The association between overactive bladder and systemic immunity-inflammation index: a cross-sectional study of NHANES 2005 to 2018.

Current research indicate that inflammation is linked to the development of overactive bladder (OAB). The aim of this study was to examine the correlation between OAB and the systemic immunity-inflammation index (SII) in the USA. We analyzed data from 31,881 participants in the National Health and Nutrition Examination Survey 2005-2018. SII, calculated as platelet count × neutrophil count/lymphocyte count, was categorized into quartiles. OAB was defined by the presence of urge urinary incontinence and nocturia. Weighted logistic regression models were used to examine the independent relationship between SII and OAB, adjusting for demographic factors, kidney function, and diabetes status. The results showed that each tenfold increase in log-transformed SII was associated with an 18% higher odds of OAB (OR 1.18, 95% CI 1.08-1.28) in the fully adjusted model. Compared to the lowest SII quartile, the highest quartile had a 28% increased OAB risk (OR 1.28, 95% CI 1.12-1.47). The positive association between SII and OAB risk was consistently observed across subgroups stratified by age, sex, race, marital status, education, and poverty level. Our study reveals a positive correlation between SII levels and OAB, indicating that higher SII levels are associated with an increased likelihood of developing OAB.

Advanced deep learning algorithm for instant discriminating of tea leave stress symptoms by smartphone-based detection.

The primary challenges in tea production under multiple stress exposures have negatively affected its global market sustainability, so introducing an infield fast technique for monitoring tea leaves' stresses has tremendous urgent needs. Therefore, this study aimed to propose an efficient method for the detection of stress symptoms based on a portable smartphone with deep learning models. Firstly, a database containing over 10,000 images of tea garden canopies in complex natural scenes was developed, which included healthy (no stress) and three types of stress (tea anthracnose (TA), tea blister blight (TB) and sunburn (SB)). Then, YOLOv5m and YOLOv8m algorithms were adapted to discriminate the four types of stress symptoms; where the YOLOv8m algorithm achieved better performance in the identification of healthy leaves (98%), TA (92.0%), TB (68.4%) and SB (75.5%). Furthermore, the YOLOv8m algorithm was used to construct a model for differentiation of disease severity of TA, and a satisfactory result was obtained with the accuracy of mild, moderate, and severe TA infections were 94%, 96%, and 91%, respectively. Besides, we found that CNN kernels of YOLOv8m could efficiently extract the texture characteristics of the images at layer 2, and these characteristics can clearly distinguish different types of stress symptoms. This makes great contributions to the YOLOv8m model to achieve high-precision differentiation of four types of stress symptoms. In conclusion, our study provided an effective system to achieve low-cost, high-precision, fast, and infield diagnosis of tea stress symptoms in complex natural scenes based on smartphone and deep learning algorithms.

Production performance analysis of sheep MSTN gene C2361T locus.

The myostatin (MSTN) gene exhibits significant nucleotide sequence variations in sheep, impacting growth characteristics and muscular traits of the body. However, its influence on specific growth traits in some sheep remains to be further elucidated. This study utilized single nucleotide polymorphism sequence analysis to investigate the role of the MSTN gene in meat production performance across four sheep breeds: Charolais sheep, Australian White sheep, crossbreeds of Australian White and Small-tailed Han, and crossbreeds of Charolais and Small-tailed Han. At a SNP locus of the MSTN gene, the C2361T site was identified, with three genotypes detected: CC, CT, and TT, among which CC predominated. Gene substitution effect analysis revealed that replacing C with T could elevate the phenotypic value. Comparative analysis of data from different genotypes within the same breed highlighted the superiority of CC and TT genotypes in phenotypic values, underscoring the significance of specific genotypes in influencing key traits. Contrasting the performance of different genotypes across breeds, Charolais sheep and Charolais Han hybrids demonstrated superiority across multiple indicators, offering valuable insights for breeding new sheep varieties. Analysis of gender effects on growth characteristics indicated that ewes exhibited significantly wider chest, waist, and hip widths compared to rams, while rams displayed better skeletal growth and muscle development. Additionally, the MSTN gene also exerted certain effects on lamb growth characteristics, with the CC genotype closely associated with weight. These findings not only contribute crucial insights for sheep breeding but also pave the way for future research exploring the interaction of this gene with others.

Spindle cell embryonal rhabdomyosarcoma of the prostate in an adult patient: a case report and review of the literature.

