Characterization and function of particulate organic matter: Evidence from lakes undergoing ecological restoration.

Particulate organic matter (POM) plays a crucial role in the organic composition of lakes; however, its characteristics remain poorly understood. This study aimed to characterize the structure and composition of POM in Lake Baiyangdian using many kinds of techniques and investigate the effects of different extracted forms of POM on water quality. The suspended particulate matter in the lake had complex compositions, with its components primarily derived from aquatic plants and their detritus. The organic matter content of the suspended particulate matter was relatively high (organic carbon content 27.29-145.94 g/kg) for the sum of three extractable states (water-extracted organic matter [WEOM], humic acid, and fulvic acid) and one stable bound state (humin). Spatial distribution analysis revealed that the POM content in the water increased from west to east, which was consistent with the water flow pattern influenced by the Baiyangdian water diversion project. Fluorescence spectroscopy analysis of the WEOM showed three prominent peaks with excitation/emission wavelengths similar to those of dissolved organic matter peaks. These peaks were potentially initial products of POM conversion into dissolved organic matter. Furthermore, the intensity of the WEOM fluorescence peak (total fluorescence peak intensity) was negatively correlated with the inorganic nitrogen concentration in water (p < 0.01), while the intensity of the HA fluorescence peak showed a positive correlation with the inorganic nitrogen concentration (p < 0.01). This suggested that exogenous organic matter inputs led to the diffusion of alkaline dissolved nitrogen from sediment into water, while degradation processes of aquatic plant debris contributed to the decrease in inorganic nitrogen concentrations in the water column. These findings enhance our understanding of POM characteristics in shallow lakes and the role of POM in shallow lake ecosystems.

Novel combination therapy using recombinant oncolytic adenovirus silk hydrogel and PD-L1 inhibitor for bladder cancer treatment.

Recombinant oncolytic adenovirus offers a novel and promising cancer treatment approach, but its standalone efficacy remains limited. This study investigates a combination treatment strategy by co-administering recombinant oncolytic Adv-loaded silk hydrogel with a PD-L1 inhibitor for patients with bladder cancer to enhance treatment outcomes. Bladder cancer tissues from mice were collected and subjected to single-cell sequencing, identifying CRB3 as a key gene in malignant cells. Differential expression and functional enrichment analyses were performed, validating CRB3's inhibitory role through in vitro experiments showing suppression of bladder cancer cell proliferation, migration, and invasion. Recombinant oncolytic adenoviruses encoding CRB3 and GM-CSF were constructed and encapsulated in silk hydrogel to enhance drug loading and release efficiency. In vivo experiments demonstrated that the nano-composite hydrogel significantly inhibited tumor growth and increased immune infiltration in tumor tissues. Co-administration of adenovirus silk hydrogel (Adv-CRB3@gel) with a PD-L1 inhibitor significantly enhanced T-cell infiltration and tumor killing. The combination of recombinant oncolytic Adv-loaded nano-composite hydrogel encoding CRB3 and GM-CSF with a PD-L1 inhibitor improves bladder cancer treatment outcomes by effectively recruiting T cells, providing a novel therapeutic strategy.

Application of graft-derived cell-free DNA for solid organ transplantation.

Monitoring the status of grafts and the occurrence of postoperative complications, such as rejection, is crucial for ensuring the success and long-term survival of organ transplants. Traditional histopathological examination, though effective, is an invasive procedure and poses risks of complications, making frequent use impractical. In recent years, graft-derived cell-free DNA (gd-cfDNA) has emerged as a promising non-invasive biomarker. It not only provides early warnings of rejection and other types of graft injury but also offers important information about the effectiveness of immunosuppressive therapy and prognosis. gd-cfDNA shows potential in the monitoring of organ transplants. The early, real-time information on graft injury provided by gd-cfDNA facilitates timely individualized treatment and improves patient outcomes. However, the progress of research on gd-cfDNA varies across different organs. Therefore, this article will comprehensively review the application and findings of gd-cfDNA in monitoring various solid organs, discussing the advantages, limitations, and some future research directions to aid in its clinical application.

