Breaking the Activity-Selectivity Trade-off for CH4-to-C2H6 Photoconversion.

Photocatalytic conversion of methane (CH4) to ethane (C2H6) has attracted extensive attention from academia and industry. Typically, the traditional oxidative coupling of CH4 (OCM) reaches a high C2H6 productivity, yet the inevitable overoxidation limits the target product selectivity. Although the traditional nonoxidative coupling of CH4 (NOCM) can improve the product selectivity, it still encounters unsatisfied activity, arising from being thermodynamically unfavorable. To break the activity-selectivity trade-off, we propose a conceptually new mechanism of H2O2-triggered CH4 coupling, where the H2O2-derived ·OH radicals are rapidly consumed for activating CH4 into ·CH3 radicals exothermically, which bypasses the endothermic steps of the direct CH4 activation by photoholes and the interaction between ·CH3 and ·OH radicals, affirmed by in situ characterization techniques, femtosecond transient absorption spectroscopy, and density-functional theory calculation. By this pathway, the designed Au-WO3 nanosheets achieve unprecedented C2H6 productivity of 76.3 mol molAu-1 h-1 with 95.2% selectivity, and TON of 1542.7 (TOF = 77.1 h-1) in a self-designed flow reactor, outperforming previously reported photocatalysts regardless of OCM and NOCM pathways. Also, under outdoor natural sunlight irradiation, the Au-WO3 nanosheets exhibit similar activity and selectivity toward C2H6 production, showing the possibility for practical applications. Interestingly, this strategy can be applied to other various photocatalysts (Au-WO3, Au-TiO2, Au-CeO2, Pd-WO3, and Ag-WO3), showing a certain universality. It is expected that the proposed mechanism adds another layer to our understanding of CH4-to-C2H6 conversion.

Methanetriol─Formation of an Impossible Molecule.

Orthocarboxylic acids─organic molecules carrying three hydroxyl groups at the same carbon atom─have been distinguished as vital reactive intermediates by the atmospheric science and physical (organic) chemistry communities as transients in the atmospheric aerosol cycle. Predicted short lifetimes and their tendency to dehydrate to a carboxylic acid, free orthocarboxylic acids, signify one of the most elusive classes of organic reactive intermediates, with even the simplest representative methanetriol (CH(OH)3)─historically known as orthoformic acid─not previously been detected experimentally. Here, we report the first synthesis of the previously elusive methanetriol molecule in low-temperature mixed methanol (CH3OH) and molecular oxygen (O2) ices subjected to energetic irradiation. Supported by electronic structure calculations, methanetriol was identified in the gas phase upon sublimation via isomer-selective photoionization reflectron time-of-flight mass spectrometry combined with isotopic substitution studies and the detection of photoionization fragments. The first synthesis and detection of methanetriol (CH(OH)3) reveals its gas-phase stability as supported by a significant barrier hindering unimolecular decomposition. These findings progress our fundamental understanding of the chemistry and chemical bonding of methanetriol, hydroxyperoxymethane (CH3OOOH), and hydroxyperoxymethanol (CH2(OH)OOH), which are all prototype molecules in the oxidation chemistry of the atmosphere.

Gestational diabetes mellitus is associated with greater incidence of dementia during long-term post-partum follow-up.

BACKGROUND: The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship. METHODS: This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates. RESULTS: A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03-2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction = 0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women. CONCLUSIONS: A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.

Cultivation of phosphate-accumulating biofilm: Study of the effects of acyl-homoserine lactones (AHLs) and cyclic dimeric guanosine monophosphate (c-di-GMP) on the formation of biofilm and the enhancement of phosphate metabolism capacity.

