Electrochemical Oxidation of Furfural on NiMoP/NF: Boosting Current Density with Enhanced Adsorption of Oxygenates.

Substituting the low-value oxygen evolution reaction (OER) with thermodynamically more favored organic oxidation such as furfural oxidation reaction (FOR) is regarded as a perspective approach to decrease energy cost of hydrogen evolution from water splitting. However, the kinetic of FOR can be even more sluggish than OER under large current density. In this work, a strategy is proposed to accelerate FOR by enhancing the adsorption of oxygenates on active sites. Over the prepared NiMoP/NF anode, only 1.46 V versus RHE is required in furfural solution to achieve 500 mA cm-2 , significantly better than the OER activity over commercial RuO2 /NF under the same current density (1.57 V vs RHE).

A new score for predicting intracranial hemorrhage in patients using antiplatelet drugs.

Antiplatelet drugs in patients increase the risk of intracranial hemorrhage (ICH), which can seriously affect patients' quality of life and even endanger their lives. Currently, there is no specific score for predicting the risk of ICH caused by antiplatelet drugs. We aimed to identify factors associated with ICH in patients on antiplatelet drugs and to construct and validate a predictive model that would provide a validated tool for the clinic. Data were obtained from the patient medical records inpatient system. Prediction models were built by logistic regression, the area under the curve (AUC), and column line plots. Internal validation, analytical identification and calibration of the model using AUC, calibration curves and Hosmer-Lemeshow test. The registration number of this study is ChiCTR2000031909, and the ethical review number is 2020KY087. This single-center retrospective study enrolled 753 patients treated with antiplatelet drugs, including 527 in the development cohort. Multifactorial analysis showed that male, headache or vomiting, hypertension, cerebrovascular disease, CT-defined white matter hypodensity, abnormal GCS, fibrinogen and D-dimer were independent risk factors for ICH, and lipid-lowering drugs was a protective factor. The model was constructed using these nine factors with an AUC value of 0.949. In the validation cohort, the model showed good discriminatory power with an AUC value of 0.943 and good calibration (Hosmer-Lemeshow test P value of 0.818). Based on 9 factors, we derived and validated a predictive model for ICH with antiplatelet drugs in patients. The model has good predictive value and may be an effective tool to reduce the occurrence of ICH.

Effect of oral administration of microcin Y on growth performance, intestinal barrier function and gut microbiota of chicks challenged with Salmonella Pullorum.

The lasso peptide microcin Y (MccY) effectively inhibits various serotypes of Salmonella in vitro, but the antibacterial effect against S. Pullorum in poultry is still unclear. This study was the first to evaluate the safety and anti-S. Pullorum infection of MccY in specific pathogen-free (SPF) chicks. The safety test showed that the body weight, IgA and IgM levels of serum, and cecal microbiota structure of 3 groups of chicks orally administrated with different doses of MccY (5 mg/kg, 10 mg/kg, 20 mg/kg) for 14 days were not significantly different from those of the control group. Then, the chicks were randomized into 3 groups for the experiment of anti-S. Pullorum infection: (I) negative control group (NC), (II) S. Pullorum-challenged group (SP, 5 × 108 CFU/bird), (III) MccY-treated group (MccY, 20 mg/kg). The results indicated that compared to the SP group, treatment of MccY increased body weight and average daily gain (P < 0.05), reduced S. Pullorum burden in feces, liver, and cecum (P < 0.05), enhanced the thymus, and decreased the spleen and liver index (P < 0.05). Additionally, MccY increased the jejunal villus height, lowered the jejunal and ileal crypt depth (P < 0.05), and upregulated the expression of IL-4, IL-10, ZO-1 in the jejunum and ileum, as well as CLDN-1 in the jejunum (P < 0.05) compared to the SP group. Furthermore, MccY increased probiotic flora (Barnesiella, etc.), while decreasing (P < 0.05) the relative abundance of pathogenic flora (Escherichia and Salmonella, etc.) compared to the SP group.

Diazotization of o-Aminoamidoximes for the Preparation of Energetic 6,5,6-Fused 1,2,3-Triazine-3-oxides.

