IgG4-related autoimmune pancreatitis and sclerosing cholangitis: A case report and literature review.

RATIONALE: Immunoglobulin G4-related disease (IgG4-RD) can involve various organs throughout the body, primarily manifesting as endocrine dysfunction, visual impairment, jaundice, and limited sexual function. IgG4-related autoimmune pancreatitis is triggered by autoimmune reactions and characterized by structural changes in the pancreas and pancreatic ducts. The disease mainly affects middle-aged and elderly males, typically presenting as progressive painless jaundice and misdiagnosed as cholangiocarcinoma or pancreatic cancer. PATIENT CONCERNS: This study reports a 54-year-old male who consulted with different institutions multiple times due to diabetes, pancreatitis, elevated liver enzymes, and jaundice. DIAGNOSES: Magnetic resonance imaging revealed swollen head of the pancreas and atrophic tail. Liver and pancreatic tissue pathology showed IgG4 plasma cell infiltration, while liver biopsy indicated interface hepatitis, liver fibrosis, and pseudolobule formation, with no evidence of bile duct damage. INTERVENTIONS: Following hormone therapy, the patient's serum IgG4 levels and liver enzyme levels returned to normal. OUTCOMES: The disease relapsed 2 years after maintaining hormone therapy, and the patient underwent additional hormone-induced remission therapy combined with azathioprine. LESSONS: The purpose of this research report is to enhance the awareness and understanding of IgG4-RD, emphasizing the necessity for personalized treatment strategies that take into account its recurrence, associations, and imaging features. This report provides valuable insights and guidance for clinicians in managing and diagnosing patients with IgG4-RD.

Microcystin-LR improves anti-tumor efficacy of oxaliplatin through induction of M1 macrophage polarization.

Tumor-associated macrophages within the tumor microenvironment play an immunosuppressive role by promoting tumor growth and immune evasion. Macrophages are highly plastic and can be stimulated to adopt an anti-tumor M1 phenotype. In this study, we used microcystin-LR (MC-LR), a cyclic heptapeptide produced by cyanobacteria, to induce in vitro macrophage innate immunity and transition into the anti-tumor M1 phenotype. MC-LR was also tested in vivo in a mouse model of colorectal cancer. An intraperitoneal injection of MC-LR increased the proportion of CD86⁺ M1 macrophages and triggered the maturation of CD11c⁺ dendritic cells within tumor tissues. MC-LR combined with the chemotherapeutic drug oxaliplatin significantly inhibited tumor growth in vivo. Flow cytometry analysis revealed increased infiltration of activated cytotoxic (CD8⁺, PD-1⁺) T-cells and anti-tumor cytokines (IFNγ and Granzyme B) in the tumor tissues of the combination therapy group, suggesting that this may be the primary mechanism behind the anti-tumor effect of the combination treatment. These findings indicate that MC-LR regulates the immune stimulation of macrophage polarization and dendritic cell maturation, effectively reversing tumor immunosuppression, activating an anti-tumor immune response, and enhancing tumor therapy.

Modified whitehead hemorrhoidectomy versus partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids: A retrospective analysis.

