Unveiling the Etiology of Urological Tumors: A Systematic Review of Mendelian Randomization Applications in Renal Cell Carcinoma, Bladder Cancer, and Prostate Cancer.

BACKGROUND: Our study aims to address two pivotal questions: "What are the recent advancements in understanding the etiology of urological tumors through Mendelian Randomization?" and "How can Mendelian Randomization be more effectively applied in clinical settings to enhance patient health outcomes in the future?" METHODS: In our systematic review conducted in April 2023, we utilized databases like PubMed and Web of Science to explore the influence of Mendelian Randomization in urological oncological diseases. We focused on studies published from January 2018, employing keywords related to urological tumors and Mendelian Randomization, supplemented with MeSH terms and manual reference checks. Our inclusion criteria targeted original research studies, while we excluded reports and non-relevant articles.  Data extraction followed a PICO-based approach, and bias risk was independently evaluated, with discrepancies resolved through discussion. This systematic approach adhered to PRISMA guidelines for accuracy and thoroughness in reporting. RESULTS: From the initial 457 publications, we narrowed down to 43 full-text articles after screening and quality assessments.A deeper understanding of Mendelian Randomization can help us explore risk factors with a clear causal relationship to urological tumors.This insight may pave the way for future research in early diagnosis, treatment, and management of associated diseases. CONCLUSION: Our review underscores the value of MR in urogenital tumor research, highlighting its efficacy in establishing causality and its potential to clarify disease mechanisms. Despite challenges like large sample sizes and variant identification, MR offers new perspectives for understanding and managing these tumors, suggesting a trend towards more inclusive and diverse research approaches.

Engineering Co3O4@3DOM LaCoO3 multistage-pore nanoreactor with superior SO2 resistance for toluene catalytic combustion.

Sulfur dioxide poisoning is a significant factor in catalyst deactivation during the catalytic combustion of volatile organic compounds. In this study, we prepared the LaCoO3 and Co3O4 composite catalysts using both the Ship-in-Bottle and Building-Bottle-Around-Ship approaches. Three-dimensionally ordered macropores (3DOM LaCoO3) were utilized as nanoreactors to protect the active sites during the catalytic combustion of toluene, preventing SO2 poisoning. Additionally, we grew ZIF-67 confined in the nanoreactor to create a multistage-pore structure. The Co3O4@3DOM LaCoO3 catalysts exhibited excellent activity in the complete catalytic oxidation of toluene. Various characterization studies confirmed the presence of a significant number of Co3+ species and an abundance of surface weak acid sites in the Co3O4@3DOM LaCoO3 catalysts, which synergistically enhanced the conversion of VOCs at low temperatures. Notably, the multistage pore structure provided a favorable reaction environment, accelerating the adsorption and diffusion of toluene and intermediates, resulting in excellent sulfur resistance of the catalysts. Moreover, XPS analysis confirmed a strong interaction between Co3O4 and LaCoO3, promoting rapid electron transfer and increasing the activation of O2-. In situ DRIFTS experiments verified that toluene mainly follows the MvK mechanism over Co3O4@3DOM LaCoO3 catalysts, indicating the following reaction pathway: toluene adsorption → benzyl alcohol → benzaldehyde → benzoate → anhydride → CO2 and H2O.

Basal metabolic rate and the risk of urolithiasis: a two-sample Mendelian randomization study.

OBJECTIVE: Few studies have investigated the impact of basal metabolic rate (BMR) on the development of urolithiasis, and the causal relationship is yet to be established. In this study, a two-sample Mendelian randomization (MR) analysis was utilized to identify the causal relationship between BMR and risk of urolithiasis. METHOD: Genetic instruments for BMR were drawn from a public genome-wide association study (GWAS). Summary dates on BMR and urolithiasis were obtained from a GWAS meta-analysis with sample sizes of 454,874 and 212,453, respectively. The inverse-variance weighted (IVW) method was provided as the main approach to estimate the causal relationship. The weighted-median method and the MR-Egger method were used as supplements to the IVW method. In addition, we conducted sensitivity analyses, including heterogeneity tests, pleiotropy tests and leave-one-out analysis, to assess the robustness of the outcomes. Furthermore, the funnel plot asymmetry was visually inspected to evaluate possible bias. RESULTS: The inverse-variance weighted data revealed that genetically predicted BMR significantly decreased the risk of urolithiasis [beta coefficient (beta): - 0.2366, odds ratio (OR): 0.7893, 95% confidence interval (CI) 0.6504-0.9579, p = 0.0166]. CONCLUSIONS: BMR has causal effects on urolithiasis in an MR study, and the risk of urolithiasis in patients with lower levels of BMR is higher.

