Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

Manual acupuncture ameliorates inflammatory pain by upregulating adenosine A3 receptor in complete Freund's adjuvant-induced arthritis rats.

BACKGROUND: Adenosine A3 receptor (A3R) exerts analgesic, anti-inflammatory, and anti-nociceptive effects. In this study, we determined the analgesic mechanism of manual acupuncture (MA) in rats with complete Freund's adjuvant (CFA)-induced arthritis and explored whether MA ameliorates inflammation in these rats by upregulating A3R. METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into the following groups: Control, CFA, CFA + MA, CFA + sham MA, CFA + MA + DMSO, CFA + MA + IB-MECA, and CFA + MA + Reversine groups. The arthritis rat model was induced by injecting CFA into the left ankle joints. Thereafter, the rats were subjected to MA (ST36 acupoint) for 3 days. The clinical indicators paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and open field test (OFT) were used to determine the analgesic effect of MA. In addition, to explore the effect of A3R on inflammation after subjecting arthritis rats to MA, IB-MECA (A3R agonist) and Reversine (A3R antagonist) were injected into ST36 before MA. RESULTS: MA ameliorated the pathological symptoms of CFA-induced arthritis, including the pain indicators PWL and PWT, number of rearing, total ambulatory distance, and activity trajectory. Furthermore, after MA, the mRNA and protein expression of A3R was upregulated in CFA-induced arthritis rats. In contrast, the protein levels of TNF-α, IL-1ß, Rap1, and p-p65 were downregulated after MA. Interestingly, the A3R agonist and antagonist further downregulated and upregulated inflammatory cytokine expression, respectively, after MA. Furthermore, the A3R antagonist increased the degree of ankle swelling after MA. CONCLUSION: MA can alleviate inflammatory pain by inhibiting the NF-κB signaling pathway via upregulating A3R expression of the superficial fascia of the ST36 acupoint site in CFA-induced arthritis rats.

The Relationship between Indoor and Outdoor Fine Particulate Matter in a High-Rise Building in Chicago Monitored by PurpleAir Sensors.

In urban areas like Chicago, daily life extends above ground level due to the prevalence of high-rise buildings where residents and commuters live and work. This study examines the variation in fine particulate matter (PM2.5) concentrations across building stories. PM2.5 levels were measured using PurpleAir sensors, installed between 8 April and 7 May 2023, on floors one, four, six, and nine of an office building in Chicago. Additionally, data were collected from a public outdoor PurpleAir sensor on the fourteenth floor of a condominium located 800 m away. The results show that outdoor PM2.5 concentrations peak at 14 m height, and then decline by 0.11 µg/m3 per meter elevation, especially noticeable from midnight to 8 a.m. under stable atmospheric conditions. Indoor PM2.5 concentrations increase steadily by 0.02 µg/m3 per meter elevation, particularly during peak work hours, likely caused by greater infiltration rates at higher floors. Both outdoor and indoor concentrations peak around noon. We find that indoor and outdoor PM2.5 are positively correlated, with indoor levels consistently remaining lower than outside levels. These findings align with previous research suggesting decreasing outdoor air pollution concentrations with increasing height. The study informs decision-making by community members and policymakers regarding air pollution exposure in urban settings.

Construction of a nomogram for predicting compensated cirrhosis with Wilson's disease based on non-invasive indicators.

