Strategy to mitigate substrate inhibition in wastewater treatment systems.

Global urbanization requires more stable and sustainable wastewater treatment to reduce the burden on the water environment. To address the problem of substrate inhibition of microorganisms during wastewater treatment, which leads to unstable wastewater discharge, this study proposes an approach to enhance the tolerance of bacterial community by artificially setting up a non-lethal high substrate environment. And the feasibility of this approach was explored by taking the inhibition of anammox process by nitrite as an example. It was shown that the non-lethal high substrate environment could enhance the nitrite tolerance of anammox bacterial community, as the specific anammox activity increasing up to 24.71 times at high nitrite concentrations. Moreover, the system composed of anammox bacterial community with high nitrite tolerance also showed greater resistance (two-fold) in response to nitrite shock. The antifragility of the system was enhanced without affecting the operation of the main reactor, and the non-lethal high nitrite environment changed the dominant anammox genera to Candidatus Jettenia. This approach to enhance tolerance of bacterial community in a non-lethal high substrate environment not only allows the anammox system to operate stably, but also promises to be a potential strategy for achieving stable biological wastewater treatment processes to comply with standards.

Inulin enhanced rifaximin-inhibited colon cancer pulmonary metastasis by flora-regulated bile acid pathway.

Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria, while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.

Influence of multiple risk factor control level on cardiovascular outcomes in hypertensive patients.

OBJECTIVE: The relationship between the level of baseline risk factor control and cardiovascular outcomes in hypertensive patients with blood pressure intervention is not well understood. It is also unclear whether the level of baseline risk factor control is persuasively associated with cardiovascular outcomes in hypertensive patients with blood pressure lowering strategy. METHOD: We performed an analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants without complete baseline risk factor data were excluded. The primary outcome was a composite of cardiovascular events and all-cause mortality. Cox proportional hazard models were used to calculate the hazard ratio (HR) and estimate association between risk factor control levels (≥6, 5, 4, and ≤ 3) and cardiovascular outcomes. RESULTS: A total of 8337 participants were involved in the analysis and the median follow-up period was 3.19 years. Each additional risk factor uncontrolled was associated with a 24% higher cardiovascular risk (HR 1.24, 95% CI 1.11-1.37). Compared with participants with optimal risk factor control, those with ≤ 3 factors control exhibited 95% higher cardiovascular risk (HR 1.95, 95% CI 1.37-2.77). The corresponding protective effects of multiple risk factor modification were not influenced by intensive or standard antihypertensive treatment (P for interaction = 0.71). CONCLUSIONS: A stepwise association was observed between cardiovascular risk and the number of risk factor control in hypertensive patients. The more risk factor was modified, the less cardiovascular risk was observed, irrespective of different blood pressure lowering strategies. Comprehensive risk factor control strategies are warranted to reduce cardiovascular disease risk in hypertensive patients. Trial registration STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Impact of Hypertension Duration on the Cardiovascular Benefit of Intensive Blood Pressure Control.

BACKGROUND: The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment. METHODS: From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model. RESULTS: The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (P>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (Pinteraction=0.05). CONCLUSIONS: Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

Impact of ZnO NPs on photosynthesis in rice leaves plants grown in saline-sodic soil.

Saline-sodic stress restricts the absorption of zinc by rice, consequently impacting the photosynthesis process of rice plants. In this experiment, Landrace 9 was selected as the test material and the potting method was employed to investigate the influence of ZnO nanoparticles (ZnO NPs) on zinc absorption and chlorophyll fluorescence in rice grown in saline-sodic land. The research findings demonstrate that the application of ZnO NPs proves to be more advantageous for the growth of rice in saline-sodic soil. Notably, the application of ZnO NPs significantly decreases the levels of Na+ and MDA in rice leaves in saline-sodic soil, while increasing the levels of K+ and Zn2+. Additionally, ZnO NPs enhances the content of chloroplast pigments, specific energy flux, quantum yield, and the performance of active PSII reaction center (PIABS) in rice leaves under saline-sodic stress. Furthermore, the relative variable fluorescence (WK and VJ) and quantum energy dissipation rate (φDo) of rice are also reduced. Therefore, the addition of ZnO NPs enhances the transfer of electrons and energy within the rice photosystem when subjected to saline-sodic stress. This promotes photosynthesis in rice plants growing in saline-sodic land, increasing their resistance to saline-sodic stress and ultimately facilitating their growth and development.

