Platelet integrin αIIbß3 plays a key role in venous thrombogenesis in a mouse model.

Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. Previous studies have shown that the accumulation of platelets and neutrophils at sites of endothelial cell activation is a primary event in VT, but a role for platelet αIIbß3 in the initiation of venous thrombosis has not been established. This task has been complicated by the increased bleeding linked to partial agonism of current αIIbß3 inhibitory drugs such as tirofiban (Aggrastat ® ). Here, we show that m-tirofiban, an engineered version of tirofiban, is not a partial agonist of αIIbß3. This is based on its cryo-EM structure in complex with human full-length αIIbß3 and its inability to increase expression of an activation-sensitive epitope on platelet αIIbß3. m-tirofiban abolished agonist-induced platelet aggregation ex vivo at concentrations that preserved clot retraction and markedly suppressed the accumulation of platelets, neutrophils, and fibrin on thrombin-activated endothelium in real-time using intravital microscopy in a mouse model of venous thrombogenesis. Unlike tirofiban, however, m-tirofiban did not increase bleeding at the thrombosis-inhibitory dose. These findings establish a key role for αIIbß3 in the initiation of VT, provide a guiding principle for designing potentially safer inhibitors for other integrins, and suggest that pure antagonists of αIIbß3 like m-tirofiban merit further consideration as potential thromboprophylaxis agents in patients at high-risk for VT and hemorrhage.

Interactions between oxidative stress and senescence in cancer: Mechanisms, therapeutic implications, and future perspectives.

BACKGROUND: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. AIM: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. METHODS: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. CONCLUDSION: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area.

Efficiency of transurethral en-bloc resection vs. conventional transurethral resection for non-muscle-invasive bladder cancer: An umbrella review.

BACKGROUND: En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT). METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages. RESULTS: There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I2 = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I2 = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I2 = 50%). CONCLUSION: Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.

Ferromanganese oxide-functionalized TiO2 for rapid catalytic ozonation of PPCPs through a coordinated oxidation process with adjusted composition and strengthened generation of reactive oxygen species.

Ferromanganese oxide (MFOx) was first utilized to functionalize TiO2 and an MFOx@TiO2 catalyst was developed for catalytic ozonation for rapid attack of pharmaceutical and personal care products (PPCPs) with adjusted reactive oxygen species (ROSs) composition and strengthened ROSs generation. Unlike Al2O3, which strongly relied on adsorption and was significantly influenced by MFOx loading, synergistic catalytical effects of MFOx and TiO2 were observed, and optimal MFOx doping of 2 wt% and MFOx@TiO2 dosage of 500 ppm were obtained for catalyzing ozonation. In ibuprofen (IBP) degradation, MFOx@TiO2-catalyzed ozonation (MFOx@TiO2/O3) obtained 2.0-, 4.7- and 6.9-folds the kobs of TiO2/O3, MFOx/O3 and bare ozonation (B/O3). Stronger O3 decomposition was observed by MFOx@TiO2 over bare TiO2 with the participation of redox pairs Fe(II)/Fe(III) and Mn(II)/Mn(III)/Mn(IV) and increased surface oxygen vacancies (SOVs) from 9.8 % to 33.7 % was detected. The results revealed that Fe(II), Mn(II) and Mn(III) with low valance accelerated Ti(III) generation from Ti(VI), obtaining an unprecedented high Ti(III) composition occupying 35.3 % of the total Ti atoms. Ti(III) catalyzed the direct reduction of SOVs-O2 to •O2-, and it accelerated the formation of Ti(VI)-OH and Ti(VI)-O which catalyzed O3 decomposition into •O2-. •O2- was found to primarily initiate IBP degradation with nucleophilic addition and dominated over 66 % IBP removal. The enhanced •O2- generation further strengthened •OH and 1O2 production. MFOx@TiO2/O3 obtained 17 %, 21 % and 30 % higher TOC removal over TiO2/O3, MFOx/O3 and B/O3, respectively. Acute toxicity tests confirmed the effective toxicity control of organics by MFOx@TiO2/O3 process (inhibition rate: 10.9 %). Degradation test of atenolol and sulfamethoxazole confirmed the catalytic effects of MFOx@TiO2. MFOx@TiO2 performed strong resistance to water matrix in application test and showed good stability and reusability. The study proposed an effective catalyst for strengthening the ozonation process on PPCPs degradation and provided an in-depth understanding of the mechanisms and characteristics of the MFOx@TiO2 catalyst and MFOx@TiO2/O3 process.

Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

An endothelial-related prognostic index for bladder cancer patients.

BACKGROUND: Within the tumor microenvironment, endothelial cells hold substantial sway over bladder cancer (BC) prognosis. Herein, we aim to elucidate the impact of endothelial cells on BC patient outcomes by employing an integration of single-cell and bulk RNA sequencing data. METHODS: All data utilized in this study were procured from online databases. R version 3.6.3 and relevant packages were harnessed for the development and validation of an endothelial-associated prognostic index (EPI). RESULTS: EPI was formulated, incorporating six genes (CYTL1, FAM43A, GSN, HSPG2, RBP7, and SLC2A3). EPI demonstrated significant prognostic value in both The Cancer Genome Atlas (TCGA) and externally validated dataset. Functional results revealed a profound association between EPI and endothelial cell functionality, as well as immune-related processes. Our findings suggest that patients with low-risk EPI scores are more likely to respond positively to immunotherapy, as indicated by immune checkpoint activity, immune infiltration, tumor mutational burden, stemness index, TIDE, and IMvigor210 analyses. Conversely, individuals with high-risk EPI scores exhibited heightened sensitivity to cisplatin, docetaxel, and gemcitabine treatment regimens. CONCLUSION: We have effectively discerned pivotal genes from the endothelial cell perspective and constructed an EPI for BC patients, thereby offering promising prospects for precision medicine.

Cyclin-dependent kinase inhibitor 1A inhibits pyroptosis to enhance human lung adenocarcinoma cell radioresistance by promoting DNA repair.

Purpose: One of the best anticancer treatments available is radiotherapy, which can be used either alone or in conjunction with other forms of treatment including chemotherapy and surgery. Nevertheless, a number of biochemical and physiological processes that react to ionizing radiation might provide tumor cells radioresistance, which makes radiotherapy ineffective. It has been found that CDKN1A regulates DNA damage repair, which contributes to tumor radioresistance. However, the precise mechanism is still unknown. Therefore, this study aimed to explore the mechanisms underlying CDKN1A-enhanced radioresistance in tumor cells. Methods: Cells were irradiated with 4 Gy after CDKN1A overexpression or knockdown. CDKN1A expression was measured using real-time PCR, cell viability was evaluated using cell counting kit-8 and colony formation assays, and cytotoxicity was assessed using a lactate dehydrogenase assay. Pyroptosis in cells was analyzed using caspase-1 activity assay, enzyme-linked immunosorbent assay, and flow cytometry. Inflammation activation was detected through a co-immunoprecipitation assay. Activation of pyroptosis-related proteins was analyzed using immunohistochemistry, Western blot, and immunofluorescence. Tumor radioresistance in vivo was evaluated in a mouse xenograft model. Results: Radiotherapy upregulated CDKN1A expression, which promoted lung adenocarcinoma cell survival. CDKN1A influenced radiation-induced pyroptosis in A549, which mainly depended on inhibiting the activation of the AIM2 inflammasome by promoting DNA repair. Additionally, CDKN1A upregulation enhanced A549 xenograft tumor radioresistance by inhibiting radiation-induced pyroptosis in vivo. Conclusions: CDKN1A inhibits pyroptosis to enhance the radioresistance of lung adenocarcinoma cells by promoting DNA repair. This study may serve as a reference for developing novel targeted therapies against cancer.

Key genes involved in nonalcoholic steatohepatitis improvement after bariatric surgery.