Rhabdomyosarcoma of the prostate is a rare mesenchymal tumor that originates from undifferentiated mesenchymal cells. Spindle cell rhabdomyosarcoma is a variant of embryonal rhabdomyosarcoma. The vast majority of these two pathological types occur in children, with only a few adult cases reported to date, and both are associated with poor clinical outcomes. We herein report a case involving a man in his early 40s with spindle cell embryonal rhabdomyosarcoma of the prostate. His chief complaint was difficult urination. The diagnosis was confirmed by puncture biopsy of the prostate, and pelvic lymph node metastasis was already present at the time of diagnosis. The patient underwent three courses of chemotherapy. However, his response to the treatment was very poor, and he died of the disease 4 months after diagnosis.

"Loop-Neurorrhaphy Technique for Preventing Bone Resorption and Preserving Lower Lip Sensation in Mandibular Reconstruction using Vascularized Iliac Bone Flap: A Single-Center Randomized Clinical Trial".

BACKGROUND: The aim of this study was to investigate whether using an innervated vascularized iliac bone flap could effectively prevent bone resorption and maintain sensory function in the lower lip. METHODS: In the innervated group, the deep circumflex iliac artery and recipient vessels were anastomosed, with simultaneous microanastomosis of ilioinguinal nerve, mental nerve and inferior alveolar nerve. Conversely, the control group underwent solely vascular anastomosis. CT was utilized to assess bone quality. Sensory recovery of the lower lip was recorded using two-point discrimination and current perception threshold testing. RESULTS: The study comprised a total of 40 subjects, with each group accounting for 20 participants, equally distributed in terms of gender. Hounsfield unit loss was significantly lower in the innervated group (13.26±8.65 %) as compared to the control group (37.98±8.60 %) (P < 0.001). Moreover, two-point discrimination values were lower in the innervated group (15.11±8.39 mm) when compared to the control group (21.44±7.24 mm) (P = 0.02). The current perception threshold values for the innervated group were 176.19 ± 31.89, 64.21 ± 19.23, and 42.29 ± 18.96 in 2kHz, 250Hz, and 5Hz respectively, while in the control group, the current perception threshold values were 204.47 ± 36.99, 82.26 ± 27.29, and 58.89 ± 25.38 in 2kHz, 250Hz, and 5Hz (P =0.02, 0.02, and 0.03, respectively). CONCLUSIONS: The innervated vascularized iliac bone flap represents a safe and effective novel approach to preserving lower lip sensation and preventing bone resorption through functional mandibular reconstruction.

Common proteins analysis of different mammals' mature milk by 4D-Label-Free.

The milk proteins from samples of 13 different animals were identified utilizing 4D-Label-Free proteomics technology, leading to the identification of a substantial number of proteins. Among the various samples, Chinese people (CHP) milk proteins exhibited the highest count, with 1149 distinct proteins. Simultaneously, we identified common proteins present in these animal milk. It's notable presence in goat milk contributes to enhancing infant infection resistance, showcasing the beneficial role of lactoperoxidase. Galectin-3 binding protein (Gal-3BP) and tetraspanin in human milk are significantly higher than those in other animals, which determine the prominent antiviral effect of human milk and the important processes related to cell transduction. Furthermore, human milk, camel milk, goat milk and sheep milk proved to be rich sources of milk fat globule membrane (MFGM) proteins. The insights obtained from this study can serve as a foundational framework for exploring the role of different animal milk proteins in disease treatment and the composition of infant formula.

The Efficacy of Tiaoshen Acupuncture in Traditional Chinese Medicine for Insomnia Treatment: A Systematic Review and Meta-analysis.