Sophora subprostrate polysaccharide targets LncRNA MSTRG.5823.1 to suppress PCV2-mediated immunosuppression via TNF/NF-κB signaling.

Current evidence suggests that porcine circovirus type 2 (PCV2) infection induces immunosuppression in piglets. Sophora subprostrate polysaccharide (SSP) exhibits various pharmacological activities, including immunoregulatory, anti-inflammatory, antiviral, and antioxidant properties. However, the acts of lncRNAs in regulating the therapeutic effects of SSP on PCV2-infected RAW264.7 cells remains poorly understood. This study aimed to investigate the molecular mechanisms by which lncRNAs regulate PCV2-induced immunosuppression during SSP treatment. Our findings revealed that 1699 mRNAs, 373 lncRNAs, and 129 miRNAs were differentially expressed in PCV2-infected RAW264.7 cells. Additionally, 359 mRNAs, 271 lncRNAs, and 79 miRNAs exhibited differential expression in SSP-treated PCV2-infected RAW264.7 cells. GO and KEGG analyses indicated that the candidate genes were enriched in the TNF/NF-κB signaling pathway. Furthermore, based on GO and KEGG pathway analysis, a ceRNA network involving chemokine (C-X-C motif) ligand 2 (CXCL2), miR-217-x, and MSTRG.5823.1 was constructed. We demonstrated that lncRNA MSTRG.5823.1 localized to the cytoplasm. Moreover, we found that silencing or overexpressing lncRNA MSTRG.5823.1 significantly modulated PCV2-induced immunosuppression by regulating the activation of the TNF/NF-κB signaling pathway. Specifically, lncRNA MSTRG.5823.1 overexpression increased the expression of TNF/NF-κB signaling pathway-related genes and proteins in PCV2-infected RAW264.7 cells. Conversely, silencing lncRNA MSTRG.5823.1 decreased their expression. Rescue assays further revealed that the suppressive effects of miR-217-x overexpression on TNF/NF-κB signaling pathway-related genes and proteins could be reversed by MSTRG.5823.1 overexpression. These findings highlight the critical role of lncRNA MSTRG.5823.1 in PCV2 infection progression and suggest a new strategy for the prevention and treatment of PCV2 infection.

SNPS within the SLC27A6 gene are highly associated with Hu sheep fatty acid content.

Fatty acids (FA) are an important factor affecting meat quality and human health, and the important role of the solute carrier family 27 member 6 (SLC27A6) in FA metabolism has been demonstrated in several species. However, the expression profile of the SLC27A6 in different tissues and the effect of its polymorphism on FA in sheep are currently unknown. This study aimed to explore the differences in FAs in the longissimus dorsi (LD) of 1,085 Hu sheep, the expression profile of SLC27A6, and confirm the effect of single nucleotide polymorphisms (SNPs) on FA phenotypes. We found that many FA phenotypes differ significantly across different seasons, and winter promoted the deposition of polyunsaturated fatty acids (PUFA). The mRNA expression level of SLC27A6 in the lung was significantly higher than that in the heart, testis, and LD. A total of 16 SNPs were detected in the SLC27A6, and 14 SNPs were successfully genotyped by improved multiplex ligase detection reaction (iMLDR) technology. Correlation analysis showed that 7 SNPs significantly affected at least one FA phenotype. Among them, SNP14 contributes to the selection of lamb with low saturated fatty acid content and high PUFA content. Combined genotypes also significantly affected a variety of beneficial FAs such as C18:3n3, C20:4n6, C22:6n3, and monounsaturated fatty acids. This study suggests that SLC27A6 plays an important role in FA metabolism and SNPs that are significantly associated with FA phenotype could be used as potential molecular markers for later targeted regulation of FA profiles in sheep.