Effect of laterality on the postoperative survival of non-small cell lung cancer patients undergoing pneumonectomy.

Background: Pneumonectomy is one of the important surgical methods for non-small cell lung cancer (NSCLC). This study evaluated the effects of laterality on the short- and long-term survival of NSCLC patients undergoing pneumonectomy. Methods: We reviewed the Surveillance, Epidemiology, and End Results database to retrieve the data of patients who underwent pneumonectomy for stage I-III NSCLC from 2004 to 2015. Propensity score matching (PSM) was used to reduce the selection bias. Logistic regression was used to analyze the correlation between laterality and mortality at 3, 6, and 9 months. The Kaplan-Meier curve was used to further assess the effect of laterality on overall survival (OS). Results: A total of 4,763 patients met the enrollment criteria [right-sided, 1,988 (41.7%); left-sided, 2,775 (58.3%)]. After PSM, 1,911 patients for each side were included in the further analysis. The first 6 months following pneumonectomy was the main period of death, with 32.0% (428/1,336) and 19.9% (250/1,258) of right- and left-sided deaths occurring during this period. The logistic regression analysis showed that right-sided pneumonectomy was an independent risk factor for 3- (P<0.001) and 6-month (P<0.001) mortality. However, laterality had no significant effect on postoperative death at 7-9 months (P=0.82). In the total cohort, right-sided patients had worse OS (P<0.001), but the subgroup survival analysis of patients with a follow-up period >6 months revealed that laterality had no statistically significant effect on OS (P=0.75). Conclusions: Right-sided pneumonectomy was associated with a higher perioperative mortality risk that lasted about 6 months. After that period, laterality was not observed to have a significant prognostic effect on the OS of patients undergoing pneumonectomy.

Association between Ward's triangle bone mineral density levels and abdominal aortic calcification: Data from the national health and nutrition examination survey 2013-2014.

BACKGROUND & AIMS: Despite extensive research into the cardiovascular implications of abdominal aortic calcification (AAC), there is a scarcity of robust studies exploring its association with Ward's triangle bone mineral density (BMD). This study aimed to evaluate this relationship in a nationally representative sample and compare the predictive value with femoral neck BMD and total femur BMD. METHODS: We conducted a cross-sectional analysis of 2013-2014 National Health and Nutrition Examination Survey (NHANES) data, utilizing a complex, stratified, multistage, cluster sampling design. BMD measurements at Ward's triangle, femoral neck, and total femur were assessed using DXA scans. AAC severity was defined by a Kauppila score of ≥5. Predictors of AAC-24 scores were identified through correlation and linear regression models. Stratified regression and restricted cubic splines were applied to explore subgroup and dose-response relationships. RESULTS: Of the 2965 participants representing 116, 562, 500 individuals in the U.S., 11 % had severe AAC. Ward's triangle BMD showed a significant negative association with AAC-24 scores (ß = -1.90, 95 % CI: -2.80 to -1.00, P < 0.002) and a reduced risk of severe AAC (OR = 0.85, 95 % CI: 0.76 to 0.95, P = 0.010). Non-linear associations were observed between Ward's triangle BMD and AAC outcomes. Ward's triangle BMD outperformed femoral neck and total femur BMD in predicting AAC. CONCLUSIONS: Higher Ward's triangle BMD is linked to lower odds of severe AAC, highlighting its potential for improved early detection of AAC over femoral neck and total femur BMD. Healthcare providers should consider the implications of reduced Ward's triangle BMD for systemic atherosclerosis and recommend early AAC screening for enhanced cardiovascular risk management.

The increasing rate of net carbon uptake in Eurasia has been declining since the early 2000s.