Background: Grade IV circular hemorrhoids are difficult to treat. We aim to describe the modified whitehead hemorrhoidectomy procedure and to assess the effectiveness and safety of this procedure for grade IV circular hemorrhoid patients. Methods: Patients with grade Ⅳ circular hemorrhoids who underwent modified Whitehead hemorrhoidectomy and partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids were retrospectively reviewed. Clinical data were extracted from the database at our institution, and long-term postoperative complications were assessed through repeated outpatient examinations and telephonic communication. Results: A total of 205 patients were included in this study. The mean operative time was 59.2 ± 13.8 min. The average hospital stay was 4.6 ± 1.0 days. For postoperative complications, 66 (32.2%) patients had urinary retention, 10 (4.9%) patients had a sense of incomplete rectal emptying, 5 (2.4%) patients had anal incontinence, and 6 (2.9%) patients had wound infection. For long-term postoperative complications, 3 (1.5%) patients experienced mild to moderate anal stricture, 2 (1%) patients experienced mucosal ectropion, they all had smooth recoveries, and none of them needed secondary surgery. None of these patients had a hemorrhoid recurrence. A total of 205 patients who received modified Whitehead hemorrhoidectomy and 161 who received partial hemorrhoidectomy were included. There were no residual hemorrhoids in patients who received modified Whitehead hemorrhoidectomy, and none had hemorrhoid recurrence. Fifty-eight patients who received partial hemorrhoidectomy had hemorrhoidal residues, and 19 patients experienced hemorrhoid recurrence. After modified Whitehead hemorrhoidectomy, 3 patients developed anal stenosis, and 2 had mucosal ectropion. Four patients developed anal stricture after partial hemorrhoidectomy, and none had mucosal ectropion. They all had smooth recoveries, and none of them needed a secondary surgery. For the mean duration of surgery, postoperative bleeding, postoperative pain, wound infection, sense of incomplete rectal emptying, anal incontinence, and urinary retention, no statistically significant differences were found between the two groups. Conclusions: Compared with partial hemorrhoidectomy, modified whitehead hemorrhoidectomy is an effective and safe surgical procedure and does not significantly increase the risk of anal stenosis and mucosal ectropion for grade IV circular hemorrhoid patients. Prospective randomized controlled trials are needed to verify our results.

Exploring the effects of calycosin on anthracycline-induced cardiotoxicity: a network pharmacology, molecular docking, and experimental study.

Background: Chemotherapy with anthracyclines can cause cardiotoxicity, possibly leading to stopping treatment in some cancer patients. In cardio-oncology research, preventing and minimizing anthracycline-induced cardiotoxicity (AIC) is a hot issue. For the treatment of AIC, calycosin (CA), an isoflavone component in astragali radix (AR), has become a research focus. However, the elaborate mechanisms of calycosin treating AIC remain to be unrevealed. Aim of the study: To explore the effects of CA on AIC through multiple dimensions concerning network pharmacology, molecular docking, and experimental evaluations. Methods: The study evaluated calycosin's potential targets and mechanisms for treating AIC using network pharmacology and molecular docking. The candidate genes/targets of CA and AIC were screened using the online-available database. Protein-protein interactions (PPI) between the common targets were constructed using the STRING platform, and the results were then visualized using Cytoscape. Molecular docking was used to evaluate the strength of the binding force between CA and the common targets. The possible pharmacological mechanisms of CA were explained by pathway enrichment and GSEA. Subsequently, the candidate targets were identified in vitro experiments. Results: Network pharmacology effectively discovered the CA's multitarget intervention in AIC, including TNF, ABCC1, TOP2A, ABCB1, and XDH. CA binds to the ATP-binding cassette subfamily B member 1(ABCB1) had the highest binding energy (-7.5 kcal/mol) according to the molecular docking analysis and was selected and visualized for subsequent analysis. In vitro experiments showed that ABCB1 exhibited significant time-curve changes under different doses of doxorubicin (DOX) compared with DMSO control experiments. The anti-AIC pharmacological mechanism of CA were revealed by highlighting the biological processes of oxidative stress (OR) and inflammation. Conclusions: We employed a practicable bioinformatics method to connect network and molecular docking to determine the calycosin's therapeutic mechanism against AIC and identified some bioinformatics results in in vitro experiments. The results presented show that CA may represent an encouraging treatment for AIC.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Thermal ablation for hepatic tumors in high-risk locations.

Thermal ablative techniques such as radiofrequency and microwave ablation are minimally invasive and cost-effective approaches that are currently being adopted as alternatives to surgical resection for primary and metastatic liver malignancies. However, they are considered to be relatively contraindicated for tumors in high-risk locations due to technical difficulties and a perceived increased risk of perioperative complications. Several techniques, including artificial ascites, non-touch multibipolar ablation, and laparoscopically assisted ablation, can be used to improve the outcomes of ablation for high-risk tumors. This review aims to provide a comprehensive summary of the techniques currently used to improve thermal ablation outcomes for high-risk liver tumors.

A pathologic scoring system for predicting postoperative prognosis in patients with ruptured hepatocellular carcinoma.