This study investigated the mechanisms of microbial growth and metabolism during biofilm cultivation in the biofilm sequencing batch reactor (BSBR) process for phosphate (P) enrichment. The results showed that the sludge discharge was key to biofilm growth, as it terminated the competition for carbon (C) source between the nascent biofilm and the activated sludge. For the tested reactor, after the sludge discharge on 18 d, P metabolism and C source utilization improved significantly, and the biofilm grew rapidly. The P concentration of the recovery liquid reached up to 157.08 mg/L, which was sufficient for further P recovery via mineralization. Meta-omics methods were used to analyze metabolic pathways and functional genes in microbial growth during biofilm cultivation. It appeared that the sludge discharge activated the key genes of P metabolism and inhibited the key genes of C metabolism, which strengthened the polyphosphate-accumulating metabolism (PAM) as a result. The sludge discharge not only changed the types of polyphosphate-accumulating organisms (PAOs) but also promoted the growth of dominant PAOs. Before the sludge discharge, the necessary metabolic abilities that were spread among different microorganisms gradually concentrated into a small number of PAOs, and after the sludge discharge, they further concentrated into Candidatus_Contendobacter (P3) and Candidatus_Accumulibacter (P17). The messenger molecule C-di-GMP, produced mostly by P3 and P17, facilitated P enrichment by regulating cellular P and C metabolism. The glycogen-accumulating organism (GAO) Candidatus_Competibacter secreted N-Acyl homoserine lactones (AHLs), which stimulated the secretion of protein in extracellular polymeric substances (EPS), thus promoting the adhesion of microorganisms to biofilm and improving P metabolism via EPS-based P adsorption. Under the combined action of the dominant GAOs and PAOs, AHLs and C-di-GMP mediated QS to promote biofilm development and P enrichment. The research provides theoretical support for the cultivation of biofilm and its wider application.

Imaging and quantification of neuropeptides in mouse pituitary tissue by atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry.

RATIONALE: Atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) mass spectrometry has enabled the untargeted analysis and imaging of neuropeptides and proteins in biological tissues under ambient conditions. Sensitivity in AP-MALDI can be improved by using sample-specific preparation methods. METHODS: A comprehensive and detailed optimization strategy including instrument parameters, matrix spraying and sample tissue washing pretreatment was implemented to enhance the sensitivity and coverage of neuropeptides in mouse pituitary tissues by commercial AP-MALDI mass spectrometry imaging (MSI). RESULTS: The sensitivity of a commercial AP-MALDI system for endogenous neuropeptides in mouse pituitary was enhanced by up to 15.2-fold by shortening the transmission gap from the sample plate to the inlet, attaching copper adhesive tape to an indium tin oxide-coated glass slide, optimizing the matrix spray solvent and using sample tissue washing pretreatment. Following careful optimization, the distributions of nine endogenous neuropeptides were successfully visualized in the pituitary. Furthermore, the quantitative capability of AP-MALDI for neuropeptides was evaluated and the concentrations of neuropeptides oxytocin and vasopressin in the pituitary posterior lobe were increased approximately twofold under hypertonic saline stress. CONCLUSION: Mouse pituitary neuropeptides have emerged as important signaling molecules due to their role in stress response. This work indicates the potential of modified AP-MALDI as a promising AP MSI method for in situ visualization and quantification of neuropeptides in complex biological tissues.

Association of sarcopenia with osteoporosis in Chinese patients with type 2 diabetes.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) present a higher tendency to develop sarcopenia and osteoporosis compared with the normal population. Currently, osteoporosis screening has been frequently performed among T2DM patients, but sarcopenia screening is relatively less, and the association between the two diseases remains unclear. Herein, this study aims to determine the association between sarcopenia and osteoporosis in Chinese T2DM patients. METHODS: This was a retrospective study of 678 patients with T2DM in the First Affiliated Hospital of Wenzhou Medical University. The bone mineral density (BMD) and muscle mass were measured by using dual-energy X-ray absorptiometry scanning. The diagnostic criteria of sarcopenia referred to the consensus by the Asia Working Group for Sarcopenia (AWGS). RESULT: Among T2DM patients, the proportion of the sarcopenia population complicated with osteoporosis was higher than that of the non-sarcopenia (30.9% vs. 8.6% in men and 46.9% vs. 33.9% in women), but only significantly in men. The BMD of the hip and femoral neck was positively correlated with skeletal muscle mass index (SMI), grip strength, and gait speed (P < 0.01). After adjusting all covariates, the association between sarcopenia and BMD showed odds ratios of 0.43 (95% CI:0.28-0.66) for the femoral neck and 0.49 (95% CI:0.32-0.73) for the hip. CONCLUSIONS: The BMD of the hip and femoral neck in T2DM patients is related to sarcopenia-related indicators and represents an independent protective factor for sarcopenia. To reduce the risk of falls, fractures, and weakness, it is necessary to take sarcopenia assessment in people with T2DM and osteopenia/osteoporosis.