Background: In recent years, Tiaoshen acupuncture in Traditional Chinese Medicine (TCM) has been employed for treating patients with insomnia, but the clinical efficacy remains to be substantiated. Objective: To assess the efficacy and safety of acupuncture in treating insomnia using the Tiaoshen method in TCM. Design: A systematic review and meta-analysis was conducted. Setting: The research was conducted in Shenzhen. Methods: Electronic databases, including Chinese National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, Weipu, PubMed, Web of Science, EMBASE, and Cochrane databases, were retrieved up to September 15, 2023. Randomized controlled trials (RCTs) meeting inclusion criteria were screened. Quality assessment of included articles was performed using the Cochrane Risk of Bias tool. Valid data were then extracted and analyzed via meta-analysis using Review Manager 5.3. The study was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 2023100051. Results: A total of 13 articles were included, comprising 849 patients with insomnia (diagnosed as chronic insomnia or primary insomnia). Meta-analysis results indicated that acupuncture with the Tiaoshen method could decrease the Pittsburgh Sleep Quality Index (PSQI) score [RR=-3.03, 95% CI (-3.73, -2.33), P < .00001], hyperarousal (HAS) scale score [RR=-7.75, 95% CI (-12.29, -3.22), P < .0008], and fatigue scale-14 (FS-14) score [RR=-2.11, 95% CI (-2.83, -1.38), P < .00001] compared with superficial acupuncture on non-effective acupoints or conventional acupuncture manipulation. Additionally, acupuncture with the Tiaoshen method demonstrated safety. However, the funnel plot suggested the presence of publication bias. Conclusions: Acupuncture with the Tiaoshen method could enhance sleep quality and efficiency. Due to the low quality of some literature, further high-quality RCTs are needed to improve the level of evidence.

Electroacupuncture alleviates streptozotocin-induced diabetic neuropathic pain via suppressing phosphorylated CaMKIIα in rats.

Diabetic neuropathic pain (DNP) is a frequent complication of diabetes. Calcium/calmodulin-dependent protein kinase II α (CaMKIIα), a multi-functional serine/threonine kinase subunit, is mainly located in the surface layer of the spinal cord dorsal horn (SCDH) and the primary sensory neurons in dorsal root ganglion (DRG). Numerous studies have indicated electroacupuncture (EA) takes effect in various kinds of pain. In this research, we explored whether CaMKIIα on rats' SCDH and DRG participated in DNP and further explored the mechanisms underlying the analgesic effects of EA. The DNP model in rats was successfully established by intraperitoneal injection of streptozotocin. Certain DNP rats were treated with intrathecal injections of KN93, a CaMKII antagonist, and some of the DNP rats received EA intervention. The general conditions, behaviors, the expressions of CaMKIIα and phosphorylated CaMKIIα (p-CaMKIIα) were evaluated. DNP rats' paw withdrawal threshold was reduced and the expressions of p-CaMKIIα in SCDH and DRG were upregulated compared with the Normal group, while the level of CaMKIIα showed no significance. KN93 attenuated DNP rats' hyperalgesia and reduced the expressions of p-CaMKIIα. We also found EA attenuated the hyperalgesia of DNP rats and reduced the expressions of p-CaMKIIα. The above findings suggest that p-CaMKIIα in SCDH and DRG is involved in DNP. The analgesic effect of EA in DNP might be related to the downregulation of p-CaMKIIα expression level. Our study further supports that EA can be an effective clinical treatment for DNP.

Global warming potential assessment under reclaimed water and livestock wastewater irrigation coupled with co-application of inhibitors and biochar.

The application of nitrification inhibitors (nitrapyrin) and urease inhibitors (N-(N-butyl) thiophosphoric triamide) under conventional water resources has been considered as an effective means to improve nitrogen utilization efficiency and mitigate soil greenhouse gas emissions. However, it is not known whether the inhibitors still have an inhibitory effect under unconventional water resources (reclaimed water and livestock wastewater) irrigation and whether their use in combination with biochar improves the mitigation effect. Therefore, unconventional water resources were used for irrigation, with groundwater (GW) control. Nitrapyrin and N-(N-butyl) thiophosphoric triamide were used alone or in combination with biochar in a pot experiment, and CO2, N2O, and CH4 emissions were measured. The results showed that irrigation of unconventional water resources exacerbated global warming potential (GWP). All exogenous substance treatments increased CO2 and CH4 emissions and suppressed N2O emissions, independent of the type of water, compared to no substances (NS). The inhibitors were ineffective in reducing the GWP whether or not in combination with biochar, and the combined application of inhibitors with biochar further increased the GWP. This study suggests that using inhibitors and biochar in combination to regulate the greenhouse effect under unconventional water resources irrigation should be done with caution.

KEAP1 promotes anti-tumor immunity by inhibiting PD-L1 expression in NSCLC.

Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.

Three-Step Depletion Strategy of Glutathione: Tunable Metal-Organic-Framework-Engineered Nanozymes for Driving Oxidative/Nitrative Stress to Maximize Ferroptosis Therapy.

