Association between the recommended volume of leisure-time physical activity and erectile dysfunction: A cross-sectional analysis of the national health and nutrition examination survey, 2001-2004.

Objective: Physical activity-related interventions alleviate the severity of erectile dysfunction (ED), but it is unknown whether the recommended volume of physical activity (PA) or a higher level of physical activity reduces the likelihood of ED in adult males. We aimed to evaluate the association between the recommended volume of PA and ED among US male adults. Design: A nationally representative cross-sectional survey. Setting: National Health and Nutrition Examination Survey 2001-2004. Participants: A total of 2509 men aged ≥20 years were enrolled. Primary and secondary outcome measures: ED and PA were assessed by a standardised self-report questionnaire. Weighted logistic regression analysis and spline fitting were used to assess the relationship between PA volume and the odds of ED. Results: Among 2509 US adult males, the mean (standard error) age was 43.7 (0.46) years. A total of 61.1 % of men reached the recommended volume of aerobic PA. Compared with participants not meeting the PA guidelines, individuals who had recommended aerobic activities demonstrated a 34 % reduction in the odds of having ED (OR 0.66, 95 % CI 0.48-0.90; p = 0.011). Notably, according to the restricted cubic spline, we revealed a dose‒response pattern between PA volume and reduced odds of ED, even when exceeding the recommended PA levels. When compared to males with moderate-equivalent PA of less than 150 min/week, the odds of ED in those with moderate-equivalent PA levels of 150-300 min/week and >300 min/week decreased by 22 % and 39 %, respectively. Compared with participants who did not meet the PA guidelines, the multivariable-adjusted ORs (95 % CIs) of ED associated with adequate PA volumes were 0.37 (0.22-0.61) among non-smokers and 0.85 (0.57-1.25) among current smokers (p for interaction = 0.023). Conclusions and Relevance: Our findings supported the benefit of meeting the guideline-recommended PA equivalents or higher volumes for ED prevention. However, PA-related benefit might be significantly diminished by smoking.

LILRB2 inhibition enhances radiation sensitivity in non-small cell lung cancer by attenuating radiation-induced senescence.

Radiotherapy (RT) in non-small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) in modulating RT-induced senescence and radiosensitivity in NSCLC. Through methodologies including irradiation, lentivirus transfection, and various molecular assays, we assessed LILRB2's expression and its impact on cellular senescence levels and tumor cell behaviors. Our findings reveal that RT upregulates LILRB2, facilitating senescence and a senescence-associated secretory phenotype (SASP), which in turn enhances tumor proliferation and resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting the JAK2/STAT3 pathway, significantly increasing radiosensitivity in NSCLC models. Clinical data correlate high LILRB2 expression with reduced RT response and poorer prognosis, suggesting LILRB2's pivotal role in RT-induced senescence and its potential as a therapeutic target to improve NSCLC radiosensitivity.

Flagellimonas baculiformis sp. nov. and Flagellimonas crocea sp. nov., isolated from surface seawater of the Pacific Ocean.

Two Gram-negative, non-spore-forming, non-motile, non-flagellated bacteria, designated strains D6T and DH64T, were isolated from surface water of the Pacific Ocean. For strain D6T, growth occurred at 10-40 °C, pH 5.5-9.0 and in the presence of 0-8.0 % NaCl (w/v). For strain DH64T, growth occurred at 10-40 °C, pH 5.5-8.5 and in the presence of 0.5-8.0 % NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains D6T and DH64T both belonged to the genera Flagellimonas, with the highest sequence identities to Flagellimonas taeanensis JCM 17757T (98.2 %) and Flagellimonas marinaquae JCM 11811T (98.6 %), respectively. The 16S rRNA gene sequence identity between strains D6T and DH64T was 95.9 %. The average amino acid identity and digital DNA-DNA hybridization values between the two strains and the nearest phylogenetic neighbours were 66.7-93.3 % and 16.1-38.5 %, respectively. The major respiratory quinone of both strains was menaquinone-6. The major polar lipid was phosphatidylethanolamine. The major fatty acids were identified similarly as iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. The genomic G+C contents of strains D6T and DH64T were determined to be 45.5 and 42.6 mol%, respectively. The combined genotypic and phenotypic data show that the strains represent two novel species within genera Flagellimonas, for which the names Flagellimonas baculiformis sp. nov. and Flagellimonas crocea sp. nov. are proposed, with type strains D6T (=MCCC M28982T=KCTC 92604T) and DH64T (=MCCC M28986T=KCTC 92975T).