Degradation behaviors of Nabumetone and its metabolite during UV/monochloramine process: Experimental and theoretical study.

This study investigated degradation behaviors of a nonsteroidal anti-inflammatory drug Nabumetone (NMT) and its major metabolite 6-methoxy-2-naphthylacetic acid (MNA) in the coupling process of ultraviolet and monochloramine (UV/NH2Cl). The second-order rate constants of the contaminants reacting with reactive radicals (HO•, Cl•, Cl2•⁻, and CO3•⁻) were determined by laser flash photolysis experiments. HO• and Cl• contributed predominantly with 52.3% and 21.7% for NMT degradation and 60.8% and 22.3% for MNA degradation. The presence of chlorides retarded the degradation of NMT, while promoted the destruction of MNA, which was ascribed to the photosensitization effects of MNA under UV irradiation. Density functional theory (DFT) calculations revealed that radical adduct formation (RAF) was dominant pathway for both HO• and Cl• reacting with the contaminants, and hydrogen atom transfer (HAT) preferred to occur on side chains of NMT and MNA. NMT reacted with NO2• through single electron transfer (SET) with the second-order rate constant calculated to be 5.35 × 107 (mol/L)-1 sec-1, and the contribution of NO2• was predicted to be 13.0% of the total rate constant of NMT in pure water, which indicated that NO2• played a non-negligible role in the degradation of NMT. The acute toxicity and developmental toxicity of NMT were enhanced after UV/NH2Cl treatment, while those of MNA were alleviated. The transformation products of both NMT and MNA exhibited higher mutagenicity than their parent compounds. This study provides a deep understanding of the mechanism of radical degradation of NMT and MNA in the treatment of UV/NH2Cl.

Synthesis and Biological Evaluation of New Dihydrofuro[3,2-b]piperidine Derivatives as Potent α-Glucosidase Inhibitors.

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC50 = 0.07 µM) and 28 (IC50 = 0.5 µM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure-activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors.

Variable Time-Step Physics Engine with Continuous Compliance Contact Model for Optimal Robotic Grinding Trajectory Planning.

In the transition from virtual environments to real-world applications, the role of physics engines is crucial for accurately emulating and representing systems. To address the prevalent issue of inaccurate simulations, this paper introduces a novel physics engine uniquely designed with a compliant contact model designed for robotic grinding. It features continuous and variable time-step simulations, emphasizing accurate contact force calculations during object collision. Firstly, the engine derives dynamic equations considering spring stiffness, damping coefficients, coefficients of restitution, and external forces. This facilitates the effective determination of dynamic parameters such as contact force, acceleration, velocity, and position throughout penetration processes continuously. Secondly, the approach utilizes effective inertia in developing the contact model, which is designed for multi-jointed robots through pose transformation. The proposed physics engine effectively captures energy conversion in scenarios with convex contact surface shapes through the application of spring dampers during collisions. Finally, the reliability of the contact solver in the simulation was verified through bouncing ball experiments and robotic grinding experiments under different coefficients of restitution. These experiments effectively recorded the continuous variations in parameters, such as contact force, verifying the integral stability of the system. In summary, this article advances physics engine technology beyond current geometrically constrained contact solutions, enhancing the accuracy of simulations and modeling in virtual environments. This is particularly significant in scenarios wherein there are constant changes in the outside world, such as robotic grinding tasks.

[Detection, Generation, and Control of Disinfection By-products of Reclaimed Water].

