Xiaowugui decoction alleviates experimental rheumatoid arthritis by suppressing Rab5a-mediated TLR4 internalization in macrophages.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by exacerbated synovial inflammation and joint destruction. Recent studies suggest toll-like receptor 4 (TLR4) internalization facilitate inflammatory response of macrophage. The role of TLR4 internalization in the pathogenesis of RA is unknown. PURPOSE: To investigate the role and mechanism of TLR4 internalization in macrophage inflammatory response of RA and explore whether TLR4 internalization mediates the anti-arthritic effect of Xiaowugui (XWG) decoction, a patented herbal formula used in China. METHODS: The co-expression of TLR4 and the internalization marker, early endosome antigen 1 (EEA1), in the synovial samples of RA patients and joint tissue of collagen-induced arthritis (CIA) mice, were evaluated using immunofluorescence. The effect of Rab5a-mediated early internalization of TLR4 on the activation induced by lipopolysaccharide (LPS) in RAW264.7 cells was investigated using small interfering RNAs that act against Rab5a. CIA was induced in Rab5a-/- mice to evaluate the role of Rab5a in vivo. The disease progression and expression of Rab5a and TLR4 in the joint tissue were evaluated in CIA mice treated with XWG. Inflammatory factors production, TLR4 internalization, and activation of downstream signaling pathways were examined in RAW264.7 cells treated with XWG in vitro. RESULTS: The co-expression and co-localization of TLR4 and EEA1 were elevated in the synovial samples of RA patients and joint tissue of CIA mice. Pharmaceutical inhibition of TLR4 internalization reduced macrophages inflammatory responses induced by LPS. The co-expression and co-localization of Rab5a and TLR4 were significantly increased in macrophages treated with LPS. Silencing Rab5a reduced LPS-induced TLR4 internalization, inflammatory factors production, and phosphorylation of Jun N-terminal kinases (JNK) and p65. Genetic deletion of Rab5a inhibited TLR4 internalization and the development of arthritis in vivo. The co-expression of TLR4 and Rab5a was also elevated in the synovial samples of RA patients. XWG treatment of mice with CIA alleviated arthritis and reduced the co-expression of Rab5a and TLR4 in the joint tissue. XWG treatment of macrophage inhibited LPS-induced IL-6 and TNF-α production, co-expression of Rab5a and TLR4, and phosphorylation of JNK and p65. CONCLUSIONS: Our findings highlight the pathogenic role of TLR4 internalization in patients with RA and identify a novel Rab5a-dependent internalization pathway that promotes macrophage inflammatory response. XWG treatment demonstrated outstanding therapeutic effects in experimental arthritis, and targeting the Rab5a-mediated internalization of TLR4 may be the main underlying mechanism.

Menopausal stages and overactive bladder symptoms in middle-aged women: A cross-sectional study.

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

Effect analysis of applying high-quality service model to surgical nursing.