Integrated genomic and proteomic analyses identify PYGL as a novel experimental therapeutic target for clear cell renal cell carcinoma.

Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL.

Highly efficient catalytic Fenton-Like reactions of bimetallic Fe/Cu chelated on radiation functionalized nonwoven fabric for pollutant control.

A remarkably efficient and affordable Fe/Cu bimetallic catalyst featuring a substantial light energy utilization and compatibility with a sizable substrate was developed for Fenton-like reactions aimed at pollutant control. Specifically, a novel strategy was employed to synthesize high-density metal sites (Fe:Cu ≈ 3:1) robustly embedded on polyethylene/polyethylene terephthalate nonwoven fabric (PE/PET NWF) via radiation-induced graft polymerization (RIGP) and subsequent chemical modification, labeled as Fe/Cu-PPAO. Its high effectiveness was demonstrated by degrading 50 mg/L of tetracycline hydrochloride within 30 min in the presence of H2O2 under simulate sunlight irradiation. It was investigated that amidoxime groups regulated the optical gaps and HOMO-LUMO gaps of metal ions to enable the absorption of a broader spectrum light while the Cu2+ facilitated the transfer of electrons between the bimetal ions to achieve an improved reaction path. Furthermore, X-ray absorption fine structure (XAFS) and density functional theory (DFT) calculations further revealed its special complex state and delicate electronic structure between bimetal ions and amidoxime groups. Our study offers a new strategy to synthesize high-density bimetallic sites catalyst for environmental remediation and pushes forward insight into understanding the catalytic mechanism of bimetallic Fenton-like catalysts.

Genetic landscape of breast cancer subtypes following radiation therapy: insights from comprehensive profiling.

Background: In breast cancer, in the era of precision cancer therapy, different patterns of genetic mutations dictate different treatments options. However, it is not clear whether the genetic profiling of breast cancer patients undergoing breast-conserving surgery is related to the adverse reactions caused by radiotherapy. Methods: We collected formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 54 breast cancer patients treated with radiation after breast-conserving surgery and identified comprehensive molecular information in hundreds of cancer-associated genes by FoundationOne CDx (F1CDx), a next-generation sequencing (NGS)-based assay. Results: Among our cohort of 54 breast cancer patients, we found high-frequency mutations in cancer-related genes such as TP53 (56%), RAD21 (39%), PIK3CA (35%), ERBB2 (24%), and MYC (22%). Strikingly, we detected that the WNT pathway appears to be a signaling pathway with specific high-frequency mutations in the HER2 subtype. We also compared the mutation frequencies of the two groups of patients with and without cutaneous radiation injury (CRI) after radiotherapy and found that the mutation frequencies of two genes, FGFR1 and KLHL6, were significantly higher in patients with CRI : No subgroup than in those with CRI : Yes. Conclusion: Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

Quantitative evaluation of warm acupuncture-moxibustion in improvement of cartilage damage in rabbits with early knee osteoarthritis based on MR T2 mapping. / åŸºäºŽæ ¸ç£å ±æŒ¯T2 mappingå®šé‡è¯„ä»·æ¸©é’ˆç¸å¯¹æ—©æœŸå ”è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žè½¯éª¨æŸä¼¤çš„ä¿®å¤ä½œç”¨.