At the time when water resources are in short supply,wastewater recycling is both an important environmental protection strategy and also a resource strategy. Disinfection is essential to ensure the biological safety of reclaimed wastewater by killing pathogens and preventing the spread of waterborne diseases. However,the disinfection process could inevitably produce toxic disinfection byproducts(DBPs)due to the reaction between the disinfectants and wastewater organic matters. Regarding wastewater DBPs,this study reviewed their identification methods,formation conditions(including precursors,the effect of water quality,disinfectants,and operational parameters on DBPs),and control methods(including source control,process control,and end control). In addition,future research trends of wastewater DBPs were discussed.

Molecular mechanism of endophytic bacteria DX120E regulating polyamine metabolism and promoting plant growth in sugarcane.

Introduction: Sugarcane endophytic nitrogen-fixing bacterium Klebsiella variícola DX120E displayed broad impact on growth, but the exact biological mechanism, especially polyamines (PAs) role, is still meager. Methods: To reveal this relationship, the content of polyamine oxidase (PAO), PAs, reactive oxygen species (ROS)-scavenging antioxidative enzymes, phytohormones, 1-aminocyclopropane-1-carboxylic synthase (ACS), chlorophyll content, and biomass were determined in sugarcane incubated with the DX120E strain. In addition, expression levels of the genes associated with polyamine metabolism were measured by transcriptomic analysis. Results: Genomic analysis of Klebsiella variícola DX120E revealed that 39 genes were involved in polyamine metabolism, transport, and the strain secrete PAs in vitro. Following a 7-day inoculation period, DX120E stimulated an increase in the polyamine oxidase (PAO) enzyme in sugarcane leaves, however, the overall PAs content was reduced. At 15 days, the levels of PAs, ROS-scavenging antioxidative enzymes, and phytohormones showed an upward trend, especially spermidine (Spd), putrescine (Put), catalase (CAT), auxin (IAA), gibberellin (GA), and ACS showed a significant up-regulation. The GO and KEGG enrichment analysis found a total of 73 differentially expressed genes, involving in the cell wall (9), stimulus response (13), peroxidase activity (33), hormone (14) and polyamine metabolism (4). Discussion: This study demonstrated that endophytic nitrogen-fixing bacteria stimulated polyamine metabolism and phytohormones production in sugarcane plant tissues, resulting in enhanced growth. Dual RNA-seq analyses provided insight into the early-stage interaction between sugarcane seedlings and endophytic bacteria at the transcriptional level. It showed how diverse metabolic processes selectively use distinct molecules to complete the cell functions under present circumstances.

Palladium-Catalyzed Directed Carbon-Carbon Bond Activation of Aryl Nitriles for Cyano Transfer.

Herein, we report the C-H cyanation of indoles via a palladium-catalyzed directed C-CN activation reaction using aryl nitrile as a cyano source. The employment of the phenoxy-oriented group is the key to the cleavage of the C-CN bond. This protocol features a broad substrate scope, good efficiency, and high regioselectivity. Furthermore, the practical application of this protocol was showcased in the late-stage functionalization and synthesis of indole derivatives, which were derived from drugs and natural products, through the process of cyanation.

Associations between onset age of orthostatic hypotension and incident myocardial infarction, stroke, and dementia: a prospective cohort study.

BACKGROUND: The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia. METHODS: Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006-2010) and follow-ups (median=13 years). The propensity score matching method and the Cox proportional hazard models were employed. RESULTS: A total of 448 374 adults (mean age: 56.8±8.1 years), of whom 3795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR=3.15, 95% CI: 2.54 to 3.90, P<0.001), stroke (HR=1.72, 95% CI: 1.33 to 2.23, P<0.001), and dementia (HR=1.26, 95% CI: 1.02 to 1.57, P=0.034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age. CONCLUSIONS: Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia.

Association between Age at Diagnosis of Hyperlipidemia and Subsequent Risk of Dementia.