The association between wet overactive bladder and consumption of tea, coffee, and caffeine: Results from 2005-2018 National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Previous studies have reported an inconsistent relationship between overactive bladder (OAB) and the consumption of tea, coffee, and caffeine. Our study aims to determine these associations in a large and nationally representative adult sample. METHODS: This cross-sectional study included 15,379 participants from the 2005-2018 US National Health and Nutrition Examination Survey (NHANES) database. The outcome was the risk of wet OAB that was diagnosed when the OAB symptom score was ≥3 with urgent urinary incontinence and excluded other diseases affecting diagnosis. The exposures were the consumption of tea, coffee, and caffeine. Weighted logistic regression models were established to explore these associations by calculating odds ratios (OR) and 95% confidence intervals (CI), as did restricted cubic splines (RCS) used to analyze the nonlinear associations. RESULT: Of all the participants (n = 15,379), 2207 had wet OAB. Mean [SE] consumption of tea, total coffee, caffeinated coffee, decaffeinated coffee, and caffeine was 233.6 [15.7] g/day, 364.3 [15.5] g/day, 301.6 [14.9] g/day, 62.7 [7.9] g/day, 175.5 [6.6] mg/day in participants with wet OAB, respectively. In the fully adjusted model, compared to those without tea consumption, the high consumption of tea (>481 g/day) was associated with an increased risk of wet OAB (OR: 1.29; 95%CI: 1.01-1.64). Low decaffeinated coffee (0.001-177.6 g/day) had a negative association with the risk (OR: 0.66; 95%CI: 0.49-0.90). In the RCS analysis, tea consumption showed a positive linear association with the risk of wet OAB, and decaffeinated coffee showed a nonlinear relationship with the risk and had a turning point of 78 g/day in the U-shaped curve between 0 and 285 g/day. Besides, total coffee, caffeinated coffee, and caffeine consumption had no significant association with the risk. Interestingly, in the high tea consumption, participants with high total coffee consumption [>527.35 g/day, OR and 95%CI: 2.14(1.16-3.94)] and low caffeine consumption [0.1-74.0 mg/day, OR and 95%CI: 1.50(1.03-2.17)] were positively associated with the risk of wet OAB. CONCLUSION: High tea consumption was associated with the increased risk of wet OAB, especially intake together with high total coffee and low caffeine consumption, but no significant association with the single consumption of total coffee and caffeine. Low decaffeinated coffee was associated with a decreased risk of wet OAB. It is necessary to control tea intake when managing the liquid intake of wet OAB patients.

AMPK-mediated autophagy pathway activation promotes ΔFosB degradation to improve levodopa-induced dyskinesia.

BACKGROUND: Parkinson's disease patients on chronic levodopa often suffer from motor complications, which tend to reduce their quality of life. Levodopa-induced dyskinesia (LID) is one of the most prevalent motor complications, often characterized by abnormal involuntary movements, and the pathogenesis of LID is still unclear but recent studies have suggested the involvement of autophagy. METHODS: The onset of LID was mimicked by chronic levodopa treatment in a unilateral 6-hydroxydopamine (6-OHDA) -lesion rat model. Overexpression of ΔFosB in HEK293 cells to mimic the state of ΔFosB accumulation. The modulation of the AMP-activated protein kinase (AMPK)-mediated autophagy pathway using by metformin, AICAR (an AMPK activator), Compound C (an AMPK inhibitor) and chloroquine (an autophagy pathway inhibitor). The severity of LID was assessed by axial, limb, and orofacial (ALO) abnormal involuntary movements (AIMs) score and in vivo electrophysiology. The activity of AMPK pathway as well as autophagy markers and FosB-ΔFosB levels were detected by western blotting. RT-qPCR was performed to detect the transcription level of FosB-ΔFosB. The mechanism of autophagy dysfunction was further explored by immunofluorescence and transmission electron microscopy. RESULTS: In vivo experiments demonstrated that chronic levodopa treatment reduced AMPK phosphorylation, impaired autophagosome-lysosomal fusion and caused FosB-ΔFosB accumulation in the striatum of PD rats. Long-term metformin intervention improved ALO AIMs scores as well as reduced the mean power of high gamma (hγ) oscillations and the proportion of striatal projection neurons unstable in response to dopamine for LID rats. Moreover, the intervention of metformin promoted AMPK phosphorylation, ameliorated the impairment of autophagosome-lysosomal fusion, thus, promoting FosB-ΔFosB degradation to attenuate its accumulation in the striatum of LID rats. However, the aforementioned roles of metformin were reversed by Compound C and chloroquine. The results of in vitro studies demonstrated the ability of metformin and AICAR to attenuate ΔFosB levels by promoting its degradation, while Compound C and chloroquine could block this effect. CONCLUSIONS: In conclusion, our results suggest that long-term metformin treatment could promote ΔFosB degradation and thus attenuate the development of LID through activating the AMPK-mediated autophagy pathway. Overall, our results support the AMPK-mediated autophagy pathway as a novel therapeutic target for LID and also indicate that metformin is a promising therapeutic candidate for LID.