BACKGROUND: Wilson's disease (WD) often leads to liver fibrosis and cirrhosis, and early diagnosis of WD cirrhosis is essential. Currently, there are few non-invasive prediction models for WD cirrhosis. The purpose of this study is to non-invasively predict the occurrence risk of compensated WD cirrhosis based on ultrasound imaging features and clinical characteristics. METHODS: A retrospective analysis of the clinical characteristics and ultrasound examination data of 102 WD patients from November 2018 to November 2020 was conducted. According to the staging system for WD liver involvement, the patients were divided into a cirrhosis group (n = 43) and a non-cirrhosis group (n = 59). Multivariable logistic regression analysis was used to identify independent influencing factors for WD cirrhosis. A nomogram for predicting WD cirrhosis was constructed using R analysis software, and validation of the model's discrimination, calibration, and clinical applicability was completed. Due to the low incidence of WD and the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model. RESULTS: Acoustic Radiation Force Impulse (ARFI), portal vein diameter (PVD), and serum albumin (ALB) are independent factors affecting WD cirrhosis. A nomogram for WD cirrhosis was constructed based on these factors. The area under the ROC curve (AUC) of the model's predictive ability is 0.927 (95% CI: 0.88-0.978). As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Clinical decision curve analysis shows that the model has high clinical practical value. ROC curve analysis of the model's rationality indicates that the model's AUC is greater than the AUC of using ALB, ARFI, and PVD alone. CONCLUSION: The nomogram model constructed based on ARFI, PVD, and ALB can serve as a non-invasive tool to effectively predict the risk of developing WD cirrhosis.

Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis: A case report and review of literature.

BACKGROUND: Venous thromboembolism significantly contributes to patient deterioration and mortality. Management of its etiology and anticoagulation treatment is intricate, necessitating a comprehensive consideration of various factors, including the bleeding risk, dosage, specific anticoagulant medications, and duration of therapy. Herein, a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience. CASE SUMMARY: An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d. Considering her medical history and relevant post-admission investigations, it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors, including multiple primary malignant tumors, iliac venous compression syndrome, previous novel coronavirus infection, and inadequate treatment for prior thrombotic events. However, the selection of appropriate anticoagulant medications, determination of optimal drug dosages, and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia, decreased quantitative fibrinogen levels, and renal insufficiency. CONCLUSION: Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis. Individualized anticoagulation therapy is required for complex thrombosis.

Exogenous insulin autoimmune syndrome: A case report and review of literature.

BACKGROUND: Insulin autoimmune syndrome (IAS) is a severe manifestation of spontaneous hypoglycemia. It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies (IAAs), which are induced by endogenous insulin circulating in the bloodstream. It is distinguished by recurring instances of spontaneous hypoglycemia, the presence of IAA within the body, a substantial elevation in serum insulin levels, and an absence of prior exogenous insulin administration. Nevertheless, recent studies show that both conventional insulin and its analogs can induce IAS episodes, giving rise to the notion of non-classical IAS. Therefore, more attention should be paid to these diseases. CASE SUMMARY: In this case report, we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder. Upon symptom onset, the patient exhibited Whipple's triad (including hypoglycemia, blood glucose level less than 2.8 mmol/L during onset, and rapid relief of hypoglycemic symptoms after glucose administration). Concurrently, his serum insulin level was significantly elevated, which contradicted his C-peptide levels. After a comprehensive examination, the patient was diagnosed with exogenous insulin autoimmune syndrome. Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset, it was presumed that non classical IAS was induced by this condition. The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches. CONCLUSION: The occurrence of non-classical IAS is associated with exogenous insulin or its analogs, as well as with sulfhydryl drugs. Symptoms can be effectively alleviated through the discontinuation of relevant medications, administration of hormones or immunosuppressants, plasma exchange, and lifestyle adjustments.

Effects of movement training based on rhythmic auditory stimulation in cognitive impairment: a meta-analysis of randomized controlled clinical trial.