BACKGROUND: Surgical care of the hand plays a crucial role in the medical field, as problems with the hand can profoundly affect a patient's quality of life and function. In order to meet the needs of patients, improve patient satisfaction and improve treatment outcomes, high-quality service models have been introduced in the field of nursing. AIM: To explore the effect analysis of applying high-quality service model to surgical nursing. METHODS: We conducted a retrospective study of patients who underwent hand surgery at our hospital between 2019 and 2022, using a quality service model that included improved patient education, pain management, care team collaboration, and effective communication. Another group of patients received traditional care as a control group. We compared postoperative recovery, satisfaction, complication rate, and length of hospital stay between the two groups. Inferential statistics were used to compare the difference between the two groups by independent sample t test, Chi-square test and other methods to evaluate the effect of intervention measures. RESULTS: Postoperative recovery time decreased from 17.8 ± 2.3 d to 14.5 ± 2.1 d, pain score decreased from 4.7 ± 1.9 to 3.2 ± 1.4, and hand function score increased from 78.4 ± 7.1 to 88.5 ± 6.2. In terms of patient satisfaction, the quality service model group scored 87.3 ± 5.6 points, which was significantly higher than that of the traditional care group (74.6 ± 6.3 points). At the same time, patients' understanding of medical information also improved from 6.9 ± 1.4 to 8.6 ± 1.2. In terms of postoperative complications, the application of the quality service model reduced the incidence of postoperative complications from 26% to 10%, the incidence of infection from 12% to 5%, and the incidence of bleeding from 10% to 3%. The reduction in these data indicates that the quality service model plays a positive role in reducing the risk of complications. In addition, the average hospital stay of patients in the quality service model group was shortened from 6.8 ± 1.5 d to 5.2 ± 1.3 d, and the hospitalization cost was also reduced from 2800 ± 600 yuan to 2500 ± 500 yuan. CONCLUSION: Applying a quality service model to hand surgery care can significantly improve patient clinical outcomes, including faster recovery, less pain, greater satisfaction, and reduced complication rates.

An NMPC-Based Integrated Longitudinal and Lateral Vehicle Stability Control Based on the Double-Layer Torque Distribution.

With the ongoing promotion and adoption of electric vehicles, intelligent and connected technologies have been continuously advancing. Electrical control systems implemented in electric vehicles have emerged as a critical research direction. Various drive-by-wire chassis systems, including drive-by-wire driving and braking systems and steer-by-wire systems, are extensively employed in vehicles. Concurrently, unavoidable issues such as conflicting control system objectives and execution system interference emerge, positioning integrated chassis control as an effective solution to these challenges. This paper proposes a model predictive control-based longitudinal dynamics integrated chassis control system for pure electric commercial vehicles equipped with electro-mechanical brake (EMB) systems, centralized drive, and distributed braking. This system integrates acceleration slip regulation (ASR), a braking force distribution system, an anti-lock braking system (ABS), and a direct yaw moment control system (DYC). This paper first analyzes and models the key components of the vehicle. Then, based on model predictive control (MPC), it develops a controller model for integrated stability with double-layer torque distribution. The required driving and braking torque for each wheel are calculated according to the actual and desired motion states of the vehicle and applied to the corresponding actuators. Finally, the effectiveness of this strategy is verified through simulation results from Matlab/Simulink. The simulation shows that the braking deceleration of the braking condition is increased by 32% on average, and the braking distance is reduced by 15%. The driving condition can enter the smooth driving faster, and the time is reduced by 1.5 s~5 s. The lateral stability parameters are also very much improved compared with the uncontrolled vehicles.

Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

PURPOSE: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). METHODS: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. RESULTS: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). CONCLUSION: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Osteoblast-specific down-regulation of NLRP3 inflammasome by aptamer-functionalized liposome nanoparticles improves bone quality in postmenopausal osteoporosis rats.