Significant Enhanced SO2 Resistance of Pt/SiO2 Catalysts by Building the Ultrathin Metal Oxide Shell for Benzene Catalytic Combustion.

A noble metal catalyst shows excellent low-temperature oxidation activity in the catalytic combustion of benzene but has the problem of SO2 poisoning. We all know that SO2 easily competes with the reactant molecules for adsorption of the active site and has electronic effects on the active site to deactivate the catalyst. Therefore, the sulfur resistance of catalysts is the key problem to be solved in the process of catalytic combustion of benzene. Herein, the Pt/SiO2 catalyst with an ordered mesoporous structure was prepared by a one-step hydrothermal method, and MgO, ZnO, and MnOx were, respectively, coated on the surface of Pt/SiO2 as ultrathin shells to improve the sulfur resistance of Pt/SiO2. We observed that the sulfur resistance of the Pt/SiO2 catalyst was significantly improved due to the protective effect of the metal oxide shell. By comparing the three core-shell catalysts, it was found that the Pt/SiO2@MnOx catalyst coated with a MnOx shell had the best performance. The reason was that the MnOx shell not only protected the Pt active site but also had a good electron transfer effect on the core Pt, so it could effectively avoid the rapid adsorption poisoning of SO2 on the active Pt0 site. In addition, it was verified that the excellent redispersion of MnOx species in a SO2 atmosphere could increase the low-temperature oxidation activity of the Pt/SiO2@MnOx catalyst. Meanwhile, in situ DRIFT results also confirmed that the MnOx shell could significantly promote the oxidation of benzene molecules in the SO2 atmosphere.

The Association between Dietary Sugar Intake and Nephrolithiasis: Results from National Health and Nutrition Examination Survey 2007-2018.

BACKGROUND: Dietary sugar intake is gradually considered a risk factor for many diseases. A sugary diet was positively associated with risk of nephrolithiasis, but the specific relationships remain undefined. OBJECTIVES: To determine associations between risk of nephrolithiasis and dietary sugar intake. METHODS: This cross-sectional study involved 21,590 participants based on the National Health and Nutrition Examination Survey from 2007 to 2018. Amounts of dietary sugar intake (g/d) were the main exposure, including total sugar intake, added sugar intake, and food sources. Associations were analyzed by logistic regression models and restricted cubic splines using complex weighted designs. RESULTS: Weighted mean intake [standard error] of total sugar and added sugar were 111.2 [2.0] g/d and 73.7 [1.9] g/d in participants with nephrolithiasis, respectively. In the fully adjusted regression model, compared to those in quartile 1, the population in quartile 4 of total sugar intake showed a significant risk of nephrolithiasis [odds ratio (OR): 1.23; 95% confidence interval (CI): 1.00-1.51]; OR for added sugar intake was 1.56 (95% CI: 1.25-1.94). The risks of nephrolithiasis increased steadily when total sugar and added sugar intake exceeded ∼150 g/d and 63 g/d in restricted cubic spline analyses, respectively. The highest sugar intake from beverages was associated with an increased risk of nephrolithiasis (OR for total sugar: 1.36; 95% CI: 1.07-1.72; OR for added sugar: 1.37; 95% CI: 1.09-1.73). Added sugar intake from meat, egg, and oil was significantly associated with risk of nephrolithiasis (quartile 4, OR: 1.22; 95% CI: 1.02-1.47), whereas total sugar intake from dairy products was in reverse (quartile 4, OR: 0.67; 95% CI: 0.54-0.82). CONCLUSIONS: Total and added sugar intake, sugar intake from beverages, and added sugar intake from meat, egg, and oil were associated with an increased risk of nephrolithiasis, whereas total sugar intake from dairy products was negatively associated.

