scCorrector: a robust method for integrating multi-study single-cell data.

The advent of single-cell sequencing technologies has revolutionized cell biology studies. However, integrative analyses of diverse single-cell data face serious challenges, including technological noise, sample heterogeneity, and different modalities and species. To address these problems, we propose scCorrector, a variational autoencoder-based model that can integrate single-cell data from different studies and map them into a common space. Specifically, we designed a Study Specific Adaptive Normalization for each study in decoder to implement these features. scCorrector substantially achieves competitive and robust performance compared with state-of-the-art methods and brings novel insights under various circumstances (e.g. various batches, multi-omics, cross-species, and development stages). In addition, the integration of single-cell data and spatial data makes it possible to transfer information between different studies, which greatly expand the narrow range of genes covered by MERFISH technology. In summary, scCorrector can efficiently integrate multi-study single-cell datasets, thereby providing broad opportunities to tackle challenges emerging from noisy resources.

Prediction of image interpretation cognitive ability under different mental workloads: a task-state fMRI study.

Visual imaging experts play an important role in multiple fields, and studies have shown that the combination of functional magnetic resonance imaging and machine learning techniques can predict cognitive abilities, which provides a possible method for selecting individuals with excellent image interpretation skills. We recorded behavioral data and neural activity of 64 participants during image interpretation tasks under different workloads. Based on the comprehensive image interpretation ability, participants were divided into two groups. general linear model analysis showed that during image interpretation tasks, the high-ability group exhibited higher activation in middle frontal gyrus (MFG), fusiform gyrus, inferior occipital gyrus, superior parietal gyrus, inferior parietal gyrus, and insula compared to the low-ability group. The radial basis function Support Vector Machine (SVM) algorithm shows the most excellent performance in predicting participants' image interpretation abilities (Pearson correlation coefficient = 0.54, R2 = 0.31, MSE = 0.039, RMSE = 0.002). Variable importance analysis indicated that the activation features of the fusiform gyrus and MFG played an important role in predicting this ability. Our study revealed the neural basis related to image interpretation ability when exposed to different mental workloads. Additionally, our results demonstrated the efficacy of machine learning algorithms in extracting neural activation features to predict such ability.

Intracellular Magnetic Hyperthermia Enables Concurrent Down-Regulation of CD47 and SIRPα To Potentiate Antitumor Immunity.

Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.

DNA methylation of promoter region inhibits galectin-1 expression in BMSCs of aged mice.

Senile osteoporosis increases fracture risks. Bone marrow stromal cells (BMSCs) are sensitive to aging. Deep insights into BMSCs aging are vital to elucidate the mechanisms underlying age-related bone loss. Recent advances showed that osteoporosis is associated with aberrant DNA methylation of many susceptible genes. Galectin-1 (Gal-1) has been proposed as a mediator of BMSCs functions. In our previous study, we showed that Gal-1 was downregulated in aged BMSCs and global deletion of Gal-1 in mice caused bone loss via impaired osteogenesis potential of BMSCs. Gal-1 promoter is featured by CpG islands. However, there are no reports concerning the DNA methylation status in Gal-1 promoter during osteoporosis. In the current study, we sought to investigate the role of DNA methylation in Gal-1 downregulation in aged BMSCs. The potential for anti-bone loss therapy based on modulating DNA methylation is explored. Our results showed that Dnmt3b-mediated Gal-1 promoter DNA hypermethylation plays an important role in Gal-1 downregulation in aged BMSCs, which inhibited ß-catenin binding on Gal-1 promoter. Bone loss of aged mice was alleviated in response to in vivo deletion of Dnmt3b from BMSCs. Finally, when bone marrow of young wild-type (WT) mice or young Dnmt3bPrx1-Cre mice was transplanted into aged WT mice, Gal-1 level in serum and trabecular bone mass were elevated in recipient aged WT mice. Our study will benefit for deeper insights into the regulation mechanisms of Gal-1 expression in BMSCs during osteoporosis development, and for the discovery of new therapeutic targets for osteoporosis via modulating DNA methylation status.NEW & NOTEWORTHY There is Dnmt3b-mediated DNA methylation in Gal-1 promoter in aged bone marrow stromal cell (BMSC). DNA methylation causes Gal-1 downregulation and osteogenesis attenuation of aged BMSC. DNA methylation blocks ß-catenin binding on Gal-1 promoter. Bone loss of aged mice is alleviated by in vivo deletion of Dnmt3b from BMSC.

Structure of Amorphous Selenium: Small Ring, Big Controversy.

Selenium (Se) discovered in 1817 belongs to the family of chalcogens. Surprisingly, despite the long history of over two centuries and the chemical simplicity of Se, the structure of amorphous Se (a-Se) remains controversial to date regarding the dominance of chains versus rings. Here, we find that vapor-deposited a-Se is composed of disordered rings rather than chains in melt-quenched a-Se. We further reveal that the main origin of this controversy is the facile transition of rings to chains arising from the inherent instability of rings. This transition can be inadvertently triggered by certain characterization techniques themselves containing above-bandgap illumination (above 2.1 eV) or heating (above 50 °C). We finally build a roadmap for obtaining accurate Raman spectra by using above-bandgap excitation lasers with low photon flux (below 1017 phs m-2 s-1) and below-bandgap excitation lasers measured at low temperatures (below -40 °C) to minimize the photoexcitation- and heat-induced ring-to-chain transitions.

PI3Kδ Mediates Fibrosis by Patient-Derived Vitreous.

The epithelial-mesenchymal transition (EMT) is a fundamental process in developing fibrotic diseases, including forming epiretinal membranes (ERMs). ERMs can result in irreversible vision loss. Previous research has demonstrated that vitreous (VIT) derived from patients with proliferative diabetic retinopathy can stimulate angiogenesis through the Axl/PI3K/Akt pathway. Building upon this knowledge, we aimed to explore the influence of VIT from patients with macular membranes in ARPE-19 cells. Our findings reveal that patient-derived VIT from individuals with macular membranes promotes EMT and phosphoinositide 3-kinase-delta (PI3Kδ) expression in ARPE-19 cells. To elucidate the function of PI3Kδ in the ERM, we conducted experiments involving the knockout of p110δ, a key subunit of PI3Kδ, and observed that its absence hinders EMT induced by patient-derived VIT. Moreover, p110δ depletion reduces cell proliferation and migration in ARPE-19 cells. Remarkably, these effects were further corroborated by applying the p110δ inhibitor idelalisib, which blocks fibrosis in the laser-induced fibrosis model. Collectively, our results propose that p110δ plays a critical role in the progression of ERMs. Consequently, targeting p110δ emerges as a promising therapeutic approach for mitigating fibrosis. These findings contribute to a better understanding of the underlying mechanisms involved in ERM formation and highlight the potential for p110δ-directed antifibrotic therapy in retinal diseases.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Outcomes Following Cytoreductive Surgery and Hyperthermic Intraoperative Thoraco-Abdominal Chemotherapy with Diaphragm Resection for Peritoneal Carcinomatosis: A Retrospective Cohort Study.

PURPOSE: We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. METHODS: PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. RESULTS: Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60 years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. CONCLUSIONS: HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Efficacy of indocyanine green fluorescence-guided inguinal lymph node dissection for penile cancer: a randomised trial.

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.

Acid-Promoted Multicomponent Reaction To Synthesize 4-Phosphorylated 4H-Chromenes.

An effective multicomponent reaction for the synthesis of 4-phosphorylated 4H-chromenes via a tandem phosphorylation/alkylation/cyclization/dehydration sequence with water as the only byproduct was developed. Extensive mechanistic investigations involving in situ NMR experiments, time control experiments, and in situ HRMS experiment allowed us to elucidate the order of each subreaction to arrive at a complete understanding of the underlying mechanism of this multicomponent reaction. Mechanistic data confirm that the reaction begins with a phospha-aldol-elimination, followed by addition of a ketone enolate, intermolecular alkylation, intramolecular cyclization, and dehydration under acidic conditions.

Voluntary running wheel exercise induces cognitive improvement post traumatic brain injury in mouse model through redressing aberrant excitation regulated by voltage-gated sodium channels 1.1, 1.3, and 1.6.