Rationale: NLRP3 inflammasome is critical in the development and progression of many metabolic diseases driven by chronic inflammation, but its effect on the pathology of postmenopausal osteoporosis (PMOP) remains poorly understood. Methods: We here firstly examined the levels of NLRP3 inflammasome in PMOP patients by ELISA. Then we investigated the possible mechanisms underlying the effect of NLRP3 inflammasome on PMOP by RNA sequencing of osteoblasts treated with NLRP3 siRNA and qPCR. Lastly, we accessed the effect of decreased NLRP3 levels on ovariectomized (OVX) rats. To specifically deliver NLRP3 siRNA to osteoblasts, we constructed NLRP3 siRNA wrapping osteoblast-specific aptamer (CH6)-functionalized lipid nanoparticles (termed as CH6-LNPs-siNLRP3). Results: We found that the levels of NLRP3 inflammasome were significantly increased in patients with PMOP, and were negatively correlated with estradiol levels. NLRP3 knock-down influenced signal pathways including immune system process, interferon signal pathway. Notably, of the top ten up-regulated genes in NLRP3-reduced osteoblasts, nine genes (except Mx2) were enriched in immune system process, and five genes were related to interferon signal pathway. The in vitro results showed that CH6-LNPs-siNLRP3 was relatively uniform with a dimeter of 96.64 ± 16.83 nm and zeta potential of 38.37 ± 1.86 mV. CH6-LNPs-siNLRP3 did not show obvious cytotoxicity and selectively delivered siRNA to bone tissue. Moreover, CH6-LNPs-siNLRP3 stimulated osteoblast differentiation by activating ALP and enhancing osteoblast matrix mineralization. When administrated to OVX rats, CH6-LNPs-siNLRP3 promoted bone formation and bone mass, improved bone microarchitecture and mechanical properties by decreasing the levels of NLRP3, IL-1ß and IL-18 and increasing the levels of OCN and Runx2. Conclusion: NLRP3 inflammasome may be a new biomarker for PMOP diagnosis and plays a key role in the pathology of PMOP. CH6-LNPs-siNLRP3 has potential application for the treatment of PMOP.

PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Development and Psychometric Evaluation of the Social Participation Questionnaire: A Methodological and Cross-Sectional Study.

PURPOSE: Social participation is vital for the health maintenance of general populations as well as the functional recovery and social ties of clinical patients. To develop a Social Participation Questionnaire (SPQ) to evaluate participation in social activities in an individual's life and to test the reliability and validity of the SPQ. DESIGN: Cross-sectional study. SETTING: Community and clinic in China. SUBJECTS: A total of 1419 healthy adults and 486 breast cancer patients. MEASURES: The initial items were developed from a theoretical framework, a literature review, and Delphi expert consultation. Item analysis, exploratory (EFA) and confirmatory factor analysis (CFA), criterion validity, construct reliability, and internal consistency reliability were performed to examine the psychometric properties of the SPQ. RESULTS: The final SPQ was comprised of 11 different types of social activities, falling under the 3 dimensions of activities of daily life, sports and entertainment activities, and social service activities. EFA explained 50.674% of the total item variance contributing to the tool. CFA showed that the SPQ fit well. The total SPQ score was significantly associated with social network, quality of life, and cognitive function (r = |.180∼.466|, P < .001). The internal consistency coefficient was acceptable (range of Cronbach's alpha, .695 to .720). CONCLUSIONS: The SPQ has robust properties, wide application, and provides a culturally relevant tool to evaluate the social participation of individuals, thus facilitating rigorous clinical and population-based research.

Evaluation of the World Health Organization-HEARTS hypertension control package in Bangladesh: a quasi-experimental trial.

BACKGROUND: The World Health Organization (WHO) promotes the HEARTS technical package for improving hypertension control worldwide, but its effectiveness has not been rigorously evaluated. OBJECTIVE: To compare hypertension outcomes in clinics implementing HEARTS versus clinics continuing usual hypertension care in rural Bangladesh. METHODS: A matched-pair cluster quasi-experimental trial in Upazila Health Complexes (UHCs; primary healthcare facilities) was conducted in rural Bangladesh. A total of 3935 patients (mean age 52.3 years, 70.5% female) with uncontrolled hypertension (blood pressure (BP) ≥140/90 mm Hg regardless of treatment history) were enrolled: 1950 patients from 7 HEARTS UHCs and 1985 patients from 7 matched usual care UHCs. The primary outcome was systolic BP at 6 months measured at the patient's home; secondary outcomes were diastolic BP, hypertension control rate (<140/90 mm Hg) and loss to follow-up. Multivariable mixed-effects linear and Poisson models were conducted. RESULTS: Baseline mean systolic BP was 158.4 mm Hg in the intervention group and 158.8 mm Hg in the usual care group. At 6 months, 95.5% of participants completed follow-up. Compared with usual care, the intervention significantly lowered systolic BP (-23.7 mm Hg vs -20.0 mm Hg; net difference -3.7 mm Hg (95% CI -5.1 to -2.2)) and diastolic BP (-10.2 mm Hg vs -8.3 mm Hg; net difference -1.9 mm Hg (95% CI -2.7 to -1.1)) and improved hypertension control (62.0% vs 49.7%, net difference 12.3% (95% CI 9.0 to 16.8)). Rate of missed clinic visits was lower in the intervention group (8.8% vs 39.3%, p<0.001). CONCLUSIONS: After WHO-HEARTS package implementation in rural Bangladesh, BP was lowered and hypertension control improved significantly compared with usual care. TRIAL REGISTRATION NUMBER: NCT04992039.

