Guanylate binding protein 4 shapes an inflamed tumor microenvironment and identifies immuno-hot tumors.

PURPOSE: Guanylate binding protein 4 (GBP4) is induced by interferons and various cytokines and has been recognized as functionally relevant in numerous types of human cancers. While the role of GBP4 in cancer has been preliminarily summarized, its correlation with antitumor immunity remains unclear and requires further research. METHODS: First, a comprehensive pan-cancer analysis was conducted, focusing on GBP4's expression patterns and immunological functions. Subsequently, we explored the correlations between GBP4 and immunological features within the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) patients. Additionally, we examined the relationships between GBP4 and emerging immunobiomarkers, such as N6-methyladenosine (m6A) genes. Moreover, we assessed the utility of GBP4 in predicting the clinical characteristics and treatment responses of patients with NSCLC. RESULTS: Pan-cancer analysis revealed that GBP4 plays a positive role in most cancer types via the majority of immunomodulators. Furthermore, GBP4 demonstrated positive associations with immunomodulatory factors, tumor-infiltrating immune cells (TIICs) and inhibitory immune checkpoints. Remarkably, the expression of GBP4 was found to be a predictor of significantly enhanced responsiveness to anti-EGFR therapy and immunotherapy. CONCLUSIONS: GBP4 expression profiles offer a promising avenue for identifying highly immunogenic tumors across a wide spectrum of cancers. GBP4 holds potential as a robust pan-cancer biomarker for assessing the immunological characteristics of tumors, with particular relevance to its ability to predict therapeutic responses, notably in the context of anti-EGFR therapy and immunotherapy.

Comparison of Monotherapies and Combination Therapy of Tamsulosin and Tadalafil for Treating Lower Urinary Tract Symptoms Caused by Benign Prostatic Hyperplasia with or without Erectile Dysfunction: A Meta-Analysis.

BACKGROUND: There is limited research into the efficacy and safety of tadalafil combined with tamsulosin for the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), with or without erectile dysfunction (ED). Therefore, we aimed to investigate the efficacy and safety of combination therapy compared to that of monotherapy. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang Data Service Platform, and ClinicalTrials.gov to identify eligible studies. A total of 639 articles were retrieved, of which 12 were randomized controlled trials (RCTs) published as of February 2023 and included in this meta-analysis. RESULTS: After screening 639 articles, 12 RCTs including 1,531 subjects were considered eligible for the meta-analysis. The results showed that the total International Prostate System Score (total IPSS), maximum flow rate (Qmax), and quality of life (QoL) in tadalafil combined with tamsulosin were significantly better than those in monotherapy. Compared with tadalafil monotherapy, combination therapy mainly improved IPSS voiding. As for postvoid residual urine (PVR), the combination therapy did not improve PVR compared to the tadalafil group, but significantly improved PVR compared to the tamsulosin group. For the International Index of Erectile Function (IIEF), the curative effect of the combined group was better than that of the tamsulosin group but not better than that of the tadalafil group. In terms of safety, the adverse reactions (AEs) in the combined treatment group were significantly higher than those in the monotherapy group. None of the 12 RCTs reported serious adverse events. CONCLUSIONS: Tadalafil combined with tamsulosin was more effective in the treatment of male LUTS/BPH, with or without ED, on the improvement of total IPSS, QoL, and Qmax. However, the benefits of combination therapy for ED remain unclear. However, combination therapy seemed to have a higher incidence of adverse reactions.

MMP-9 inhibition alleviates postoperative cognitive dysfunction by improving glymphatic function via regulating AQP4 polarity.

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase（MMP-9）inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood-brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.

AQP4 is an Emerging Regulator of Pathological Pain: A Narrative Review.