Background: Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver diseases. The effectiveness of bariatric surgery in treating NASH and preventing or even reversing liver fibrosis has been demonstrated in numerous clinical studies, but the underlying mechanisms and crucial variables remain unknown. Methods: Using the GSE135251 dataset, we examined the gene expression levels of NASH and healthy livers. Then, the differentially expressed genes (DEGs) of patients with NASH, at baseline and one year after bariatric surgery, were identified in GSE83452. We overlapped the hub genes performed by protein-protein interaction (PPI) networks and DEGs with different expression trends in both datasets to obtain key genes. Genomic enrichment analysis (GSEA) and genomic variation analysis (GSVA) were performed to search for signaling pathways of key genes. Meanwhile, key molecules that regulate the key genes are found through the construction of the ceRNA network. NASH mice were induced by a high-fat diet (HFD) and underwent sleeve gastrectomy (SG). We then cross-linked the DEGs in clinical and animal samples using quantitative polymerase chain reaction (qPCR) and validated the key genes. Results: Seven key genes (FASN, SCD, CD68, HMGCS1, SQLE, CXCL10, IGF1) with different expression trends in GSE135251 and GSE83452 were obtained with the top 30 hub genes selected by PPI. The expression of seven key genes in mice after SG was validated by qPCR. Combined with the qPCR results from NASH mice, the four genes FASN, SCD, HMGCS1, and CXCL10 are consistent with the biological analysis. The GSEA results showed that the 'cholesterol homeostasis' pathway was enriched in the FASN, SCD, HMGCS1, and SQLE high-expression groups. The high-expression groups of CD68 and CXCL10 were extremely enriched in inflammation-related pathways. The construction of the ceRNA network obtained microRNAs and ceRNAs that can regulate seven key genes expression. Conclusion: In summary, this study contributes to our understanding of the mechanisms by which bariatric surgery improves NASH, and to the development of potential biomarkers for the treatment of NASH.

[Traceability Analysis and Environmental Quality Assessment of Soil Heavy Metal Pollution in West Hunan Province].

In order to explore the status of soil heavy metal pollution and environmental quality in west Hunan, relevant areas of Phoenix County were selected as the study area. Using data from 440 soil samples collected in the study area from June to August 2022, the pH value of the soil and contents of eight heavy metal elements, namely, As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, were analyzed. The PMF model was used for traceability analysis and geochemical evaluation of soil environmental quality. The results showed that the average values of soil heavy metals ω(Zn), ω(Cr), ω(Pb), ω(Ni), ω(Cu), ω(As), ω(Cd), and ω(Hg) were 81.02, 64.67, 31.63, 29.27, 25.52, 9.93, 0.28, and 0.13 mg·kg-1, respectively. The soil in the study area was mainly weakly acidic, and the contents of the Cd and Hg elements were relatively high compared to the national soil background values and were highly variable. The contents of the Hg and Cd elements in forest land were higher than that in other land uses. The PMF model results showed that the contribution rates of heavy metal pollution sources in the study area were mining sources (37.4%), atmospheric sedimentation sources (7.7%), natural sources (41.1%), and agricultural activity sources (13.8%) and provided suggestions on pollution control measures according to the spatial distribution of the four types of pollution sources. Through the comprehensive assessment of soil environmental geochemistry, the study area was divided into three types of plots, namely, non-risk areas (94.27 km2), accounting for 76.38%; risk-controllable areas (27.45 km2), accounting for 22.24%; and high-risk areas (1.7 km2), accounting for 1.38%. This study provided data support for the prevention and control measures of land pollution in the research area, as well as the delineation of the prevention and control scope.

Novel inhibitors targeting the PGK1 metabolic enzyme in glycolysis exhibit effective antitumor activity against kidney renal clear cell carcinoma in vitro and in vivo.