Ni-Co hexacyanoferrate hollow nanoprism with CN vacancy for electrocatalytic benzyl alcohol oxidation.

An innovative method to improve the oxidation efficiency of benzyl alcohol utilizes Ni-Co hexacyanoferrate hollow nanoprisms. Synthesized via a gentle self-sacrificial template method, this catalyst exhibits substantial catalytic activity and selectivity towards benzyl alcohol oxidation, facilitated by the strategic incorporation of Co to modulate CN vacancy density. Impressively, it achieves a current density of 10 mA cm-2 at 1.33 V and a remarkable 98% efficiency in benzyl alcohol conversion at 1.4 V.

Experimental Investigation on Ultra-Thin Vapor Chamber with Composite Wick for Electronics Thermal Management.

Ultra-thin vapor chambers (UTVCs) are widely used to cool high-power electronics due to their excellent thermal conductivity. In this study, a UTVC of 82 mm × 58 mm × 0.39 mm with composite wick was prepared. The composite wick is composed of two layers of copper mesh and multiple spiral-woven meshes (SWMs), and the composite wick was applied in UTVC to improve liquid replenishment performance and temperature uniformity. Furthermore, the thermal performance of UTVCs with different support column diameters, filling ratios (FRs), and SWM structures was experimentally studied. The results found that the equivalent thermal conductivity (ETC) decreases as the diameter of the support column increases; the UTVC with 0.5 mm support column diameter has the highest ETC, at 3473 W/(m·K). Then, the effect of FR on the heat transfer performance of UTVCs with SWM numbers of 0, 1, 2, and 3 (0 SWMs, 1 SWM, 2 SWMs, 3 SWMs) is consistent, the 30% FR UTVC with 3 SWMs having the highest ETC, at 3837 W/(m·K). Finally, the increased number of SWMs can significantly improve the ultimate power of the UTVCs, the UTVC with 3 SWMs having the highest ultimate power, at 26 W. The above experimental studies indicate that the designed and manufactured UTVCs have great potential advantages in thermal dissipation for electronics.

Association of intensive blood pressure management with cardiovascular outcomes in patients using multiple classes of antihypertensive medications: a post-hoc analysis of the STEP Trial.

High medication burden is associated with poor treatment effect and high risk of cardiovascular outcomes. This study aimed to investigate the association between the antihypertensive medication burden and cardiovascular outcomes in the STEP trial. This post-hoc analysis of the STEP trial enrolled 8511 participants, including 8041 with low burden and 470 with high burden. High antihypertensive medication burden was defined as being treated with ≥3 different classes of prescribed antihypertensive medications. The primary outcome was a composite of cardiovascular outcomes. Fine-Gray model was used in this study. Among all participants, high antihypertensive medication burden was associated with a higher risk of the primary outcome compared with low medication burden (HR, 1.52; 95% CI, 1.03-2.24), which was consistent in the standard group (HR, 1.95; 95% CI, 1.20-3.18) and the intensive group (HR, 1.10; 95% CI, 0.57-2.13; Pinteraction = 0.18). The beneficial effects of intensive systolic blood pressure (SBP) control on the primary outcome remained significant in the high burden group (HR, 0.42; 95% CI, 0.19-0.95) and the low burden group (HR, 0.79; 95% CI, 0.63-0.98; Pinteraction = 0.18). At 24 months, the percentage of participants achieving the target SBP was lower in the high medication burden group (risk ratio, 0.93; 95% CI, 0.89-0.98). In both standard and intensive treatment groups, participants with a high medication burden were harder to achieve the target SBP (Pinteraction = 0.65). High antihypertensive medication burden was associated with worse SBP control and a greater risk of cardiovascular events. Intensive SBP control showed cardiovascular benefits in both medication burden groups. Trial registration: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Mean platelet volume is associated with periodontitis: a cross-sectional study.