Ferroptosis is a novel type of nonapoptotic programmed cell death involving the accumulation of lipid peroxidation (LPO) to a lethal threshold. Herein, we propose tunable zeolitic imidazolate framework (ZIFs)-engineered biodegradable nanozymes for ferroptosis mediated by both reactive oxygen species (ROS) and nitrogen species (RNS). l-Arginine is utilized as an exogenous nitric oxide donor and loaded into hollow ZIFs@MnO2 artificial nanozymes, which are formed by etching ZIFs with potassium permanganate and simultaneously generating a MnO2 shell in situ. The constructed nanozymes with multienzyme-like activities including peroxidase, oxidase, and catalase can release satisfactory ROS and RNS through a cascade reaction, consequently promoting the accumulation of LPO. Furthermore, it can improve the efficiency of ferroptosis through a three-step strategy of glutathione (GSH) depletion; that is, the outer MnO2 layer consumes GSH under slightly acidic conditions and RNS downregulates SLC7A11 and glutathione reductase, thus directly inhibiting GSH biosynthesis and indirectly preventing GSH regeneration.

Single-cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non- to metastatic lymph node OTSCC.

Lymph node metastasis (LNM) is one of the common features of oral tongue squamous cell carcinoma (OTSCC). LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single-cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer-associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single-cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.

Choroid plexus volume enlargement in first-episode antipsychotic-naïve schizophrenia.

Investigation of the choroid plexus in schizophrenia has seen growing interest due to its role in the interaction between neuroinflammation and brain dysfunction. Most previous studies included treated and long-term ill patients, while antipsychotics and illness course might both affect the choroid plexus. Here, we recruited first-episode antipsychotic-naïve schizophrenia patients, performed high-resolution structural brain scan and manually extracted choroid plexus volume. Choroid plexus volume was compared between patients and healthy controls after controlling for age, sex and intracranial volume. Age and sex effects were examined on choroid plexus volume in patient and healthy control groups respectively. In patients, we also examined the correlation of choroid plexus volume with volume measures of cortical and subcortical gray matter, white matter, lateral ventricular as well as symptom severity and cognitive function. Schizophrenia patients showed significantly enlarged choroid plexus volume compared with healthy controls. Choroid plexus volume was positively correlated with age in only patient group and we found significantly larger choroid plexus volumes in males than females in both patient and healthy control groups, while the sex effects did not differ between groups. Choroid plexus volume was only found correlated with lateral ventricular volume among the brain volume measures. No significant correlation between choroid plexus volume and clinical ratings or cognitive performance was observed. Without potential confounding effects of pharmacotherapy or illness course, our findings indicated the enlargement of choroid plexus in schizophrenia might be an enduring trait for schizophrenia.

Prostate Volume is A Predictor of Gleason Score Upgrading after Radical Prostatectomy in Low-Risk Prostate Cancer: A Systematic Review and Meta-analysis.

PURPOSE: The prediction of Gleason score (GS) upgrading in patients diagnosed with low-risk prostate cancer is particularly important when opting for active surveillance (AS). Thus, we aimed to explore the association between prostate volume and GS upgrading after radical prostatectomy in low-risk prostate cancer through a meta-analysis. METHODS: Multiple databases (Web of Science, MEDLINE, Embase, Scopus, and the Cochrane Library) were searched for eligible studies regarding this issue and reporting sufficient data up to May 2023. Specific search terms such as prostate cancer, radical prostatectomy, and prostate volume were used in our search strategy. Multivariable-adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random effects models according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. RESULTS: Twenty studies comprising 14,823 patients who underwent radical prostatectomy matched our eligibility criteria. Moreover, GS upgrading between biopsy and surgical pathological specimens occurs in 32.2% (4,771) of cases. The results showed that smaller prostate volume is significantly associated with GS upgrading in patients with low-risk prostate cancer (OR = 1.08, 95% CI = 1.05-1.11; P < 0.001; I-square [I2] = 89.8%) from biopsy to radical prostatectomy after adjusting for confounding factors. Moreover, the results of our subgroup analyses revealed that smaller prostate volume remained a substantial risk factor of GS upgrading in the studies designed as retrospective cohorts and case-control studies performed in America, Italy, Turkey, and China. The findings are robust as indicated by sensitivity and meta-regression analyses. CONCLUSION: Smaller prostate volume predicts clinically substantial GS upgrading in patients diagnosed with lowrisk prostate cancer after radical prostatectomy. The intriguing findings might be helpful when management options other than surgery are selected based on the inability to recognise the true pathological GS of patients for AS. Further studies focus on risk-stratification and treatment planning for patients with low-grade prostate cancer are still needed to verify our results.