A Machine Learning Analysis of Prognostic Genes Associated With Allograft Tolerance After Renal Transplantation.

In this study, we aimed to identify transplantation tolerance (TOL)-related gene signature and use it to predict the different types of renal allograft rejection performances in kidney transplantation. Gene expression data were obtained from the Gene Expression Omnibus (GEO) database, differently expressed genes (DEGs) were performed, and the gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also conducted. The machine learning methods were combined to analyze the feature TOL-related genes and verify their predictive performance. Afterward, the gene expression levels and predictive performances of TOL-related genes were conducted in the context of acute rejection (AR), chronic rejection (CR), and graft loss through heatmap plots and the receiver operating characteristic (ROC) curves, and their respective immune infiltration results were also performed. Furthermore, the TOL-related gene signature for graft survival was conducted to discover gene immune cell enrichment. A total of 25 TOL-related DEGs were founded, and the GO and KEGG results indicated that DEGs mainly enriched in B cell-related functions and pathways. 7 TOL-related gene signature was constructed and performed delightedly in TOL groups and different types of allograft rejection. The immune infiltration analysis suggested that gene signature was correlated with different types of immune cells. The Kaplan-Meier (KM) survival analysis demonstrated that BLNK and MZB1 were the prognostic TOL-related genes. Our study proposed a novel gene signature that may influence TOL in kidney transplantation, providing possible guidance for immunosuppressive therapy in kidney transplant patients.

Unveiling a remarkable enhancement role by designing a confined structure Ho-TNTs@Mn catalyst for low-temperature NH3-SCR reaction.

MnOx-based catalysts are considered promising alternative catalysts for NH3-SCR to remove NOx at low temperature. However, their poor SO2 or H2O tolerance and unfavorable N2 selectivity are still the main obstacles restraining their further practical application. Herein, we carefully confined the manganese oxide active species in Ho-modified titanium nanotubes to improve their SO2 resistance and N2 selectivity. Ho-TNTs@Mn exhibits excellent catalytic activity, strong SO2 and H2O tolerance and superior N2 selectivity, and more than 80% NO conversion can be achieved in the range 80-300 °C with 100% N2 selectivity. The characterization results verify that the pore confinement effect of Ho-TNTs for Mn increases the dispersion of Mn to promote the interfacial effect between Mn and Ho. The electron synergistic effect between Mn and Ho improves the electron transformation of Mn and Ho, which inhibits electron transfer between SO2 and Mn to avoid poisoning from SO2. We also find that the interaction between Ho and Mn induces electron migration to restrain the production of Mn4+, contributing to the suitable redox capacity to decrease the creation of byproducts, which serves as the motivation for high N2 selectivity. In situ DRIFTs analysis clarifies that Langmuir-Hinshelwood (L-H) and Eley-Rideal (E-R) mechanisms co-exist in the NH3-SCR reaction over Ho-TNTs@Mn, and the E-R reaction mechanism predominates We believe that Ho-TNTs@Mn with a well-designed nanotube structure will show preferable development and application prospects in the NH3-SCR reaction.

Polymorphonuclear myeloid-derived suppressor cells play a proinflammatory role via TNF-α+ B cells through BAFF/BTK/NF-κB signalling pathway in the pathogenesis of collagen-induced arthritis mice.

