Enzyme-accelerated catalytic DNA circuits enable rapid and one-pot detection of bacterial pathogens.

Catalytic DNA circuits, serving as signal amplification strategies, can enable simple and accurate detection of pathogenic bacteria in complex matrices but suffer from low reaction rates and depths. Herein, we design an enzyme-accelerated catalytic hairpin assembly (EACHA) in which duplex DNA products are converted into hairpin reactants to continue participating in the next circuit reaction with the assistance of RNase H. Profiting from the high recyclability of the reactants, EACHA exhibits an approximately 37.6-fold enhancement in the rate constant and a two-order-of-magnitude improvement in sensitivity compared to conventional catalytic hairpin assembly (CHA). By integrating an allosteric probe with EACHA, a one-pot method is developed for rapid and direct detection of S. enterica Enteritidis (S. Enteritidis). This method is capable of detecting 15 CFU mL-1 of S. Enteritidis within 20 min, which is superior to that of real-time PCR. By testing 60 milk samples, we demonstrate this method's high accuracy in discriminating contaminated samples, with an area under the curve (AUC) of 0.997. Moreover, this method can be employed to accurately diagnose early-stage infected mice, with an AUC of 1.00 for feces samples and 0.986 for serum samples. Therefore, this study offers a simple and feasible method for identifying pathogens in complex matrices.

The effect of brain-computer interface controlled functional electrical stimulation training on rehabilitation of upper limb after stroke: a systematic review and meta-analysis.

Introduction: Several clinical studies have demonstrated that brain-computer interfaces (BCIs) controlled functional electrical stimulation (FES) facilitate neurological recovery in patients with stroke. This review aims to evaluate the effectiveness of BCI-FES training on upper limb functional recovery in stroke patients. Methods: PubMed, Embase, Cochrane Library, Science Direct and Web of Science were systematically searched from inception to October 2023. Randomized controlled trials (RCTs) employing BCI-FES training were included. The methodological quality of the RCTs was assessed using the PEDro scale. Meta-analysis was conducted using RevMan 5.4.1 and STATA 18. Results: The meta-analysis comprised 290 patients from 10 RCTs. Results showed a moderate effect size in upper limb function recovery through BCI-FES training (SMD = 0.50, 95% CI: 0.26-0.73, I2 = 0%, p < 0.0001). Subgroup analysis revealed that BCI-FES training significantly enhanced upper limb motor function in BCI-FES vs. FES group (SMD = 0.37, 95% CI: 0.00-0.74, I2 = 21%, p = 0.05), and the BCI-FES + CR vs. CR group (SMD = 0.61, 95% CI: 0.28-0.95, I2 = 0%, p = 0.0003). Moreover, BCI-FES training demonstrated effectiveness in both subacute (SMD = 0.56, 95% CI: 0.25-0.87, I2 = 0%, p = 0.0004) and chronic groups (SMD = 0.42, 95% CI: 0.05-0.78, I2 = 45%, p = 0.02). Subgroup analysis showed that both adjusting (SMD = 0.55, 95% CI: 0.24-0.87, I2 = 0%, p = 0.0006) and fixing (SMD = 0.43, 95% CI: 0.07-0.78, I2 = 46%, p = 0.02). BCI thresholds before training significantly improved motor function in stroke patients. Both motor imagery (MI) (SMD = 0.41 95% CI: 0.12-0.71, I2 = 13%, p = 0.006) and action observation (AO) (SMD = 0.73, 95% CI: 0.26-1.20, I2 = 0%, p = 0.002) as mental tasks significantly improved upper limb function in stroke patients. Discussion: BCI-FES has significant immediate effects on upper limb function in subacute and chronic stroke patients, but evidence for its long-term impact remains limited. Using AO as the mental task may be a more effective BCI-FES training strategy. Systematic review registration: Identifier: CRD42023485744, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023485744.