BACKGROUND: It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. METHODS: We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009-2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. RESULTS: Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019-1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052-1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p < 0.05). However, none of the subgroups exhibited significant interactions (p for interaction > 0.05). CONCLUSION: A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States.

Enhancing recurrence risk prediction for bladder cancer using multi-sequence MRI radiomics.

OBJECTIVE: We aimed to develop a radiomics-clinical nomogram using multi-sequence MRI to predict recurrence-free survival (RFS) in bladder cancer (BCa) patients and assess its superiority over clinical models. METHODS: A retrospective cohort of 229 BCa patients with preoperative multi-sequence MRI was divided into a training set (n = 160) and a validation set (n = 69). Radiomics features were extracted from T2-weighted images, diffusion-weighted imaging, apparent diffusion coefficient, and dynamic contrast-enhanced images. Effective features were identified using the least absolute shrinkage and selection operator (LASSO) method. Clinical risk factors were determined via univariate and multivariate Cox analysis, leading to the creation of a radiomics-clinical nomogram. Kaplan-Meier analysis and log-rank tests assessed the relationship between radiomics features and RFS. We calculated the net reclassification improvement (NRI) to evaluate the added value of the radiomics signature and used decision curve analysis (DCA) to assess the nomogram's clinical validity. RESULTS: Radiomics features significantly correlated with RFS (log-rank p < 0.001) and were independent of clinical factors (p < 0.001). The combined model, incorporating radiomics features and clinical data, demonstrated the best prognostic value, with C-index values of 0.853 in the training set and 0.832 in the validation set. Compared to the clinical model, the radiomics-clinical nomogram exhibited superior calibration and classification (NRI: 0.6768, 95% CI: 0.5549-0.7987, p < 0.001). CONCLUSION: The radiomics-clinical nomogram, based on multi-sequence MRI, effectively assesses the BCa recurrence risk. It outperforms both the radiomics model and the clinical model in predicting BCa recurrence risk. CRITICAL RELEVANCE STATEMENT: The radiomics-clinical nomogram, utilizing multi-sequence MRI, holds promise for predicting bladder cancer recurrence, enhancing individualized clinical treatment, and performing tumor surveillance. KEY POINTS: • Radiomics plays a vital role in predicting bladder cancer recurrence. • Precise prediction of tumor recurrence risk is crucial for clinical management. • MRI-based radiomics models excel in predicting bladder cancer recurrence.

Transcriptomic analysis of the HPG axis-related tissues reveals potential candidate genes and regulatory pathways associated with testicular size in Hu sheep.

Testicular size is an excellent proxy for selecting high-fertility rams. The hypothalamus-pituitary-gonadal (HPG) axis plays an important role in regulating reproductive capacity in vertebrates, while key genes and regulatory pathways within the HPG axis associated with testicular size remain largely unknown in sheep. This study comprehensively compared the transcriptomic profiles in the hypothalamus, pituitary and testis of rams after sexual maturity between the large-testis group (LTG, testicular weight = 454.29 ± 54.24 g) and the small-testis group (STG, testicular weight = 77.29 ± 10.76 g). In total, 914, 795 and 10518 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary and testis between LTG and STG, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these DEGs were mainly involved in the biological processes of reproduction, biological regulation, and development process. Notably, the neuroactive ligand-receptor interaction and cAMP signaling pathways, commonly enriched by the DEGs in the hypothalamus and pituitary between two groups, were considered as two key signal pathways regulating testicular development through the HPGs axis. Weighted gene co-expression network analysis (WGCNA) identified two modules that were significantly associated with testicular size, and 97 key genes were selected with high module membership (MM) and gene significance (GS) in these two modules. Finally, a protein-protein interaction (PPI) network was constructed, and ten genes with the highest degree were represented as hub genes, including FOS, NPY, SST, F2, AGT, NTS, OXT, EDN1, VIP and TAC1. Taken together, these results provide new insights into the molecular mechanism underlying the HPG axis regulating testicular size of Hu sheep.