Although various studies have been performed on the function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in RA, the results were conflicting. Here we were trying to clarify the role of PMN-MDSCs in the pathogenesis of RA and its specific mechanisms. We detected the frequencies and counts of PMN-MDSCs, TNF-α+ B cells and Ki67+ B cells in spleen and inflamed joints of collagen-induced arthritis (CIA) mice using flow cytometry. The pathological role of PMN-MDSCs was examined by anti-Ly6G neutralizing antibodies against PMN-MDSCs or adoptive transfer of PMN-MDSCs. And the modulation of PMN-MDSCs on B cells was conducted by coculture assays, RNA-Seq, RT-qPCR, and so on. The mechanism of BAFF regulating B cells was verified through western blot and flow cytometry. PMN-MDSCs accumulated in the spleen and joints of CIA mice. PMN-MDSCs depletion could alleviate the arthritis severity, which was accompanied by decreased TNF-α secretion and proliferation of B cells. And its adoptive transfer also facilitated disease progress. Furthermore, PMN-MDSCs from CIA mice had higher expression level of BAFF, which regulated TNF-α expression, proliferation and apoptosis of B cells in vitro. What's more, BAFF promoted phosphorylation of BTK/NF-κB signalling pathway. And Ibrutinib (BTK inhibitor) could reverse the effect of BAFF on TNF-α expression of B cells. Our study suggested that PMN-MDSCs enhanced disease severity of CIA and manipulated TNF-α expression, proliferation and apoptosis of B cells via BAFF, furthermore, BAFF promoted TNF-α expression through BTK/NF-κB signalling pathway, which demonstrated a novel pathogenesis of PMN-MDSCs in CIA.

Insights into the Electronic Structure Effect of SnMnOx Nanorod Catalysts for Low-Temperature Catalytic Combustion of o-Dichlorobenzene.

For the catalytic combustion reaction of chlorinated volatile organic compounds (CVOCs), the redox properties and acid sites of the catalyst surface are key factors in determining the activity, selectivity, and chlorine-resistance stability. Herein, a series of SnMnOx catalysts for the catalytic combustion of CVOCs were prepared by the changing of Sn-doping way to regulate the electron valance state of Mn element, including reflux (R-SnMnOx ), co-precipitation (C-SnMnOx ) and impregnation (I-SnMnOx ). It was discovered that the R-SnMnOx catalyst had better activity and chlorine resistance than the R-MnOx , C-SnMnOx and I-SnMnOx catalyst, and we discovered that the doping ways of Sn in MnOx catalyst could regulate greatly the surface acidity, active oxygen species, the chemical state of Mnn+ species, and redox ability. Especially, the R-SnMnOx catalysts exhibit excellent water resistance, and the reasons were related to the strong interaction of Snn+ and Mnn+ , which could promote obviously the dispersion of active Mn species, form a large number of acid sites, provide the abundant lattice oxygen species, and own the excellent redox ability, which accelerate the rate of charge transfer between Snn+ and Mnn+ (Sn4+ +Mn2+ →Sn2+ +Mn4+ ) to produce the abundant active species and accelerate the rapid conversion of benzene and intermediates conversion.

Engineering 3D structure Mn/YTiOx nanotube catalyst with an efficient H2O and SO2 tolerance for low-temperature selective catalytic reduction of NO with NH3.

TiO2 with a 3D structure is considered to be a promising support for Mn-based catalysts for the NH3-SCR reaction, but it is still insufficient to solve problems such as poor N2 selectivity and tolerance of H2O/SO2 at low temperature. In this work, a novel 3D-structured Mn/YTiOx nanotube catalyst was designed and the role of Y on the catalytic performance was investigated for the NH3-SCR reaction at low temperature. The results indicated that the Y-doped TiOx gradually transformed from nanotubes to nanosheets with the increase in Y doping, leading to a reduction in specific surface area and Brønsted acid sites. An appropriate amount of Y doping could distinctly improve the dispersion of MnOx and increase the concentration of surface Mn4+, Lewis acid sites and chemisorbed oxygen of catalysts, which was beneficial to the low-temperature NH3-SCR reaction, while excessive Y doping could cause a sharp decrease in specific surface area and Lewis acid sites. Therefore, Mn/YTiOx catalysts exhibited a volcano-type tendency in NO conversion with an increase in Y doping, and the highest activity was obtained at 3% doping, showing more than 90% NO conversion and N2 selectivity in a wide temperature window from 120 to 320 °C. The N2 selectivity and H2O/SO2 resistance of the catalysts was also enhanced with the increase in Y doping mainly due to the increased chemisorbed oxygen and electron transfer between Y and Mn. An in situ DRIFTS study demonstrated that Lewis acid sites played a more important role in the reaction than Brønsted acid sites, and the coordinated NH3 absorbed on Lewis acid sites, -NH2, monodentate nitrate and free nitrate ions were the main reactive intermediate species in the NH3-SCR reaction over an Mn/3%YTiOx catalyst. Langmuir-Hinshelwood (L-H) and Eley-Rideal (E-R) reaction mechanisms co-existed in the NH3-SCR reaction, but the L-H reaction mechanism predominated.