Efficacy and safety of mind-body exercise for patients with axial spondyloarthritis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of mind-body exercise (MBE) interventions, including Tai Chi, Yoga, Pilates, and Qigong, in patients with axial spondyloarthritis (axSpA), a systematic review and meta-analysis was conducted. METHODS: Eight electronic databases were searched from their inception to May 2024. RevMan 5.4 and Stata 16.0 software were used for statistical analysis. Outcome measures included Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Visual Analog Scale (VAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL) Scale, and adverse events. The methodological quality of the included studies was evaluated using the Cochrane risk of bias (RoB) tool (2.0). The certainty of evidence for each outcome was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Of the 330 studies retrieved, 15 studies satisfied the criteria for meta-analysis. Compared with the controls, MBE interventions significantly improved physical function (measured by BASFI, MD = -0.76, 95% CI: -1.01 to -0.50, P < 0.00001), disease activity (measured by BASDAI, MD = -0.76, 95% CI: -0.94 to -0.57, P < 0.00001), pain intensity (measured by VAS, MD = -0.89, 95% CI: -1.21 to -0.57, P < 0.00001), spinal mobility (measured by BASMI, MD = -0.44, 95% CI: -0.70 to -0.19, P = 0.0006), and quality of life (measured by ASQoL, MD = -2.14, 95% CI: -3.54 to -0.75, P = 0.003). Subgroup analyses revealed that Tai Chi appeared to demonstrate a more pronounced effect on pain reduction when compared to Qigong (test for subgroup difference: P = 0.005). The quality of evidence for these outcomes was estimated as moderate to low. Additionally, no serious adverse events related to MBE were identified among the included studies. CONCLUSIONS: Overall, MBE may be a promising non-pharmacological treatment to improve physical function, disease activity, pain intensity, spinal mobility, and quality of life in patients with axSpA. To enhance the certainty of the evidence, additional rigorous studies are needed to verify these findings.

PdPtCu mesoporous nanocube-based electrochemical sandwich immunosensor for detection of HIV-p24.

The construction of simple, stable, low-cost and reproducible enzyme-free electrochemical biosensors can effectively avoid the problem of signal attenuation caused by enzyme inactivation. Hererin, we prepared a novel nanoenzymes PdPtCu mesoporous nanocubes (MNCs) to construct a label-free sandwich electrochemical immunosensor for the highly sensitivity detection of HIV-p24. PdPtCu MNCs have excellent peroxidase activity against hydrogen peroxide (H2O2) due to their synergistic ternary composition, large surface area and ability to penetrate mesoporous channels. Moreover, highly conductive and biocompatible gold nanoparticles@graphene oxide (AuNPs@GO) was introduced as a substrate to modify a glassy carbon electrode (GCE). Owing to the excellent electrochemical performance of the PdPtCu MNCs and AuNPs@GO, the developed immunosensors exhibited a good linear response from 0.04 pg/mL to 100 ng/mL with a low detection limit of 20 fg/mL. In addition, the established method exhibited excellent practical performance in human serum. This novel strategy provides a promising platform for ultrasensitive detection of the HIV-p24 in the field of clinical diagnostics.

Efficacy of different analgesic strategies combined with conventional physiotherapy program for treating chronic shoulder pain: a systematic review and network meta-analysis.

BACKGROUND: This study aims to investigate the efficacy of five analgesic strategies combined with conventional physiotherapy program (CPT) in managing chronic shoulder pain. METHODS: Two authors independently screened studies, extracted data using a pre-formatted chart, and assessed bias using the Cochrane Risk of Bias tool. A network meta-analysis was performed by the Stata 17.0 and R 4.3.2 software. RESULTS: A total of 14 studies with 862 subjects were identified. These analgesic strategies included extracorporeal shock wave therapy (ESWT), suprascapular nerve block (SSNB), corticosteroid injection (CSI), hyaluronic acid injection (HAI), and kinesio taping (KT). ESWT plus CPT was the most efficient intervention in alleviating pain intensity and improving physical function. SSNB plus CPT was the optimal intervention in improving shoulder mobility. Compared to CPT alone, CSI + CPT only significantly improved the SPADI total score, but showed no difference in pain intensity or shoulder mobility. HAI + CPT showed no significant difference in improving pain intensity, physical function, or shoulder mobility compared to CPT alone. Adding KT to CPT did not yield additional benefits in improving shoulder mobility. CONCLUSION: Overall, in managing chronic shoulder pain, ESWT + CPT was the most effective intervention for reducing pain intensity and improving physical function. SSNB + CPT was optimal for enhancing shoulder mobility. Future rigorous clinical trials with larger sample sizes and higher methodological rigor are strongly required to confirm the current results.