OBJECTIVES: The relationship between age at diagnosis of hyperlipidemia and dementia remains unclear. We examined whether younger age at diagnosis of hyperlipidemia is associated with higher risk of subsequent dementia. DESIGN: A longitudinal population-based study with a median follow-up of 12.8 years. SETTING AND PARTICIPANTS: We analyzed data on a sample of 489,642 participants in the United Kingdom. METHODS: This study was based on the UK Biobank. Information on hyperlipidemia and dementia diagnoses was collected at baseline (2006-2010) and follow-up [median = 12.8 years, interquartile range (IQR): 12.1-13.6 years]. Propensity score matching method and Cox proportional hazards models were used to assess the association between age at diagnosis of hyperlipidemia and dementia. RESULTS: Among 489,642 participants (mean age: 56.9 ± 8.1 years; female: 54.7%), 114,112 (23.3%) were diagnosed with hyperlipidemia. Younger age at diagnosis of hyperlipidemia (per 10-year decrease) was significantly associated with higher risks of all-cause dementia [hazard ratio (HR), 1.12; 95% CI, 1.07-1.18; P < .001], Alzheimer's disease (AD) (HR, 1.22; 95% CI, 1.14-1.31; P < .001), and vascular dementia (VD) (HR, 1.16; 95% CI, 1.05-1.27; P < .001). After propensity score matching, patients with hyperlipidemia diagnosed before 50 years had the highest HR for all-cause dementia (HR, 1.46; 95% CI, 1.15-1.86; P = .002), followed by patients diagnosed between 50 and 69 years (HR, 1.21; 95% CI, 1.12-1.31; P < .001) and then patients diagnosed aged 70 years and older (HR, 0.94; 95% CI, 0.84-1.06; P = .302). Similar results were observed for AD and VD. CONCLUSIONS AND IMPLICATIONS: A dose-response relationship between age at hyperlipidemia diagnosis and risk of dementia was found in the longitudinal cohort study, with younger age at diagnosis of hyperlipidemia being associated with higher subsequent risk.

Twice-daily rivaroxaban after percutaneous left atrial appendage closure for atrial fibrillation.

Background and aim: Rivaroxaban is an emerging oral anticoagulant for postoperative anticoagulation after percutaneous left atrial appendage closure (LAAC). Because a once-daily dosing regimen of rivaroxaban causes fluctuations in the drug plasma concentration, we studied the feasibility and safety of twice-daily rivaroxaban as a postoperative anticoagulation regimen for patients with atrial fibrillation (AF) undergoing LAAC. Methods: This study involved patients with AF who underwent LAAC and took rivaroxaban postoperatively. A total of 326 patients who received a standard total dose (15 or 20 mg) of rivaroxaban based on their creatinine clearance rate were divided into the twice-daily (BID) rivaroxaban group (n = 208) and once-daily (QD) rivaroxaban group (n = 118) according to their anticoagulation strategy. Transesophageal echocardiography was recommended at 3-6 months postoperatively to check for device-related thrombosis (DRT). Clinical outcomes were evaluated during postoperative anticoagulation. Results: The median CHA2DS2-VASc score (4 [3, 5] vs. 4 [3, 5], p = 0.28) and HAS-BLED score (2 [2, 3] vs. 2 [2, 3], p = 0.48) were not significantly different between the groups. During the anticoagulation period (4.1 ± 0.7 vs. 4.1 ± 0.9 months, p = 0.58), 148 (71.2%) patients in the BID group and 75 (63.6%) in the QD group underwent follow-up transesophageal echocardiography. There were no statistically significant differences between the two groups in terms of DRT (1.4% vs. 2.7%, p = 0.60), minor bleeding (8.2% vs. 11.0%, p = 0.39), thromboembolic events (1.0% vs. 0.8%, p = 1.00), major bleeding (0.5% vs. 0.8%, p = 1.00), or death. Conclusion: A short course of twice-daily rivaroxaban following LAAC is a feasible alternative regimen with a low rate of major bleeding events, DRT, and thromboembolic events for patients with AF.

Single-cell sequencing revealed metabolic reprogramming and its transcription factor regulatory network in prostate cancer.

