 years, whereas the advantages of chemoradiotherapy were not reflected in stages III-IV and age <60 years. CONCLUSIONS: Chemoradiotherapy improves the OS of patients with PB-DLBCL who are aged >60 years or have stage I-II disease. The nomograms established in this study can help clinicians determine prognosis and select treatment strategies.

A sensitive, robust and high-throughput isotope dilution LC-MS/MS method for quantifying three folate forms in serum.

This study aimed to establish an isotope dilution LC-MS/MS method for the determination of folic acid, 5-formyltetrahydrofolate and 5-methyltetrahydrofolate in human serum. This method was then used to quantify these three folate forms in the healthy adult population and supplement users. A stable 96-well solid-phase extraction system was used to prepare serum samples. The highly sensitive method was established using a Shimadzu LCMS-8060NX. The linearity was good in the range of 0.1-10 nmol/l for folic acid and 5-formyltetrahydrofolate and 1.0-100 nmol/l for 5-methyltetrahydrofolate. The accuracy and precision were good. The method was sensitive, robust and high-throughput and could be used for the routine clinical monitoring of these three folate forms in the Chinese population.

Indirect Comparison of Cryoablation and Radiofrequency Ablation as Initial Therapy for Symptomatic Paroxysmal Atrial Fibrillation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Data on first-line ablation treatment for patients with symptomatic atrial fibrillation (AF) are scarce. This study indirectly compared the efficacy and safety of cryoballoon ablation (CBA) versus radiofrequency ablation (RFA) as initial therapy for symptomatic AF. METHODS: We searched the EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) that compared CBA or RFA with antiarrhythmic drugs (AADs) as first-line treatment for AF from the time of database establishment up to December 2021. The odds ratio (OR) with a 95% confidence interval (CI) was used as a measure of the treatment effect. RESULTS: Six RCTs (3 CBA, 3 RFA) that enrolled a total of 1,215 patients were included in this analysis. There were no significant differences in atrial arrhythmia (AA) (OR 0.993, 95% CI: 0.602-1.638), symptomatic AA (OR 0.638, 95% CI: 0.344-1.182), or serious adverse events (OR 1.474, 95% CI: 0.404-5.376) between the two ablation techniques. The incidences of additional CBA therapy (OR 2.693, 95% CI: 1.277-5.681) and patients who crossed over to AAD therapy (OR 0.345, 95% CI: 0.179-0.664) in the CBA group were significantly lower than those in the RFA group. CONCLUSION: Among patients with paroxysmal AF receiving initial therapy, CBA and RFA share a similar efficacy and safety profile. When pulmonary vein isolation is performed by CBA, study crossover and the need for additional ablation are substantially lower.

Single nucleotide polymorphisms (SNPs) and indels identified from whole-genome re-sequencing of four Chinese donkey breeds.

This paper represents the fundamental report of the survey of genome-wide changes of four Chinese indigenous donkey breeds, Dezhou (DZ), Guangling (GL), North China (NC), and Shandong Little donkey (SDL), and the findings will prove usefully for identification of biomarkers that perhaps predict or characterize the growth and coat color patterns. Three genomic regions in CYP3A12, TUBGCP5, and GSTA1 genes, were identified as putative selective sweeps in all researched donkey populations. The loci of candidate genes that may have contributed to the phenotypes in body size (ACSL4, MSI2, ADRA1B, and CDKL5) and coat color patterns (KITLG and TBX3) in donkey populations would be found in underlying strong selection signatures when compared between large and small donkey types, and between different coat colors. The results of the phylogenetic analysis, FST, and principal component analysis (PCA) supported that each population cannot clearly deviate from each other, showing no obvious population structure. We can conclude from the population history that the formation processes between DZS and NC, GL, and SDL are completely different. The genetic variants discovered here provide a rich resource to help identify potential genomic markers and their associated molecular mechanisms that impact economically important traits for Chinese donkey breeding programs.

Comparison of gut microflora of donkeys in high and low altitude areas.