Crotonylation of NAE1 Modulates Cardiac Hypertrophy via Gelsolin Neddylation.

BACKGROUND: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8 [neural precursor cell expressed developmentally downregulated protein 8]-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets. However, the function of crotonylated NAE1 has not been defined. This study aims to elucidate the effects and mechanisms of NAE1 crotonylation on cardiac hypertrophy. METHODS: Crotonylation levels were detected in both human and mouse subjects with cardiac hypertrophy through immunoprecipitation and Western blot assays. Tandem mass tag (TMT)-labeled quantitative lysine crotonylome analysis was performed to identify the crotonylated proteins in a mouse cardiac hypertrophic model induced by transverse aortic constriction. We generated NAE1 knock-in mice carrying a crotonylation-defective K238R (lysine to arginine mutation at site 238) mutation (NAE1 K238R) and NAE1 knock-in mice expressing a crotonylation-mimicking K238Q (lysine to glutamine mutation at site 238) mutation (NAE1 K238Q) to assess the functional role of crotonylation of NAE1 at K238 in pathological cardiac hypertrophy. Furthermore, we combined coimmunoprecipitation, mass spectrometry, and dot blot analysis that was followed by multiple molecular biological methodologies to identify the target GSN (gelsolin) and corresponding molecular events contributing to the function of NAE1 K238 (lysine residue at site 238) crotonylation. RESULTS: The crotonylation level of NAE1 was increased in mice and patients with cardiac hypertrophy. Quantitative crotonylomics analysis revealed that K238 was the main crotonylation site of NAE1. Loss of K238 crotonylation in NAE1 K238R knock-in mice attenuated cardiac hypertrophy and restored the heart function, while hypercrotonylation mimic in NAE1 K238Q knock-in mice significantly enhanced transverse aortic constriction-induced pathological hypertrophic response, leading to impaired cardiac structure and function. The recombinant adenoviral vector carrying NAE1 K238R mutant attenuated, while the K238Q mutant aggravated Ang II (angiotensin II)-induced hypertrophy. Mechanistically, we identified GSN as a direct target of NAE1. K238 crotonylation of NAE1 promoted GSN neddylation and, thus, enhanced its protein stability and expression. NAE1 crotonylation-dependent increase of GSN promoted actin-severing activity, which resulted in adverse cytoskeletal remodeling and progression of pathological hypertrophy. CONCLUSIONS: Our findings provide new insights into the previously unrecognized role of crotonylation on nonhistone proteins during cardiac hypertrophy. We found that K238 crotonylation of NAE1 plays an essential role in mediating cardiac hypertrophy through GSN neddylation, which provides potential novel therapeutic targets for pathological hypertrophy and cardiac remodeling.

Age-associated growth control modifies leaf proximodistal symmetry and enabled leaf shape diversification.

Biological shape diversity is often manifested in modulation of organ symmetry and modification of the patterned elaboration of repeated shape elements.1,2,3,4,5 Whether and how these two aspects of shape determination are coordinately regulated is unclear.5,6,7 Plant leaves provide an attractive system to investigate this problem, because they often show asymmetries along the proximodistal (PD) axis of their blades, along which they can also produce repeated marginal outgrowths such as serrations or leaflets.1 One aspect of leaf shape diversity is heteroblasty, where the leaf form in a single genotype is modified with progressive plant age.8,9,10,11 In Arabidopsis thaliana, a plant with simple leaves, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9) controls heteroblasty by activating CyclinD3 expression, thereby sustaining proliferative growth and retarding differentiation in adult leaves.12,13 However, the precise significance of SPL9 action for leaf symmetry and marginal patterning is unknown. By combining genetics, quantitative shape analyses, and time-lapse imaging, we show that PD symmetry of the leaf blade in A. thaliana decreases in response to an age-dependent SPL9 expression gradient, and that SPL9 action coordinately regulates the distribution and shape of marginal serrations and overall leaf form. Using comparative analyses, we demonstrate that heteroblastic growth reprogramming in Cardamine hirsuta, a complex-leafed relative of A. thaliana, also involves prolonging the duration of cell proliferation and delaying differentiation. We further provide evidence that SPL9 enables species-specific action of homeobox genes that promote leaf complexity. In conclusion, we identified an age-dependent layer of organ PD growth regulation that modulates leaf symmetry and has enabled leaf shape diversification.

Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

BACKGROUND: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). METHODS: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. RESULTS: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. CONCLUSIONS: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF. REGISTRATION: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.

Clinical and Imaging Features of Pulmonary Nodular Lymphoid Hyperplasia.

PURPOSE: To investigate the clinical and radiographic features of PNLH and the relationship with pathologic features. MATERIALS AND METHODS: A total of 11 patients in whom PNLH was confirmed in our department were retrospectively studied. The clinical and radiographic features were extracted and analyzed, and we also discussed the relationship between radiologic and pathologic features. RESULTS: Of the 11 patients with PNLH, 5 were discovered incidentally, while 4 presented with chest symptoms. Laboratory tests showed no specificity and the lesions were located under the pleura with an adjacent pleural indentation. Most lesions were solid, with some showing signs of spiculation or spiculate protuberance. In some cases, hypodense areas and vocules were visible. The enhanced scan showed marked enhancement, but most had no lymph node enlargement, and there was no pleural effusion. CONCLUSIONS: The clinical manifestations of PNLH are nonspecific and the imaging features overlap with those of malignant lung tumors, and the diagnosis depends on pathologic examination.

Impact of intra-tumoral immunity on predicting response and survival after neoadjuvant cisplatin-based chemotherapy in patients with muscle invasive bladder cancer.

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Pathologic complete response (pCR) is associated with favorable outcomes, but only 30%-40% of patients achieve that response. The aim of this study is to investigate the role played by the Tumor and Immune Microenvironment (TIME) in association with the clinical outcome of patients with MIBC undergoing NAC. METHODS: Nineteen patients received NAC and were classified as pCR (n = 10) or non-pCR (n = 9). Bulk RNA-seq and immune protein evaluations using Digital Spatial Profiling (DSP) were performed on formalin-fixed paraffin-embedded (FFPE) tumor biopsies collected before NAC (baseline). Immunohistochemistry (IHC) evaluation focused on CD3 and CD20 expression was performed on baseline and end-of-treatment (EOT) FFPEs. Baseline peripheral blood was assessed for lymphocyte and neutrophil counts. Kaplan-Meier analyses and Cox PH regression models were used for survival analyses (OS). RESULTS: In the periphery, pCR patients showed lower neutrophil counts, and neutrophil/ lymphocyte ratio (NLR) when compared to non-pCR patients. In the tumor microenvironment (TME), gene expression analysis and protein evaluations highlighted an abundance of B cells and CD3+ T cells in pCR versus non-pCR patients. On the contrary, increased protein expression of ARG1+ cells, and cells expressing immune checkpoints such as LAG3, ICOS, and STING were observed in the TME of patients with non-pCR. CONCLUSIONS: In the current study, we demonstrated that lower NLR levels and increased CD3+ T cells and B cell infiltration are associated with improved response and long-term outcomes in patients with MIBC receiving NAC. These findings suggest that the impact of immune environment should be considered in determining the clinical outcome of MIBC patients treated with NAC.

Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial.

BACKGROUND: The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension. METHODS: We performed a double-blind randomized placebo-controlled trial including 23 patients with hypertension. Antihypertensive medication was discontinued for the duration of the study with a washout period of 4 weeks before starting the intervention. Participants received daily oral capsules containing either sodium butyrate or placebo with an equivalent dosage of sodium chloride for 4 weeks. The primary outcome was daytime 24-hour systolic BP. Differences between groups over time were assessed using linear mixed models (group-by-time interaction). RESULTS: Study participants (59.0±3.7 years; 56.5% female) had an average baseline office systolic BP of 143.5±14.6 mm Hg and diastolic BP of 93.0±8.3 mm Hg. Daytime 24-hour systolic and diastolic BP significantly increased over the intervention period in the butyrate compared with the placebo group, with an increase of +9.63 (95% CI, 2.02-17.20) mm Hg in daytime 24-hour systolic BP and +5.08 (95% CI, 1.34-8.78) mm Hg in diastolic BP over 4 weeks. Butyrate levels significantly increased in plasma, but not in feces, upon butyrate intake, underscoring its absorption. CONCLUSIONS: Four-week treatment with oral butyrate increased daytime systolic and diastolic BP in subjects with hypertension. Our findings implicate that butyrate does not have beneficial effects on human hypertension, which warrants caution in future butyrate intervention studies. REGISTRATION: URL: https://onderzoekmetmensen.nl/; Unique identifier: NL8924.

