Glycolysis and chemoresistance in acute myeloid leukemia.

While traditional high-dose chemotherapy can effectively prolong the overall survival of acute myeloid leukemia (AML) patients and contribute to better prognostic outcomes, the advent of chemoresistance is a persistent challenge to effective AML management in the clinic. The therapeutic resistance is thought to emerge owing to the heterogeneous and adaptable nature of tumor cells when exposed to exogenous stimuli. Recent studies have focused on exploring metabolic changes that may afford novel opportunities to treat AML, with a particular focus on glycolytic metabolism. The Warburg effect, a hallmark of cancer, refers to metabolism of glucose through glycolysis under normoxic conditions, which contributes to the development of chemoresistance. Despite the key significance of this metabolic process in the context of malignant transformation, the underlying molecular mechanisms linking glycolysis to chemoresistance in AML remain incompletely understood. This review offers an overview of the current status of research focused on the relationship between glycolytic metabolism and AML resistance to chemotherapy, with a particular focus on the contributions of glucose transporters, key glycolytic enzymes, signaling pathways, non-coding RNAs, and the tumor microenvironment to this relationship. Together, this article will provide a foundation for the selection of novel therapeutic targets and the formulation of new approaches to treating AML.

NOX1-mediated oxidative stress induces chondrocyte ferroptosis by inhibiting the Nrf2/HO-1 pathway.

Osteoarthritis (OA) is a common joint disease associated with the aging of the population, and it reduces the quality of life of patients. It is characterized by the destruction of articular cartilage and the secretion of inflammatory cytokines. Owing to the unclear pathogenesis of OA, current treatment methods have significant limitations. Oxidative stress has been revealed to play an important role in the development of OA. Our experiments indicated that the levels of GSH decreased and the level of MDA increased in chondrocytes, which induced ferroptosis in chondrocytes in OA. We also revealed that ferroptosis was the main mechanism of cartilage destruction caused by the addition of the ferroptosis activator erastin and the ferroptosis inhibitor ferrostatin-1. NOX1 is the main modulator of oxidative stress by increasing the generation of reactive oxidative species (ROS). We suppressed the expression of NOX1 in chondrocytes through cell transfection. The expression of collagen II and MMP13, and the secretion of IL-1ß and TNF-α were reversed. An increase in the mitochondrial membrane potential and a decrease in the level of intracellular ROS indicate an improvement in oxidative damage. Additionally, we determined the effect of the Nrf2/HO-1 pathway on NOX1-mediated chondrocyte injury. We found that NOX1 inhibited the expression of Nrf2/HO-1, but the activation of Nrf2 improved the oxidative damage to chondrocytes in vivo and vitro. This study revealed that NOX1-mediated oxidative stress induces chondrocyte ferroptosis by inhibiting the Nrf2/HO-1 pathway. Our findings contribute to revealing the pathogenesis of OA, providing targets for drug design and optimizing the clinical treatment of OA.

Exosomal lncRNA HCP5 derived from human bone marrow mesenchymal stem cells improves chronic periodontitis by miR-24-3p/HO1/P38/ELK1 pathway.