The analysis of terrestrial ecosystem carbon dynamics, based on scarce carbon flux observations or carbon flux products simulated by reanalysis meteorological data, has great uncertainties. A more accurate understanding of carbon dynamics in Eurasia was achieved by using a carbon flux dataset (CFD) from meteorological stations with quasi-observational characteristics. The growth of net carbon uptake of ecosystems over Eurasia has been decreasing since the early 2000s. The net ecosystem productivity (NEP) increased significantly with the growth rate of 8.7 × 10-3 g C m-2d-1 yr-1 in spring, summer, and autumn (SSA) during 2003-2011 (p < 0.05), which was correlated with the enhanced vegetation index (EVI) and land surface water index (LSWI). This growth was mostly in dry subhumid and humid regions. However, the change in Eurasian NEP was not significant after 2011. Additionally, about 79 % of the stations in Eurasia were in net carbon uptake in SSA, and net carbon emission stations were mainly located in southwestern Eurasia. The intensity of net carbon uptake was highest in the forest, with a mean carbon uptake of 1.73 ± 0.76 g C m-2d-1 in SSA during 2003-2018, and almost all stations demonstrated carbon uptake. During 2011-2018, the number of stations experiencing reduced NEP exceeded those with increased NEP, and this ratio was higher compared to 2003-2011, mainly due to the decrease in EVI and LSWI. The rate of NEP decline at stations with reduced NEP was 5.2 × 10-3 g C m-2d-1 yr-1 faster during 2011-2018 than in the previous period (p < 0.01). Most of the decreases in NEP during 2011-2018 occurred in cropland, grassland and urban land. The spatio-temporal dynamic analysis of Eurasian NEP could provide references for effective carbon management.

Biotemplated Janus Magnetic Microrobots Based on Diatomite for Highly Efficient Detection of Salmonella.

Foodborne illnesses caused by Salmonella bacteria pose a significant threat to public health. It is still challenging to detect them effectively. Herein, biotemplated Janus disk-shaped magnetic microrobots (BJDMs) based on diatomite are developed for the highly efficient detection of Salmonella in milk. The BJDMs were loaded with aptamer, which can be magnetically actuated in the swarm to capture Salmonella in a linear range of 5.8 × 102 to 5.8 × 105 CFU/mL in 30 min, with a detection limit as low as 58 CFU/mL. In addition, the silica surface of BJDMs exhibited a large specific surface area to adsorb DNA from captured Salmonella, and the specificity was also confirmed via tests of a mixture of diverse foodborne bacteria. These diatomite-based microrobots hold the advantages of mass production and low cost and could also be extended toward the detection of other types of bacterial toxins via loading different probes. Therefore, this work offers a reliable strategy to construct robust platforms for rapid biological detection in practical applications of food safety.

ßAR-mTOR-lipin1 pathway mediates PKA-RIIß deficiency-induced adipose browning.

Background: Enhancing white adipose tissue (WAT) browning combats obesity. The RIIß subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIß gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored. Methods: This study investigates the mechanisms underlying WAT browning in RIIß-KO mice. Genetic approaches such as ß3-adrenergic receptors (ß3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 in vitro, while AAV-shRNAs were used for the same purpose in vivo. Results: We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIß-KO mice. The WAT browning can be dampened by ß3ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIß-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, ß3AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, in vivo knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity. Conclusions: The ß3AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.

Activated persulfate for efficient bisphenol A degradation via nitrogen-doped Fe/Mn bimetallic biochar.

To achieve the purpose of treating waste by waste, in this study, a nitrogen-doped Fe/Mn bimetallic biochar material (FeMn@N-BC) was prepared from chicken manure for persulfate activation to degrade Bisphenol A (BPA). The FeMn@N-BC was characterized by scanning electron microscopy (SEM), X-ray diffract meter (XRD), fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS) and found that N doping can form larger specific surface area. Catalytic degradation experiments showed that Fe/Mn bimetal doping not only accelerated the electron cycling rate on the catalyst surface, but also makes the biochar magnetic and easy to separate, thus reducing environmental pollution. Comparative experiments was concluded that the highest degradation efficiency of BPA was achieved when the mass ratios of urea and chicken manure, Fe/Mn were 3:1 and 2:1, respectively, and the pyrolysis temperature was 800 °C, which can almost degrade all the BPA in 60 min. FeMn@N-BC/PS system with high catalytic efficiency and low consumables is promising for reuse of waste resources and the remediation of wastewater.