Exploring the therapeutic efficacy and pharmacological mechanism of Guizhi Fuling Pill on ischemic stroke: a meta-analysis and network pharmacology analysis.

The role of Guizhi Fuling Pill (GZFL) in the treatment of ischemic stroke (IS) is still controversial, and its pharmacological mechanism remains unclear. To evaluate the efficacy and potential pharmacological mechanisms of GZFL on IS, a comprehensive method integrating meta-analysis, network pharmacology, and molecular docking was employed. Eight electronic databases were searched from inception to November 2023. Review Manager 5.4.1 software was used for meta-analysis. Active compounds and targets of GZFL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. Relevant targets of IS were obtained from the DisGeNet, Genecards, and DrugBank databases. GO biological function analysis and KEGG enrichment analysis were performed in the Metascape database. AutoDock Tools and PyMOL software were employed for Molecular docking. The intervention group significantly increased the total effective rate and decreased the NIHSS score. Administration of GZFL also improved the whole blood viscosity (low and high shear rates) and levels of fibrinogen, TNF-α, and IL-6. The key active compounds included quercetin, kaempferol, catechin, and beta-sitosterol, and the core target proteins included SRC, MAPK1, TP53, JUN, RELA, AKT1, and TNF. GO analysis mainly involved inflammation response, cellular response to lipids, and regulation of ion transport. The core pathways were lipid and atherosclerosis, cAMP, calcium, IL-17, and MAPK signaling pathways. Key active compounds showed good affinity with the core targets. The underlying mechanisms of GZFL in IS treatment are primarily related to its anti-inflammatory, anti-atherosclerosis, and neuroprotective effects.

Cobalt Nanoparticles Catalyzed N-Heterocycles Synthesis via Acceptorless Dehydrogenative Coupling.

The acceptorless dehydrogenation reaction is a sustainable and atom-economical methodology in organic synthesis, resulting in the byproducts of only hydrogen or water. Herein, a robust Co-Si/CN catalyst (derived from ZIF@SiO2 composite) has been synthesized through a one-step assembly process via pyrolysis and etching. This catalyst has been employed for the acceptorless dehydrogenative coupling of 2-aminoalcohols with secondary alcohols, enabling efficient conversion of various substrates into desired quinoline or pyridine derivatives with a yield of up to 94 %.

Machine learning and bioinformatics analysis of diagnostic biomarkers associated with the occurrence and development of lung adenocarcinoma.

Objective: Lung adenocarcinoma poses a major global health challenge and is a leading cause of cancer-related deaths worldwide. This study is a review of three molecular biomarkers screened by machine learning that are not only important in the occurrence and progression of lung adenocarcinoma but also have the potential to serve as biomarkers for clinical diagnosis, prognosis evaluation and treatment guidance. Methods: Differentially expressed genes (DEGs) were identified using comprehensive GSE1987 and GSE18842 gene expression databases. A comprehensive bioinformatics analysis of these DEGs was conducted to explore enriched functions and pathways, relative expression levels, and interaction networks. Random Forest and LASSO regression analysis techniques were used to identify the three most significant target genes. The TCGA database and quantitative polymerase chain reaction (qPCR) experiments were used to verify the expression levels and receiver operating characteristic (ROC) curves of these three target genes. Furthermore, immune invasiveness, pan-cancer, and mRNA-miRNA interaction network analyses were performed. Results: Eighty-nine genes showed increased expression and 190 genes showed decreased expression. Notably, the upregulated DEGs were predominantly associated with organelle fission and nuclear division, whereas the downregulated DEGs were mainly associated with genitourinary system development and cell-substrate adhesion. The construction of the DEG protein-protein interaction network revealed 32 and 19 hub genes with the highest moderate values among the upregulated and downregulated genes, respectively. Using random forest and LASSO regression analyses, the hub genes were employed to identify three most significant target genes.TCGA database and qPCR experiments were used to verify the expression levels and ROC curves of these three target genes, and immunoinvasive analysis, pan-cancer analysis and mRNA-miRNA interaction network analysis were performed. Conclusion: Three target genes identified by machine learning: BUB1B, CENPF, and PLK1 play key roles in LUAD development of lung adenocarcinoma.