Traumatic brain injury (TBI) leads to disturbed brain discharge rhythm, elevated excitability, anxiety-like behaviors, and decreased learning and memory capabilities. Cognitive dysfunctions severely affect the quality of life and prognosis of TBI patients, requiring effective rehabilitation treatment. Evidence indicates that moderate exercise after brain injury decreases TBI-induced cognitive decline. However, the underlying mechanism remains unelucidated. Our results demonstrate that TBI causes cognitive impairment behavior abnormalities and overexpression of Nav1.1, Nav1.3 and Nav1.6 proteins inside the hippocampus of mice models. Three weeks of voluntary running wheel (RW) exercise treatments before or/and post-injury effectively redressed the aberrant changes caused by TBI. Additionally, a 10% exercise-conditioned medium helped recover cell viability, neuronal sodium current and expressions of Nav1.1, Nav1.3 and Nav1.6 proteins across cultured neurons after injury. Therefore, the results validate the neuroprotection induced by voluntary RW exercise treatment before or/and post-TBI. The RW exercise-induced improvement in cognitive behaviors and neuronal excitability could be associated with correcting the Nav1.1, Nav1.3, and Nav1.6 expression levels. The current study proves that voluntary exercise is an effective treatment strategy against TBI. The study also highlights novel potential targets for rehabilitating TBI, including the Navs proteins.

Association of Life's essential 8 score with the risk of all-cause mortality and cardio-cerebrovascular mortality in patients with stroke.

BACKGROUND: A higher Life's Essential 8 (LE8)-based cardiovascular health (CVH) has been reported to be associated with a lower risk of both all-cause mortality and cardio-cerebrovascular diseases (CCVDs) related mortality in adults in the United States. At the same time, multiple studies have shown a significant negative association of CVH with the risk of stroke and CCVDs. Since no research has investigated the applicability of the LE8 in stroke patients, this study aimed to explore the association of LE8 with all-cause mortality and cardio-cerebrovascular mortality in stroke patients. METHODS: Data of patients were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2007-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were utilized to investigate the associations of LE8 with all-cause mortality and cardio-cerebrovascular mortality. We further explored these relationships in subgroups of age, gender, body mass index (BMI), cancer, congestive heart failure (CHF), and coronary heart disease (CHD). The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among the eligible patients, 278 died from all-cause and 89 (8.38%) of them died due to CCVDs. After adjusting for covariates, patients with LE8 score ≥ 58.75 seemed to have both lower risk of all-cause mortality (HR = 0.46, 95%CI: 0.31-0.69) and cardio-cerebrovascular mortality (HR = 0.51, 95%CI: 0.26-0.98), comparing to those with LE8 score < 48.123. Higher LE8 scores were associated with lower risk of all-cause mortality in patients aged < 65 years old, without cancer, and whatever the gender, BMI, CHF or CHD conditions (all P < 0.05). The relationships between high LE8 scores and low cardio-cerebrovascular mortality risk were only found in age < 65 years old and non-cancer subgroups (all P < 0.05). CONCLUSION: A higher LE8 score was associated with lower risk of both all-cause mortality and cardio-cerebrovascular mortality in patients with stroke, which may provide some reference for risk management and prognosis improvement in stoke. However, more evidences are needed to verify this beneficial role of high LE8 score in stroke prognosis.

Kinematic difference and asymmetries during level walking in adolescent patients with different types of mild scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS), three-dimensional spine deformation, affects body motion. Previous research had indicated pathological gait patterns of AIS. However, the impact of the curve number on the walking mechanism has not been established. Therefore, this study aimed to compare the gait symmetry and kinematics in AIS patients with different curve numbers to healthy control. RESULTS: In the spinal region, double curves AIS patients demonstrated a smaller sagittal symmetry angle (SA) and larger sagittal convex ROM of the trunk and lower spine than the control group. In the lower extremities, the single curve patients showed a significantly reduced SA of the knee joint in the frontal plane, while the double curves patients showed a significantly reduced SA of the hip in the transverse plane. CONCLUSION: The curve number indeed affects gait symmetry and kinematics in AIS patients. The double curves patients seemed to adopt a more "careful walking" strategy to compensate for the effect of spinal deformation on sensory integration deficits. This compensation mainly occurred in the sagittal plane. Compared to double curves patients, single curve patients unitized a similar walking strategy with healthy subjects.