Robotic-assisted extended thymectomy for large resectable thymoma: 21 years' experience.

OBJECTIVE: This study aims to evaluate the perioperative and midterm oncological outcomes of robotic-assisted thoracic surgery extended thymectomy for patients with large resectable thymomas compared with small thymomas. METHODS: This retrospective single-center study included 204 patients with thymomas who underwent robotic-assisted thoracic surgery extended thymectomy between January 2003 and February 2024. Patients were divided into 2 groups based on the thymoma size (5-cm threshold). RESULTS: The study comprised 114 patients (55.9%) in the small thymoma group and 90 patients (44.1%) in the large thymoma group. No significant differences were found between the groups regarding gender, age, proportion of elderly patients, or pathologic high-risk classifications. Apart from a longer operative time (P = .009) in the large thymoma group, no differences were observed between the 2 groups regarding surgical parameters and postoperative outcomes. No deaths occurred within 30 days in either group. During a median follow-up of 61.0 months (95% CI, 48.96-73.04), 4 patients experienced recurrence (1.96%). No significant differences in the 5-year overall survival (P = .25) or recurrence-free survival (P = .43) were observed between groups. CONCLUSIONS: Robotic-assisted thoracic surgery extended thymectomy is technically feasible, safe, and effective for treating large resectable thymomas. Moreover, midterm outcomes for patients with completely resected large thymomas were comparable to those with small thymomas during a median follow-up period of up to 5 years.

Associations of sleep with cardiometabolic risk factors and cardiovascular diseases: An umbrella review of observational and mendelian randomization studies.

Two researchers independently assessed studies published up to February 5, 2023, across PubMed, Web of Science, Embase, and Cochrane Library, to investigate the associations of sleep traits with cardiometabolic risk factors, as well as with cardiovascular diseases. Fourteen systematic reviews consisting of 23 meta-analyses, and 11 Mendelian randomization (MR) studies were included in this study. Short sleep duration was associated with a higher risk of obesity, type 2 diabetes (T2D), hypertension, stroke, and coronary heart disease (CHD) in observational studies, while a causal role was only demonstrated in obesity, hypertension, and CHD by MR. Similarly, long sleep duration showed connections with a higher risk of obesity, T2D, hypertension, stroke, and CHD in observational studies, none was supported by MR analysis. Both observational and MR studies indicated heightened risks of hypertension, stroke, and CHD in relation to insomnia. Napping was linked to elevated risks of T2D and CHD in observational studies, with MR analysis confirming a causal role in T2D. Additionally, snoring was correlated with increased risks of stroke and CHD in both observational and MR studies. This work consolidates existing evidence on a causal relationship between sleep characteristics and cardiometabolic risk factors, as well as cardiovascular diseases.

Gut microbiome: a novel preventive and therapeutic target for prostatic disease.

The human gut microbiome (GM) impacts various physiological processes and can lead to pathological conditions and even carcinogenesis if homeostasis is disrupted. Recent studies have indicated a connection between the GM and prostatic disease. However, the underlying mechanisms are still unclear. This review aims to provide a summary of the existing information regarding the connection between the GM and various prostatic conditions such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Furthermore, the review aims to identify possible pathogenic mechanisms and suggest potential ways of targeting GM to prevent and treat prostatic disease. Due to the complexity of the mechanism between GM and prostatic diseases, additional research is required to comprehend the association between the two. This will lead to more effective treatment options for prostatic disease.