Transformation of crystal structure induced by the temperatures in carbon dots (CDs)-based composites with multicolor fluorescence for white Light-Emitting-Diode (WLED).

Regulation of the fluorescence through crystalizing from the matrix in the Carbon dots (CDs)-based solid-state materials has been verified to be one of the effective methods, yet there are not only challenges in preparing such materials efficiently, but also insufficient insight into their regulation mechanisms. Here, a one-pot solvothermal route to synthesize a series of CDs-based composites with crystalline matrix is reported. These crystals exhibited multicolor fluorescence with the feature of multi-peaks emissions with increasing temperatures from 140 ℃ to 220 ℃, in which the orange emitting O-CDs@PA and the yellow emitting Y-CDs@PA crystals obtained the FLQYs of 22% and 68% respectively due to relatively stable crystalline structures. After comparative analysis to both crystals in detail, the core and the groups associated with them on the interface between CDs and matrix were adjusted in size and species during structural transformation of the crystal matrix, which changes radically the energy band structures to influence fluorescent emitting of both crystals ultimately. In addition, the reasons resulting in higher FLQY for Y-CDs@PA were provided leveraging the schematic illustration presumed based on the PL properties of both crystals. Because of the optimal optical performances, these fluorescent materials promised to fabricate WLED devices and obtained a number of photometric parameters endowed these WLED devices with the feature of warm-white light.

Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline lowered the threshold defining hypertension to 130/80 mmHg. However, how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear. This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population. METHODS: Participants with stage 1 hypertension ( n = 69,509) or normal BP ( n = 34,142) were followed in this study from 2006/2007 to 2020. Stage 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 mmHg. None were taking antihypertensive medication or had a history of myocardial infarction (MI), stroke, or cancer at baseline. The primary outcome was a composite of MI, stroke, and all-cause mortality. The secondary outcomes were individual components of the primary outcome. Cox proportional hazards models were used for the analysis. RESULTS: During a median follow-up of 11.09 years, we observed 10,479 events (MI, n = 995; stroke, n = 3408; all-cause mortality, n = 7094). After multivariable adjustment, the hazard ratios for stage 1 hypertension vs. normal BP were 1.20 (95% confidence interval [CI], 1.13-1.25) for primary outcome, 1.24 (95% CI, 1.05-1.46) for MI, 1.45 (95% CI, 1.33-1.59) for stroke, and 1.11 (95% CI, 1.04-1.17) for all-cause mortality. The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90 (95% CI, 0.85-0.96). CONCLUSIONS: Using the new definition, Chinese adults with untreated stage 1 hypertension are at higher risk for MI, stroke, and all-cause mortality. This finding may help to validate the new BP classification system in China.

MRI radiomics for predicting poor disease-free survival in muscle invasive bladder cancer: the results of the retrospective cohort study.