OBJECTIVES: To observe the application value of MR T2 mapping for evaluating the effect of warm acupuncture-moxibustion on articular cartilage degeneration, and to observe the relationship between T2 value and expression of matrix metalloproteinases (MMP)-1 and MMP-13 of chondrocytes in rabbits with early knee osteoarthritis (KOA). METHODS: Thirty male New Zealand rabbits were randomly divided into blank control, KOA model and warm acupuncture-moxibustion groups, with 10 rabbits in each group. The early KOA model was established by right hind limb tubular plaster extension fixation method for 2 weeks. The rabbits of the warm acupuncture-moxibustion group received warm acupuncture-moxibustion stimulation at "Heding"(EX-LE2), "Neixiyan"(EX-LE4), "Waixiyan" (EX-LE5) and"Zusanli"(ST36) on the right hind limb for 15 min, once a day for 2 weeks. After intervention, MR T2 mapping of the right knee joint was performed in each group. The H.E. staining was used to evaluate the histopathological changes of cartilage, followed by giving a score according to the standards of Mankin scoring. The TUNEL method was used to analyze the apoptosis state of chondrocytes, and the positive expressions of MMP-1 and MMP-13 in the articular cartilage were detected by immunohistochemical staining. RESULTS: Compared with the blank control group, the Mankin score, chondrocyte apoptosis index, T2 value and the positive expressions of MMP-1 and MMP-13 in the cartilage tissue were significantly increased in the model group (P<0.01). Compared with the model group, the Mankin score, chondrocyte apoptosis index, T2 value and the positive expressions of MMP-1 and MMP-13 in the cartilage tissue were markedly decreased in the warm acupuncture-moxibustion group (P<0.01). The T2 value was positively correlated with the expression levels of MMP-1 and MMP-13 (P<0.01). H.E. staining showed disordered arrangement of chondrocytes and thinner cartilage layer in the model group, and a clear and relative ordered arrangement of chondrocyte in the warm acupuncture-moxibustion group. CONCLUSIONS: Warm acupuncture-moxibustion can reduce the T2 value of articular cartilage in early KOA rabbits, which is positively correlated with the decreased expression of MMP-1 and MMP-13 in the extracellular matrix of cartilage. The MR T2 mapping has certain value in evaluating the effect of warm acupuncture-moxibustion on KOA rabbits with early cartilage degeneration.

Quantitative susceptibility mapping in rats with minimal hepatic encephalopathy: Does iron overload aggravate cognitive impairment by promoting neuroinflammation?

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. MATERIALS AND METHODS: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. RESULTS: MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. CONCLUSION: MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.

Inhibition of tumor intrinsic BANF1 activates antitumor immune responses via cGAS-STING and enhances the efficacy of PD-1 blockade.

BACKGROUND: BANF1 is well known as a natural opponent of cyclic GMP-AMP synthase (cGAS) activity on genomic self-DNA. However, the roles of BANF1 in tumor immunity remain unclear. Here, we investigate the possible impact of BANF1 on antitumor immunity and response to immunotherapy. METHODS: The Cancer Genome Atlas public data were analyzed to evaluate the relevance of the expression of BANF1, patients' survival and immune cell infiltration. We monitored tumor growth and explored the antitumor efficacy of targeting tumor-intrinsic BANF1 in combination with anti-programmed cell death protein-1 (PD-1) in MC38 or B16F10 tumor models in both immunocompetent and immunodeficient mice. Flow cytometry, immunofluorescence and T cells depletion experiments were used to validate the role of BANF1 in tumor immune microenvironment reprogramming. RNA sequencing was then used to interrogate the mechanisms how BANF1 regulated antitumor immunity. RESULTS: We show that upregulated expression of BANF1 in tumor tissues is significantly associated with poor survival and is negatively correlated with immune cell infiltration. Deficiency of BANF1 in tumor cells markedly antagonizes tumor growth in immunocompetent but not immunocompromised mice, and enhances the response to immunotherapy in murine models of melanoma and colon cancer. In the immunotherapy clinical cohort, patients with high BANF1 expression had a worse prognosis. Mechanistically, BANF1 knockout activates antitumor immune responses mediated by cGAS-synthase-stimulator of interferon genes (cGAS-STING) pathway, resulting in an immune-activating tumor microenvironment including increased CD8+ T cell infiltration and decreased myeloid-derived suppressor cell enrichment. CONCLUSIONS: BANF1 is a key regulator of antitumor immunity mediated by cGAS-STING pathway. Therefore, our study provides a rational that targeting BANF1 is a potent strategy for enhancing immunotherapy for cancer with BANF1 upregulation.

Inhibition of CDC20 potentiates anti-tumor immunity through facilitating GSDME-mediated pyroptosis in prostate cancer.