Educational interventions to reduce depression and anxiety in older adults with cancer in the community: a systematic review, meta-analysis and meta-regression of randomised controlled trials.

BACKGROUND: Older adults make up half of those with cancer and are prone to mood disorders, such as depression and severe anxiety, resulting in negative repercussions on their health-related quality-of-life (HRQOL). Educational interventions have been shown to reduce adverse psychological outcomes. We examined the effect of educational interventions on the severity of psychological outcomes in older adults with cancer (OAC) in the community. METHOD: This PRISMA-adherent systematic review involved a search of PubMed, MedLine, Embase and PsycINFO for randomised controlled trials (RCTs) that evaluated educational interventions impacting the severity of depression, anxiety and HRQOL in OAC. Random effects meta-analyses and meta-regressions were used for the primary analysis. RESULTS: Fifteen RCTs were included. Meta-analyses showed a statistically insignificant decrease in the severity of depression (SMD = -0.30, 95%CI: -0.69; 0.09), anxiety (SMD = -0.30, 95%CI: -0.73; 0.13) and improvement in overall HRQOL scores (SMD = 0.44, 95%CI: -0.16; 1.04). However, subgroup analyses revealed that these interventions were particularly effective in reducing the severity of depression and anxiety in specific groups, such as OAC aged 60-65, those with early-stage cancer, those with lung cancer and those treated with chemotherapy. A systematic review found that having attained a higher education and income level increased the efficacy of interventions in decreasing the severity of adverse psychological outcomes. CONCLUSION: Although overall meta-analyses were statistically insignificant, subgroup meta-analyses highlighted a few specific subgroups that the educational interventions were effective for. Future interventions can be implemented to target these vulnerable groups.

Inter-module gap filling method for photon counting detectors based on dual acquisition.

The use of photon counting detectors in X-ray imaging missions can effectively improve the signal-to-noise ratio and image resolution. However, the stitching of photon counting detector modules leads to large-size localized information loss in the acquired projected image, which seriously affects the regional observation. In this paper, we propose a method to fill the inter-module gap based on dual acquisition, referred to as the GFDA algorithm, which is divided into three main steps: (i) acquire the main projection by short-exposure scanning, and then scan again by vertically moving the carrier table to acquire the reference projection; (ii) use the alignment method to locate the projected region of interest; (iii) use image stitching and image fusion to recover the missing information. We analyzed the gray value of the region of interest of the Siemens star projection and the reconstructed conch slice data, and proved that the proposed method can recover the information more smoothly and perfectly. The GFDA algorithm is able to achieve a better image restoration effect without additional scanning time and better retain image details. In addition, the GFDA algorithm is scalable, which is demonstrated in the task of filling the stitching of multiple types of photonic technology detectors.

Bioinformatics-based identification of key candidate genes and signaling pathways in patients with Parkinson's disease and obstructive sleep apnea.

OBJECTIVES: Existing evidence exhibits that obstructive sleep apnea (OSA) is a potential consequence of Parkinson's disease (PD) or a contributor to PD progression. This investigation aimed to detect potential critical genes and molecular mechanisms underlying interactions between PD and OSA through bioinformatics analyses. METHODS: The Gene Expression Omnibus (GEO) database was employed to obtain the expression profiles GSE20163 and GSE135917. The identification of common genes connected to PD and OSA was performed utilizing weighted gene co-expression network analysis and the R 4.0.4 program. The Cytoscape program was utilized to generate a network of protein-protein interactions (PPI), and the CytoHubba plugin was utilized to detect hub genes. Subsequently, functional enrichment analyses of the hub genes were conducted. Markers with increased diagnostic values for PD and OSA were confirmed using the GEO datasets GSE8397 and GSE38792. RESULTS: Typically, 57 genes that are common were identified in PD and OSA. Among these common genes, the top 10 hub genes in the PPI network were chosen. The verified datasets confirmed the presence of three important genes: CADPS, CHGA, and SCG3. Functional enrichment analysis revealed that these hub genes mostly participate in GABAergic synapses. CONCLUSION: Our findings suggest that CADPS, CHGA, and SCG3 are key genes involved in molecular mechanisms underlying interactions between OSA and PD. Functional enrichment of hub genes indicated a link between GABAergic synapses and the shared pathogenesis of PD and OSA. These candidate genes and corresponding pathways offer novel insights regarding biological targets that underlie the transcriptional connection between OSA and PD.

Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome-mediated Caspase-1/GSDMD pyroptosis pathway.

Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin-eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis-related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase-1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p-NF-κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis-related proteins NLRP3, Caspase-1, ASC, and GSDMD, reversed the levels of IL-1ß, IL-18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome-mediated Caspase-1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP.

Management and Nursing Approaches to Low Back Pain: Investigating the Causal Association with Lifestyle-Related Risk Factors.

BACKGROUND: Notwithstanding a plethora of observational studies, the causal implications of obesity, encompassing both body mass index (BMI) and waist circumference (WC), as well as type 2 diabetes (T2D), and lifestyle factors, in relation to the vulnerability to low back pain (LBP), remain enigmatic. AIMS: This study was designed to investigate the related causal associations DESIGN: A two-sample Mendelian randomization (MR) analysis. SETTINGS: By utilizing genetic variants associated with pertinent factors gleaned from genome-wide association studies (GWASs), We extracted independent genetic variants about exposures such as BMI, WC, T2D, smoking, alcohol consumption, and coffee intake from published GWASs, ensuring their genome-wide significance. PARTICIPANTS/SUBJECTS: The GWASs were selected from the most up-to-date and largest publicly accessible databases. METHODS: The summary data concerning LBP emanated from a GWAS of European cases and controls, which was based on the esteemed MRC-IEU (Medical Research Council Integrative Epidemiology Unit) consortium. RESULTS: Heightened body mass index and waist circumference exhibited odds ratios of 1.003 (95% confidence interval [CI] = 1.002-1.004, p < 0.001) and 1.003 (95% CI = 1.002-1.004, p < 0.001) for LBP, respectively, per each standard deviation (SD) increase. As for smoking initiation and every SD increase in the frequency of alcohol intake, the odds ratios were 1.002 (95% CI = 1.001-1.003, p = 0.003) and 1.002 (95% CI = 1.000-1.003, p = 0.011), respectively, for LBP. Conversely, an increased log odds ratio for T2D, and prevalence of coffee intake, divulged no discernible causal effects on the risk of LBP. CONCLUSION: This study provides suggestive evidence to support the causal involvement of obesity, smoking, and the frequency of alcohol intake in the development of LBP, which suggests that implementing measures to mitigate these risk factors may aid in preventing LBP.

External Guide Sequence Effectively Suppresses the Gene Expression and Replication of Herpes Simplex Virus 2.

Ribonuclease P (RNase P) complexed with an external guide sequence (EGS) represents a promising nucleic acid-based gene targeting approach for gene expression knock-down and modulation. The RNase P-EGS strategy is unique as an EGS can be designed to basepair any mRNA sequence and recruit intracellular RNase P for hydrolysis of the target mRNA. In this study, we provide the first direct evidence that the RNase P-based approach effectively blocks the gene expression and replication of herpes simplex virus 2 (HSV-2), the causative agent of genital herpes. We constructed EGSs to target the mRNA encoding HSV-2 single-stranded DNA binding protein ICP8, which is essential for viral DNA genome replication and growth. In HSV-2 infected cells expressing a functional EGS, ICP8 levels were reduced by 85%, and viral growth decreased by 3000 folds. On the contrary, ICP8 expression and viral growth exhibited no substantial differences between cells expressing no EGS and those expressing a disabled EGS with mutations precluding RNase P recognition. The anti-ICP8 EGS is specific in targeting ICP8 because it only affects ICP8 expression but does not affect the expression of the other viral immediate-early and early genes examined. This study shows the effective and specific anti-HSV-2 activity of the RNase P-EGS approach and demonstrates the potential of EGS RNAs for anti-HSV-2 applications.