Depression, anxiety, and poor well-being at discharge from psychiatric hospitals: prevalence and risk factors.

Background: Being ready for discharge is vital to successful hospital-to-home transitions. For many patients, however, the transition from psychiatric hospital care to outpatient care can be challenging. An in-depth understanding of the mental health conditions of patients at discharge is crucial and instructive for recovery research. Objective: The purpose of this study was to determine the prevalence and risk factors of depression, anxiety, and poor well-being symptoms among patients who are about to be discharged from psychiatric units in Alberta, Canada. Our aim was to help determine the prevalence of anxiety, depression, and overall well-being among the general psychiatric inpatient population in Alberta before discharge and the potential factors which may influence this. Methods: This epidemiological study used a cross-sectional quantitative survey from March 8, 2022, to November 5, 2023, to assess depression, anxiety, and well-being. Participants were invited to complete an online questionnaire that contained demographics, clinical information, and responses to the PHQ-9, GAD-7, and WHO-5 questionnaires. SPSS version 25 was used to analyze the data. Descriptive, univariate, and multivariate regression analyses were employed. Result: The study found that the prevalence of likely depression, anxiety, and poor well-being among patients about to be discharged was 37.1%, 56.4%, and 48.3%, respectively. Based on a logistic regression model, there was a statistically significant association between anxiety, depression, and poor well-being diagnoses and multiple socio-demographic and clinical factors such as ethnicity, primary mental health diagnoses, education level, housing status, depression, anxiety, and well-being at baseline. Conclusion: Mental health assessment at discharge is a critical step in the recovery and transition of care. There is still a need for further research to identify the underlying causes and robust predictors of mental health symptoms in patients about to be discharged and to provide appropriate interventions and supportive resources both before and following discharge. Future research utilizing these findings may help identify key opportunities to improve outcomes for patients after discharge.

Xylitol is prothrombotic and associated with cardiovascular risk.

BACKGROUND AND AIMS: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute. METHODS: Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10). RESULTS: In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects. CONCLUSIONS: Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.

Exploration of new ways for CRISPR/Cas12a activation: DNA hairpins without PAM and toehold and single strands containing DNA and RNA bases.

The CRISPR/Cas12a system is emerging as a promising candidate for next-generation diagnostic biosensing platforms, with the discovery of new activation modes greatly expanding its applications. Here, we have identified two novel CRISPR/Cas12a system activation modes: PAM- and toehold-free DNA hairpins, and DNA-RNA hybrid strands. Utilizing a well-established real-time fluorescence method, we have demonstrated a strong correlation between DNA hairpin structures and Cas12a activation. Compared with previously reported activation modes involving single-stranded DNA and PAM-contained double-stranded DNA, the DNA hairpin activation way exhibits similar specificity and generality. Moreover, our findings indicate that increasing the number of RNA bases in DNA-RNA hybrid strands can decelerate the kinetics of Cas12a-triggered trans-cleavage of reporter probes. These newly discovered CRISPR/Cas12a activation ways hold significant potential for the development of high-performance biosensing strategies.

Natural Prenylflavonoids from Sophora flavescens Root Bark against Multidrug-Resistant Methicillin-Sensitive Staphylococcus aureus Targeting the Membrane Permeability.

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds (1-30) were isolated from the root bark of S. flavescens, consisting of 20 new compounds (1-20). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 µg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.

Alterations in brain network connectivity and subjective experience induced by psychedelics: a scoping review.

Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics' neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics.