The research advances in Kirsten rat sarcoma viral oncogene homolog (KRAS)-related cancer during 2013 to 2022: a scientometric analysis.

Introduction: Cancer represents a significant global public health concern. In recent years, the incidence of cancer has been on the rise worldwide due to various factors, including diet, environment, and an aging population. Simultaneously, advancements in tumor molecular biology and genomics have led to a shift from systemic chemotherapy focused on disease sites and morphopathology towards precise targeted therapy for driver gene mutations. Therefore, we propose a comprehensive review aimed at exploring the research hotspots and directions in the field of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant cancers over the past decade, providing valuable insights for cancer treatment strategies. Specifically, we aim to present an intellectual landscape using data obtained from the Web of Science (WoS) regarding KRAS mutation. Methods: Bibliometrix, VOSviewer, CiteSpace, and HistCite were employed to conduct scientometric analyses on national publications, influential authors, highly cited articles, frequent keywords, etc. Results: A total of 16,609 publications met the screening criteria and exhibited a consistent annual growth trend overall. Among 102 countries/regions, the United States occupied the vast majority share of the published volume. The journal Oncotarget had the highest circulation among all scientific publications. Moreover, the most seminal articles in this field primarily focus on biology and targeted therapies, with overcoming drug resistance being identified as a future research direction. Conclusion: The findings of the thematic analysis indicate that KRAS mutation in lung cancer, the prognosis following B-Raf proto-oncogene, serine/threonine kinase (BRAF) or rat sarcoma (RAS) mutations, and anti-epidermal growth factor receptor (EGFR)-related lung cancer are the significant hotspots in the given field. Considering the significant advancements made in direct targeting drugs like sotorasib, it is anticipated that interest in cancers associated with KRAS mutations will remain steadfast.

Unveiling Immune Infiltration Characterizing Genes in Hypertrophic Cardiomyopathy Through Transcriptomics and Bioinformatics.

Background: Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways. Methods: First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database. Results: Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings. Conclusion: Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications.

A molecularly imprinted electrochemical sensor MIP/Cu-MOF/rGO/AuNPs/GCE for highly sensitive detection of electroneutral organophosphorus pesticide residues.

A novel electrochemical sensor, MIP/Cu-MOF/rGO/AuNPs/GCE, was developed by depositing gold nanoparticles, coating Cu-MOF/GO on the surface of glassy carbon electrode (GCE) before electroreducing graphene oxide (GO) to rGO and covering molecularly imprinted membrane by electropolymerization for highly sensitive detection of electroneutral organophosphorus pesticide residues in agricultural product. Cyclic voltammetry, differential pulse voltametry, scanning electron microscopy, energy-dispersive spectroscopy, and atomic force microscopy were used to characterize the imprinted sensor. Several key factors such as chitosan concentration, suspension volume, pH of polymerization solution, and polymerization scanning rate during preparation of the imprinted sensor were optimized in detail. When electroneutral phosmet was used as a template, the linear range of MIP/Cu-MOF/rGO/AuNPs/GCE for detecting phosmet was 1.00 × 10-14-5.00 × 10-7 mol/L with the limit of detection of 7.20 × 10-15 mol/L at working potentials of - 0.2 to 0.6 V. The selectivity, reproducibility, and repeatability of MIP/Cu-MOF/rGO/AuNPs/GCE were all acceptable. The recoveries of this method for determining phosmet in real samples ranged from 94.2 to 106.5%. The MIP/Cu-MOF/rGO/AuNPs/GCE sensor could be applied to detect electroneutral pesticide residues in organisms and agricultural products.

Energy stress promotes P-bodies formation via lysine-63-linked polyubiquitination of HAX1.

Energy stress, characterized by the reduction of intracellular ATP, has been implicated in various diseases, including cancer. Here, we show that energy stress promotes the formation of P-bodies in a ubiquitin-dependent manner. Upon ATP depletion, the E3 ubiquitin ligase TRIM23 catalyzes lysine-63 (K63)-linked polyubiquitination of HCLS1-associated protein X-1 (HAX1). HAX1 ubiquitination triggers its liquid‒liquid phase separation (LLPS) and contributes to P-bodies assembly induced by energy stress. Ubiquitinated HAX1 also interacts with the essential P-body proteins, DDX6 and LSM14A, promoting their condensation. Moreover, we find that this TRIM23/HAX1 pathway is critical for the inhibition of global protein synthesis under energy stress conditions. Furthermore, high HAX1 ubiquitination, and increased cytoplasmic localization of TRIM23 along with elevated HAX1 levels, promotes colorectal cancer (CRC)-cell proliferation and correlates with poor prognosis in CRC patients. Our data not only elucidate a ubiquitination-dependent LLPS mechanism in RNP granules induced by energy stress but also propose a promising target for CRC therapy.

Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation.

Pathogenic gut microbiota is responsible for a few debilitating gastrointestinal diseases. While the host immune cells do produce extracellular vesicles to counteract some deleterious effects of the microbiota, the extracellular vesicles are of insufficient doses and at unreliable exposure times. Here we use mechanical stimulation of hydrogel-embedded macrophage in a bioelectronic controller that on demand boost production of up to 20 times of therapeutic extracellular vesicles to ameliorate the microbes' deleterious effects in vivo. Our miniaturized wireless bioelectronic system termed inducible mechanical activation for in-situ and sustainable generating extracellular vesicles (iMASSAGE), leverages on wireless electronics and responsive hydrogel to impose mechanical forces on macrophages to produce extracellular vesicles that rectify gut microbiome dysbiosis and ameliorate colitis. This in vivo controllable extracellular vesicles-produced system holds promise as platform to treat various other diseases.

A radiomics strategy based on CT intra-tumoral and peritumoral regions for preoperative prediction of neoadjuvant chemoradiotherapy for esophageal cancer.

OBJECTIVE: Develop a method for selecting esophageal cancer patients achieving pathological complete response with pre-neoadjuvant therapy chest-enhanced CT scans. METHODS: Two hundred and one patients from center 1 were enrolled, split into training and testing sets (7:3 ratio), with an external validation set of 30 patients from center 2. Radiomics features from intra-tumoral and peritumoral images were extracted and dimensionally reduced using Student's t-test and least absolute shrinkage and selection operator. Four machine learning classifiers were employed to build models, with the best-performing models selected based on accuracy and stability. ROC curves were utilized to determine the top prediction model, and its generalizability was evaluated on the external validation set. RESULTS: Among 16 models, the integrated-XGBoost and integrated-random forest models performed the best, with average ROC AUCs of 0.906 and 0.918, respectively, and RSDs of 6.26 and 6.89 in the training set. In the testing set, AUCs were 0.845 and 0.871, showing no significant difference in ROC curves. External validation set AUCs for integrated-XGBoost and integrated-random forest models were 0.650 and 0.749. CONCLUSION: Incorporating peritumoral radiomics features into the analysis enhances predictive performance for esophageal cancer patients undergoing neoadjuvant chemoradiotherapy, paving the way for improved treatment outcomes.

Automated segmentation of cell organelles in volume electron microscopy using deep learning.

Recent advances in computing power triggered the use of artificial intelligence in image analysis in life sciences. To train these algorithms, a large enough set of certified labeled data is required. The trained neural network is then capable of producing accurate instance segmentation results that will then need to be re-assembled into the original dataset: the entire process requires substantial expertise and time to achieve quantifiable results. To speed-up the process, from cell organelle detection to quantification across electron microscopy modalities, we propose a deep-learning based approach for fast automatic outline segmentation (FAMOUS), that involves organelle detection combined with image morphology, and 3D meshing to automatically segment, visualize and quantify cell organelles within volume electron microscopy datasets. From start to finish, FAMOUS provides full segmentation results within a week on previously unseen datasets. FAMOUS was showcased on a HeLa cell dataset acquired using a focused ion beam scanning electron microscope, and on yeast cells acquired by transmission electron tomography. RESEARCH HIGHLIGHTS: Introducing a rapid, multimodal machine-learning workflow for the automatic segmentation of 3D cell organelles. Successfully applied to a variety of volume electron microscopy datasets and cell lines. Outperforming manual segmentation methods in time and accuracy. Enabling high-throughput quantitative cell biology.

ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer.

Breast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 (TET3) is a DNA demethylase. Prior research has demonstrated that TET3 is highly expressed in various human malignant tumors. However, the exact function and mechanism of TET3 in breast cancer remain unclear. In this study, we investigated TET3 expression in breast cancer and its correlation with clinicopathological characteristics of breast cancer patients. The results presented that TET3 expression was significantly increased in breast cancer and associated with the PAM50 subtype. Subsequently, we performed receiver operating characteristic, survival, and Cox hazard regression analyses. These results suggest that TET3 expression is associated with a poor prognosis and may be an indirect independent prognostic indicator in breast cancer. We also established a protein-protein interaction (PPI) network of TET3 and executed enrichment analyses of TET3 co-expressed genes, revealing their primary association with the cell cycle. Moreover, we identified noncoding RNAs (ncRNAs) contributing to TET3 overexpression using expression, correlation, and survival analyses. We identified the LINC01521/hsa-miR-29a-3p axis as the primary TET3 upstream ncRNA-related pathway in breast cancer. Furthermore, TET3 expression was positively associated with immune cell infiltration, immune cell biomarkers, and eight immune checkpoint gene expressions in breast cancer. TET3 expression also correlated with patient responses to immunotherapy. Finally, we conducted subcellular localization and immunohistochemical staining analysis of TET3 in breast cancer. We found that TET3 localized to the nucleoplasm, vesicles, and cytosol in the MCF-7 cell line, and TET3 expression was significantly upregulated in breast cancer tissues compared to para-tumor tissues. Our findings indicate that ncRNA-mediated overexpression of TET3 predicts an unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Identification of C4BPA as biomarker associated with immune infiltration and prognosis in breast cancer.

Background: C4BPA is a gene that encodes the C4BP protein α chain and is involved in the complement system. C4BPA is regarded as a new biomarker for cancer, especially for non-small cell lung cancer and ovarian cancer. However, its role in breast cancer (BC) has not yet been determined. Methods: In this research, we used a bioinformatics approach to assess the prognostic significance of C4BPA in BC. Utilizing a variety of databases and analysis tools, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), R, STRING, and the Kaplan-Meier plotter, we specifically assessed the connection between C4BPA and BC. Results: C4BPA expression was markedly decreased in BC tissues compared to its expression in normal breast tissues (P<0.05). Additionally, a receiver operating characteristic (ROC) curve revealed that C4BPA has a significant capacity for prognostication and diagnostics. Additionally, C4BPA expression was linked to some immune infiltrating cells' functionality, according to gene set enrichment analysis (GSEA) and immune infiltration analysis. Low C4BPA expression was additionally related to poor progression-free interval (PFI) and overall survival (OS), according to the Kaplan-Meier method. We also found that C4BPA expression was independently connected to PFI and OS through Cox regression analysis. Finally, prognostic analysis of the various subgroups of breast invasive carcinoma (BRCA/BIC) in TCGA showed that patients with low C4BPA expression might have worse PFI and OS in patients with Luminal A compared to other BC subtypes. Conclusions: In conclusion, these results revealed that C4BPA could potentially act as a diagnostic biomarker for BC patients indicating unfavorable prognoses and offers valuable knowledge for creating therapeutics and prognostic indicators.

Identification of serum exosomal miRNA biomarkers for diagnosis of Rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation-induced joint damage, which can cause lasting disability. Therefore, early diagnosis and treatment of RA are crucial. Herein, we evaluated whether exosomal microRNAs (miRNAs) could be served as promising biomarkers that can accelerate the diagnosis of RA and development of therapies for RA. METHODS: First, we performed small RNA sequencing to determine the miRNA profiles of serum exosomes within a screening cohort comprised of 18 untreated active RA patients, along with 18 age and gender-matched healthy controls (HCs). Subsequently, the miRNA profiles were then validated in a training cohort consisting of 24 RA patients and 24 HCs by RT-qPCR. Finally, the selected exosomal miRNAs were validated in a larger cohort comprising 108 RA patients and 103 HCs. The diagnostic efficacy of the exosomal miRNAs was evaluated by receiver operating characteristic (ROC) curve analysis. Biological functions of the miRNAs were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Our results first demonstrated a noteworthy upregulation of three candidate miRNAs (miR-885-5p, miR-6894-3p, and miR-1268a) in the RA patients' serum exosomes compared to HCs. The combination of three miRNAs along with anti- citrullinated peptide antibodies (ACPA) exhibited excellent diagnostic accuracy, yielding an area under the curve (AUC) of 0.963 (95 % CI : 0.941-0.984), sensitivity of 87.96 %, and specificity of 93.20 %. Notably, miR-885-5p exhibited remarkable discriminatory capacity by itself in indistinguishing ACPA- negative RA patients from HCs, with an AUC of 0.993 (95 % CI : 0.978-1.000), sensitivity of 96.67 %, and specificity of 100 %. Moreover, the expression of miR-1268a in the assessment of therapeutic effectiveness displayed significant reduction on 29th day of Methotrexate (MTX) treatment in RA patients. This decreased expression paralleled with trends observed in tender 28-joint count (TJC28), swollen 28-joint count (SJC28), and disease activity score with 28-joint count using C-reactive protein (DAS28-CRP), all of which are indicative of RA disease activity. Finally, predictive analysis indicated that, these three exosomal miRNAs target pivotal signaling molecules involved in inflammatory pathways, thereby demonstrating effective modulation of the immune system. CONCLUSIONS: In this study, we successfully demonstrated the promising potential for serum exosomal miRNAs, particularly miR-885-5p, miR-6894-3p and miR-1268a as biomarkers for early diagnosis and prediction of RA for the first time.

Integral trends in research of lead exposure and child health from 2012 to 2022: a bibliometric analysis.

Lead poisoning in children is a non-negligible and ongoing threat to children's health and optimal development worldwide. There is no sufficient scientometric analysis available on this subject, though. Aiming to uncover the research development, hotspots, and possible future orientation, we performed a scientometric analysis of related publications from 2012 to 2022. Initial information was accessed using the "Analysis Results" and "Create Citation Report" sections of the Web of Science core collection database, which were utilized to find original publications in this field of research. Biblioshiny and VOSviewer software were applied to further analyze and visualize the data. The research addressed a range of topics, including yearly publications, highly cited articles, co-cited references, journals, authors, nations, organizations, and keywords. A total of 883 articles were retrieved. From 2018 to 2021, the annual publication output was abundant and peaked in 2019. Among 111 countries, the USA obtained the highest number of documents issued, total citations, and total link strength. Meanwhile, most of the top 15 institutions, including the top four, are located in the USA. Further, we spotted greater scopes with development potential, including enhancing records to lessen exposure to harmful risks, improving methods for observing lead sources, and elucidating the gradient link between lead poisoning symptoms and concentrations. We anticipate that our research will assist researchers in summarizing previous research and providing perspectives for workable prospective study topics.

Catalytic Enantioselective Nucleophilic α-Chlorination of Ketones with NaCl.

Catalytic enantioselective α-chlorination of ketones is a highly desirable process. Different from the conventional approaches that employ corrosive electrophilic chlorination reagents, the process disclosed here employs nucleophilic chloride, aqueous NaCl solution, and even seawater, as green inexpensive chlorine sources. This mechanistically distinct and electronically opposite approach provides facile access to diverse highly enantioenriched acyclic α-chloro ketones that are less straightforward by conventional approaches. With a chiral thiourea catalyst, a range of racemic α-keto sulfonium salts underwent enantioconvergent carbon-chlorine bond formation with high efficiency and excellent enantioselectivity under mild conditions. The sulfonium motif plays a crucial triple role by permitting smooth dynamic kinetic resolution to take place via a chiral anion binding mechanism in a well-designed phase-transfer system. This protocol represents a new general platform for the asymmetric nucleophilic α-functionalization of carbonyl compounds.

Mn2+/CpG Oligodeoxynucleotides Codecorated Black Phosphorus Nanosheet Platform for Enhanced Antitumor Potency in Multimodal Therapy.

Manganese ions (Mn2+)-coordinated nanoparticles have emerged as a promising class of antitumor nanotherapeutics, capable of simultaneously disrupting the immunosuppressive tumor microenvironment (TME) and triggering the stimulator of interferon genes (STING) pathway-dependent antitumor immunity. However, the activation of STING signaling by Mn2+-based monotherapies is suboptimal for comprehensive stimulation of antigen presenting cells and reversal of immunosuppression in the TME. Here, we report the design of a Mn2+/CpG oligodeoxynucleotides (ODNs) codecorated black phosphorus nanosheet (BPNS@Mn2+/CpG) platform based on the Mn2+ modification of BPNS and subsequent adsorption of synthetic CpG ODNs. The coordination of Mn2+ significantly improved the stability of BPNS and the adsorption of CpG ODNs. The acidic TME and endosomal compartments can disrupt the Mn2+ coordination, triggering pH-responsive release of CpG ODNs and Mn2+ to effectively activate the Toll-like receptor 9 and STING pathways. As a result, M2-type macrophages and immature dendritic cells were strongly stimulated in the TME, thereby increasing T lymphocyte infiltration and reversing the immunosuppression within the TME. Phototherapy and chemodynamic therapy, utilizing the BPNS@Mn2+/CpG platform, have demonstrated efficacy in inducing immunogenic cell death upon 808 nm laser irradiation. Importantly, the treatment of BPNS@Mn2+/CpG with laser irradiation exhibited significant therapeutic efficacy against the irradiated primary tumor and effectively suppressed the growth of nonirradiated distant tumor. Moreover, it induced a robust immune memory, providing long-lasting protection against tumor recurrence. This study demonstrated the enhanced antitumor potency of BPNS@Mn2+/CpG in multimodal therapy, and its proof-of-concept application as a metal ion-modified BPNS material for effective DNA/drug delivery and immunotherapy.