BACKGROUND: The accuracy of pathological factors to predict the prognosis of patients with ruptured hepatocellular carcinoma (rHCC) is unclear. We aimed to develop and validate a novel scoring system based on pathological factors to predict the postoperative survival of patients with rHCC. METHOD: Patients with rHCC who underwent hepatectomy were recruited from three hospitals and allocated to the training (n = 221) and validation (n = 194) cohorts. A new scoring system, namely the MSE (microvascular invasion-satellite foci-Edmondson Steiner) score, was established based on three pathological factors using univariate and multivariate Cox proportional hazards regression analyses, including microvascular invasion, satellite foci, and differentiation grade. Finally, patients were stratified into three groups based on their risk of prognosis (low, intermediate, or high) according to their MSE score. We also constructed MSE score-based nomograms. The performance of the nomograms was assessed by receiver operating characteristic and calibration curve analyses and validated using the validation cohort. RESULTS: Three pathological factors were significantly correlated with overall survival (OS) and recurrence-free survival (RFS), three of which were included in the MSE score. The score can clearly stratify rHCC patients after hepatectomy (P < 0.05). And we established nomograms based on the MSE score (MSE score, Barcelona Clinic Liver Cancer stage, and alpha-fetoprotein concentration) to predict postoperative OS and RFS in patients with rHCC. The nomograms showed good discrimination, with C-indices over 0.760 for OS and RFS at 1, 3, and 5 years, respectively. The calibration curve showed excellent nomogram calibration, which was also verified in the validation cohort. CONCLUSION: The clinical MSE score were accurate in predicting OS and RFS in patients with rHCC with resectable lesions after hepatectomy.

Colorectal image analysis for polyp diagnosis.

Colorectal polyp is an important early manifestation of colorectal cancer, which is significant for the prevention of colorectal cancer. Despite timely detection and manual intervention of colorectal polyps can reduce their chances of becoming cancerous, most existing methods ignore the uncertainties and location problems of polyps, causing a degradation in detection performance. To address these problems, in this paper, we propose a novel colorectal image analysis method for polyp diagnosis via PAM-Net. Specifically, a parallel attention module is designed to enhance the analysis of colorectal polyp images for improving the certainties of polyps. In addition, our method introduces the GWD loss to enhance the accuracy of polyp diagnosis from the perspective of polyp location. Extensive experimental results demonstrate the effectiveness of the proposed method compared with the SOTA baselines. This study enhances the performance of polyp detection accuracy and contributes to polyp detection in clinical medicine.

Integrinß-1 in disorders and cancers: molecular mechanisms and therapeutic targets.

Integrinß-1 (ITGB1) is a crucial member of the transmembrane glycoprotein signaling receptor family and is also central to the integrin family. It forms heterodimers with other ligands, participates in intracellular signaling and controls a variety of cellular processes, such as angiogenesis and the growth of neurons; because of its role in bidirectional signaling regulation both inside and outside the membrane, ITGB1 must interact with a multitude of substances, so a variety of interfering factors can affect ITGB1 and lead to changes in its function. Over the past 20 years, many studies have confirmed a clear causal relationship between ITGB1 dysregulation and cancer development and progression in a wide range of benign diseases and solid tumor types, which may imply that ITGB1 is a prognostic biomarker and a therapeutic target for cancer treatment that warrants further investigation. This review summarizes the biological roles of ITGB1 in benign diseases and cancers, and compiles the current status of ITGB1 function and therapy in various aspects of tumorigenesis and progression. Finally, future research directions and application prospects of ITGB1 are suggested. Video Abstract.

Salinization of groundwater in shale gas extraction area in the Sichuan Basin, China: Implications for water protection in shale regions with well-developed faults.