Pathological pain presents significant challenges in clinical practice and research. Aquaporin-4 (AQP4), which is primarily found in astrocytes, is being considered as a prospective modulator of pathological pain. This review examines the association between AQP4 and pain-related diseases, including cancer pain, neuropathic pain, and inflammatory pain. In cancer pain, upregulated AQP4 expression in tumor cells is linked to increased pain severity, potentially through tumor-induced inflammation and edema. Targeting AQP4 may offer therapeutic strategies for managing cancer pain. AQP4 has also been found to play a role in nerve damage. Changes in AQP4 expression have been detected in pain-related regions of the brain and spinal cord; thus, modulating AQP4 expression or function may provide new avenues for treating neuropathic pain. Of note, AQP4-deficient mice exhibit reduced chronic pain responses, suggesting potential involvement of AQP4 in chronic pain modulation, and AQP4 is involved in pain modulation during inflammation, so understanding AQP4-mediated pain modulation may lead to novel anti-inflammatory and analgesic therapies. Recent advancements in magnetic resonance imaging (MRI) techniques enable assessment of AQP4 expression and localization, contributing to our understanding of its involvement in brain edema and clearance pathways related to pathological pain. Furthermore, targeting AQP4 through gene therapies and small-molecule modulators shows promise as a potential therapeutic intervention. Future research should focus on utilizing advanced MRI techniques to observe glymphatic system changes and the exchange of cerebrospinal fluid and interstitial fluid. Additionally, investigating the regulation of AQP4 by non-coding RNAs and exploring novel small-molecule medicines are important directions for future research. This review shed light on AQP4-based innovative therapeutic strategies for the treatment of pathological pain. Dark blue cells represent astrocytes, green cells represent microglia, and red ones represent brain microvasculature.

Correction to "Development of a Reduced Methane-Hydrogen-Polyoxymethylene Dimethyl Ether Mechanism under Engine-Relevant Conditions".

[This corrects the article DOI: 10.1021/acsomega.1c03763.].

Biophilic virtual reality on children's anxiety and pain during circumcision: A randomized controlled study.

INTRODUCTION: The aim of this study was to evaluate the effects of the biophilic virtual reality (BVR) method on children's pain and anxiety undergoing circumcision. MATERIALS AND METHODS: This randomized controlled study used a parallel trial design guided by the CONSORT checklist. A total of 106 children were included in the analysis. Intraoperative anxiety was assessed by using the simplified Chinese version of the modified Yale Preoperative Anxiety Scale (CmYPAS), Visual Analogue Scale (VAS), heart rate (HR), and Anxiety index (Ai). Intraoperative pain was assessed by using the Faces Pain Scale-Revised (FPS-R), and Pain index (Pi). The Pearson correlation analysis was used to analyze the relationship between Ai and the CmYPAS. The primary outcomes were CmYPAS, VAS, and FPS-R, which were analyzed using the Kruskal-Wallis test. RESULTS: Baseline variables were not significantly different between the BVR group (34 patients), the indoor virtual reality (IVR) group (36 patients), and the blank control group (36 patients). The CmYPAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (25.0[22.9-29.2], 22.9[22.9-29.2], 33.3[33.3-38.5] respectively; P < 0.001). The VAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (5.0[3.0-7.0], 3.0[2.0-5.0], 6.0[5.0-8.8] respectively; P < 0.001). The FPS-R scores during surgery were significantly lower in the BVR group and IVR group versus the blank control group (2.0[1.8-4.2], 3.0[2.0-4.8], 5.5[5.0-8.0], respectively; P < 0.001). At removal of the foreskin, Pi were significantly lower in the BVR group and IVR group versus the blank control group (6.9[4.1], 7.7[3.3], 9.8[6.2] respectively; P = 0.033). The Ai scores at each time point were significantly lower in the BVR group and IVR group versus the control (P = 0.015, P = 0.006 respectively). The correlation analysis of Ai (at removal of the foreskin) and CmYPAS scores in children showed that the Pearson correlation coefficient was 0.194 (P = 0.046). DISCUSSION: This is the first RCT to investigate the effects of BVR in children undergoing circumcision. This study demonstrates a reduction in pediatric intraoperative pain and anxiety with the use of virtual reality (VR). CONCLUSION: Intraoperative VR may be an effective noninvasive modality for reducing pain and anxiety during circumcision. Pi and Ai might be used to assess subjective pain and anxiety in patients.

Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction.

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S-rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient - 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood-brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation of APP/PS1 by upregulating benificial  gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.

Protective Effect of Combined Metoprolol and Atractylenolide I in Rats with Acute Myocardial Infarction via Modulation of the SIRT3/ß-CATENIN/PPAR-γ Signaling Pathway

ABSTRACT Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/ß-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, ß-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, ß-catenin, and PPAR-γ

The clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C after transurethral resection of bladder tumour in patients with nonmuscular invasive bladder cancer: A meta-analysis.

BACKGROUND: This review and meta-analysis aimed to systematically evaluate the clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C (MMC) in patients with nonmuscular invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). METHODS: The Embase, PubMed, CNKI, CBM, WANGFANG, VIP, Cochrane Library, and Clinicaltrial.com databases were searched for articles published before April 2022. The experimental group was treated with intravesical instillation of MMC assisted by equipment, including radiofrequency-induced thermochemotherapy, conductive thermochemical therapy, electromotive drug administration, or locoregional hyperthermia. The control group was treated with simple MMC perfusion. The outcomes of interest in the meta-analysis were recurrence, progression, side-effects, gross haematuria, and bladder irritation. RESULTS: A total of 15 studies that enrolled 1,190 patients were included in the meta-analysis. Compared to that of the control group, device-assisted intravesical instillation of MMC significantly reduced both tumour recurrence (odds ratio [OR] = 0.32, 95% confidence interval [CI] [0.24, 0.42], P <0.00001) and progression (OR = 0.29, 95% CI [0.12, 0.67], P = 0.004). There were no significant differences between the two groups in terms of safety (OR = 1.21, 95% CI [0.66,2.21], P = 0.54), bladder irritation (OR = 1.06, 95% CI [0.72,1.55], P = 0.78), or gross haematuria (OR = 1.11, 95% CI [0.64,1.94], P = 0.72). CONCLUSIONS: Equipment-assisted intravesical instillation of MMC significantly reduced the recurrence and progression of patients with NMIBC who underwent TURBT and improved their quality of life. Given the significant heterogeneity in research quality and sample size among earlier studies, more prospective, multicentre, large sample randomized controlled trials are needed to supplement and verify this in the future.

High expression COL10A1 promotes breast cancer progression and predicts poor prognosis.

Background: As a common malignant disease in females, breast cancer (BCa) causes increasing numbers of cancer-related death. Collagen X alpha 1 chain (COL10A1) plays a critical role in the oncogenesis and progression of malignant tumors. However, a systematic analysis of COL10A1 in BCa has not been conducted. Methods: The COL10A1 expression level and prognostic value in BCa were defined through the Cancer Genome Atlas (TCGA) as well as the Kaplan-Meier plotter data respectively. The expression pattern of COL10A1 was subsequently confirmed on tissue microarray (TMA) by immunochemistry (IHC) staining. Moreover, cellular functional assays which aimed to evaluate cell proliferation, migration, invasion, and apoptosis, were conducted to investigate the oncogenic activity of COL10A1 in BCa. Then, Tumor Immune Estimation Resource (TIMER) was adopted to determine the association between COL10A1 expression and immune cell infiltration. Results: Bioinformatics analysis revealed that COL10A1 was significantly overexpressed and had notable prognostic value, especially for distant metastasis-free survival (DMFS) in BCa. Moreover, IHC analysis of 140 BCa tissues on TMA chips exhibited the overexpression of COL10A1 was correlated to advanced clinical stage, poor overall survival (OS), and worse recurrence-free survival (RFS). Besides, knockdown of COL10A1 remarkably suppressed cell proliferation, migration, and invasion in BCa cells, and notably promoted cell apoptosis as well. Furthermore, COL10A1 was positively associated with immune cell infiltration including B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell. Conclusion: The results revealed that COL10A1 is a novel oncogene and could serve as a potential prognostic biomarker in BCa. Besides, the downregulation of COL10A1 could inhibit BCa progression, which could be a potential target for BCa therapy.

Curcumin relieved the rheumatoid arthritis progression via modulating the linc00052/miR-126-5p/PIAS2 axis.

Curcumin, with its antioxidant, anti-inflammatory, and antitumor properties, is widely used in the treatment of bone disorders, including rheumatoid arthritis (RA). We investigated the effects of curcumin on fibroblast-like synoviocytes in RA and its underlying mechanism. mRNA and microRNA (miRNA) expression levels were determined using reverse transcription-quantitative polymerase chain reaction. Cellular functions were detected using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell, and flow cytometric assays. Enzyme-linked immunosorbent assay was performed to measure the cytokine release. Western blotting was used to determine the protein expression levels. An in vivo assay was performed to verify the role of linc00052 in RA. Curcumin promoted apoptosis and inhibited the growth, migration, and invasion of RA fibroblast-like synovial (RAFLS) cells. Curcumin treatment suppressed the inflammatory response of RAFLS cells. Moreover, curcumin increased linc00052 levels, and linc00052 knockdown reversed the effects of curcumin. Additionally, linc00052 functioned as a competing endogenous RNA to upregulate the expression of the protein inhibitor of activated STAT 2 (PIAS2) by sponging miR-126-5p. Curcumin inhibited the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In vivo assays showed that curcumin decreased the arthritis score and improved inflammatory infiltration and synovial cell proliferation. These results reveal that curcumin protects against RA by regulating the inc00052/miR-126-5p/PIAS2 axis through JAK2/STAT3 signaling pathway.