Interleukin-13 reduces bone erosion in rheumatoid arthritis by up-regulating osteoprotegerin expression in fibroblast-like synoviocytes : an in vitro and in vivo study.

OBJECTIVES: Bone erosion in rheumatoid arthritis (RA) is partly caused by excessive activation of osteoclasts. Osteoclasts can be derived from RA synovium and their differentiation can be inhibited by osteoprotegerin (OPG), a decoy receptor of the osteoclastogenesis-promoting cytokine receptor activator of nuclear factor κB ligand (RANKL). Fibroblast-like synoviocytes (FLSs) are the main stromal cells in the synovium that can secret OPG. The OPG secretion of FLSs can be modulated by various cytokines. Interleukin (IL)-13 can alleviate bone erosion in RA mouse models, but the mechanisms remain unclear. Therefore, we aimed to investigate whether IL-13 can induce OPG secretion by RA-FLSs, thus ameliorating bone destruction in RA by inhibiting osteoclast differentiation. METHODS: OPG, RANKL, and IL-13 receptors expression by RA-FLSs were evaluated by RT-qPCR. OPG secretion was determined by ELISA. Western blot was performed to analyse OPG expression and the activation of the STAT6 pathway. IL-13 and (or) OPG siRNA pre-treated RA-FLSs conditioned medium were used in osteoclast induction to test if IL-13 can inhibit osteoclastogenesis by up-regulating OPG in RA-FLSs. Micro-CT and immunofluorescence were performed to determine if IL-13 can induce OPG expression and alleviate bone erosion in vivo. RESULTS: IL-13 can promote OPG expression of RA-FLSs, and the promotion can be overcome by IL-13Rα1 or IL-13Rα2 siRNA transfection, or STAT6 inhibitor. Osteoclast differentiation can be inhibited by IL-13 pre-treated RA-FLSs conditioned medium. The inhibition can be reversed by OPG siRNA transfection. IL-13 injection can increase OPG expression in the joints while reducing bone destruction in collagen-induced arthritis mice. CONCLUSIONS: IL-13 can inhibit osteoclastogenesis by up-regulating OPG in RA-FLSs through IL-13 receptors via the STAT6 pathway, thus may ameliorate bone erosion in RA.

Core-shell CoCuOx@MOx (MNb, Ti and Ce) catalysts with outstanding durability and resistance to H2O for the catalytic combustion of o-dichlorobenzene.

Configuring Co-based catalysts with excellent activity, durability, anti-H2O capability and superior chlorine resistance is an effective strategy for catalytic combustion of CVOCs. In this work, we elaborated a CoCuOx catalysts with the same core but different shell. The CoCuOx dodecahedron surface was successfully coated with shells of Nb2O5, TiO2, and CeO2 using a range of conventional synthesis methods. The prepared core-shell catalysts (CoCuOx@TiO2 and CoCuOx@Nb2O5) were found to generate plentiful acid sites and abundant lattice oxygen species, indicating a strong interaction between the core and shell layers that resulted in a significant enhancement of catalytic activity. Additionally, by-products generation was successfully controlled by acid sites and lattice oxygen species. More importantly, the core-shell structure design significantly improved the thermal stability and anti-H2O capability of the catalysts. Furthermore, the possible formation pathways and reaction mechanisms were proposed based on in-situ FTIR and selectivity analysis.

SHIP1 is required for the formation of neutrophil extracellular traps in rheumatoid arthritis.