The expanding growth of shale gas development has sparked global concern over water-related environmental issues. However, research on groundwater contamination in shale gas areas in China remains limited, impeding environmentally friendly industry practices. To address this gap, we investigated the Wufeng-Longmaxi shale region in the Sichuan Basin, encompassing both operational and prospective shale gas extraction sites, to assess the effects of shale gas operations on shallow groundwater quality. We found there was no significant correlation between groundwater quality and the minimum distance from the shale gas well pads, and some groundwater samples located far from shale gas well pads, rather than those close to pads, were salinized. These findings suggest minimal impacts from shale gas drilling and hydraulic fracturing. The salinized groundwater samples are characterized by high salinity levels and ion concentrations, and are located near fault zones. The primary source of shallow groundwater salinization was derived from the Triassic formation brines confirmed through the assessment of the sensitivity and conservative mixing models. Faults in the study area were identified as pathways for the upward migration of Triassic brines, evidenced by the proximity of salinized samples to fault zones. However, further investigation is required to ascertain whether shale gas extraction activities have induced the migration of formation brines. The occurrence and reactivation of faults, induced by microseismic activities, may pose an increased risk of groundwater contamination in tectonically complex fault zones during shale gas extraction. Therefore, it is imperative to enhance extraction strategies and technologies, particularly in shale regions with well-developed faults, such as optimizing well placement regulation, controlling hydraulic fracturing scale, and strengthening environmental monitoring. By shedding light on potential environmental ramifications of shale gas extraction, especially in fault-rich regions, our study informs water protection strategies and the sustainable advancement of the shale gas industry.

Association of gestational cardiovascular health with infant neurodevelopment: A prospective study in Hefei of Anhui, China.

We investigate the prospective the association of gestational cardiovascular health (CVH) with infant neurodevelopment, and whether such relation was mediated by cord blood metabolites. The data come from the prospective birth cohort study in Hefei of Anhui, China. A total of 1714 mother-infant pairs are included from March 2018 and June 2021. CVH was evaluated at 24 to 28 gestational weeks by the combination of five metrics: body mass index, blood pressure, total cholesterol, glucose, and smoking. Cord blood samples were collected at delivery for the detection of related indicators. Infant neurodevelopment at 12 months was assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). We stratified the status of CVH into three levels, ideal, intermediate, and poor. Compared with the ideal CVH, poor CVH was associated with infant communication domain failure (RR = 2.06; 95 %CI, 1.24-3.42) and cord blood C-peptide levels (ß = 0.09; 95 %CI, 0.06-0.13) were higher. Cord blood C-peptide level with infant communication domain failure risk increased (RR = 3.43, 95 %CI: 2.11-5.58). Mediation analysis showed that cord blood C-peptide mediated 13.9 % of the effect. Key findings indicated that maternal poor CVH at 24 to 28 weeks gestation was associated with an increased risk of infant neurodevelopment at ASQ-3 failure in the communication domain, and cord blood C-peptide might mediate this association. The findings, if confirmed by replications, specific nursing cares among pregnant women with poor CVH, might have implications for the offspring neurodevelopment prevention strategies targeting.

SP1-activated USP27X-AS1 promotes hepatocellular carcinoma progression via USP7-mediated AKT stabilisation.

BACKGROUND: Hepatocellular carcinoma (HCC) continues to pose a significant threat to patient survival. Emerging evidence underscores the pivotal involvement of long non-coding RNAs (lncRNAs) in the cancer process. Nevertheless, our understanding of the roles and processes of lncRNAs in HCC remains limited. METHODS: The expression level of USP27X-AS1 was assessed in an HCC patient cohort through a combination of bioinformatics analysis and qRT-PCR. Subsequent biological experiments were conducted to delve into the functional aspects of USP27X-AS1. Additional molecular biology techniques, including RNA pulldown and RNA immunoprecipitation (RIP), were employed to elucidate the potential mechanisms involving USP27X-AS1 in HCC. Finally, CUT-RUN assay and other investigations were carried out to determine the factors contributing to the heightened expression of USP27X-AS1 in HCC. RESULTS: High expression of the novel oncogene USP27X-AS1 predicted poor prognosis in HCC patients. Further investigation confirmed that USP27X-AS1 promoted the proliferation and metastasis of HCC by enabling USP7 to interact with AKT, which reduced level of AKT poly-ubiquitylation and enhanced AKT protein stability, which improves protein stabilisation of AKT and promotes the progression of HCC. Moreover, we also revealed that SP1 binds to USP27X-AS1 promoter to activate its transcription. CONCLUSIONS: Novel oncogenic lncRNA USP27X-AS1 promoted HCC progression via recruiting USP7 to deubiquitinate AKT. SP1 transcriptionally activated USP27X-AS1 expression. These findings shed light on HCC and pointed to USP27X-AS1 as a potential predictive biomarker and treatment target for the malignancy.

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

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

Predictive value of NLR and PLR for immune-related adverse events: a systematic review and meta-analysis.