Kappa-carrageenan in a pork-based high-fat diet inhibited lipid bioavailability through interactions with pork protein.

κ-Carrageenan is a soluble dietary fiber widely used in meat products. Although its regulatory effect on glycolipid metabolism has been reported, the underlying mechanism remains unclear. The present study established a pork diet model for in vitro digestion to study how κ-carrageenan affected its digestive behavior and lipid bioavailability. The results revealed that κ-carrageenan addition to a pork-based high-fat diet reduced the rate of lipolysis and increased the number and size of lipid droplets in an in vitro digestion condition. However, κ-carrageenan did not inhibit lipolysis when lipids and κ-carrageenan were mixed directly or with the addition of pork protein. Furthermore, the pork protein in the diet significantly enhanced the inhibitory effect of κ-carrageenan on lipolysis with decreased proteolysis and raised hydrophobicity of protein hydrolysate. Our findings suggest that κ-carrageenan can inhibit dietary lipid bioavailability by interacting with pork protein in meat products or meat-based diets during digestion and indicate the positive role of carrageenan in the food industry to alleviate the excessive accumulation of lipids in the body.

Multi-Functional Lanthanide Metallopolymer: Self-Healing and Photo-Stimuli-Responsive Dual-Emitting Luminescence for Diverse Applications.

Photoluminescent metallopolymers displaying photo-stimuli-responsive properties are emerging as promising materials with versatile applications in photo-rewritable patterns, wearable UV sensors, and optical encryption anti-counterfeiting. However, integrating these materials into practical applications that require fast response times, lightweight qualities, fatigue resistance, and multiple encryption capabilities poses challenges. In this study, luminescent photochromic lanthanide (Ln) metallopolymers with rapid self-healing properties are developed by cross-linking terpyridine (Tpy)- and spiropyran (SP)- functionalized polyurethane chains through Ln-Tpy coordination bonds and H-bonds among polymer chains. The resulting products exhibit a range of intriguing features: i) photo-stimuli responsiveness using spiropyran monomers without additional dopants; ii) dual-emitting performance under UV-light due to Ln-Tpy and open-ring spiropyran moieties; iii) satisfactory mechanical properties and self-healing abilities from polymer chains; iv) multiple control switches for luminescence colors through photostimulation or feed ratio adjustments. Leveraging these attributes, the developed material introduces novel opportunities for light-writing applications, advanced information encryption, UV-sensing wearable devices, and insights into designing multifunctional intelligent materials for the future.

Metabolic shifts during coffee consumption refresh the immune response: insight from comprehensive multiomics analysis.