Two 6,5,6-fused 1,2,3-triazine-3-oxides (4 and 6) were designed and synthesized via the reaction of o-aminoamidoximes with sodium nitrite. In addition, the ring-opening products (5, 7, and 8) derived from 1,2,3-triazine-3-oxides were isolated and characterized. A comprehensive exploration of the reaction mechanism governing the ring-opening process was performed through a combination of theoretical and experimental studies. Notably, compound 4 exhibited commendable detonation properties and low sensitivity, demonstrating its promising potential as an energetic material.

Single-Cell RNA Sequencing of Coronary Perivascular Adipose Tissue From End-Stage Heart Failure Patients Identifies SPP1+ Macrophage Subpopulation as a Target for Alleviating Fibrosis.

BACKGROUND: Perivascular adipose tissue (PVAT) is vital for vascular homeostasis, and PVAT dysfunction is associated with increased atherosclerotic plaque burden. But the mechanisms underlining coronary PVAT dysfunction in coronary atherosclerosis remain elusive. METHODS: We performed single-cell RNA sequencing of the stromal vascular fraction of coronary PVAT from 3 groups of heart transplant recipients with end-stage heart failure, including 3 patients with nonobstructive coronary atherosclerosis, 3 patients with obstructive coronary artery atherosclerosis, and 4 nonatherosclerosis control subjects. Bioinformatics was used to annotate the cellular populations, depict the cellular developmental trajectories and interactions, and explore the differences among 3 groups of coronary PVAT at the cellular and molecular levels. Pathological staining, quantitative real-time polymerase chain reaction, and in vitro studies were performed to validate the key findings. RESULTS: Ten cell types were identified among 67 936 cells from human coronary PVAT. Several cellular subpopulations, including SPP1+ (secreted phosphoprotein 1) macrophages and profibrotic fibroadipogenic progenitor cells, were accumulated in PVAT surrounding atherosclerotic coronary arteries compared with nonatherosclerosis coronary arteries. The fibrosis percentage was increased in PVAT surrounding atherosclerotic coronary arteries, and it was positively associated with the grade of coronary artery stenosis. Cellular interaction analysis suggested OPN (osteopontin) secreted by SPP1+ macrophages interacted with CD44 (cluster of differentiation 44)/integrin on fibroadipogenic progenitor cells. Strikingly, correlation analyses uncovered that higher level of SPP1 in PVAT correlates with a more severe fibrosis degree and a higher coronary stenosis grade. In vitro studies showed that conditioned medium from atherosclerotic coronary PVAT promoted the migration and proliferation of fibroadipogenic progenitor cells, while such effect was prevented by blocking CD44 or integrin. CONCLUSIONS: SPP1+ macrophages accumulated in the PVAT surrounding atherosclerotic coronary arteries, and they promoted the migration and proliferation of fibroadipogenic progenitor cells via OPN-CD44/integrin interaction and thus aggravated the fibrosis of coronary PVAT, which was positively correlated to the coronary stenosis burden. Therefore, SPP1+ macrophages in coronary PVAT may participate in the progression of coronary atherosclerosis.

Transition Metal-Promoted Carbon-Silicon Solid Acid Catalysts for the Synthesis and Process Optimization of Benzaldehyde Glycol Acetal.

A series of transition metal (M)-promoted carbon-silicon (C-M-Si; M=Mn, Fe, Co, Ni, Cu, Zn, Zr) solid acid catalysts with designated molar ratio of M/Si=1 : 8 were fabricated and exploited for acetalization of benzaldehyde (BzH) with ethylene glycol (EG). The physical and chemical properties of these C-M-Si catalysts prepared by sol-gel method were characterized by various techniques, namely, SEM, EDS, TGA-DTG, BET, XRD, FTIR, XPS, and NH3 -TPD. Among various examined acidic C-M-Si catalysts, the C-Fe-Si catalyst exhibited the optimal catalytic activity with the benzaldehyde glycol acetal (BEGA) yield of 97.67 %, in excellent agreement with the value (97.88 %) predicted by the response surface methodology (RSM) based on a Box-Behnken design (BBD). C-Fe-Si catalyst with the high catalytic activities and excellent stability and reusability may be ascribed to the suitable acidity and uniform surface distribution of active sites requisite for the acid-catalyzed acetalization reaction.