Our previous research has revealed phosphoglycerate kinase 1 (PGK1) enhances tumorigenesis and sorafenib resistance of kidney renal clear cell carcinoma (KIRC) by regulating glycolysis, so that PGK1 is a promising drug target. Herein we performed structure-based virtual screening and series of anticancer pharmaceutical experiments in vitro and in vivo to identify novel small-molecule PGK1-targeted compounds. As results, the compounds CHR-6494 and Z57346765 were screened and confirmed to specifically bind to PGK1 and significantly reduced the metabolic enzyme activity of PGK1 in glycolysis, which inhibited KIRC cell proliferation in a dose-dependent manner. While CHR-6494 showed greater anti-KIRC efficacy and fewer side effects than Z57346765 on nude mouse xenograft model. Mechanistically, CHR-9464 impeded glycolysis by decreasing the metabolic enzyme activity of PGK1 and suppressed histone H3T3 phosphorylation to inhibit KIRC cell proliferation. Z57346765 induced expression changes of genes related to cell metabolism, DNA replication and cell cycle. Overall, we screened two novel PGK1 inhibitors, CHR-6494 and Z57346765, for the first time and discovered their potent anti-KIRC effects by suppressing PGK1 metabolic enzyme activity in glycolysis.

Selective Construction of C-S/S-N Bonds from N-Substituted O-Thiocarbamates and Indoles under Transition-Metal-Free Conditions.

A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.

Ubiquitination, SUMOylation, and NEDDylation related genes serve as prognostic and therapeutic biomarkers for oral squamous cell carcinoma.

BACKGROUND: Ubiquitination, small ubiquitin-related modifiers, and NEDDylation are now found to function in cancer biology; however, its role in the oral cancer patients remains unclear. METHODS: A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ubiquitin and ubiquitin-like (UB/UBL) genes. A UB/UBL-related risk score was developed via correlation analyses, univariate Cox regression, and multivariate Cox regression. Nomogram analysis evaluates the model's prediction performance. The drug sensitivity analysis, immune profiles of UB/UBL-classified oral squamous cell carcinoma (OSCC) patients, and their related function pathway were investigated, and the role of UB/UBL-related genes in drug therapy was analyzed. RESULTS: A total of six prognostic UB/UBL-related genes were obtained. PSMD3, PCGF2, and H2BC10 were significantly downregulated in OSCC tissue and associated with longer survival time. OSCC patients in the high-risk group showed a significantly lower overall survival and enriched in cancer-related pathways. The prognostic potential of genes associated with UB/UBL was discovered, and patients with high-risk scores showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve of the annual survival rate was 0.616, 0.671, and 0.673, respectively. Besides, patients in the high-risk group are more sensitive to docetaxel, doxorubicin, and methotrexate therapy. CONCLUSIONS: We construct a prognosis model for OSCC patients with UB/UBL-related genes and try to find a new approach to treating oral cancer patients. The UB/UBL-related signature is helpful in developing new tumor markers, prognostic prediction, and in guiding treatment for OSCC patients.

Constructing mesoporous biochar derived from waste carton: Improving multi-site adsorption of dye wastewater and investigating mechanism.

The development of cost-efficient biochar adsorbent with a simple preparation method is essential to constructing efficient wastewater treatment system. Here, a low-cost waste carton biochar (WCB) prepared by a simple two-step carbonization was applied in efficiently removing Rhodamine B (RhB) in aqueous environment. The maximum ability of WCB for RhB adsorption was 222 mg/g, 6 and 10 times higher than both of rice straw biochar (RSB) and broadbean shell biochar (BSB), respectively. It was mainly ascribed to the mesopore structure (3.0-20.4 nm) of WCB possessing more spatial sites compared to RSB (2.2 nm) and BSB (2.4 nm) for RhB (1.4 nm✕1.1 nm✕0.6 nm) adsorption. Furthermore, external mass transfer (EMT) controlled mass transfer resistance (MTR) of the RhB sorption process by WCB which was fitted with the Langmuir model well. Meanwhile, the adsorption process was dominated by physisorption through van der Waals forces and π-π interactions. A mixture of three dyes in river water was well removed by using WCB. This work provides a straightforward method of preparing mesoporous biochar derived from waste carton with high-adsorption capacity for dye wastewater treatment.

Glyoxylic Acid Monohydrate-Promoted Formation of the C-SO2 Bond Starting from Maleimides/Quinones and Sodium Sulfinates.

By using glyoxylic acid monohydrate as a promoter, a wide range of substances containing a C-SO2 bond could be obtained from N-substituted maleimides or quinones and sodium sulfinates. The protocol features mild reaction conditions, short reaction time, and good atomic economics, which provides an alternative protocol for the α-sulfonylation of α,ß-unsaturated ketones.