BACKGROUND: Currently, there is a lack of affordable and accessible indicators that can accurately predict immune-related adverse events (irAEs) resulting from the use of immune checkpoint inhibitors (ICIs). In order to address this knowledge gap, our study explore the potential predictive value of two ratios, namely the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), for irAEs in cancer patients. METHODS: A systematic search was performed in PubMed, Embase, and the Cochrane library. Studies involving NLR or PLR with irAEs were included. Quality and risk of bias of the selected studies were assessed. Forest plots were created based on Cox model analysis. Random effects meta-analyses were conducted to estimate odds ratio (OR) and its 95% confidence interval (CI). RESULTS: After screening 594 studies, a total of 7 eligible studies with 1068 cancer patients were included. Analysis based on Cox regression showed that low neutrophil-lymphocyte ratio (L-NLR) (OR = 3.02, 95% CI 1.51 to 6.05, P = 0.002) and low platelet-lymphocyte ratio (L-PLR) (OR = 1.83, 95% CI 1.21 to 2.76, P = 0.004) were associated with irAEs. In the subgroup analysis of cut-off value, when the NLR cut-off value was 3, irAEs was significantly correlated with NLR (OR = 2.63, 95% CI 1.63 to 4.26, P < 0.001). CONCLUSIONS: Both L-NLR and L-PLR have been found to be significantly associated with irAEs. Consequently, patients identified as being at a higher risk for irAEs should be subjected to more diligent monitoring and close observation.

Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Distinctly altered lipid components in hepatocellular carcinoma relate to impaired T cell-dependent antitumor immunity.

BACKGROUND AND AIMS: T cells are master effectors of anti-tumor immunity in cancer. Recent studies suggest that altered lipid metabolism imposed by the tumor microenvironment constrains anti-tumor immunity. However, the tumor-associated lipid species changes that dampen T cell ability to control tumor progression are not fully understood. Here, we plan to clarify the influences of distinctly altered lipid components in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) on T-cell function, aiming to seek lipid metabolic targets for improving T cell anti-tumor effects. METHODS: Tumor tissues and non-tumor liver from HCC patients were collected for RNA-sequencing, lipid profiling and T cell characterizing, followed by correlation analysis. Additionally, the effects of significantly changed lipid components on anti-tumor potential of T cells were tested by in vitro cell experiments and/or in vivo tumor inoculated model. RESULTS: Altered lipid metabolism coincides with impaired T cell response in HBV-related HCC. Characteristic lipid composition, significantly marked by accumulation of long-chain acylcarnitines (LCACs) and reduction of lysophosphatidylcholines (LPCs), are found in the tumor tissue. Notably, LCACs accumulated are associated with T cells exhaustion and deficient functionality, while LPCs correlate to anti-tumor effects of T cells. In particular, supplement of LPCs, including LPC (20:0) and LPC (22:0), directly promote the activation and IFN-γ secretion of T cells in vitro, and suppress tumor growth in vivo. CONCLUSIONS: Our study highlights the distinctly changed lipid components closely related to T cell dysregulation in HCC, and suggests a promising strategy by decreasing LCACs and increasing LPCs for anti-tumor immunotherapy.

Electrosynthesis of Hydrogen Peroxide Enabled by Exceptional Molecular Ni Sites in a Graphene-Supported Nickel Organic Framework.

Electrosynthesis of hydrogen peroxide (H2O2) from 2e- transfer of the oxygen reduction reaction (2e--ORR) is a potential alternative to the traditional anthraquinone process. Two-dimensional (2D) metal-organic frameworks (MOFs) supported by carbon are frequently reported as promising 2e--ORR catalysts. Herein, a graphene-supported 2D MOF of Ni3(2,3,6,7,10,11-hexahydrotriphenylene)2 is synthesized through a common hydrothermal method, which exhibits high 2e--ORR performance. It is discovered that except for emerging MOFs, exceptional molecularly dispersed Ni sites coexist in the synthesis that have the same coordination sphere of the NiO4C4 moiety as the MOF. The molecular Ni sites are more catalytically active. The graphene support contains a suitable amount of residual oxygen groups, leading to the generation of those molecularly dispersed Ni sites. The oxygen groups exhibit a moderate electron-withdrawing effect at the outer sphere of Ni sites to slightly increase their oxidation state. This interaction decreases overpotentials and kinetically improves the selectivity of the 2e- reaction pathway.