Risk factors for thrombolysis-related intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: Thrombolysis-related intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been updated. AIM: We conducted a systematic review to identify risk factors for thrombolysis-related intracranial hemorrhage. METHOD: The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316160). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. RESULTS: Of 6083 citations, we included 105 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with age, National Institutes of Health stroke scale, leukoaraiosis, hypertension, atrial fibrillation, diabetes, total cholesterol, proteinuria, fibrinogen levels, creatinine, homocysteine, early infarct signs, antiplatelet therapy and anticoagulant therapy; In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and weight, sex, platelet count, uric acid, albumin and white matter hyperintensity. Leukoaraiosis, cardiovascular disease, total cholesterol, white blood cell count, proteinuria, fibrinogen levels, creatinine, homocysteine and early CT hypodensities are not included in most intracranial hemorrhage risk assessment models. CONCLUSION: This study informs risk prediction for thrombolysis-related intracranial hemorrhage, it also informs guidelines for intracranial hemorrhage prevention and future research.

Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

PURPOSE: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Risk Factors for Anticoagulant-Associated Intracranial Hemorrhage: A Systematic Review and Meta-analysis.

BACKGROUND: Anticoagulant-associated intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been published. METHODS: We conducted a systematic review to identify risk factors for anticoagulant-associated intracranial hemorrhage. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316750). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. I2 statistics were used to evaluate heterogeneity. RESULTS: Of 7322 citations, we included 20 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with race, Glasgow Coma Scale, stroke, leukoaraiosis, cerebrovascular disease, tumor, atrial fibrillation, previous bleeding, international normalized ratio, serum albumin, prothrombin time, diastolic blood pressure, and anticoagulant. Low-certainty evidence may be associated with age, cerebral microbleeds, smoking, alcohol intake, platelet count, and antiplatelet drug. In addition, we found very low-certainty evidence that there may be little to no association between the risk of intracranial hemorrhage and hypertension and creatinine clearance. Leukoaraiosis, cerebral microbleeds, cerebrovascular disease, and international normalized ratio are not included in most risk assessment models. CONCLUSIONS: This study informs risk prediction for anticoagulant-associated intracranial hemorrhage and informs guidelines for intracranial hemorrhage prevention and future research.

The Identification of Prognostic and Metastatic Alternative Splicing in Skin Cutaneous Melanoma.

Skin cutaneous melanoma (SKCM) is a type of highly invasive cancer originated from melanocytes. It is reported that aberrant alternative splicing (AS) plays an important role in the neoplasia and metastasis of many types of cancer. Therefore, we investigated whether ASEs of pre-RNA have such an influence on the prognosis of SKCM and the related mechanism of ASEs in SKCM. The RNA-seq data and ASEs data for SKCM patients were obtained from the TCGA and TCGASpliceSeq database. The univariate Cox regression revealed 1265 overall survival-related splicing events (OS-SEs). Screened by Lasso regression, 4 OS-SEs were identified and used to construct an effective prediction model (AUC: .904), whose risk score was proved to be an independent prognostic factor. Furthermore, Kruskal-Wallis test and Mann-Whitney-Wilcoxon test showed that an aberrant splicing type of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) regulated by CDC-like kinase 1 (CLK1) was associated with the metastasis and stage of SKCM. Besides, the overlapped signal pathway for AIMP2 was galactose metabolism identified by the co-expression analysis. External database validation also confirmed that AIMP2, CLK1, and the galactose metabolism were associated with the metastasis and stage of SKCM patients. ChIP-seq and ATAC-seq methods further confirmed the transcription regulation of CLK1, AIMP2, and other key genes, whose cellular expression was detected by Single Cell Sequencing. In conclusion, we proposed that CLK1-regulated AIMP2-78704-ES might play a critical role in the tumorigenesis and metastasis of SKCM via galactose metabolism. Besides, we established an effective model with MTMR14-63114-ES, URI1-48867-ES, BATF2-16724-AP, and MED22-88025-AP to predict the metastasis and prognosis of SKCM patients.

From Nitro- to Heterocycle-Functionalized 1,2,4-Triazol-3-one Derivatives: Achieving High-Performance Insensitive Energetic Compounds.

5-Nitro-1,2,4-triazol-3-one, a nitro-functionalized 1,2,4-triazol-3-one (TO) derivative, shows excellent energetic properties and promising application potential. However, the use of the TO skeleton as an energetic material is still largely underexplored both theoretically and practically. We report here a mild and efficient method for obtaining the TO skeleton via a reaction of aminocarbohydrazide with BrCN. Two energetic compounds (2 and 5) were synthesized and fully characterized by 15N nuclear magnetic resonance, two-dimensional 1H-15N heteronuclear multiple-bond correlation, and single-crystal X-ray diffraction. The reaction mechanism was also studied with the aid of quantum calculations. Compound 2 shows promising properties as a high-performance insensitive energetic material.