Coffee, a widely consumed beverage, has shown benefits for human health but lacks sufficient basic and clinical evidence to fully understand its impacts and mechanisms. Here, we conducted a cross-sectional observational study of coffee consumption and a 1-month clinical trial in humans. We found that coffee consumption significantly reshaped the immune system and metabolism, including reduced levels of inflammatory factors and a reduced frequency of senescent T cells. The frequency of senescent T cells and the levels of the senescence-associated secretory phenotype were lower in both long-term coffee consumers and new coffee consumers than in coffee nondrinking subjects, suggesting that coffee has anti-immunosenescence effects. Moreover, coffee consumption downregulated the activities of the The Janus kinase/signal transduction and activator of transcription (JAK/STAT) and mitogen-activated protein kinases (MAPK) signaling pathways and reduced systemic proinflammatory cytokine levels. Mechanistically, coffee-associated metabolites, such as 1-methylxanthine, 3-methylxanthine, paraxanthine, and ceramide, reduced the frequency of senescent CD4+CD57+ T cells in vitro. Finally, in vivo, coffee intake alleviated inflammation and immunosenescence in imiquimod-induced psoriasis-like mice. Our results provide novel evidence of the anti-inflammatory and anti-immunosenescence effects of coffee, suggesting that coffee consumption could be considered a healthy habit.

DRGATAN: Directed relation graph attention aware network for asymmetric drug-drug interaction prediction.

In scenarios involving the treatment of complex or coexisting diseases with multiple drugs, the potential for severe adverse drug reactions in patients necessitates the identification of potential drug-drug interactions (DDIs). Most existing computational methods have not taken into account the asymmetry and relation types of drug interactions caused by the relation information between drugs, which may lead to missing information in embedded learning. Therefore, this paper proposes a directed relation graph attention aware network (DRGATAN) to predict asymmetric drug interactions. DRGATAN leverages an encoder to learn multi-relational role embeddings of drugs across different types of relations. The experimental results show that DRGATAN's performance is superior to recognized advanced methods. The visualization demonstrates the effect of utilizing asymmetric information, and the case analysis validates the reliability of the proposed method. This study provides guidance for predicting asymmetric drug interactions.

Individual and additive-effect relationships of menopausal symptoms and subjective cognitive decline among nurses during menopausal transition: a cross-sectional study.

OBJECTIVE: This study aimed to examine the individual and additive-effect relationships between menopausal symptoms and subjective cognitive decline among nurses during menopausal transition. METHODS: Between February and September 2019, a convenience sampling strategy was used, involving 1,335 Chinese nurses undergoing menopausal transition. A general information survey that included the Subjective Cognitive Decline Scale and the Menopause Rating Scale was completed. Based on a cut-off point of the subjective cognitive decline score of 7.5, the overall sample was divided into mild and severe groups. Propensity score matching was performed to balance covariates of mild and severe subjective cognitive decline. The individual and cumulative effects of menopausal symptoms and subjective cognitive decline were analyzed using binary logistic regression and the Cochran-Armitage trend test, respectively. RESULTS: After propensity score matching, none of the parameters showed significant differences between the groups. Logistic regression analysis revealed that four menopausal symptoms were closely associated with severe subjective cognitive decline. The Cochran-Armitage trend test indicated odds ratios linking the presence of these symptoms with increased severe subjective cognitive impairment. In addition, nurses simultaneously experiencing two or more core menopausal symptoms were over six times more likely to have severe subjective cognitive decline than nurses experiencing none or one core menopausal symptom during menopausal transition. CONCLUSIONS: Individual and additive numbers of menopausal symptoms significantly influenced subjective cognitive decline in nurses during their menopausal transition. These findings suggest that interventions aimed at enhancing the cognitive performance of nurses experiencing menopause should consider menopausal symptoms.

Investigation into the fabrication of plant-based simulant connective tissue utilizing algae polysaccharide-derived hydrogel.

Connective tissue is an important component of meat products that provides support to animal muscles. Hydrogels are considered a promising alternative to connective tissues and simulate actual products by adjusting the gel texture and mouthfeel. This study used soybean protein isolate (SPI), corn starch (CS), konjac glucomannan (KGM), and seaweed powder (SP) as raw materials to examine the effect of different added SP and KGM concentrations on the gel texture. The G' of the gel increased five-fold when the SP and KGM concentration was increased from 1 % to 3 %. The results of mechanical property tests showed that with the addition of SP, the gel hardness increased from 316.00 g to 1827.23 g and the tensile strength increased from 0.027 MPa to 0.089 MPa. Sensory evaluation showed that the samples with 2 % SP and KGM presented the highest overall acceptability score and the most significant similarity to real connective tissue. The connective tissue simulants exhibited excellent water-holding capacity (>90 %), significantly increasing their juiciness. SEM indicated that 2 % KGM addition improved gel network structure stability. The results demonstrate the potential of seaweed polysaccharide-derived hydrogels as connective tissue mimics. This provides a new strategy for the preparation of high mechanical strength hydrogels and lays the foundation for structural diversification of plant-based meat.