The advances of E2A-PBX1 fusion in B-cell acute lymphoblastic Leukaemia.

The E2A-PBX1 gene fusion is a common translocation in B-cell acute lymphoblastic leukaemia. Patients harbouring the E2A-PBX1 fusion gene typically exhibit an intermediate prognosis. Furthermore, minimal residual disease has unsatisfactory prognostic value in E2A-PBX1 B-cell acute lymphoblastic leukaemia. However, the mechanism of E2A-PBX1 in the occurrence and progression of B-cell acute lymphoblastic leukaemia is not well understood. Here, we mainly review the roles of E2A and PBX1 in the differentiation and development of B lymphocytes, the mechanism of E2A-PBX1 gene fusion in B-cell acute lymphoblastic leukaemia, and the potential therapeutic approaches.

Performance of DNA methylation analysis in the detection of high-grade cervical intraepithelial neoplasia or worse (CIN3+): a cross-sectional study.

It is commonly accepted that host genes show high methylation in cervical intraepithelial neoplasia 3 (CIN3) or worse (CIN3+). However, study quality varies, as does the clinical performance of markers in different populations. We aimed to validate candidate gene DNA methylation with standardized testing methods in the same batch of samples. We first compared the performance of 16 DNA methylation markers for detecting CIN3+ in the 82-sample training set, including 24 subjects with ≤ CIN1, 10 subjects with CIN2, 23 subjects with CIN3, and 25 subjects with cervical cancer (CC). Then five methylation markers were selected and subsequently validated among an independent set of 74 subjects, including 47 subjects with ≤ CIN1, 13 subjects with CIN2, 6 subjects with CIN3, and 8 subjects with CC. The results in the validation set revealed that methylation analysis of the SOX1 (SOX1m) showed a superior level of clinical performance (AUC = 0.879; sensitivity = 85.7%; specificity = 90.0%). SOX1m had better accuracy than cytology, with a reduced referral rate (23.0% vs. 31.4%) and a lower number of overtreatment (5 vs. 13) cases among high-risk human papillomavirus (hrHPV)-positive women. Importantly, among hrHPV-positive and SOX1m-negative women, only 1 CIN3 patient was at risk for follow-up after 1 year, whereas 1 CIN3 patient and 1 CC patient were at risk among hrHPV-positive and cytology-negative women. In this investigation, we screened 16 reported methylation markers to provide a basis for future studies related to potential precancerous lesion/cancer methylation markers in the Chinese population. The study also revealed that SOX1m has optimal CIN3+ detection performance, suggesting that it may be a promising biomarker for detecting CIN3+ in the Chinese population.

A Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Pharmacological Mechanism of Astragalus membranaceus for Glioma.

Glioma treatment in traditional Chinese medicine has a lengthy history. Astragalus membranaceus, a traditional Chinese herb that is frequently utilized in therapeutic practice, is a component of many Traditional Chinese Medicine formulas that have been documented to have anti-glioma properties. Uncertainty persists regarding the molecular mechanism behind the therapeutic effects. Based on results from network pharmacology and molecular docking, we thoroughly identified the molecular pathways of Astragalus membranaceus' anti-glioma activities in this study. According to the findings of the enrichment analysis, 14 active compounds and 343 targets were eliminated from the screening process. These targets were mainly found in the pathways in cancer, neuroactive ligand-receptor interaction, protein phosphorylation, inflammatory response, positive regulation of phosphorylation, and inflammatory mediator regulation of Transient Receptor Potential (TRP) channels. The results of molecular docking showed that the active substances isoflavanone and 1,7-Dihydroxy-3,9-dimethoxy pterocarpene have strong binding affinities for the respective targets ESR2 and PTGS2. In accordance with the findings of our investigation, Astragalus membranaceus active compounds exhibit a multicomponent and multitarget synergistic therapeutic impact on glioma by actively targeting several targets in various pathways. Additionally, we propose that 1,7-Dihydroxy-3,9-dimethoxy pterocarpene and isoflavanone may be the main active ingredients in the therapy of glioma.