Editor's Choice - Severe Bleeding Risks of Direct Oral Anticoagulants in the Prevention and Treatment of Venous Thromboembolism: A Network Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 - 4.12) and edoxaban (OR 2.64, 95% CI 1.36 - 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 - 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6). CONCLUSIONS: For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

Risk of nonmajor bleeding upon use of direct oral anticoagulants for preventing and treating venous thromboembolism: A network meta-analysis.

INTRODUCTION: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to nonmajor bleeding, which may lead to venous thromboembolism (VTE) recurrence. We aimed to determine the risk of nonmajor bleeding using different DOACs to prevent and treat VTE. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception until January 6, 2021. The incidence of clinically relevant nonmajor bleeding and minor bleeding was investigated. In frequentist-based network meta-analysis, we analyzed the odds ratio (OR) with 95% CI and the surface under the cumulative ranking curves (SUCRA). RESULTS: Twenty-seven randomized controlled trials (RCTs) (involving 64,493 patients) were included. For preventing VTE, the risk for clinically relevant nonmajor bleeding was lowest for apixaban, followed by that for low-molecular weight heparin (LMWH), dabigatran, edoxaban, and rivaroxaban. The risk for minor bleeding was lowest for apixaban, followed by that for rivaroxaban, LMWH, dabigatran, and edoxaban. For treating VTE, the risk for clinically relevant nonmajor bleeding was also lowest for apixaban, followed by that for edoxaban, vitamin K antagonists (VKAs), and rivaroxaban. The risk for minor bleeding was lowest for apixaban, followed by that for rivaroxaban and VKAs. CONCLUSIONS: Regardless of whether it was used for preventing or treating VTE, apixaban had the lowest risk of nonmajor bleeding. This suggests that apixaban may have a lower risk of nonmajor bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA). RESULTS: We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8). CONCLUSIONS: For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.

Efficacy and safety of app-based remote warfarin management during COVID-19-related lockdown: a retrospective cohort study.

This study aimed to explore the effectiveness, and safety of internet-based warfarin management during the pandemic. In this single-center retrospective cohort study, we compared the safety and efficacy of online warfarin management using a smartphone app (the Alfalfa app) versus conventional outpatient clinic management from January 1, 2020 to March 31, 2020. Patients in the online management group used the Alfalfa app to communicate coagulation test results and other relevant information to a doctor or clinical pharmacist, who then responded with the dose adjustment plan and the date of the next blood test. The outcomes examined were the time in therapeutic range (TTR), incidence of clinical events (i.e., bleeding events, thrombotic events, warfarin-related emergency department visits, and warfarin-related hospital admissions), and the distribution of international normalized ratio (INR) values. Data from 117 patients were analyzed in this study. TTR was significantly higher in the online group than in the offline group (61.0% vs. 39.6%, P < 0.01). Incidence of major bleeding events, thrombotic events, and warfarin-related hospital admissions were comparable between the online and offline groups. However, minor bleeds (5.3% vs. 28.3%, P < 0.01) and warfarin-related emergency department visits (1.8% vs. 23.3%, P = 0.02) were significantly fewer in the online group than in the offline group. The proportion of INR values in the therapeutic range (53.8% vs. 40.1%, P < 0.01) was significantly higher in the online group. Warfarin management using the Alfalfa app appears to be a safe and effective method for warfarin management when patients cannot physically visit hospitals for follow-up.

Risk factors for antiplatelet drug-associated intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet drug-associated intracranial hemorrhage has a high mortality rate, and many factors can cause antiplatelet drug-associated intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been published. AIM: We conducted a systematic review to identify risk factors of antiplatelet drug-associated intracranial hemorrhage. METHOD: The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022311647). All studies written in English that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for antiplatelet drug-associated intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. I2 statistics were used to evaluate heterogeneity. RESULTS: Of 2844 citations, we included 6 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with race, low BMI, GCS, severe bleeding, headache or vomiting, cerebrovascular disease, lacunar small vessel disease, cardiovascular disease, blood sugar, blood pressure, CT-defined white matter hypodensity, antihypertensive drugs, and antiplatelet therapy. In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and age, sex, and dual antithrombotic treatment or anticoagulant. CT-defined white matter hypodensity is not included in most intracranial hemorrhage risk assessment models. CONCLUSION: This study summarizes risk factors for antiplatelet drug-associated intracranial hemorrhage, which is significant in preventing intracranial hemorrhage.