The Long-Term Prognostic Role of Nighttime Resting Heart Rate in Obstructive Sleep Apnea in Patients with Acute Coronary Syndrome.

AIM: A close relationship exists between resting heart rate (RHR) and obstructive sleep apnea (OSA). Still, the prognostic importance of nighttime RHR in patients with acute coronary syndrome (ACS) with or without OSA remains unclear. METHODS: In this prospective cohort study, OSA was defined as an apnea-hypopnea index of ≥ 15 events/h, and the high nighttime RHR (HNRHR) was defined as a heart rate of ≥ 70 bpm. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for heart failure. RESULTS: Among the 1875 enrolled patients, the mean patient age was 56.3±10.5 years, 978 (52.2%) had OSA, and 425 (22.7%) were in HNRHR. The proportion of patients with HNRHR is higher in the OSA population than in the non-OSA population (26.5% vs. 18.5%; P＜0.001). During 2.9 (1.5, 3.5) years of follow-up, HNRHR was associated with an increased risk of MACCE in patients with OSA (adjusted HR: 1.56, 95% CI: 1.09-2.23, P=0.014), but not in patients without OSA (adjust HR: 1.13, 95% CI: 0.69-1.84, P=0.63). CONCLUSIONS: In patients with ACS, a nighttime RHR of ≥ 70 bpm was associated with a higher risk of MACCE in those with OSA but not in those without it. This identifies a potential high-risk subgroup where heart rate may interact with the prognosis of OSA. Further research is needed to determine causative relationships and confirm whether heart rate control impacts cardiovascular outcomes in patients with ACS-OSA.

Oxygen and pH responsive theragnostic liposomes for early-stage diagnosis and photothermal therapy of solid tumours.

The development of cancer treatment is of great importance, especially in the early stage. In this work, we synthesized a pH-sensitive amphiphilic ruthenium complex containing two alkyl chains and two PEG chains, which was utilized as an oxygen sensitive fluorescent probe for co-assembly with lipids to harvest a liposomal delivery system (RuPC) for the encapsulation of a photothermal agent indocyanine green (ICG). The resultant ICG encapsulated liposome (RuPC@ICG) enabled the delivery of ICG into cells via a membrane fusion pathway, by which the ruthenium complex was localized in the cell membrane for better detection of the extracellular oxygen concentration. Such characteristics allowed ratiometric imaging to distinguish the tumour location from normal tissues just 3 days after cancer cells were implanted, by monitoring the hypoxia condition and tracing the metabolism. Moreover, the pH sensitivity of the liposomes favoured cell uptake, and improved the anti-tumour efficiency of the formulation in vivo under NIR irradiation. Assuming liposomal systems have fewer safety issues, our work not only provides a facile method for the construction of a theragnostic system by combining phototherapy with photoluminescence imaging, but hopefully paves the way for clinical translation from bench to bedside.

Analysis for lipid nutrient differences in the milk of 13 species from a quantitative non-targeted lipidomics perspective.

Lipids are essential organic components in milk and have been associated with various health benefits for newborns. However, a comprehensive analysis of lipid profiles across multiple species and levels has been lacking. In this study, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to accurately determine the absolute content of lipid molecules. It revealed that ruminants exhibit a higher concentration of short-chain fatty acids compared to non-ruminants. Additionally, we identified ALC (camel), MGH (horse), and DZD (donkey) as species that display similarities to components found in human milk fat. Remarkably, it reveals that porcine milk fat is characterized by long chain lengths, low saturation, and a high proportion of essential fatty acids. PS (22:5_18:2) could potentially serve as a biomarker in porcine milk. These unique characteristics present potential opportunities for the utilization of porcine milk. Overall, our findings provide valuable insights into the lipidomics profiles of milk from different species.

Prognostic implications of obstructive sleep apnea in patients with acute coronary syndrome stratified by homocysteine level: a prospective cohort study.