Effect of electroacupuncture on urodynamics and Raf/MEK/ERK signaling pathway in spinal cord tissue of rats with detrusor hyperreflexia after suprasacral spinal cord injury. / ç”µé’ˆå¯¹éª¶ä¸Šè„Šé«“æŸä¼¤åŽé€¼å°¿è‚Œåå°„äº¢è¿›åž‹å¤§é¼ å°¿æµåŠ¨åŠ›å­¦åŠè„Šé«“Raf/MEK/ERK信号通路的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on urodynamics and Raf/MEK/ERK signaling pathway in spine cord tissue of rats after suprasacral spinal cord injury (SSCI), so as to explore its possible mechanism in improving bladder function in rats with detrusor hyperreflexia after SSCI. METHODS: Female SD rats were randomly divided into blank, sham operation, model, EA and EA+PD98059 groups, with 12 rats in each group. Thorax (T) 10 spinal cord transection was performed by surgery. Rats in the EA group were given EA (10 Hz/50 Hz, 20 min) at "Ciliao" (BL32), "Zhongji" (CV3), "Sanyinjiao" (SP6) and "Dazhui" (GV14) once daily for 7 d. Rats of the EA+PD98059 group received intraperitoneal injection of PD98059 (5 mg/kg) 2 h before EA intervention. The urodyna-mics was used to measure the base pressure, leak point pressure, maximum pressure, maximum capacity and comp-liance of bladder, and the morphology of bladder detrusor tissue was observed with HE staining. The TUNEL staining was used to detect the cell apoptosis of the spinal cord tissue. The expression levels of exchange protein directly activated by cAMP 2 (Epac2), Rap, phosphorylated rapidly accelerated fibrosarcoma (p-Raf), phosphorylated mitogen-activated extracellular signal-regulated kinase (p-MEK), phosphorylated extracellular signal regulated kinase 1 and 2 (p-ERK1/2), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) were determined by Western blot. RESULTS: Compared with the sham operation group, the base pressure, leak point pressure and maximum pressure of bladder were significantly increased (P<0.01), the maximum bladder capacity and bladder compliance were decreased (P<0.01), the cell apoptosis rate of spinal cord tissue was increased (P<0.01), and the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were decreased (P<0.01), while the expression level of Bax protein was increased (P<0.01) in the model group. After the treatment and compared with the model group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate of spinal cord tissue, the expression level of Bax protein were decreased (P<0.05) in the EA group, while the maximum bladder capacity and bladder compliance, the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were all increased (P<0.05, P<0.01). In comparison with the EA group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate, the expression level of Bax protein were significantly increased (P<0.05), whereas the maximum bladder capacity, bladder compliance, and the expression levels of p-MEK, p-ERK1/2, and Bcl-2 protein were decreased (P<0.05) in the EA+PD98059 group. Results of HE staining showed disordered transitional epithelial cells and destroyed lamina propria in bladder detrusor tissue, with the infiltration of monocytes in the model group, which was obviously milder in both EA and EA+PD98059 groups, especially in the EA group. CONCLUSIONS: EA can improve the bladder function in detrusor hyperreflexia rats after SSCI, which may be related to its effect in up-regulating Epac2 and Rap, activating the Raf-MEK-ERK pathway, and reducing the cell apoptosis of spinal cord tissue.

Integrative analysis of lysine acetylation-related genes and identification of a novel prognostic model for oral squamous cell carcinoma.