Objective: The present study aimed to explore the function of human bone marrow mesenchymal stem cells (hBMMSCs)-derived exosomal long noncoding RNA histocompatibility leukocyte antigen complex P5 (HCP5) in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to improve chronic periodontitis (CP). Methods: Exosomes were extracted from hBMMSCs. Alizarin red S staining was used to detect mineralised nodules. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure HCP5 and miR-24-3p expression. The mRNA and protein levels of alkaline phosphatase (ALP), osteocalcin, osterix, runt-related transcription factor 2, bone morphogenetic protein 2, osteopontin, fibronectin, collagen 1, heme oxygenase 1 (HO1), P38, and ETS transcription factor ELK1 (ELK1) were detected using RT-qPCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the HO1 and carbon monoxide concentrations. Heme, biliverdin, and Fe2+ levels were determined using detection kits. Micro-computed tomography, hematoxylin and eosin staining, ALP staining, tartrate-resistant acid phosphatase staining, ELISA, and RT-qPCR were conducted to evaluate the effect of HCP5 on CP mice. Dual luciferase, RNA immunoprecipitation, and RNA pulldown experiments were performed to identify the interactions among HCP5, miR-24-3p, and HO1. Results: The osteogenic ability of hPDLSCs significantly increased when co-cultured with hBMMSCs or hBMMSCs exosomes. Overexpression of HCP5 and HO1 in hBMMSCs exosomes promoted the osteogenic differentiation of hPDLSCs, and knockdown of HCP5 repressed the osteogenic differentiation of hPDLSCs. HCP5 knockdown enhanced the inflammatory response and repressed osteogenesis in CP mice. MiR-24-3p overexpression diminished the stimulatory effect of HCP5 on the osteogenic ability of hPDLSCs. Mechanistically, HCP5 acted as a sponge for miR-24-3p and regulated HO1 expression, and HO1 activated the P38/ELK1 pathway. Conclusion: HBMMSCs-derived exosomal HCP5 promotes the osteogenic differentiation of hPDLSCs and alleviates CP by regulating the miR-24-3p/HO1/P38/ELK1 signalling pathway.

A pilot study of optical coherence tomography-guided transbronchial biopsy in peripheral pulmonary lesions.

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPLs) remains challenging. Despite advancements in guided transbronchial biopsy (TBB) techniques, diagnostic yields haven't reached ideal levels. Optical coherence tomography (OCT) has been developed for application in pulmonary diseases, yet no data existed evaluating effectiveness in diagnosing PPLs. RESEARCH DESIGN AND METHODS: This study included patients who underwent OCT and radial endobronchial ultrasound (R-EBUS)-guided TBB. OCT and R-EBUS imaging features were analyzed to differentiate between benign and malignant PPLs and subtypes of lung cancer. RESULTS: A total of 89 patients were included in this study. The diagnostic yield of OCT-guided TBB stood at 56.18%, R-EBUS-guided TBB was 83.15% (P<0.01). The accuracy of OCT to judge the nature of lesions was 92.59%, while R-EBUS was 77.92%. The accuracy of OCT in predicting squamous carcinoma (SCC) and adenocarcinoma were both 91.30%. CONCLUSIONS: Although the diagnostic yield of OCT-guided TBB fell short of that achieved by R-EBUS, OCT possessed the capability to judge the nature of lesions and guide the pathological classification of malignant lesions. Further extensive prospective studies are necessary to thoroughly assess the characteristics of this procedure. CLINICAL TRIAL REGISTRATION: https://register.clinicaltrials.gov/ identifier is NCT06419114.

Brain region-specific action of ketamine as a rapid antidepressant.

Ketamine has been found to have rapid and potent antidepressant activity. However, despite the ubiquitous brain expression of its molecular target, the N-methyl-d-aspartate receptor (NMDAR), it was not clear whether there is a selective, primary site for ketamine's antidepressant action. We found that ketamine injection in depressive-like mice specifically blocks NMDARs in lateral habenular (LHb) neurons, but not in hippocampal pyramidal neurons. This regional specificity depended on the use-dependent nature of ketamine as a channel blocker, local neural activity, and the extrasynaptic reservoir pool size of NMDARs. Activating hippocampal or inactivating LHb neurons swapped their ketamine sensitivity. Conditional knockout of NMDARs in the LHb occluded ketamine's antidepressant effects and blocked the systemic ketamine-induced elevation of serotonin and brain-derived neurotrophic factor in the hippocampus. This distinction of the primary versus secondary brain target(s) of ketamine should help with the design of more precise and efficient antidepressant treatments.

Inhibition of ANGPTL8 protects against diabetes-associated cognitive dysfunction by reducing synaptic loss via the PirB signaling pathway.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Investigation of METTL3 as an inhibitor of kanamycin-induced ototoxicity via stress granule formation.