BACKGROUND: Sporadic studies have examined the impact of OSA on ACS patients by homocysteine (Hcy) level. This study attempted to comprehensively evaluate the effects of the interaction between Hcy and OSA on long-term cardiovascular outcomes in ACS patients. METHODS: In this prospective, large-scale cohort study, 2160 patients admitted for ACS were recruited to undergo overnight sleep monitoring. OSA was diagnosed when apnea-hypopnea index ≥ 15 events/h. Patients with normohomocysteinemia (NHcy) were defined as having serum Hcy ≤ 15 µmol/L, and the others had hyperhomocysteinemia (HHcy). The primary endpoint was major adverse cerebrocardiovascular event (MACCE), a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization and hospitalization for unstable angina and heart failure. RESULTS: A total of 1553 eligible ACS patients (average age: 56.3 ± 10.5 years) were enrolled, among which 819 (52.7%) had OSA, and 988 (63.6%) were with NHcy. OSA did not significantly affect the level of Hcy. During a median follow-up of 2.9 (1.6, 3.5) years, after adjustment for clinical confounders, OSA was associated with increased risk for MACCE occurrence versus non-OSA ones in ACS patients with NHcy (adjusted hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.02-1.83, P = 0.039), but not in those with HHcy (adjusted HR = 0.92, 95%CI 0.62-1.36, P = 0.668). There was an absence of interaction between homocysteine level and OSA in relation to MACCE (interaction P = 0.106). CONCLUSIONS: OSA was independently associated with worse prognosis in ACS patients with NHcy. Our study emphasized the necessity to identify potential presence of OSA in such a population. TRIAL REGISTRATION: ClinicalTrials.gov; Number: NCT03362385; URL: www. CLINICALTRIALS: gov .

Effect of complete revascularization in acute coronary syndrome after 75 years old: insights from the BleeMACS registry.

BACKGROUND: The prognostic benefit of complete revascularization in elderly patients (aged over 75 years) with multi-vessel disease and acute coronary syndrome (ACS) is currently unclear. This study aimed to determine the long-term prognostic impact of complete revascularization in this population. METHODS: We conducted this study using data obtained from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry, which was carried out from 2003 to 2014. The objective was to categorize older patients diagnosed with ACS into two groups: those who underwent complete revascularization and those who did not. Propensity score matching and the Kaplan-Meier analysis were employed to examine differences in one-year clinical outcomes. The primary endpoint was major adverse cardiovascular event (MACE), which encompassed a combination of all-cause mortality and myocardial infarction. RESULTS: Out of 1263 patients evaluated, 445 patients (35.2%) received complete revascularization. Patients who underwent complete revascularization had a higher prevalence of hypertension and prior percutaneous coronary intervention compared to those who did not. During the one-year follow-up period, complete revascularization was associated with a significantly decreased risk of MACE [13.7% vs. 20.5%, hazard ratio (HR) = 0.63, 95% CI: 0.45-0.88, P = 0.007] and a lower risk of myocardial infarction (5.9% vs. 9.9%, HR = 0.55, 95% CI: 0.33-0.92, P = 0.02). However, it was not linked to a lower risk of all-cause death (9.5% vs. 13.5%, HR = 0.68, 95% CI: 0.45-1.02, P = 0.06). Similar results were observed in the subgroup analysis. CONCLUSIONS: Long-term clinical improvements were observed in ACS patients aged over 75 years with multi-vessel disease who achieved complete revascularization. Therefore, adhering to guidelines for complete revascularization should be recommended for elderly patients.

Lysine-372-dependent SUMOylation inhibits the enzymatic activity of glutamine synthases.

Glutamine synthetase (GS) is a crucial enzyme involved in de novo synthesis of glutamine and participates in several biological processes, including nitrogen metabolism, nucleotide synthesis, and amino acid synthesis. Post-translational modification makes GS more adaptable to the needs of cells, and acetylation modification of GS at double sites has attracted considerable attention. Despite very intensive research, how SUMOylation affects GS activity at a molecular level remains unclear. Here, we report that previously undiscovered GS SUMOylation which is deficient mutant K372R of GS exhibits more bluntness under glutamine starvation. Mechanistically, glutamine deprivation triggers the GS SUMOylation, and this SUMOylation impaired the protein stability of GS, within a concomitant decrease in enzymatic activity. In addition, we identified SAE1, Ubc9, and PIAS1 as the assembly enzymes of GS SUMOylation respectively. Furthermore, Senp1/2 functions as a SUMO-specific protease to reverse the SUMOylation of GS. This study provides the first evidence that SUMOylation serves as a regulatory mechanism for determining the GS enzymatic activity, contributing to understanding the GS regulation roles in various cellular and pathophysiological processes.