Donkeys' gut microbe is critical for their health and adaptation to the environment. Little research has been conducted on the donkey gut microbiome compared with other domestic animals. The Tibetan Plateau is an extreme environment. In this study, 6 Qinghai donkeys (QH) from the Tibetan Plateau and 6 Dezhou donkeys (DZ) were investigated, and the contents of 4 parts-stomach, small intestine, cecum, and rectum-were collected. 16S rRNA sequencing and metagenomic sequencing were used to analyze the composition and diversity of gut microbial communities in donkeys. The results showed that the flora diversity and richness of the hindgut were significantly higher than those of the foregut (p < 0.01), with no sex differences, and the community structure and composition of the same or adjacent regions (stomach, small intestine, cecum, and rectum) were similar. Besides, the flora diversity and richness of QH on the Tibetan Plateau were significantly higher than those of DZ (p < 0.05). The major pathways associated with QH were signal transduction mechanisms and carbohydrate transport and metabolism, and Bacteroidales were the major contributors to these functions. Our study provides novel insights into the contribution of microbiomes to the adaptive evolution of donkeys.

The pattern of expression and prognostic value of key regulators for m7G RNA methylation in hepatocellular carcinoma.

N7-methylguanosine (m7G) modification on internal RNA positions plays a vital role in several biological processes. Recent research shows m7G modification is associated with multiple cancers. However, in hepatocellular carcinoma (HCC), its implications remain to be determined. In this place, we need to interrogate the mRNA patterns for 29 key regulators of m7G RNA modification and assess their prognostic value in HCC. Initial, the details from The Cancer Genome Atlas (TCGA) database concerning transcribed gene data and clinical information of HCC patients were inspected systematically. Second, according to the mRNA profiles of 29 m7G RNA methylation regulators, two clusters (named 1 and 2, respectively) were identified by consensus clustering. Furthermore, robust risk signature for seven m7G RNA modification regulators was constructed. Last, we used the Gene Expression Omnibus (GEO) dataset to validate the prognostic associations of the seven-gene risk signature. We figured out that 24/29 key regulators of m7G RNA modification varied remarkably in their grades of expression between the HCC and the adjacent tumor control tissues. Cluster one compared with cluster two had a substandard prognosis and was also positively correlated with T classification (T), pathological stage, and vital status (fustat) significantly. Consensus clustering results suggested the expression pattern of m7G RNA modification regulators was correlated with the malignancy of HCC strongly. In addition, cluster one was extensively enriched in metabolic-related pathways. Seven optimal genes (METTL1, WDR4, NSUN2, EIF4E, EIF4E2, NCBP1, and NCBP2) were selected to establish the risk model for HCC. Indicating by further analyses and validation, the prognostic model has fine anticipating command and this probability signature might be a self supporting presage factor for HCC. Finally, a new prognostic nomogram based on age, gender, pathological stage, histological grade, and prospects were established to forecast the prognosis of HCC patients accurately. In essence, we detected association of HCC severity and expression levels of m7G RNA modification regulators, and developed a risk score model for predicting prognosis of HCC patients' progression.

Gas Sensing Mechanism and Adsorption Properties of C2H4 and CO Molecules on the Ag3-HfSe2 Monolayer: A First-Principle Study.

The detection of dissolved gases in oil is an important method for the analysis of transformer fault diagnosis. In this article, the potential-doped structure of the Ag3 cluster on the HfSe2 monolayer and adsorption behavior of CO and C2H4 upon Ag3-HfSe2 were studied theoretically. Herein, the binding energy, adsorption energy, band structure, density of state (DOS), partial density of state (PDOS), Mulliken charge analysis, and frontier molecular orbital were investigated. The results showed that the adsorption effect on C2H4 is stronger than that on CO. The electrical sensitivity and anti-interference were studied based on the bandgap and adsorption energy of gases. In particular, there is an increase of 55.49% in the electrical sensitivity of C2H4 after the adsorption. Compared to the adsorption energy of different gases, it was found that only the adsorption of the C2H4 system is chemisorption, while that of the others is physisorption. It illustrates the great anti-interference in the detection of C2H4. Therefore, the study explored the potential of HfSe2-modified materials for sensing and detecting CO and C2H4 to estimate the working state of power transformers.

Adsorption and Sensing Performances of Pristine and Au-Decorated Gallium Nitride Monolayer to Noxious Gas Molecules: A DFT Investigation.