The effects of scar in psychological disorder: A bibliometric analysis from 2003 to 2022.

Scars are fibrous tissues that replace normal tissue during the wound healing process. Scarring can lead to low self-esteem, social impairment, depression, anxiety, and other psychiatric and psychological distress, necessitating a comprehensive understanding of the latest perspectives, topical research, and directions in scarring-mental health. This is a biblioshiny and VOSviewer based bibliometric analysis study. All data were obtained from the Web of Science, and a total of 664 articles from 2003 to 2022 met the criteria. The last 7 years have been a period of rapid growth in the field, with 2022 having the highest number of articles. The United States is the core country with the highest production and citation rate. The most cited literature was written in 2003 by Van Loey NE et al. Van Loey NE is the most prolific and influential author in this field. The top five popular keywords include "quality of life", "depression", "management", "anxiety", and "prevalence". The paper concludes that the current focus of scholars in the field is on the treatment of scars and that multidisciplinary treatment of such patients is worth exploring. These findings provide relevant researchers with the current state of research and possible future directions in this field.

Treatment of brainstem and fourth ventricle lesions by the full neuroendoscopic telovelar approach.

OBJECTIVE: To explore the surgical techniques, advantages, and disadvantages of neuroendoscopic telovelar approach in the treatment of brainstem and fourth ventricle lesions. METHODS: The clinical data of 5 patients treated by neuroendoscopic telovelar approach from March 2020 to March 2022 were analyzed retrospectively. RESULTS: Among the 5 patients, there were 3 cavernous hemangiomas in pontine arm and 2 tumors in brainstem and fourth ventricle. All patients could successfully complete the operation, and 4 patients recovered well, other 1 patient discharged automatically for serious complications of other systems after the operation. CONCLUSION: The telovelar approach has gained popularity as a safe and effective strategy for lesions in fourth ventricular and brainstem. However, without removing the posterior arch of the atlas, it is difficult to enter the upper part of the fourth ventricle under a microscope. Transcranial neuroendoscopy can effectively compensate for the shortcomings of microscopy, whether used as an auxiliary measure for microsurgery or alone with proficient endoscopic techniques, it will provide greater application in minimally invasive surgery for fourth ventricle and brainstem lesions. By utilizing the excellent degree of freedom of transcranial neuroendoscopy, there is no need to open the posterior arch of the atlas, making the surgery more minimally invasive. However, the sample size of this study is small, and it was completed under the very mature neuroendoscopic technology of our team. Its general safety and practicality still require extensive clinical research validation.

Surgical Clipping of Intracranial Aneurysms Using a Transcranial Neuroendoscopic Approach.

OBJECTIVE: This retrospective study was performed to evaluate the feasibility and safety of surgically clipping intracranial aneurysms using a transcranial neuroendoscopic approach. METHODS: A total of 229 patients with cerebral aneurysms were included in our study, all of whom were treated with clamping surgery at Wuhan University People's Hospital. They were divided into neuroendoscopic and microscopic groups, according to whether or not neuroendoscopy was used for the clamping surgery. We statistically analyzed the patients' baseline data, surgical outcomes, and complications, which were then evaluated to assess the treatment effect. RESULTS: The baseline characteristics were not statistically significant, except for gender, for which the proportions of female patients in the two groups were 69 (56.1%) and 46 (43.4%). There were no patients with incomplete aneurysm clamping or parent vessel occlusion in the neuroendoscopic group, and there were 4 (3.8%) and 2 (1.9%) in the microscopic group, respectively; however, there was no statistically significant difference in the comparison of the two groups. The mean operative times of the two groups were 181 min and 154 min, respectively, and were statistically different. However, the mRS scores of the two groups showed no significant difference in patient prognosis. The differences in complications (including limb hemiplegia, hydrocephalus, vision loss, and intracranial infection) were not statistically significant, except for cerebral ischemia, for which the proportions of patients in the two groups were 8 (6.5%) and 16 (15.1%). CONCLUSIONS: Neuroendoscopy can provide clear visualization and multi-angle views during aneurysm clipping, which is helpful for ensuring adequate clipping and preventing complications.

Access to Amides and Lactams via Pyridotriazole as a Transformable Directing Group.

Amide and lactam frameworks were synthesized via an efficient two-step strategy. In this protocol, pyridotriazoles were first treated with isocyanates to form the corresponding amides, which were found to be sufficiently reactive to undergo subsequent intramolecular N-H insertion in the absence of any additional reagents or catalysts.

Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway.

The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1ß, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.