Identification of Synovial Fibroblast-Associated Neuropeptide Genes and m6A Factors in Rheumatoid Arthritis Using Single-Cell Analysis and Machine Learning.

OBJECTIVES: Synovial fibroblasts (SFs) play an important role in the development and progression of rheumatoid arthritis (RA). However, the pathogenic mechanism of SFs remains unclear. The objective of this study was to investigate how neuropeptides and N6-methyladenosine (m6A) played an important role in the underlying pathogenic processes of SFs that contribute to the development of RA. METHODS: Single-cell RNA sequencing data were examined using single-cell analysis and machine learning. SF subgroups were identified based on the clustering and annotation results of the single-cell analysis. Moreover, cell-cell communication was used to analyse neuropeptide-related receptor and ligand pairs on the surface of SF cell membranes. Machine learning was used to explore the m6A factors acting on these neuropeptide genes. RESULTS: NPR3, GHR, BDKRB2, and CALCRL, four neuropeptide genes, were shown to be differently expressed among SF subgroups. Further investigation of receptor-ligand interactions found that NPR3 (in conjunction with NPPC, OSTN, NPPB, and NPPA) and GHR (in conjunction with GH1 and GH2) may have a role in SF interactions. As predicted by machine learning, IGFBP2 and METTL3 were identified as key factors regulating m6A of NPR3 and GHR. The expression levels and enrichment pathways of METTL3 and IGFBP2 were different among SF subgroups. CONCLUSIONS: Single-cell analysis and machine learning efficiently identified neuropeptide genes and m6A factors that perform important regulatory functions in RA. Our strategy may provide a basis for future studies to identify pathogenic cell subpopulations and molecular mechanisms in RA and other diseases.

Unraveling the process of aerosols secondary formation and removal based on cosmogenic beryllium-7 and beryllium-10.

The secondary formation and diffusion processes of aerosol are extraordinarily complex and significantly impact the environment and human health. Therefore, exploring the process of aerosol formation and diffusion based on independent new tracer has always been a concern. The 7Be and 10Be, which are generated only by the action of cosmic rays, are chemically stable and adsorbed on aerosol for transmission, so they have the potential characteristics of aerosol tracers. Here, we obtained the daily resolution atmospheric 7Be, 10Be, and 10Be/7Be without dust interference in Xi'an autumn and winter (heavy pollution period in a typical polluted area) by accelerator mass spectrometry. It is found that during the rapid formation of secondary aerosols (SA) under the stable 10Be/7Be ratio, which indicates the stable atmospheric vertical structure, the concentration of 7Be and 10Be is significantly negatively correlated (R2 > 0.9) with the aerosol concentration. Therefore, SA relative content in aerosols can be estimated by the dilution amount of 7Be and 10Be to reveal the secondary-formation process of aerosol (33% average contribution to aerosols during the winter heavy air pollution period). Furthermore, we also revealed the physical removal process of aerosols based on 7Be, 10Be, and 10Be/7Be, including precipitation removal and diffusion of vertical atmospheric movement caused by stratospheric air intrusion. In summary, meteoric cosmogenic 7Be and 10Be will provide a new way to study the secondary chemical formation and physical removal of aerosols.

Sediment Soot Radiocarbon Indicates that Recent Pollution Controls Slowed Fossil Fuel Emissions in Southeastern China.

Fossil fuel (FF) combustion emissions account for a large, but uncertain, amount of the soot in the atmosphere, play an important role in climate change, and adversely affect human health. However, historical estimates of FF contributions to air pollution are limited by uncertainties in fuel usage and emission factors. Here, we constrained FF soot emissions from southeastern China over the past 110 years, based on a novel radiocarbon method applied to sedimentary soot. The reconstructed soot accumulations reflect the integrated effects of increased FF use caused by economic development and reductions in emissions due to pollution controls. A sharp increase in FF soot started in 1950 as southeastern China industrialized and developed economically, but decreased FF soot fluxes in recent years suggest that pollution controls reduced soot emissions. We compare FF soot history to changes in CO2 emissions, industrial and economic activities, and pollution controls and show that FF soot fluxes are more readily controlled than atmospheric CO2. Our independent FF soot record provides insights into the effects of economic development and controls on air pollution and the environmental impacts from the changes in soot emissions.