Objective: According to the World Alzheimer's Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment. Methods: Data from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator. Results: A total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p < 0.05)], attention [MD = -1.86, 95%CI (-3.53, -0.19), (p < 0.05)], memory [MD = 0.71, 95%CI (0.33, 1.09), (p < 0.01)], and executive function [MD = -0.23, 95% CI (-0.44, -0.02), (p < 0.05)]. Secondary outcomes indicated no statistically significant differences in verbal fluency [MD = -0.51, 95%CI (-1.30, 0.27), (p = 0.20)], while depression [MD = -0.29, 95% CI (-0.42, -0.16), (p < 0.01)] and anxiety [MD = 0.19, 95% CI (0.06, 0.32), (p < 0.01)] exhibited statistically significant differences. The GRADEpro GDT online tool assessed the quality of evidence for the outcome measures, revealing one low-quality outcome, two moderate-quality outcomes, and one high-quality outcome in this review. Conclusion: This study shows that RASMT can improve the general cognitive status, memory, attention and executive function of patients with cognitive impairment. The quality of evidence revealed that MMSE was low, attention and memory were moderate, and executive function was high. The RAMST program (type of exercise: play percussion instruments; time of exercise: 30-60 min; frequency of exercise: 2-3 times/week; duration of exercise: more than 12 weeks) was proved to be more effective in improving cognitive function. However, the sample size is relatively insufficient, the future needs further study. Systematic review registration: PROSPERO, identifier: CRD42023483561.

The effect of T cell aging on the change of human tissue structure.

The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body's immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.

Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the long-term effectiveness of Huangqi (Radix Astragali Mongolici, HQ)-based Traditional Chinese Medicine (TCM) in the treatment of diabetic peripheral neuropathy (DPN). METHODS: Nine databases were searched to retrieve available randomized controlled trials that compared HQ-based TCM and Western Medicines in the treatment of DPN. The methodological quality of the included studies was assessed using the Cochrane bias risk tool, and RevMan 5.4 was used for data analysis. The effect estimates of interest were risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM [RR = 1.30, 95% CI (1.21, 1.40), P < 0.000 01] or HQ-based TCM combined with Western Medicines [RR = 1.25, 95% CI (1.19, 1.31), P < 0.000 01] exhibited higher total efficacy rates than individuals who received Western Medicine alone. The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores [MD =－1.50, 95% CI (－1.83, －1.17), P < 0.000 01], and reduced serum interleukin 6 [SMD = －0.57, 95% CI (－0.87, －0.27), P = 0.0002] and tumor necrosis factors-α levels [SMD = －0.60, 95% CI (－0.95, －0.25), P = 0.0009]. In addition, both HQ-based TCM and HQ-based TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone. In terms of blood lipids, oxidative stress and adverse drug reactions, there were no significant differences between the HQ-based TCM groups and the Western Medicine control group. CONCLUSION: The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN, although further well-designed RCTs are required to validate these findings.

Dual inhibition of CYP17A1 and HDAC6 by abiraterone-installed hydroxamic acid overcomes temozolomide resistance in glioblastoma through inducing DNA damage and oxidative stress.

Glioblastoma (GBM) is a highly aggressive and treatment-resistant brain tumor, necessitating novel therapeutic strategies. In this study, we present a mechanistic breakthrough by designing and evaluating a series of abiraterone-installed hydroxamic acids as potential dual inhibitors of CYP17A1 and HDAC6 for GBM treatment. We established the correlation of CYP17A1/HDAC6 overexpression with tumor recurrence and temozolomide resistance in GBM patients. Compound 12, a dual inhibitor, demonstrated significant anti-GBM activity in vitro, particularly against TMZ-resistant cell lines. Mechanistically, compound 12 induced apoptosis, suppressed recurrence-associated genes, induced oxidative stress and initiated DNA damage response. Furthermore, molecular modeling studies confirmed its potent inhibitory activity against CYP17A1 and HDAC6. In vivo studies revealed that compound 12 effectively suppressed tumor growth in xenograft and orthotopic mouse models without inducing significant adverse effects. These findings highlight the potential of dual CYP17A1 and HDAC6 inhibition as a promising strategy for overcoming treatment resistance in GBM and offer new hope for improved therapeutic outcomes.

A latent profile analysis of resilience and their relation to differences in sleep quality in patients with lung cancer.

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.