A Zn(II) Coordination Polymer for Fluorescent Turn-Off Selective Sensing of Heavy Metal Cation and Toxic Inorganic Anions.

A novel coordination polymer [Zn(atyha)2]n (1) (Hatyha = 2-(2-aminothiazole-4-yl)-2- hydroxyiminoacetic acid) was constructed by hydrothermal reaction of Zn2+ with Hatyha ligand. CP 1 exhibits a 2D (4,4)-connected topological framework with Schläfli symbol of {44·62}, where atyha- anions serve as tridentate ligands, bridging with Zn2+ through carboxylate, thiazole and oxime groups. CP 1 displays a strong ligand-based photoluminescence at 390 nm in the solid state, and remains significantly structurally stable in water. Interestingly, it can be utilized as a fluorescent probe for selective and sensitive sensing of Fe3+, Cr2O72- and MnO4- through the fluorescent turn-off effect with limit of detection (LOD) of 3.66 × 10-6, 2.38 × 10-5 and 2.94 × 10-6 M, respectively. Moreover, the efficient recyclability for detection of Fe3+ and Cr2O72- is better than that for MnO4-. The mechanisms of fluorescent quenching involve reversible overlap of UV-Vis absorption bands of the analytes (Fe3+, Cr2O72- and MnO4-) with fluorescence excitation and emission bands for CP 1, respectively.

Acrosin activity negatively influences the cumulative live birth rate in patients undergoing IVF treatment.

RESEARCH QUESTION: Is acrosin activity related to cumulative live birth rate (CLBR) over 1 year after IVF, intracytoplasmic sperm injection (ICSI) treatment or both? DESIGN: Retrospective monocentric cohort study of 5704 couples who started IVF/ICSI treatments between 2016 and 2021. Acrosin activity was determined by a modified Kennedy method using a commercial kit. Patients were divided into two groups according to their acrosin activity: below 25 µIU/106 spermatozoa; and an acrosin activity 25 µIU/106 spermatozoa or above. Primary outcome was the CLBR, defined as an ongoing pregnancy leading to live birth that had arisen from all embryo transfers carried out within 1 year after the first ovum retrieval. Both conservative and optimistic methods were used for estimating CLBRs. RESULTS: The CLBRs of patients with an acrosin activity below 25 µIU/106 spermatozoa were found to be significantly lower than those of patients with an acrosin activity 25 µIU/106 spermatozoa or above by conservative (48.5% versus 55.4%, P = 0.02) and optimistic (63.7% versus 70.3%, P = 0.047) methods after adjusting for confounders. When acrosin activity was regarded as a continuous variable, significant negative relationships between acrosin activity and CLBR were identified in subgroups: young couples (men and women aged younger than 30 years) and couples from whom no more than 10 eggs were retrieved. CONCLUSION: Low acrosin activity levels were correlated with decreasing CLBRs over 1 year. These findings suggest that acrosin activity can be used as a predictor for CLBRs before starting IVF/ICSI treatment to enhance the effectiveness of counselling.

Aptamer-Based DNA Allosteric Switch for Regulation of Protein Activity.