In this study, the adsorption of noxious gas molecules (NO, Cl2, and O3) on GaN and Au-decorated GaN was systematically scrutinized, and the adsorption energy, bond length, charge, density of state (DOS), partial density of state (PDOS), electron deformation density (EDD), and orbitals were analyzed by the density functional theory (DFT) method. It is found that the interaction between NO and pristine GaN is physical adsorption, while GaN chemically reacts with Cl2 and O3. These observations suggest that pristine GaN may be a candidate for the detection of Cl2 and O3. The highly activated Au-decorated GaN can enhance the adsorption performance toward NO and convert the physical adsorption for NO into chemical adsorption, explaining the fact that precious metal doping is essential for regulating the electronic properties of the substrate material. This further confirms the well-established role of Au-decorated GaN in NO gas-sensing applications. In addition, the adsorption performance of Au-decorated GaN for Cl2 and O3 molecules is highly improved, which provides guidance to scavenge toxic gases such as Cl2 and O3 by the Au-decorated GaN material.

Neural Correlates of Facial Emotion Recognition in Non-help-seeking University Students With Ultra-High Risk for Psychosis.

Background: Since the introduction of the neurodevelopmental perspective of schizophrenia research on individuals at ultra-high risk for psychosis (UHR) has gained increasing interest, aiming at early detection and intervention. Results from fMRI studies investigating behavioral and brain functional changes in UHR during facial emotion recognition, an essential component of social cognition, showed heterogenous results, probably due clinical diversity across these investigations. This fMRI study investigated emotion recognition in a sub-group of the UHR spectrum, namely non-help-seeking, drug-naïve UHR with high cognitive functioning to reveal the neurofunctional underpinnings of their social functioning in comparison to healthy controls. Methods: Two large cohorts of students from an elite University (n 1 = 4,040, n 2 = 4,364) were screened firstly with the Prodromal Questionnaires and by surpassing predefined cut-offs then interviewed with the semi-structured Interview for Psychosis-Risk Syndromes to verify their UHR status. Twenty-one identified non-help-seeking UHR and 23 non-UHR control subjects were scanned with functional magnetic resonance imaging while classifying emotions (i.e., neutral, happy, disgust and fear) in a facial emotion recognition task. Results: Behaviorally, no group differences were found concerning accuracy, reaction times, sensitivity or specificity, except that non-help-seeking UHR showed higher specificity when recognizing neutral facial expressions. In comparison to healthy non-UHR controls, non-help-seeking UHR showed generally higher activation in the superior temporal and left Heschl's gyrus as well as in the somatosensory, insular and midcingulate cortex than the control subjects during the entire recognition task regardless of the emotion categories. In an exploratory analysis, in the non-help-seeking UHR group, functional activity in the left superior temporal gyrus was significantly correlated with deficits in the ability to experience emotions at uncorrected statistical thresholds. Conclusions: Compared to healthy controls, non-help-seeking UHR show no behavioral deficits during facial emotion recognition, but functional hyperactivities in brain regions associated with this cognitive process. Our study may inspire future early intervention and provide loci for treatment using neural stimulation.

Meta-analysis of cryoballoon ablation versus antiarrhythmic drugs as initial therapy for symptomatic atrial fibrillation.

BACKGROUND: The optimal first-line approach for patients with symptomatic atrial fibrillation (AF) remains unclear. We compared the efficacy and safety of cryoballoon ablation (CBA) and antiarrhythmic drugs (AADs) in the initial management of symptomatic AF. HYPOTHESIS: CBA is superior to AAD as initial therapy for symptomatic AF. METHODS: We searched the EMBASE, PubMed, and Cochrane Library databases for randomized controlled trials (RCTs) that compared CBA with AAD as first-line treatment for AF from the date of database establishment until March 18, 2021. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure of treatment effect. RESULTS: Three RCTs that enrolled 724 patients in total were included in this meta-analysis. Majority of the patients were relatively young and had paroxysmal AF. CBA was associated with a significant reduction in the recurrence of atrial arrhythmia compared with AAD therapy, with low heterogeneity (RR, 0.59; 95% CI, 0.49-0.71; p < .00001; I2  = 0%). There was a significant difference in the rate of symptomatic atrial arrhythmia recurrence (RR, 0.44; 95% CI, 0.29-0.65; p < .0001; I2  = 0%); however, the rate of serious adverse events was similar between the two treatment groups (RR: 1.18; 95% CI: 0.71-1.97, p = .53; I2  = 0%). Transient phrenic nerve palsy occurred in four patients after the CBA procedure. CONCLUSION: The current meta-analysis suggests that CBA is more effective than AAD as initial therapy in patients with symptomatic paroxysmal AF. Serious iatrogenic adverse events are uncommon in CBAs.