Electrolyte Chemistry toward Ultrawide-Temperature (-25 to 75 °C) Sodium-Ion Batteries Achieved by Phosphorus/Silicon-Synergistic Interphase Manipulation.

All-weather operation is considered an ultimate pursuit of the practical development of sodium-ion batteries (SIBs), however, blocked by a lack of suitable electrolytes at present. Herein, by introducing synergistic manipulation mechanisms driven by phosphorus/silicon involvement, the compact electrode/electrolyte interphases are endowed with improved interfacial Na-ion transport kinetics and desirable structural/thermal stability. Therefore, the modified carbonate-based electrolyte successfully enables all-weather adaptability for long-term operation over a wide temperature range. As a verification, the half-cells using the designed electrolyte operate stably over a temperature range of -25 to 75 °C, accompanied by a capacity retention rate exceeding 70% even after 1700 cycles at 60 °C. More importantly, the full cells assembled with Na3V2(PO4)2O2F cathode and hard carbon anode also have excellent cycling stability, exceeding 500 and 1000 cycles at -25 to 50 °C and superb temperature adaptability during all-weather dynamic testing with continuous temperature change. In short, this work proposes an advanced interfacial regulation strategy targeted at the all-climate SIB operation, which is of good practicability and reference significance.

Clinical benefit analysis of PD-1 inhibitors in patients with advanced, recurrent or metastatic cervical cancer: a meta-analysis and systematic review.

Purpose: This study aims to comprehensively evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) in patients with advanced, recurrent, or metastatic cervical cancer (ARMCC) and identify the population that may benefit the most. Methods: We conducted a search of PubMed, EMBASE, and the Cochrane Collaboration Library from their inception to September 2023. We extracted and analyzed the results related to the efficacy and safety of PD-1 in patients with ARMCC. The primary endpoints included the overall objective response rate (ORR) and adverse events (AEs), while the secondary endpoints encompassed the 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, as well as OS and PFS. We used a random effects model to conduct a meta-analysis on single-group rates, and the Mantel-Haenszel method was utilized to compare the ORR and the incidence of AEs. Results: Our study included a total of 21 trials involving 2,097 patients. The ORR of the combination of PD-1 inhibitors with chemotherapy was 56.36%, the combination of PD-1 inhibitors with anti-angiogenic agents was 38.72%, the combination of PD-1 inhibitors with Cytotoxic T-lymphocyte antigen 4 inhibitors was 25.60%, and PD-1 inhibitor monotherapy was 15.99%. The subgroup analysis showed that the group of patients with squamous cell carcinoma (SCC) exhibited a significantly higher ORR compared to the non-SCC group in patients who received PD-1 inhibitors combined with other anti-tumor drugs (Odds Ratio =2.43, P=0.002). Additionally, the group of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 exhibited a significantly higher ORR compared to the PD-L1 CPS <1 group in patients who received PD-1 inhibitor monotherapy (OR=4.14, P=0.02). PD-1 inhibitor monotherapy or PD-1 inhibitors combined with chemotherapy did not significantly increase the incidence of all grades of adverse events (Relative Risk=0.99, p=0.788) or the incidence of serious adverse events (RR=0.99, p=0.788) compared to chemotherapy alone. Conclusion: PD-1 inhibitors demonstrate outstanding efficacy in the treatment of patients with ARMCC. Patients with SCC may benefit more from treatments including PD-1 inhibitors in combination with other anti-tumor drugs, and PD-L1 CPS ≥1 can be considered a favorable indicator of immune therapy response. Importantly, the use of PD-1 inhibitor monotherapy or PD-1 inhibitors in combination with chemotherapy did not lead to an increased incidence of AEs compared with chemotherapy alone, indicting safety during treatment. Systematic Review Registration: PROSPERO (CRD42023457945).

Low-Density Lipoprotein Cholesterol to Triglyceride Ratio and Clinical Outcomes after Acute Ischaemic Stroke or Transient Ischaemic Attack.