OBJECTIVES: To develop an MRI radiomic nomogram capable of identifying muscle invasive bladder cancer (MIBC) patients with high-risk molecular characteristics related to poor 2-year disease-free survival (DFS). METHODS: We performed a retrospective analysis of DNA sequencing data, prognostic information, and radiomics features from 91 MIBC patients at stages T2-T4aN0M0 without history of immunotherapy. To identify risk stratification, we employed Cox regression based on TP53 mutation status and tumor mutational burden (TMB) level. Radiomics signatures were selected using the least absolute shrinkage and selection operator (LASSO) to construct a nomogram based on logistic regression for predicting the stratification in the training cohort. The predictive performance of the nomogram was assessed in the testing cohort using receiver operator curve (ROC), Hosmer-Lemeshow (HL) test, clinical impact curve (CIC), and decision curve analysis (DCA). RESULTS: Among 91 participants, the mean TMB value was 3.3 mut/Mb, with 60 participants having TP53 mutations. Patients with TP53 mutations and a below-average TMB value were identified as high risk and had a significantly poor 2-year DFS (hazard ratio = 4.36, 95% CI 1.82-10.44, P < 0.001). LASSO identified five radiomics signatures that correlated with the risk stratification. In the testing cohort, the nomogram achieved an area under the ROC curve of 0.909 (95% CI 0.789-0.991) and an accuracy of 0.889 (95% CI 0.708-0.977). CONCLUSION: The molecular risk stratification based on TP53 mutation status combined with TMB level is strongly associated with DFS in MIBC. Radiomics signatures can effectively predict this stratification and provide valuable information to clinical decision-making.

Areca Thirteen Pill Improves Depression in Rat by Modulation of the Chemokine/Chemokine Receptor Axis.

Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1ß were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.

Dexmedetomidine alleviates renal tubular ferroptosis in sepsis-associated AKI by KEAP1 regulating the degradation of GPX4.

Sepsis-associated acute kidney injury (SA-AKI) has a high mortality rate and lacks effective targeted treatment. We applied lipopolysaccharides-induced injury models in human and mouse renal tubular epithelial cells, and at the same time, we selected a commonly used sedative drug, dexmedetomidine, to investigate its potential for renal protection. We found a significant increase in the expression level of HSP90, and the interaction with glutathione peroxidase 4 (GPX4) led to autophagic degradation of GPX4, triggering ferroptosis. Dexmedetomidine reduced the degradation of GPX4 by increasing the binding of KEAP1 and HSP90 in the cytoplasm. Therefore, lipid peroxidation and ferroptosis were reduced. Similarly, dexmedetomidine showed renal protective effects in C57BL/6J male mice with SA-AKI induced by cecal ligation. Our study reveals a new mechanism of renal tubular epithelial cell ferroptosis in SA-AKI treated with dexmedetomidine.

Global, regional, and national burden of hypertensive heart disease among older adults in 204 countries and territories between 1990 and 2019: a trend analysis.

BACKGROUND: Hypertensive heart disease (HHD) poses a public health challenge, but data on its burden and trends among older adults are scarce. This study aimed to identify trends in the burden of HHD among older adults between 1990 and 2019 at the global, regional, and national levels. METHODS: Using the Global Burden of Diseases study 2019 data, we assessed HHD prevalence, death, and disability-adjusted life-year (DALY) rates for individuals aged 60-89 years at the global, regional, and national levels and estimated their average annual percentage changes (AAPCs) between 1990 and 2019 using joinpoint regression analysis. RESULTS: In 2019, there were 14.35 million HHD prevalent cases, 0.85 million deaths, and 14.56 million DALYs in older adults. Between 1990 and 2019, the prevalence of HHD increased globally {AAPC, 0.38 (95% confidence interval [CI], 0.36, 0.41)} with decreases observed in mortality (AAPC, -0.83 [95% CI, -0.99, -0.66]) and the DALY rate (AAPC, -1.03 [95% CI, -1.19, -0.87]). This overall global trend pattern was essentially maintained for sex, age group, and sociodemographic index (SDI) quintile except for non-significant changes in the prevalence of HHD in those aged 70-74 years and in the middle SDI quintile. Notably, males had a higher HHD prevalence rate. However, HHD-related mortality and the DALY rate were higher in females. The middle SDI quintile experienced the largest decreases in mortality and the DALY rate, with a non-significant decline in prevalence between 1990 and 2019. There were significant discrepancies in the HHD burden and its trends across regions and countries. CONCLUSIONS: In the past three decades, there has been an overall increasing trend in the prevalence of HHD among older adults worldwide despite decreasing trends in mortality and the DALY rate. Better management of hypertension, and prevention and control of HHD are needed in older adults.