BACKGROUND: Increasing evidence suggests that immunotherapy, especially immune checkpoint inhibitors (ICIs), has the potential to facilitate long-term survival in various cancer besides prostate cancer. Emerging evidence indicated that pyroptosis, an immunogenic form of cell death, could trigger an anti-tumor immune microenvironment and enhance the effectiveness of immunotherapy. Nevertheless, the mechanism underlying the regulation of pyroptosis signaling in prostate cancer remains unclear. METHODS: The differential expression of human E3 ligases in prostate cancer was integratedly analyzed from five independent public datasets. Moreover, the immunohistochemistry analysis of a tissue microarray derived from prostate cancer patients confirmed the results from the bioinformatic analysis. Furthermore, prostate cancer cell lines were evaluated via the next-generation RNA sequencing to assess transcriptomic profile upon CDC20 depletion. Next, qRT-PCR, Western blotting, cycloheximide assay, immunoprecipitation, and ubiquitination assay were employed to explore the correlation and interaction between CDC20 and GSDME. Both immune-deficient and immune-competent murine models were utilized to examine the anti-tumor efficacy of CDC20 inhibition with or without the anti-PD1 antibodies, respectively. To analyze the immune microenvironment of the xenografts, the tumor tissues were examined by immunohistochemistry and flow cytometry. RESULTS: The analysis of multiple prostate cancer cohorts suggested that CDC20 was the most significantly over-expressed E3 ligase. In addition, CDC20 exerted a negative regulatory effect on the pyroptosis pathway by targeting GSDME for ubiquitination-mediated proteolysis in a degron-dependent manner. Knockdown of CDC20 leads to increased GSDME abundance and a transition from apoptosis to pyroptosis in response to death signals. Furthermore, in our syngeneic murine models, we found that depletion of CDC20 significantly enhances the anti-tumor immunity by promoting the infiltration of CD8+ T lymphocytes dependent on the existence of GSDME, as well as reducing myeloid immune cells. More importantly, Apcin, a small molecular inhibitor that targets CDC20, exhibited synergistic effects with anti-PD1-based immunotherapy in murine models of prostate cancer. CONCLUSIONS: Overall, these findings provide new insights into the upstream regulation of GSDME-mediated pyroptosis by CDC20, which specifically interacts with GSDME and facilitates its ubiquitination in a degron-dependent manner. Importantly, our data highlight novel molecular pathways for targeting cellular pyroptosis and enhancing the effectiveness of anti-PD1-based immunotherapy.

The prognostic value of postoperative radiotherapy in right tumor for lung related death: based on SEER database and real-world data.

Background: Postoperative radiotherapy (PORT) is a therapeutic strategy for patients with non-small cell lung cancer (NSCLC). Nevertheless, some studies suggesting PORT does not improve overall survival (OS) including Lung ART phase III trial. The role of PORT and high-risk groups need to be confirmed. Methods: Patients from the Surveillance, Epidemiology, and End Results program (SEER) from 2004 to 2015 were eligible. Aged ≥18 years with stage IIIA-N2 NSCLC, accepted PORT or not were considered for the study. Cox regression analyses and multivariate competing risk model were performed. Propensity score matching (PSM) was conducted. Data from a single-center study in China were used for validation. Results: In all patients with IIIA-N2 NSCLC, death from respiratory illness increased year by year, with right lung-related deaths accounting for the main proportion. In SEER database, PORT was detrimental for OS after PSM (hazard ratio [HR], 1.088; 95% CI, 1.088-1.174; P = 0.031), with a same trend for death from the lungs (HR, 1.13; 95% CI, 1.04-1.22; P = 0.005). Right tumor receiving PORT were prone to death from lung disease(HR, 1.14; 95% CI, 1.02-1.27; P = 0.018). In China single-center cohort, PORT was significantly correlated with deteriorated OS (HR 1.356; 95% CI 1.127-1.632; P <0.01), especially in the right laterality (HR 1.365; 95% CI 1.062-1.755; P = 0.015). Conclusions: PORT was a risk factor for stage IIIA-N2 NSCLC patients, particularly with characters of right laterality, male sex, age ≥65 years, and advanced tumor stage. These patients are more likely to death from lung disease after PORT.

Membranihabitans maritimus sp. nov., a marine bacterium isolated from deep seawater.

A Gram-stain-negative, non-motile, rod-shaped bacterial strain, designated C281T, was isolated from seawater sampled at the Marshallese seamount chain. Results of 16S rRNA gene analysis revealed that strain C281T was most closely related to Membranihabitans marinus CZ-AZ5T with 92.7 % sequence similarity. Phylogenetic analysis indicated that the new isolate represented a novel species by forming a distinctive lineage within the family Saprospiraceae. The DNA G+C content of strain C281T was 38.4 mol%. The genome sizes of strain C281T and the reference strain M. marinus CZ-AZ5T were 5 962 917 and 5 395 999 bp, respectively. The average nucleotide identity and in silico DNA-DNA hybridization values between strains C281T and M. marinus CZ-AZ5T were found to be low (69.3 and 17.6 %, respectively). Different functional genes were found in the genome of strain C281T, such as CZC CBA, polysaccharide utilization loci and linear azol(in)e-containing peptide cluster coding genes. The NaCl range for growth was 0.5-15.0 %. Positive results were obtained for hydrolysis of Tween 60 and urease. MK-7 was the sole respiratory quinone. The major fatty acids were C16 : 1 ω6c and/or C16 : 1 ω7c, iso-C15 : 0 and iso-C15 : 1 F. The major polar lipids of strain C281T were phosphatidylethanolamine, phosphatidylglycerol, two unidentified lipids and five unidentified glycolipids. On the basis of its taxonomic characteristics, the isolate represents a novel species of the genus Membranihabitans, for which the name Membranihabitans maritimus sp. nov. (type strain C281T=KCTC 92171T=MCCC M27001T) is proposed.