Allostery is a fundamental way to regulate the function of biomolecules playing crucial roles in cell metabolism and proliferation and is deemed the second secret of life. Given the limited understanding of the structure of natural allosteric molecules, the development of artificial allosteric molecules brings a huge opportunity to transform the allosteric mechanism into practical applications. In this study, the concept of bionics is introduced into the design of artificial allosteric molecules and an allosteric DNA switch with an activity site and an allosteric site based on two aptamers for selective inhibition of thrombin activity. Compared with the single aptamer, the allosteric switch possesses a significantly enhanced inhibition ability, which can be precisely regulated by converting the switch states. Moreover, the dynamic allosteric switch is further subjected to the control of the DNA threshold circuit for realizing automatic concentration determination and activity inhibition of thrombin. These compelling results confirm that this allosteric switch equipped with self-sensing and information-processing modules puts a new slant on the research of allosteric mechanisms and further application of allosteric tactics in chemical and biomedical fields.

Overactive bladder and cognitive impairment in middle-aged women: A cross-sectional study.

BACKGROUND: Overactive bladder (OAB) is a common condition in middle-aged and older women. It has been reported to be potentially linked to cognitive decline, particularly in older adults. This study investigated the association between OAB symptoms and cognitive impairment in middle-aged women. MATERIALS AND METHODS: This cross-sectional study had a sample of 1652 women (mean age 49.3 ± 2.8 years) who were not taking medication for either urinary tract infection or OAB. OAB symptoms and cognitive function were evaluated by self-administered questionnaires: the Overactive Bladder Symptom Score and the Alzheimer's disease 8. Logistic regression models estimated prevalence ratios (PRs) with 95 % confidence intervals (CI) for cognitive impairment according to the presence/absence of OAB. Mediation analyses assessed the impact of poor sleep quality on this association. RESULTS: Cognitive impairment was more prevalent in women with OAB than in those without OAB (multivariable-adjusted PR: 1.88 [95 % CI: 1.52-2.24]). Women experiencing nocturia (≥twice a night), urinary urgency at least once a week, and urgency urinary incontinence at least once a week had multivariable-adjusted PRs (95 % CI) for cognitive impairment of 2.08 (1.50-2.65), 2.12 (1.66-2.58), and 1.75 (1.17-2.34), respectively. Poor sleep quality mediated 10.81 % [95 % CI: 4.55-19.44 %] of the relationship between OAB and cognitive impairment. CONCLUSIONS: Among middle-aged women not taking OAB medications, OAB symptoms were associated with cognitive impairment, partly because of poor sleep quality. Further research is needed to determine whether early screening of patients with OAB can help identify those susceptible to cognitive impairment associated with OAB medication and if preventive measures should be targeted at this group.

Salt ions improve soybean protein isolate/curdlan complex fat substitutes: Effect of molecular interactions on freeze-thaw stability.

Although emulsion gels show significant potential as fat substitutes, they are vulnerable to degreasing, delamination, and other undesirable processes during freezing, storage, and thawing, leading to commercial value loss in terms of juiciness, flavor, and texture. This study investigated the gel strength and freeze-thaw stability of soybean protein isolate (SPI)/curdlan (CL) composite emulsion gels after adding sodium chloride (NaCl). Analysis revealed that adding low salt ion concentrations promoted the hardness and water-holding capacity (WHC) of fat substitutes, while high levels displayed an inhibitory effect. With 40 mM NaCl as the optimum concentration, the hardness increased from 259.33 g (0 mM) to 418.67 g, the WHC increased from 90.59 % to 93.18 %, exhibiting good freeze-thaw stability. Confocal laser scanning microscopy (CLSM) and particle size distribution were used to examine the impact of salt ion concentrations on protein particle aggregation and the damaging effect of freezing and thawing on the proteoglycan complex network structure. Fourier-transform infrared spectroscopy (FTIR) and protein solubility evaluation indicated that the composite gel network structure consisted of covalent contacts between the proteoglycan molecules and hydrogen bonds, playing a predominant role in non-covalent interaction. This study showed that the salt ion concentration in the emulsion gel affected its molecular interactions.