Background: Methyltransferase-like 3 (METTL3), a component of the N6-methyladenosine (m6A) methyltransferase family, exhibits significant expression in HEI-OC1 cells and cochlear explants. Aminoglycoside antibiotics, known for their ototoxic potential, frequently induce irreversible auditory damage in hair cells, predominantly through oxidative stress mechanisms. However, the specific role of METTL3 in kanamycin-induced hair cell loss remains unclear. Objective: This study aims to elucidate the mechanisms by which METTL3 contributes to kanamycin-induced ototoxicity. Methods and Results: In vivo experiments demonstrated a notable reduction in METTL3 expression within cochlear explants following kanamycin administration, concomitant with the formation of stress granules (SGs). Similarly, a 24-hour kanamycin treatment led to decreased METTL3 expression and induced SG formation both in HEI-OC1 cells and neonatal cochlear explants, corroborating the in vivo observations. Lentivirus-mediated transfection was employed to overexpress and knockdown METTL3 in HEI-OC1 cells. Knockdown of METTL3 resulted in increased reactive oxygen species (ROS) levels and apoptosis induced by kanamycin, while concurrently reducing SG formation. Conversely, overexpression of METTL3 attenuated ROS generation, decreased apoptosis rates, and promoted SG formation induced by kanamycin. Therefore, METTL3-mediated SG formation presents a promising target for mitigating kanamycin-induced ROS generation and the rate of apoptosis. Conclusion: This finding indicates that METTL3-mediated SG formation holds potential in mitigating kanamycin-induced impairments in cochlear hair cells by reducing ROS formation and apoptosis rates.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing's syndrome.

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.

Fiber-optic seismic sensing of vadose zone soil moisture dynamics.

Vadose zone soil moisture is often considered a pivotal intermediary water reservoir between surface and groundwater in semi-arid regions. Understanding its dynamics in response to changes in meteorologic forcing patterns is essential to enhance the climate resiliency of our ecological and agricultural system. However, the inability to observe high-resolution vadose zone soil moisture dynamics over large spatiotemporal scales hinders quantitative characterization. Here, utilizing pre-existing fiber-optic cables as seismic sensors, we demonstrate a fiber-optic seismic sensing principle to robustly capture vadose zone soil moisture dynamics. Our observations in Ridgecrest, California reveal sub-seasonal precipitation replenishments and a prolonged drought in the vadose zone, consistent with a zero-dimensional hydrological model. Our results suggest a significant water loss of 0.25 m/year through evapotranspiration at our field side, validated by nearby eddy-covariance based measurements. Yet, detailed discrepancies between our observations and modeling highlight the necessity for complementary in-situ validations. Given the escalated regional drought risk under climate change, our findings underscore the promise of fiber-optic seismic sensing to facilitate water resource management in semi-arid regions.

The complete chloroplast genome of Blechnopsis orientalis (Linnaeus) C. Presl 1753 (Blechnaceae).

Blechnopsis orientalis (Linnaeus) C. Presl (1753) is a fern used both as food and medicine. It is found primarily in southern China and Southeast Asia, thriving in warm, humid shrublands or sparse forest. The total length of the chloroplast genome is 155,211 bp, including a large single-copy region (LSC, 81,877 bp), a small single-copy region (SSC, 21,500 bp), and two inverted repeat regions (IRs, 25,917 bp). The GC content is 41.3%. A total of 131 genes were annotated, including 88 protein-coding genes, eight rRNA genes, and 35 tRNA genes. The phylogenetic analysis using the maximum-likelihood method showed that B. orientalis and Oceaniopteris gibba were closely related. This study provides genomic resources for phylogenetic genetics and resource exploitation of B. orientalis.

A systematic review and meta-analysis compared the safety and effectiveness of the AirSeal system with traditional pneumoperitoneum systems in robot-assisted laparoscopic urologic surgery.