Cellular Atlas of Senescent Lineages in Radiation- or Immunotherapy-Induced Lung Injury by Single-Cell RNA-Sequencing Analysis.

PURPOSE: Although the combination of immunotherapy and radiation therapy to treat various malignancies is rapidly expanding, concerns regarding increased pulmonary toxicities remain. The mechanisms of immunotherapy- and irradiation-induced lung injury involve a complex interplay of cell types and signaling pathways, much of which remains to be elucidated. METHODS AND MATERIALS: C57/BL6 mice were treated with a single fraction (20 Gy) of radiation therapy to the right lung or 200 µg anti-Programmed cell death protein 1 antibody twice a week. At 7, 30, and 60 days after treatment, the lung tissues were obtained for unbiased single-cell RNA sequencing or histologic staining. The Seurat analysis pipeline, Cellchat, Monocol, and Single-Cell rEgulatory Network Inference and Clustering were used to define cell types, mechanisms, and mediators driving pathologic remodeling in response to this lung injury. Reverse transcription polymerase chain reaction, immunofluorescent staining, and multiplex immunohistochemistry were applied to validate the key results. RESULTS: Thirty distinct cell subsets encompassing 75,396 cells were identified. A comprehensive investigation of cell-cell crosstalk revealed that monokine signals derived from senescent fibroblasts were substantially elevated after lung injury. Independent analytical strategies revealed that senescence-like subtypes of fibroblasts, alveolar epithelial cells, B cells, and myeloid immune cells were functionally pathologic, with high expression of senescence-signature proteins, especially Apolipoprotein E, during injury response. Senescence markers were also elevated in irradiated human cell lines, mouse cell lines (B3T3 and L929), and the publicly available human pulmonary fibrosis data set. CONCLUSIONS: These findings demonstrate that the accumulation of senescence-like fibroblasts, macrophages, and alveolar epithelial cells is the primary common pathologic mechanism of immunotherapy- and irradiation-induced lung injury. These high-resolution transcriptomic data provide novel insights into therapeutic opportunities to predict or prevent therapy-induced lung injury.

The Infiltration of Neutrophil Granulocytes Due to Loss of PTEN Was Associated with Poor Response to Immunotherapy in Renal Cell Carcinoma.

Introduction: A primary impediment to the efficacy of immune checkpoint inhibitors is the lack of biomarkers for therapeutic responses and prognosis. Although patients with clear cell renal cell carcinoma (ccRCC) could be precisely selected for targeted therapy based on somatic mutations, it remains controversial to choose the suitable patients with a high response rate to immune checkpoint inhibitors (ICIs). The immune-dependent roles of tumor suppressor PTEN in the formation of tumor immune microenvironment remain elusive. Methods: We comprehensively analyzed the genomic and transcriptomic data from multiple ccRCC datasets, including bulk-RNA sequencing and single-cell RNA sequencing data. In vitro, immunoblotting, qRT-PCR, and RNA sequencing were conducted in ccRCC cell lines upon PTEN depletion. Gene ontology and gene set enrichment analysis were performed to screen the critical pathway and molecules in response to PTEN deletion. Immunohistochemistry staining and further bioinformatic analysis were used to validate our data. Results: Based on multi-omics analysis of public datasets of renal cancer, the frequently mutated or deleted PTEN was found to be correlated with a suppressive tumor immune microenvironment in ccRCC. Furthermore, we depleted PTEN via CRISPR-Cas9 in Caki-1 cells, which led to the upregulation of multiple neutrophil chemokines, particularly CXCL1, CXCL2, CXCL5, CXCL6, and CXCL8. The roles of neutrophil chemokines and neutrophil markers were further validated and investigated for the association with prognosis in vitro, clinical samples, and the publicly available databases. The expression of CXCL1, CXCL8, and neutrophil markers, S100A9 and BCL2A1, were significantly associated with a poor immunotherapy-related prognosis in public dataset of renal cancer patients receiving ICIs treatment. Conclusion: These results add a new layer to understanding the association between PTEN status and the role of neutrophil infiltration in ccRCC. Moreover, our findings propose low expression of PTEN as candidate factor of resistance to anti-PD-1-based immunotherapy in ccRCC.