AIMS: Studies showed that low-density lipoprotein cholesterol (LDL-C) to triglyceride (TG) ratio could be used as a predictive parameter of low-density lipoprotein oxidation in vivo and the level of small dense LDL-C. However, whether LDL-C/TG ratio is associated with stroke prognosis remains unclear. We investigated the associations of LDL-C/TG ratio with outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attacks (TIA) and explored whether it produced more predictive value than LDL-C and TG. METHODS: Data were derived from the Third China National Stroke Registry (CNSR-III). Multivariable Cox regression for stroke recurrence, composite vascular events and all-cause death and logistic regression for the poor functional outcome (modified Rankin Scale score 3-6) were used. RESULTS: A total of 14123 patients were included. After adjusting for confounding factors, quartile 4 of LDL-C/TG ratio was associated with an increased risk of recurrent stroke (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.03-1.56), composite vascular events (HR,1.23; 95% CI, 1.00-1.52), death (HR,1.70; 95% CI, 1.13-2.54) and poor functional outcome (odds ratio, 1.34; 95% CI, 1.12-1.61) at 3 months follow-up compared with quartile 1. We also found that quartile 4 of LDL-C and TG was positively and negatively associated with poor functional outcome at 3 months, respectively. LDL-C/TG ratio performed better than LDL-C or TG in predicting clinical outcomes. CONCLUSIONS: LDL-C/TG ratio was associated with the risk of stroke recurrence, composite vascular events, death and poor functional outcome in patients with AIS or TIA.

Y chromosome polymorphisms contribute to an increased risk of non-obstructive azoospermia: a retrospective study of 32,055 Chinese men.

PURPOSE: To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes. METHODS: The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes. RESULTS: The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528). CONCLUSIONS: Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.

First-in-Class Dual EZH2-HSP90 Inhibitor Eliciting Striking Antiglioblastoma Activity In Vitro and In Vivo.

Structural analysis of tazemetostat, an FDA-approved EZH2 inhibitor, led us to pinpoint a suitable site for appendage with a pharmacophoric fragment of second-generation HSP90 inhibitors. Resultantly, a magnificent dual EZH2/HSP90 inhibitor was pinpointed that exerted striking cell growth inhibitory efficacy against TMZ-resistant Glioblastoma (GBM) cell lines. Exhaustive explorations of chemical probe 7 led to several revelations such as (i) compound 7 increased apoptosis/necrosis-related gene expression, whereas decreased M phase/kinetochore/spindle-related gene expression as well as CENPs protein expression in Pt3R cells; (ii) dual inhibitor 7 induced cell cycle arrest at the M phase; (iii) compound 7 suppressed reactive oxygen species (ROS) catabolism pathway, causing the death of TMZ-resistant GBM cells; and (iv) compound 7 elicited substantial in vivo anti-GBM efficacy in experimental mice xenografted with TMZ-resistant Pt3R cells. Collectively, the study results confirm the potential of dual EZH2-HSP90 inhibitor 7 as a tractable anti-GBM agent.

Nutrition intake modifies the association between pulmonary function and cognitive performance among elderly Americans from NHANES 2011-2012.

PURPOSE: Nutrition intake is one of the modifiable risk factors for cognitive decline. Whether energy and protein intakes alter the association between pulmonary function (PF) and cognition has not been studied. METHODS: We made use of information from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011-2012. PF measures, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), were calculated, whereas cognitive function was assessed through four tests: the Immediate Recall test (IRT), the Delayed Recall test (DRT), the Animal Fluency test (AFT) and the Digit Symbol Substitution test (DSST). Energy and protein intakes were measured using the 24-h dietary recall method. Weighted generalized linear regression was performed upon adjustment for covariates. Further interaction analyses were conducted to investigate the effect of energy and protein intakes on the association between PF and cognition. RESULTS: We finally included 803 participants aged ≥ 60 years (54.4% female, weighted value). After adjusting for covariates, multiple measures (including FEV1, FVC, PEF, and composite PF) were all positively associated with better global cognition and the DSST score (P < 0.05). A stronger positive association between the DSST score and FEV1 (P for interaction = 0.001), FVC (P for interaction = 0.004), PEF (P for interaction = 0.003), and composite PF (P for interaction = 0.001) in lower energy intake. Similar results were observed in lower protein intake (all P for interaction < 0.05). CONCLUSION: Higher PF was independently associated with improved specific components of cognitive function (i.e., the DSST score). The positive association between PF and the DSST score was stronger in individuals with lower energy and protein intakes.