Advanced aromatic organic compounds removal from refractory coking wastewater in a step-feed three-stage integrated A/O bio-filter: Spectrum characterization and biodegradation mechanism.

Extensive presence of aromatic organic compounds (AOCs) is a major course for the non-biodegradability of coking wastewater (COW). In-depth understanding of bio-degradation of AOCs is crucial for optimizing the design and operation of COW biological treatment systems in practical applications. Herein, the behavior and fate of AOCs were explored in a lab-scale step-feed three-stage integrated A/O biofilter (SFTIAOB) treating synthetic COW. Long-term operation demonstrated that COD, phenol, indole, quinoline and pyridine could be simultaneously removed. Phenol and indole were chiefly removed by anoxic zones, while quinoline and pyridine removal occurred in both anoxic and aerobic zones. Ultraviolet-visible spectrum observed that initial carboxylation and subsequent ring cracking and mineralization. Infrared spectroscopy also confirmed that key functional groups were cracked and produced during AOCs bio-degradation. Three-dimensional fluorescence spectrum indicated that significant transformation and elimination of tryptophan and humic acid with high molecular weight. Ring cleavage, distinct degradation and even complete mineralization of complex AOCs were further verified by gas chromatography-mass spectrometry. Moreover, functional degrading bacteria and aromatic ring-cleavage enzymes was successfully identified. Finally, AOCs biodegradation mechanisms by alternating anoxic and aerobic treatment was unraveled. This research provides thorough insights on AOCs biodegradation using a step-feed multi-stage alternating anoxic/oxic COW treatment process.

Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis.

BACKGROUND: Soft tissue sarcomas (STS) has a high rate of early metastasis. In this study, we aimed to uncover the potential metastasis mechanisms and related signaling pathways in STS with differentially expressed genes and tumor-infiltrating cells. METHODS: RNA-sequencing (RNA-seq) of 261 STS samples downloaded from the Cancer Genome Atlas (TCGA) database were used to identify metastasis-related differentially expressed immune genes and transcription factors (TFs), whose relationship was constructed by Pearson correlation analysis. Metastasis-related prediction model was established based on the most significant immune genes. CIBERSORT algorithm was performed to identify significant immune cells co-expressed with key immune genes. The GSVA and GSEA were performed to identify prognosis-related KEGG pathways. Ultimately, we used the Pearson correlation analysis to explore the relationship among immune genes, immune cells, and KEGG pathways. Additionally, key genes and regulatory mechanisms were validated by single-cell RNA sequencing and ChIP sequencing data. RESULTS: A total of 204 immune genes and 12 TFs, were identified. The prediction model achieved a satisfactory effectiveness in distant metastasis with the Area Under Curve (AUC) of 0.808. LTB was significantly correlated with PAX5 (P < 0.001, R = 0.829) and hematopoietic cell lineage pathway (P < 0.001, R = 0.375). The transcriptional regulatory pattern between PAX5 and LTB was validated by ChIP sequencing data. CONCLUSIONS: We hypothesized that down-regulated LTB (immune gene) modulated by PAX5 (TF) in STSs may have the capability of inducing cancer cell metastasis in patients with STS.

Differential expression of microRNAs in the human fetal left and right cerebral cortex.

Human brain is anatomically and functionally asymmetric. How brain asymmetry is initiated and established during fetal development is poorly understood. Accumulating evidence has shown that microRNAs (miRNAs) play crucial roles in brain development and function. In this study, we investigate miRNA expression profiles in left and right hemispheres of human fetal brains at 12 weeks post conception (PC), and identify 42 miRNAs showing differential expression between two hemispheres using Affymetrix microarray analyses. Target genes for left- and right-biased miRNAs are largely involved in developmental and functional regulations in the cortex such as axon guidance, GABAergic synapse and dopaminergic synapse pathways. Moreover, we find that predicted targets associated with canonical and non-canonical WNT signaling pathway show variations and differential expression between two hemispheres in response to left- and right-biased miRNAs. Our results highlight a potential role of miRNAs in regulating asymmetric development of human fetal brains.