The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution.

Background and aims: Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. Materials and methods: We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. Results: BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). Conclusion: The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE.

Research Hotspots and Trends on Acupuncture for Neuropathic Pain: A Bibliometric Analysis from 2002 to 2021.

Purpose: In this study, we aimed to systematically determine the trend, research hotspots, and directions of the future development of acupuncture for neuropathic pain (NP) by bibliometric analysis. Methods: Based on the relevant literature on acupuncture for NP in the databases of Web of Science from January 2002 to December 2021, Citespace software and VOSviewer were used to determine the use of acupuncture for the treatment of NP. The annual publications, countries, authors, research institutions, keywords, co-cited references, and journals were analyzed to explore the research hotspot and development trends in this field. Results: A total of 1462 records of acupuncture for NP from 2002 to 2021 were obtained. Chingliang Hsieh (20) is the most effective author and Han JS (585 co-citations) is the most influential author. The most productive institutions and countries are Kyung Hee UNIV (88) and China, respectively (480). UNIV Maryland of the USA has the highest centrality (0.12). Evidence-based complementary and alternative medicine (89) is the most prolific journal, and Pain is the most influential journal (4200 co-citations). Ji-sheng Han (2003) is the most frequently cited article (158 co-citations). Electroacupuncture, bee-venom acupuncture, and percutaneous electrical stimulation are the most commonly studied acupuncture types. The analgesic mechanism of acupuncture and acupuncture-neuroimaging was a research hotspot over the years. The clinical evidence of acupuncture for NP should be further studied in the future. Conclusion: The study using bibliometric analysis methods to investigate the publications on acupuncture for NP so as to provide potential research directions in the future.

Understanding the underlying mechanisms governing spindle orientation: How far are we from there?

Proper spindle orientation is essential for cell fate determination and tissue morphogenesis. Recently, accumulating studies have elucidated several factors that regulate spindle orientation, including geometric, internal and external cues. Abnormality in these factors generally leads to defects in the physiological functions of various organs and the development of severe diseases. Herein, we first review models that are commonly used for studying spindle orientation. We then review a conservative heterotrimeric complex critically involved in spindle orientation regulation in different models. Finally, we summarize some cues that affect spindle orientation and explore whether we can establish a model that precisely elucidates the effects of spindle orientation without interfusing other spindle functions. We aim to summarize current models used in spindle orientation studies and discuss whether we can build a model that disturbs spindle orientation alone. This can substantially improve our understanding of how spindle orientation is regulated and provide insights to investigate this complex event.

Pivotal roles of tumor-draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy.

BACKGROUND: Currently, due to synergy enhancement of anti-tumor effects and potent stimulation of abscopal effects, combination therapy with irradiation and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint inhibition (immuno-radiotherapy, iRT) has revolutionized the therapeutic guidelines. It has been demonstrated that tumor-draining lymph nodes (TDLN) are essential for effective antitumor immunity induced by radiotherapy, immunotherapy, or iRT. Given that the function of TDLN in iRT remains unclear, this study aimed to investigate the function and mechanism of TDLN in iRT-induced abscopal effects. METHODS: The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN. The flow cytometry, multiple immunofluorescence analysis, and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment. Additionally, we tempted to interrogate the possible mechanisms via RNA-sequencing of tumor-infiltrating lymphocytes and TDLN. RESULTS: TDLN deficiency impaired the control of tumor growth by monotherapy. Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT-stimulated anti-tumor and abscopal effects. Furthermore, in the absence of TDLN, the infiltration of CD45+ and CD8+ T cells was substantially reduced in both primary and abscopal tumors, and the anti-tumor function of CD8+ T cells was attenuated as well. Additionally, the polarization of tumor-associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN. RNA-sequencing data indicated that impaired infiltration and anti-tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment. CONCLUSIONS: TDLN play a critical role in iRT by promoting the infiltration of CD8+ T cells and maintaining the M1/M2 macrophage ratio.