Dynamic Li+ Capture through Ligand-Chain Interaction for the Regeneration of Depleted LiFePO4 Cathode.

After application in electric vehicles, spent LiFePO4 (LFP) batteries are typically decommissioned. Traditional recycling methods face economic and environmental constraints. Therefore, direct regeneration has emerged as a promising alternative. However, irreversible phase changes can significantly hinder the efficiency of the regeneration process owing to structural degradation. Moreover, improper storage and treatment practices can lead to metamorphism, further complicating the regeneration process. In this study, a sustainable recovery method is proposed for the electrochemical repair of LFP batteries. A ligand-chain Zn-complex (ZnDEA) is utilized as a structural regulator, with its ─NH─ group alternatingly facilitating the binding of preferential transition metal ions (Fe3+ during charging and Zn2+ during discharging). This dynamic coordination ability helps to modulate volume changes within the recovered LFP framework. Consequently, the recovered LFP framework can store more Li-ions, enhance phase transition reversibility between LFP and FePO4 (FP), modify the initial Coulombic efficiency, and reduce polarization voltage differences. The recovered LFP cells exhibit excellent capacity retention of 96.30% after 1500 cycles at 2 C. The ligand chain repair mechanism promotes structural evolution to facilitate ion migration, providing valuable insights into the targeted ion compensation for environmentally friendly recycling in practical applications.

Epstein-Barr virus-based prognostic model in nodular sclerosis classic Hodgkin lymphoma.

The role of Epstein-Barr virus (EBV) in lymphoma cells of nodular sclerosis classic Hodgkin lymphoma (NScHL) is controversial. Our aim was to explore this and establish a clinically feasible model for risk stratification. We interrogated data from 542 consecutive subjects with NScHL receiving ABVD therapy and demonstrated EBV-infection in their lymphoma cells with EBV-encoded small RNAs (EBERs) in situ hybridization. Subjects were divided into training and validation datasets. As data from the training dataset suggested EBERs-positivity was the only independent prognostic factor for both progression-free survival (PFS) and overall survival (OS), we developed corresponding prognostic models based on it. Our models showed excellent performance in both training and validation cohort. These data indicate the close association of EBV infection and the outcomes of persons with NScHL receiving ABVD. Additionally, our newly developed models should help physicians estimate prognosis and select individualized therapy.

An injectable collagen peptide-based hydrogel with desirable antibacterial, self-healing and wound-healing properties based on multiple-dynamic crosslinking.

Conventional collagen-based hydrogels as wound dressing materials are usually lack of antibacterial activity and easily broken when encountering external forces. In this work, we developed a collagen peptide-based hydrogel as a wound dressing, which was composed of adipic acid dihydrazide functionalized collagen peptide (Col-ADH), oxidized dextran (ODex), polyvinyl alcohol (PVA) and borax via multiple-dynamic reversible bonds (acylhydrazone, amine, borate ester and hydrogen bonds). The injectable hydrogel exhibited satisfactory self-healing ability, antibacterial activity, mechanical strength, as well as good biocompatibility and biodegradability. In vivo experiments demonstrated the rapid hemostasis, accelerated cell migration, and promoted wound healing capacities of the hydrogel. These results indicate that the multifunctional collagen peptide-based hydrogel has great potentials in the field of wound dressings.