This study aimed to analyze perioperative results in robot-assisted laparoscopic urological surgeries, comparing the AirSeal system with traditional pneumoperitoneum systems. This study adhered to the PRISMA guidelines for conducting systematic reviews and meta-analyses. Extensive searches were conducted in PubMed, EMBASE, and Google Scholar, including randomized controlled trials (RCTs) and cohort studies up to June 15, 2024. A combined examination of the studies found that the AirSeal system had superior results in terms of surgery duration, end-tidal carbon dioxide levels, and tidal volume compared to the traditional pneumoperitoneum system. During robotic-assisted partial nephrectomy, the AirSeal team experienced a notable decrease in surgical time, ETCO2, and VT. In addition, the occurrence of SCE was lower in the AirSeal group. However, there were no significant differences observed between the groups regarding EBL, LOHS, overall complications, and major complications. Compared to conventional pneumoperitoneum systems, the AirSeal system offers several advantages in robot-assisted laparoscopic urological surgery: reduced operative time, lower end-tidal CO2 pressure, and decreased tidal volume. Furthermore, implementing the AirSeal system does not lead to higher rates of complications, estimated blood loss, or lengthier hospital stays.

A novel hybrid lanthanide metal-organic frameworks based on porphyrin for rapid detection of iron ions.

BACKGROUND: Iron ion (Fe3+) is essential for the environment and human health. Detecting Fe3+ in water is crucial, making high-performance detection a key objective. Lanthanide metal-organic frameworks with abundant functional sites have been deemed a promising fluorescence sensor for Fe3+ detection. Currently, most metal-organic framework-based sensors for Fe3+ detection have cumbersome and time-consuming synthesis procedures and long detection times, which greatly limits their practical application. This study aims to construct a hybrid lanthanide metal-organic frameworks-based fluorescence sensor for Fe3+ detection that promises simple and rapid iron ion quantification in water. RESULTS: A novel hybrid lanthanide metal-organic frameworks (ECTMNs) was synthesized in one step using a solvothermal method with only 4 h. The frameworks comprise two metal ions, cerium and europium, serving as metal centers, and 4,4,4,4-(Porphine-5,10,15,20-tetrayl) tetrakis (TCPP) as an organic ligand. With the addition of Fe3+, the host-guest reaction occurred between Fe3+ and ECTMNs probe, leading to the gradual fluorescence burst of ECTMNs probe. A strong linear correlation between ECTMNs fluorescence intensity and Fe3+ concentration (1-90 µM) makes it a reliable sensor for Fe3+ monitoring with a detection limit of 0.3 µM. Moreover, the method was used to analyze real samples (tap water and river water), showing good recoveries (92-98 %) and low relative standard deviations (3.96-6.11 %), making it a promising option for rapidly detecting Fe3+. SIGNIFICANCE AND NOVELTY: A rapid synthesis protocol for hybrid lanthanide metal-organic frameworks is proposed in this study. The obtained ECTMNs exhibits good water solubility, high stability, and specificity for Fe3+. Based on ECTMNs, an innovative fluorescence sensor is established for selectively detecting Fe3+ in water, which is a simple operation method with a low detection limit and short sensing time. It provides a novel method for accurately and rapidly detecting Fe3+ in environmental pollution and water safety monitoring.

Assessing the impact of temperature on acute exacerbation of chronic obstructive pulmonary disease hospitalizations in residents of Panzhihua City: a multi-districts study using a distributed lag non-linear model.

BACKGROUND: Temperature fluctuations can impact the occurrence and progression of respiratory system diseases. However, the current understanding of the impact of temperature on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains limited. Therefore, our study aims to investigate the relationship between daily mean temperature (DMT) and the risk of AECOPD hospitalizations within Panzhihua City. METHODS: We systematically collected data on AECOPD hospitalizations at Panzhihua Central Hospital from 2015 to 2020 and meteorological factors across Panzhihua City's districts. A two-stage analysis method was used to establish a distributed lag non-linear model to elucidate the influence of DMT on the frequency of admissions for AECOPD. Subgroup analyses were conducted by gender and age to identify populations potentially susceptible to the impact of DMT. RESULTS: A total of 5299 AECOPD hospitalizations cases were included. The DMT and the risk of AECOPD hospitalization showed a non-linear exposure-response pattern, with low temperatures exacerbating the risk of hospitalizations. The lag effects of low temperature and relatively low temperature peaked at 2th day, with the lag effects disappearing at 16-17 days. Females and elders aged ≥ 65 years were more sensitive to effects of low and relatively low temperature at lag 0-4 days, while male AECOPD patients exhibited longer lasting lag effects. CONCLUSIONS: Low temperatures are associated with an increased risk of AECOPD hospitalizations. Females or elders aged ≥ 65 years with chronic obstructive pulmonary disease should pay more attention to taking protective measures in cold environments. These findings are crucial for the formulation of public health policies, as they will help significantly alleviate the burden of AECOPD and improve respiratory health in the face of climate challenges.