BACKGROUND/AIMS: Prostate cancer is the most frequently diagnosed cancer among men in the United States and is the second leading cause of cancer-related deaths in men. The incidence of prostate cancer is gradually rising due to factors such as aging demographics and changes in dietary habits. The objective of this study is to investigate the metabolic reprogramming changes occurring in prostate cancer and identify potential therapeutic targets. METHODS: In this study, we utilized single-cell sequencing to comprehensively characterize the alterations in metabolism and the regulatory role of transcription factors in various subtypes of prostate cancer. RESULTS: In comparison to benign prostate tissue, prostate cancer displayed substantial metabolic variations, notably exhibiting heightened activity in fatty acid metabolism and cholesterol metabolism. This metabolic reprogramming not only influenced cellular energy utilization but also potentially impacted the activity of the androgen receptor (AR) pathway through the synthesis of endogenous steroid hormones. Through our analysis of transcription factor activity, we identified the crucial role of SREBPs, which are transcription factors associated with lipid metabolism, in prostate cancer. Encouragingly, the inhibitor Betulin effectively suppresses prostate cancer growth, highlighting its potential as a therapeutic agent for prostate cancer treatment.

Development of Transmission Ambient Pressure Laser Desorption Ionization/Postphotoionization Mass Spectrometry Imaging.

Laser-based high-resolution mass spectrometry imaging at ambient conditions has promising applications in life science. However, the ion yield during laser desorption/ablation is poor. Here, transmission atmospheric pressure laser desorption ionization combined with a compact postphotoionization (t-AP-LDI/PI) assembly with a krypton discharge lamp was developed for the untargeted imaging of various biomolecules. The spatial distributions of numerous lipid classes, fatty acids, neurotransmitters, and amino acids in the subregions of mouse cerebellum tissue were obtained. Compared with single laser ablation, the sensitivities for most analytes were increased by 1 to 3 orders of magnitude by dopant-assisted postphotoionization. After careful optimization, a spatial resolution of 4 µm could be achieved for the metabolites in mouse hippocampus tissue. Finally, the melanoma tissue slices were analyzed using t-AP-LDI/PI MSI, which revealed the metabolic heterogeneity of the melanoma microenvironment and exhibited the phenomenon of abnormal proliferation and invasion trends in tumor cells.

How to achieve adequate quenching for DBP analysis in drinking water?

Quenching is an important step to terminate disinfection during preparation of disinfected water samples for the analysis of disinfection byproducts (DBPs). However, an incomplete quenching might result in continued reactions of residual chlorine, whereas an excessive quenching might decompose target DBPs. Therefore, an adequate quenching to achieve simultaneous disinfection termination and DBP preservation is of particular importance. In this study, the two-stage reaction kinetics of chlorine and three commonly used quenching agents (i.e., ascorbic acid, sodium thiosulfate, and sodium sulfite) were determined. Stopping quenching during the first stage prevented interactions of residual chlorine with natural organic matter. Complete quenching was achieved by minimizing the quenching time for ascorbic acid and sodium sulfite, while limiting the quenching time to less than 3 min for sodium thiosulfate. At the optimized quenching times, the molar ratios (MRs) of quenching agent to chlorine were 1.05, 1.10, and 0.75 for ascorbic acid, sodium sulfite, and sodium thiosulfate, respectively. The destructive effects of the three quenching agents on total organic halogen (TOX) followed the rank order of ascorbic acid (33.7-64.8 %) < sodium sulfite (41.6-72.8 %) < sodium thiosulfate (43.3-73.2 %), and the destructive effects on aliphatic DBPs also followed the rank order of ascorbic acid (29.5-44.5 %) < sodium sulfite (34.9-51.9 %) < sodium thiosulfate (46.9-53.2 %). For total organic chlorine (TOCl) and aliphatic DBPs, the quenching behavior itself had more significant destructive effect than the quenching agent type/dose and quenching time, but for total organic bromine (TOBr), the destructive effect caused by quenching agent type/dose and quenching time was more significant. High-dose, long-duration quenching enhanced the reduction of TOX, but had little effect on aliphatic DBPs. Additionally, the three quenching agents reduced the levels of halophenols (except for tribromophenol), while maintained or increased the levels of tribromophenol, halobenzoic/salicylic acids, and halobenzaldehydes/salicylaldehydes. To achieve adequate quenching for overall DBP analysis in chlorinated water samples, it is recommended to use ascorbic acid at a quenching agent-to-chlorine MR of 1.0 for a quenching time of < 0.5 h.