Clinical analysis of transurethral holmium laser enucleation in the treatment of benign prostatic hyperplasia with prostatic inflammation: A prospective research study.

Objective: To investigate the clinical efficacy of holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with prostatic inflammation (PI). Methods: We prospectively collected and followed up data on patients with BPH who underwent HoLEP at the Affiliated Hospital of Weifang Medical University between July 2021 and July 2022. According to the postoperative pathological results, the patients were divided into two groups: BPH without PI group (BPH group) and BPH with PI group. Statistical analysis was performed on clinical data, including age and body mass index (BMI), prostate volume (PV), postoperative residual urine volume (PVR), preoperative serum total prostate-specific antigen (tPSA), serum-free prostate-specific antigen (fPSA), preoperative and postoperative maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) before and 3 months after surgery, quality of life index (QoL) before and 3 months after surgery, and postoperative complications. Results: A total of 41 patients were included in this study, including 16 in the BPH group and 25 in the BPH with PI group. There were no significant differences in preoperative age, BMI, PV, PVR, tPSA, fPSA, and f/tPSA between the BPH and BPH with PI groups (P > 0.05). The preoperative mean Qmax of the BPH and BPH with PI groups were 9.44 ± 2.449 and 7.52 ± 2.946 [mean ± standard deviation (SD)] ml/s, mean IPSS were 17.75 ± 5.335 and 24.24 ± 5.861 (mean ± SD), and mean QoL were 4.13 ± 0.806 and 4.48 ± 0.8 (mean ± SD), respectively. The postoperative mean Qmax of the BPH and BPH with PI groups were 20.38 ± 4.787 and 14.32 ± 3.827 (mean ± SD) ml/s, mean IPSS were 2.69 ± 1.25 and 5.84 ± 3.579 (mean ± SD), and mean QoL were 0.13 ± 0.342 and 0.92 ± 0.759 (mean ± SD), respectively. In both groups, Qmax significantly increased (P < 0.05) and IPSS and QoL significantly decreased after HoLEP (P < 0.05). Before and after surgery, the Qmax in the BPH with PI group was lower than that in the BPH group, and the IPSS and QoL levels in the BPH with PI group were higher than those in the BPH group (P < 0.05). Compared with the BPH group, the increase in Qmax in the BPH with PI group was smaller and the decrease in IPSS was larger (P < 0.05), but the variation in QoL was not statistically significant (P > 0.05). Conclusion: Improvements in Qmax, IPSS, and QoL in BPH patients with PI after HoLEP surgery were lower than those in BPH patients alone. PI may be a predictor of a worse response to surgical treatment. However, more multicenter randomized controlled trials with larger samples and long-term follow-up are needed to verify this.

Development of a Reduced Methane-Hydrogen-Polyoxymethylene Dimethyl Ether Mechanism under Engine-Relevant Conditions.

Polyoxymethylene dimethyl ethers (PODE n ) have a high cetane number and a high oxygen content, which can effectively reduce the soot emission. In this study, PODE3, methane, and hydrogen were used as the characterization fuel. First, the detailed reaction mechanism of PODE3 and GRI-Mech 3.0 was reduced under engine-relevant conditions by using the reduced methods of the direct relation graph, the directed relation graph with error propagation, the sensitivity analysis, and the reaction pathway analysis. Then, the simplified PODE3 and methane-hydrogen mechanism were coupled and optimized. Finally, the simplified chemical kinetics mechanism of methane-hydrogen-PODE3 (67 species, 260 reactions) was developed. After that, the methane-hydrogen-PODE3 mechanism for methane/hydrogen/PODE3 blend combustion was established, and experimental verification was performed against ignition delay times, laminar flame speeds, and premixed flame species profiles, which showed a good agreement between the predicted and experimental data. Finally, the current mechanism was found to have high reliability and can be coupled to computational fluid dynamics.

Characterization of the Clinical Significance of PD-1/PD-Ls Expression and Methylation in Patients With Low-Grade Glioma.