School Bullying Victimization and Depression Symptoms in Adolescents: The Mediating Role of Internet Addiction and Moderating Role of Living Areas.

School bullying and depression are both serious social and public health problems among adolescents. Prior studies indicated a correlation between bullying and depression. However, the potential moderators remain largely unexplored. This study aimed to identify the mediating effect of Internet addiction and the moderating effect of living in urban or rural areas in the relationship between school bullying victimization and depression symptoms among Chinese adolescents. This cross-sectional study of adolescents was conducted using two-stage random cluster sampling of students in urban and rural public high schools in China. A moderated mediation model was constructed to uncover the underlying mechanism of school bullying victimization and depression symptoms. A total of 2,376 adolescents (52.65% females, mean age ± SD a 14.69 ± 1.76 years) were included in the study. The prevalence of clinical depression symptoms with a cut-off value of 16 on the Center for Epidemiological Studies Depression Scale (CES-D) was 21.76% (95% CI: 20.15, 23.46), and with a cut-off value of 20 on the CES-D was 13.85% (95% CI: 12.51, 15.30) for overall. Our findings indicated a significant positive association between school bullying victimization and depression symptoms (p < 0.01) and a significant mediating effect of Internet addiction in the association between school bullying victimization and depression symptoms (indirect effect = 1.143, 95% CI: 0.677, 1.609; percentage of mediation: 16.7%, 95% CI: 10.3, 23.1). This indirect relationship was partially moderated by the living in urban or rural areas in the mediation process. Specifically, the effect of school bullying victimization on Internet addiction was greater among urban adolescents (simple slope: 0.774, 95% CI: 0.524, 1.024, p < 0.01) than among rural adolescents (simple slope: 0.337, 95% CI: 0.132, 0.543, p < 0.01), but moderating effect of urban-rural areas was not significant on the relationship between Internet addiction and depression symptoms. These findings highlight the mediating role of Internet addiction and the moderating role of living areas in school bullying victimization and adolescents' depression symptoms, which provide evidence for social work, mental health services, and policy interventions for adolescents in China.

Association between adherence to life's simple 7 metrics and risk of obstructive sleep apnea among adults in the United States.

BACKGROUND: We aimed to explore the impact of adherence to Life's Simple 7 (LS7) metrics on risk of obstructive sleep apnea (OSA), and the impact of inflammation on the association, in adults in the United States. METHODS: Data from 13,825 community-dwelling adults aged ≥ 20 years recruited in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008, 2015-2018 was analyzed. The LS7 score was calculated based on the AHA definition of LS7 metrics. The diagnosis of OSA was based on self-reported symptoms of sleep disturbance using a standard questionnaire. The Multivariable Apnea Prediction (MAP) Index score was also calculated to assess the risk of OSA. Log-binominal regression and negative binomial regression were performed to estimate the associations between LS7 and OSA and MAP index, with odds ratios (ORs) and prevalence ratios (PRs) and their 95% confidence intervals (CIs) calculated. Mediation analysis was performed to estimate the mediating effects of inflammatory indicators on the associations. RESULTS: A total of 4473 participants (32.4%) had OSA, and the mean MAP index was 0.39. In fully adjusted log-binominal regression models, with total score < 6 as the reference, the ORs (95% CIs) for risk of OSA were 0.90 (0.73, 1.10), 0.76 (0.65, 0.89), 0.78 (0.64, 0.95), and 0.45 (0.38, 0.54) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). When LS7 score was analyzed as a continuous variable, each 1-point increase in LS7 score was associated with a 15% decrease in OSA risk (P < 0.001). In negative binominal regression models, the adjusted PRs (95% CIs) for the MAP index were 0.93 (0.90, 0.97), 0.87 (0.84, 0.91), 0.80 (0.77, 0.84), and 0.55 (0.53, 0.57) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). For each 1-point increase in LS7 score, the risk of OSA decreased by 13% (P < 0.001). Consistent results were observed in subgroup analysis. Mediation analysis indicated that inflammatory factors, including blood cell count, neutrophil count, and C-reactive protein, positively mediated the association of LS7 with OSA, with a mediation proportion of 0.022 (P = 0.04), 0.02 (P = 0.04), and 0.02 (P = 0.02), respectively. CONCLUSIONS: In a nationally representative sample of US adults, adherence to LS7 metrics was independently associated with reduced OSA risk. Inflammation plays a mediating role in the association between LS7 and OSA.