Upregulation of CCNB2 and a novel lncRNAs-related risk model predict prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the main type of renal cell carcinoma. Cyclin B2 (CCNB2) is a subtype of B-type cyclin that is associated with the prognosis of several cancers. This study aimed to identify the relationship between CCNB2 and progression of ccRCC and construct a novel lncRNAs-related model to predict prognosis of ccRCC patients. METHODS: The data were obtained from public databases. We identified CCNB2 in ccRCC using Kaplan-Meier survival analysis, univariate and multivariate Cox regression, and Gene Ontology analysis. External validation was then performed. The risk model was constructed based on prognostic lncRNAs by the LASSO algorithm and multivariate Cox regression. Receiver operating characteristics (ROC) curves were used to evaluate the model. Consensus clustering analysis was performed to re-stratify the patients. Finally, we analyzed the tumor-immune microenvironment and performed screening of potential drugs. RESULTS: CCNB2 associated with late clinicopathological parameters and poor prognosis in ccRCC and was an independent predictor for disease-free survival. In addition, CCNB2 shared the same expression pattern with known suppressive immune checkpoints. A risk model dependent on the expression of three prognostic CCNB2-related lncRNAs (SNHG17, VPS9D1-AS1, and ZMIZ1-AS1) was constructed. The risk signature was an independent predictor of ccRCC. The area under the ROC (AUC) curve for overall survival at 1-, 3-, 5-, and 8-year was 0.704, 0.702, 0.741, and 0.763. The high-risk group and cluster 2 had stronger immunogenicity and were more sensitive to immunotherapy. CONCLUSION: CCNB2 could be an important biomarker for predicting prognosis in ccRCC patients. Furthermore, we developed a novel lncRNAs-related risk model and identified two CCNB2-related molecular clusters. The risk model performed well in predicting overall survival and immunological microenvironment of ccRCC.

An updated systematic review and meta-analysis of the effects of testosterone replacement therapy on erectile function and prostate.

Introduction: Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT remain controversial. An updated systematic review and meta-analysis aimed to determine the effectiveness and security of TRT treating for LOH. Methods: Randomized controlled trials (RCTs) of TRT for LOH were searched in the databases of Pubmed, Embase, Clinicaltrials.gov and Cochrane from 1990 to 2023 and an updated meta-analysis was conducted. Results: The results of 28 RCTs involving 3461 patients were included and scrutinized in this analysis. Among these, 11 RCTs were of long-term duration (≥12 months), while 18 RCTs were short-term studies (<12 months) comparing TRT with a placebo. TRT modalities comprised injection, oral administration, and transdermal administration. International Index of Erectile Function (IIEF) (Weighted Mean difference (WMD) 3.26; 95%; 95% confidence interval (CI) 1.65-4.88; P<0.0001) was obviously improved in the TRT group. International Prostate Symptom Score (IPSS) (WMD 0.00; 95% CI -0.45-0.45; P=1.0), Prostate Volume (PV) (WMD 0.38; 95% CI -0.64-1.41; P=0.46), Maximum Flow Rate (Qmax) (WMD 1.86; 95% CI -0.98-4.69; P=0.20), Postvoid Residual Urine Volume (PVR) (WMD 3.20; 95% CI -5.87-12.28; P=0.49) and Prostate-Specific Antigen (PSA) (WMD 0.08; 95% CI -0.00-0.17; P=0.06) were not significantly statistical between two groups. Conclusion: This meta-analysis reveals that TRT could improve the IIEF score of hypogonadal men without detriment to the IPSS score, PV, Qmax, PVR and PSA regardless of the administration method or duration of treatment.The meta-analysis was registered at PROSPERO (CRD42023413434).