Aberrant neutrophil extracellular traps (NETs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, the specific pathway leading to NET formation in RA is poorly understood. Therefore, therapies targeting NETs are not available in RA. In this study, we demonstrated Src homology 2 domain-containing inositol phosphatase-1 (SHIP1) function as a hub to regulate NETosis through SHIP1/ p38 MAPK/TNF-α pathway both in vitro and ex vivo and inhibiting SHIP1 expression ameliorated RA symptoms in vivo. Neutrophils from RA patients showed enhanced NETosis as well as increased SHIP1, p38 mitogen-activated protein kinase (MAPK) family expression and tumor necrosis factor-α (TNF-α) expression. Inhibiting SHIP1 in neutrophils using small molecules counteracted the above-mentioned dysregulations and resulted in decrease in NETosis, p38 expression and TNF-α concentration. Consistent with this, SHIP1 agonist led to upregulated p38MAPK and NET formation. Moreover, inhibiting SHIP1 in vivo led to decreased NETosis and showed beneficial therapeutic effects in Collagen-induced arthritis (CIA) mice. Taken together, these results indicated that activation of SHIP1/MAPK/TNF-α pathway was necessary for upregulated NETosis in RA, which provided evidence for targeting SHIP1 in RA treatment.

A novel autophagy-related long non-coding RNAs prognostic risk score for clear cell renal cell carcinoma.

BACKGROUND: As the main histological subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) places a heavy burden on health worldwide. Autophagy-related long non-coding RNAs (ARlncRs) have shown tremendous potential as prognostic signatures in several studies, but the relationship between them and ccRCC still has to be demonstrated. METHODS: The RNA-sequencing and clinical characteristics of 483 ccRCC patients were downloaded download from the Cancer Genome Atlas and International Cancer Genome Consortium. ARlncRs were determined by Pearson correlation analysis. Univariate and multivariate Cox regression analyses were applied to establish a risk score model. A nomogram was constructed considering independent prognostic factors. The Harrell concordance index calibration curve and the receiver operating characteristic analysis were utilized to evaluate the nomogram. Furthermore, functional enrichment analysis was used for differentially expressed genes between the two groups of high- and low-risk scores. RESULTS: A total of 9 SARlncRs were established as a risk score model. The Kaplan-Meier survival curve, principal component analysis, and subgroup analysis showed that low overall survival of patients was associated with high-risk scores. Age, M stage, and risk score were identified as independent prognostic factors to establish a nomogram, whose concordance index in the training cohort, internal validation, and external ICGC cohort was 0.793, 0.671, and 0.668 respectively. The area under the curve for 5-year OS prediction in the training cohort, internal validation, and external ICGC cohort was 0.840, 0.706, and 0.708, respectively. GO analysis and KEGG analysis of DEGs demonstrated that immune- and inflammatory-related pathways are likely to be critically involved in the progress of ccRCC. CONCLUSIONS: We established and validated a novel ARlncRs prognostic risk model which is valuable as a potential therapeutic target and prognosis indicator for ccRCC. A nomogram including the risk model is a promising clinical tool for outcomes prediction of ccRCC patients and further formulation of individualized strategy.

Regulation and Stabilization of the Zinc Metal Anode Interface by Electroless Plating of a Multifunctionalized Polydopamine Layer.

A novel electroless plating technique is utilized by coating a polydopamine layer on zinc foil (Zn@PDA) to regulate the deposition and growth of zinc dendrites, as well as suppress the occurrence of hydrogen evolution and passivation products for aqueous zinc-ion batteries. Polydopamine (PDA) has a strong adsorption ability on Zn foil due to the formation of a bidentate bonding during the electroless plating. Further, it indicates that the abundant hydroxyl groups of PDA react as zinc-philic sites to adsorb Zn2+ and further undergo redox by forming carbonyl groups to effectively induce the uniform deposition and growth of zinc dendrites. Meanwhile, the strong coordination of PDA and Zn2+ will weaken the solvated structure between Zn2+ and H2O molecules, resulting in an enhanced ionization energy of H2O and inhibited hydrogen evolution reaction. Thus, Zn@PDA can maintain stable cycling over 900 h at 0.2 mA cm-2, and a high coulombic efficiency of average 98.5% at 2 mA cm-2. Moreover, the validity of Zn@PDA has been verified using the Zn@PDA||self-standing VS2@stainless steel (VS2@SS) full battery, which displays an impressive capacity retention of 81.3% after 1000 cycles without sacrificing the rate performance. This work provides a simple, reliable, and harmless method to achieve high-performance aqueous zinc-ion batteries.

A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer.