Establishing a risk prediction model for residual pulmonary vascular obstruction after regular anticoagulant therapy for non-high-risk pulmonary embolism.

Background: The incidence of pulmonary embolism (PE) has been on the rise annually. Despite receiving regular sequential anticoagulation therapy, some patients with non-high-risk acute PE (APE) continue to experience residual pulmonary vascular obstruction (RPVO). This study sought to identify the risk factors for RPVO following 3 months of sequential anticoagulation therapy for non-high-risk PE. Machine learning techniques were utilized to construct a clinical prediction model for predicting the occurrence of RPVO. Methods: A total of 254 acute non-high-risk PE patients were included in this study, all of whom were admitted to the Third People's Hospital of Yunnan Province between 2020 and 2023. After 3 months of regular anticoagulant treatment, computed tomography pulmonary angiography (CTPA) were reviewed to identify the presence of RPVO. Patients were then categorized into either the thrombolysis group or the thrombosis residue group. Throughout the study period, 49 patients were excluded due to missing data, irregular treatment, or loss to follow-up. Clinical symptoms, physical signs, and laboratory results of 205 PE patients were recorded. Correlation and collinearity analyses were conducted on relevant risk factors, and significance tests were performed. Heat maps illustrating the relationships between influencing factors were generated. Predictors were selected using least absolute shrinkage and selection operator (LASSO) regression, followed by multivariate logistic regression analysis to create a predictive model. Internal validation of the model was also carried out. Results: By searching the literature to understand all the clinical indicators that may affect the efficacy of anticoagulation therapy. A total of 205 patients with non-high-risk acute pulmonary thromboembolism were evaluated for various risk factors. Five independent factors were identified by multivariable analysis-age, chronic obstructive pulmonary disease (COPD), acratia, pulmonary systolic blood pressure (PASP), and major arterial embolism-and their P value, odds ratio (OR) and confidence interval (CI) were as follows: (P=0.012, OR =1.123; 95% CI: 1.026-1.23), (P=0.002, OR =13.30; 95% CI: 2.673-66.188), (P=0.001, OR =14.009; 95% CI: 2.782-70.547), (P=0.003, OR =1.061; 95% CI: 1.020-1.103) and (P<0.001, OR =18.128; 95% CI: 3.853-85.293), which may indicate a poor prognosis after standard anticoagulant therapy. A nomogram was constructed using these variables and internally validated. The receiver operating characteristic (ROC) curves of the model demonstrated strong predictive accuracy, with an area under the curve (AUC) of 0.94 (95% CI: 0.89-0.96) for the training set and 0.93 (95% CI: 0.88-0.95) for the validation set. Calibration curves were utilized to assess the practicality of the nomogram. Conclusions: A novel predictive model was developed based on a single-center retrospective study to identify patients with RPVO following anticoagulant therapy for acute non-high-risk PE. This model may aid in the early detection of patients, prompt adjustment of treatment, and ultimately lead to a decrease in adverse outcomes.

Elastic Nanofibrous Dressings with Mesenchymal Stem Cell-Recruiting and Protecting Characteristics for Promoting Diabetic Wound Healing.