Introduction: Oral squamous cell carcinoma (OSCC), which accounts for a high proportion of oral cancers, is characterized by high aggressiveness and rising incidence. Lysine acetylation is associated with cancer pathogenesis. Lysine acetylation-related genes (LARGs) are therapeutic targets and potential prognostic indicators in various tumors, including oral squamous cell carcinoma. However, systematic bioinformatics analysis of the Lysine acetylation-related genes in Oral squamous cell carcinoma is still unexplored. Methods: We analyzed the expression of 33 Lysine acetylation-related genes in oral squamous cell carcinoma and the effects of their somatic mutations on oral squamous cell carcinoma prognosis. Consistent clustering analysis identified two lysine acetylation patterns and the differences between the two patterns were further evaluated. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to develop a lysine acetylation-related prognostic model using TCGA oral squamous cell carcinoma datasets, which was then validated using gene expression omnibus (GEO) dataset GSE41613. Results: Patients with lower risk scores had better prognoses, in both the overall cohort and within the subgroups These patients also had "hot" immune microenvironments and were more sensitive to immunotherapy. Disscussion: Our findings offer a new model for classifying oral squamous cell carcinoma and determining its prognosis and offer novel insights into oral squamous cell carcinoma diagnosis and treatment.

Autophagy induced by PP121 alleviates MSU crystal-induced acute gouty arthritis via inhibition of the NLRP3 inflammasome.

Acute gouty arthritis (AGA) is a frequent self-limiting inflammatory condition produced by the deposition of monosodium urate (MSU) crystals in the joints and periarticular tissues of patients with hyperuricemia. However, no effective interventional measures currently exist for AGA. Pyroptosis, a kind of pro-inflammatory programmed cell death, plays a crucial role in MSU crystal-induced inflammation and represents a potential treatment target for AGA. Therefore, we determined the therapeutic benefits and mechanism of PP121, a pyroptosis-related compound, on AGA. First, we injected an MSU crystal solution intra-articularly into the left foot pad of C57BL/6 mice to create an AGA mouse model. Subsequent treatment with PP121 substantially decreased tissue damage, pro-inflammatory cytokine release, and inflammatory cell infiltration caused by MSU crystals in the ankle joint. Consistent with these observations, the beneficial effects of PP121 on AGA were cancelled in Beclin1+/-(Becn1+/-) mice. Furthermore, after PP121 treatment, super-resolution microscopy revealed a strong relationship between lysosome-connected membrane protein/light chain 3 positive vesicles and the nucleotide-binding domain of leucine-rich family pyrin domain-containing 3 (NLPR3), demonstrating that PP121 promotes phagocytosis of the NLPR3 inflammasome. In summary, PP121-mediated autophagy can improve degradation of the NLRR3 inflammasome in AGA, which suggests the therapeutic potential of PP121 in AGA.

Pollutants removal and connections among sludge properties, metabolism potential and microbial characteristics in aerobic granular sequencing batch reactor for petrochemical wastewater treatment.

Petrochemical wastewater contains inhibitory compounds such as aromatics that are toxic to microorganisms during biological treatment. The compact and layered structure and the high amount of extracellular polymeric substances (EPS) in aerobic granular sludge (AGS) can contribute to protecting microorganisms from the harsh environment. This study evaluated the changes in the granule properties, pollutants removal, microbial metabolic potential and molecular microbial characteristics of the AGS process for petrochemical wastewater treatment. Granules treating petrochemical wastewater had a higher SVI30/SVI5 value (0.94) than that treating synthetic wastewater. An increase in bioactivity and EPS secretion with higher bio-polymer composition, specifically the functional groups such as hydroxyl, alkoxy and amino in protein, was observed, which promoted biomass aggregation. The granules also had more than 2-fold higher specific oxygen utilization rate. The AGS-SBR process obtained an average COD removal of 93% during petrochemical wastewater treatment and an effluent bCOD of below 1 mg L-1. No obvious inhibition of nitrification and denitrification activity was observed in the processes attributed to the layered structure of AGS. The average effluent NH4+-N of 5.0 mg L-1 was obtained and TN removal efficiencies of over 80.0% was achieved. Molecular microbial analysis showed that abundant functional genera Stenotrophomonas and Pseudoxanthomonas contributed to the degradation of aromatics and other petroleum organic pollutants. They were enriched with the variation of group behavior while metabolisms of amino acids and carboxylic acids by the relevant functional genera (e.g., Cytophagia) were significantly inhibited. The enrichment of Flavobacterium and Thermomonas promoted nitrification and denitrification, respectively. This research revealed the rapid start-up, enhanced granule structural strength, high inhibition resistance and considerable performance of AGS-SBR for petrochemical wastewater treatment.