BACKGROUND: Inflammation and long noncoding RNAs (lncRNAs) are gradually becoming important in the development of bladder cancer (BC). Nevertheless, the potential of inflammatory response-related lncRNAs (IRRlncRNAs) as a prognostic signature remains unexplored in BC. METHODS: The Cancer Genome Atlas (TCGA) provided RNA expression profiles and clinical information of BC samples, and GSEA Molecular Signatures database provided 1171 inflammation-related genes. IRRlncRNAs were identified using Pearson correlation analysis. After that, consensus clustering was performed to form molecular subtypes. After performing least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, a risk model constructed based on the prognostic IRRlncRNAs was validated in an independent cohort. Kaplan-Meier (KM) analysis, univariate and multivariate Cox regression, clinical stratification analysis, and time-dependent receiver operating characteristic (ROC) curves were utilized to assess clinical effectiveness and accuracy of the risk model. In clusters and risk model, functional enrichment was investigated using GSEA and GSVA, and immune cell infiltration analysis was demonstrated by ESTIMATE and CIBERSORT analysis. RESULTS: A total of 174 prognostic IRRlncRNAs were confirmed, and 406 samples were divided into 2 clusters, with cluster 2 having a significantly inferior prognosis. Moreover, cluster 2 exhibited a higher ESTIMATE score, immune infiltration, and PD-L1 expression, with close relationships with the inflammatory response. Further, 12 IRRlncRNAs were identified and applied to construct the risk model and divide BC samples into low-risk and high-risk groups successfully. KM, ROC, and clinical stratification analysis demonstrated that the risk model performed well in predicting prognosis. The risk score was identified as an independently significant indicator, enriched in immune, cell cycle, and apoptosis-related pathways, and correlated with 9 immune cells. CONCLUSION: We developed an inflammatory response-related subtypes and steady prognostic risk model based on 12 IRRlncRNAs, which was valuable for individual prognostic prediction and stratification and outfitted new insight into inflammatory response in BC.

Engineering yolk-shell MnFe@CeOx@TiOx nanocages as a highly efficient catalyst for selective catalytic reduction of NO with NH3 at low temperatures.

To broaden the reaction temperature range and improve the H2O-resistance of manganese-based catalysts, yolk-shell structured MnFe@CeOx@TiOx nanocages were prepared. The CeO2 shell could effectively increase the oxygen vacancy defect sites, and the TiO2 shell could remarkably improve the surface acid sites. Combining the advantages of the two shells could effectively solve the above questions. The catalytic efficiency of the yolk-shell MnFe@CeOx@TiOx-40 nanocages could reach above 90% in the range of 120-240 °C, and the water resistance could reach 90% at 240 °C. On the one hand, the construction of double shells could significantly increase the proportion of active species (Mn4+, Fe3+, Ce3+ and Oads) and the interface effect between the shell layers could effectively enhance the interaction between metal oxides. On the other hand, the construction of double shells could achieve an appropriate balance between the redox capacity of the catalyst and surface acidity. Simultaneously, in situ DRIFT spectroscopy indicated that the yolk-shell MnFe@CeOx@TiOx-40 nanocages mainly followed the L-H mechanism during the NH3-SCR reaction. Finally, this double-shell structure strategy provided a new idea for constructing a Mn-based catalyst with a wide temperature window and better low-temperature water resistance.

Rational Design and Construction of Monolithic Ordered Mesoporous Co3O4@SiO2 Catalyst by a Novel 3D Printed Technology for Catalytic Oxidation of Toluene.

Here, we report a novel 3D printed layered ordered mesoporous template that can encapsulate active Co-MOFs species in a confined way to achieve the goal of monolithic catalyst. The monolithic OM-Co3O4@SiO2-S catalyst can maintain a macroscopic porous layered structure and a microscopic ordered mesoporous structure. This monolithic OM-Co3O4@SiO2-S catalyst has excellent catalytic performance (T90 = 236 °C), water resistance, and thermal stability in the catalytic combustion of toluene. The catalytic performance of the monolithic OM-Co3O4@SiO2-S catalyst is much better than that of many monolithic catalysts reported in the former. Among them, the introduction of binder aluminum phosphate (AP) can effectively enhance the rheological properties of the printing ink, achieve the purpose of ink writing monolithic layered porous material, enrich the acidic point of the monolithic catalyst, and increase the number of reactive oxygen species. This work reveals a novel monolithic catalyst forming strategy that can combine the advantages of ordered mesoporous materials with active species to form macro-layered porous materials and provide ideas and an experimental basis for the elimination of VOCs in industrial applications.