Diabetic wounds that do not heal for a long time challenge global healthcare. Mesenchymal stem cell (MSC) therapy has positive significance in promoting diabetic wound healing. However, traditional MSC therapy involves exogenous MSCs, which brings many limitations and unsatisfactory treatment. Moreover, the maintenance of MSC viability and function is difficult because of the high level of reactive oxygen species (ROS) in diabetic wounds. Therefore, we developed a nanofibrous dressing to recruit and protect endogenous MSCs while avoiding the inherent disadvantages of exogenous MSCs. Ceria nanoparticles capable of ROS scavenging are integrated into the nanofibrous dressings, together with Apt19S, a DNA aptamer with affinity and selectivity for MSCs. In addition, the homogenization and freeze-drying technology give the nanofibrous dressings good elasticity, which protects the wound from external pressure. Further experiments in diabetic mice show that the dressing has excellent endogenous MSC recruitment and anti-inflammatory properties, thereby synergistically promoting diabetic wound healing. This study is expected to explore an efficient method of stem cell therapy, providing a new way to construct high-performance wound dressings.

Association between percutaneous absorption of benzophenone-3 and N, N-diethyl-m-toluamide among the general adult population.

BACKGROUND: Multiple studies have confirmed the mutual enhancement of percutaneous permeation of benzophenone-3 (BP-3) and N,N-diethyl-m-toluamide (DEET), which are effective ingredients in sunscreen products and insect repellents, respectively. However, the association between percutaneous absorption of BP-3 and DEET in a large general adult population remains to be elucidated. METHODS: This cross-sectional study included US adults who had available data on urinary BP-3 and two DEET metabolites, 3-(diethylcarbamoyl) benzoic acid (DCBA) and 3-(ethylcarbamoyl) benzoic acid (ECBA), from the National Health and Nutrition Examination Survey (NHANES) conducted in 2015-2016. We conducted three weighted multivariable linear regression models to investigate the potential correlation between percutaneous absorption of BP-3 and DEET, along with trend tests, smooth curve fitting, and subgroup analysis to assess the robustness of the findings. RESULTS: Weighted multivariable linear logistic regression revealed a positive correlation between log10 BP-3 and log10 DCBA (ß = 0.1678, 95 % CI: 0.0970 to 0.2386) as well as log10 ECBA (ß = 0.1416, 95 % CI: 0.0707 to 0.2125), after adjusting for all covariates. After converting log10 BP-3 from a continuous variable to a categorical variable (quartiles), the trend tests showed that the results were stable (all P for trend < 0.05). Smoothed curve fitting demonstrated a linear positive correlation between log10 BP-3 and both log10 DCBA and log10 ECBA. In subgroup analyses, the positive correlation between BP-3 and DEET metabolites was more pronounced in participants who were male, middle-aged, non-Hispanic white, had a moderate PIR level and reported always or most of the time using sunscreen. CONCLUSIONS: Our findings revealed a statistically significant linear and positive correlation between the percutaneous absorption of BP-3 and DEET in the general adult population.

Schlank orchestrates insect developmental transition by switching H3K27 acetylation to trimethylation in the prothoracic gland.

Insect developmental transitions are precisely coordinated by ecdysone and juvenile hormone (JH). We previously revealed that accumulated H3K27 trimethylation (H3K27me3) at the locus encoding JH signal transducer Hairy is involved in the larval-pupal transition in insects, but the underlying mechanism remains to be fully defined. Here, we show in Drosophila and Bombyx that Rpd3-mediated H3K27 deacetylation in the prothoracic gland during the last larval instar promotes ecdysone biosynthesis and the larval-pupal transition by enabling H3K27me3 accumulation at the Hairy locus to induce its transcriptional repression. Importantly, we find that the homeodomain transcription factor Schlank acts to switch active H3K27 acetylation (H3K27ac) to repressive H3K27me3 at the Hairy locus by directly binding to the Hairy promoter and then recruiting the histone deacetylase Rpd3 and the histone methyltransferase PRC2 component Su(z)12 through physical interactions. Moreover, Schlank inhibits Hairy transcription to facilitate the larval-pupal transition, and the Schlank signaling cascade is suppressed by JH but regulated in a positive feedback manner by ecdysone. Together, our data uncover that Schlank mediates epigenetic reprogramming of H3K27 modifications in hormone actions during insect developmental transition.