BACKGROUND: Immune checkpoints play crucial roles in the immune escape of cancer cells. However, the exact prognostic values of expression and methylation of programmed-death 1 (PD-1), programmed-death-ligand 1 (PD-L1) and PD-L2 in low-grade glioma (LGG) have not been well-defined yet. METHODS: A total 514 LGG samples from the Cancer Genome Atlas (TCGA) dataset containing gene expression, DNA methylation, and survival data were enrolled in our study. Besides, a total of 137 primary LGG samples from the Chinese Glioma Genome Atlas (CGGA) database were also extracted for the survival analysis of the prognostic values of PD-1/PD-Ls expression. RESULTS: PD-1/PD-Ls had distinct co-expression patterns in LGG tissues. The expression and methylation level of PD-1/PD-Ls seemed to be various in different LGG subtypes. Besides, overexpression and hypo-methylation of PD-1/PD-Ls were associated with worse prognosis. In addition, PD-1/PD-Ls expression was positively associated with TIICs infiltration, while their methylation was negatively associated with TIICs infiltration. Moreover, PD-1/PD-Ls and their positively correlated gene mainly participated in immune response related biological processes. CONCLUSION: To conclude, overexpression and hypo-methylation of PD-1/PD-Ls predicted unfavorable prognosis in LGG patients, suggesting those patients may benefit from PD1/PD-Ls checkpoint inhibitors treatment.

Wnt5a: A promising therapeutic target in ovarian cancer.

Despite the rapid development of novel adjuvant and neoadjuvant chemotherapeutic drugs in recent years, advanced ovarian cancer still lacks effective treatment strategies and remains one of the main causes of death among women. Wnt protein family is widely expressed in a variety of human tissues, and Wnt5a is an important member of the noncanonical Wnt pathway. Wnt5a has been found to induce tumor suppression as well as to function as an oncogene depending upon the specific cancer type. In ovarian cancer, Wnt5a protein expression has been observed to be significantly upregulated and associated with poor prognosis. Researchers found that downregulating Wnt5a expression levels effectively suppresses ovarian cancer cell migration and invasion abilities. We believe that the downregulation of Wnt5a will be an attractive and promising antimetastatic therapeutic approach for the future treatment of patients with advanced ovarian cancer. The present review focuses on the mechanisms and therapeutic potential of Wnt5a as a promising novel therapeutic target for ovarian cancer.

LncRNA NEAT1 regulates the proliferation and production of the inflammatory cytokines in rheumatoid arthritis fibroblast-like synoviocytes by targeting miR-204-5p.

Rheumatoid arthritis (RA) is a chronic inflammatory disease, featured by erosive arthritis, which will eventually lead to deprivation normal functions of the joint and joint malformations. Continued illness also results in more serious complications, such as cardiovascular diseases and disability. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) function in various conditions, including RA. LncRNA NEAT1 was reported to promote migration and invasion in RA-FLSs, functioning as a promising diagnostic and therapeutic indicator in RA. The present work focused on the role of lncRNA NEAT1 in RA and the related mechanism. We collected the synovial tissue samples of 30 RA patients and 20 healthy controls. Moreover, RA fibroblast-like synoviocytes (RA-FLSs) cell line was bought and treated with tumor necrosis factor-α (TNF-α) to establish in vitro model of RA. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of NEAT1 in synovial tissue and RA-FLSs. NEAT1 silencing plasmid were synthesized and co-trasnfected with miR-204-5p inhibitor into RA-FLSs. MTT and 5-Ethynyl-2'-deoxyuridine staining were used to assess cell proliferation. Flow cytometry and TUNEL assay were used to determine the cell apoptosis. miR-204-5p has been predicted as a target miRNA of NEAT1, and the interaction between NEAT1 and miR-204-5p was verified by dual-luciferase assay and RNA pull-down assay. qRT-PCR and enzyme-linked immunosorbent assay were used to determine the mRNA and protein concentration of interleukin-1ß and interleukin-6. Finally, western blot assay was applied to measure the effect of NEAT1 and on p53, NF-κB, and p-NF-κB expressions. We found that NEAT1 was up-regulated, and miR-204-5p was down-regulated in the RA patients' synovial tissue and TNF-α treated RA-FLSs. TNF-α increased NEAT1 level and decreased miR-204-5p level in RA-FLSs. There was no significant variance of p53 after transfected with NEAT1 in RA-FLSs. Meanwhile, Knockdown of NEAT1 attenuated TNF-α-induced RA-FLSs cell proliferation and inflammatory cytokine production while promoted cell apoptosis by targeting miR-204-5p through NF-κB pathway. These findings indicated that NEAT1 may be developed as a potential target for patients with RA.