Causal association between Neuroticism and risk of aortic aneurysm: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: The objective of this study was to analyze the causal relationship between Neuroticism and aortic aneurysm using Mendelian randomization (MR). The study aimed to establish a foundation for the development of effective prevention and treatment strategies. METHODS: Genetic association data for Neuroticism were obtained from the UK Biobank, which included 393,411 individuals and 11,968,760 single nucleotide polymorphisms (SNPs). Genetic association data for aortic aneurysm were obtained from a genome-wide association study (GWAS), which included 479,194 individuals and 24,191,825 SNPs. Heterogeneity was assessed using the Cochran's Q statistic test. The study also utilized the MR Pleiotropy RESidual Sum and Outlier (Mr-PRESSO) test, as well as the MR-Egger regression method, to examine horizontal pleiotropy and determine the reliability of the findings through the leave-one-out method. RESULTS: Forward MR analysis showed that the risk of aortic aneurysm was elevated in individuals with genetically predicted Neuroticism compared to those without Neuroticism (OR = 1.1315, 95 % CI: 1.0269-1.2468; P = 0.0126). The Cochran's Q test showed no heterogeneity (P > 0.05), and the MR-PRESSO test did not identify instrumental variables of horizontal pleiotropy (P > 0.05). The MR analysis remained robust after removing SNPs one by one. Inverse MR analysis did not observe an association between aortic aneurysm and having Neuroticism OR = 1.030, 95 % CI: 0.9459-1.118, P = 0.488). CONCLUSION: Our study has established a clear causal relationship between genetically determined Neuroticism and the development of aortic aneurysms. It is therefore important to intensify screening and prevention efforts for aortic aneurysms in neurotic patients. It also opens new avenues for exploring the disease's pathogenesis.

Metal-Organic Framework-Induced Rh Monocoodination on Diphosphine Ligand Enables Catalytic Hydroformylation of Aliphatic Olefins at Room Temperature and Pressure.

Persistent challenges in hydroformylation of olefins include controlling regioselectivity, particularly for short aliphatic olefins and conducting reactions under ambient conditions. We report here the synthesis of monophosphine-Rh complexes on a typical chelated diphosphine ligand mediated by a Zr-MOF through isolating a pair of phosphorus atoms. We demonstrate that single-crystal X-ray diffraction can elucidate the structural transformation of the Rh catalyst during olefin hydroformylation, providing valuable information on active site reconstruction during catalysis. The Rh-MOF catalyst demonstrates excellent catalytic and recyclable performance in the hydroformylation of short aliphatic olefins with linear to branched ratios of up to 99 : 1. Due to the framework's capacity to adsorb and concentrate gases, the catalytic reactions occur under room temperature and pressure, eliminating the need for the high temperature and pressures typically required in homogeneous systems. This study show that Zr-MOF can be a unique platform for synthesizing unusual catalytic species that cannot exist in solutions for meaningful chemical transformations and elucidate valuable structural information pertaining to metal-based catalysis.

Investigating Shear Stress of Ice Accumulated on Surfaces with Various Roughnesses: Effects of a Quasi-Water Layer.

The investigation of the anti-icing/deicing is essential because the icing phenomenon deteriorates the natural environment and various projects. By conducting molecular dynamics simulation, this work analyzes the effect of the quasi-water layer on the ice shear stress over smooth and rough surfaces, along with the underlying physics of the quasi-water layer. The results indicate that the thickness of the quasi-water layer monotonically increases with temperature, resulting in a monotonic decrease in the ice shear stress on the smooth surface. Due to the joint effects of the smooth surface wettability and the quasi-water layer, the ice shear stress increases and then decreases to almost a constant value when the surface changes from a hydrophobic to a hydrophilic one. For rough surfaces with stripe nanostructures, when the width of the bump for one case equals the depression for the other case, the variations of shear stress with height for these two cases are almost the same. The rough surface is effective in reducing the ice shear stress compared to the smooth surface due to the thickening of the quasi-water layer. Each molecule in the quasi-water layer and its four nearest neighboring molecules gradually form a tetrahedral ice-like structure along the direction away from the surface. The radial distribution function also shows that the quasi-water layer resembles the liquid water rather than the ice structure. These findings shed light on developing anti-icing and deicing techniques.

Shared genetic basis connects smoking behaviors and bone health: insights from a genome-wide cross-trait analysis.

Although the negative association of tobacco smoking with osteoporosis is well-documented, little is known regarding the shared genetic basis underlying these conditions. In this study, we aim to investigate a shared genetic architecture between smoking and heel estimated bone mineral density (eBMD), a reliable proxy for osteoporosis. We conducted a comprehensive genome-wide cross-trait analysis to identify genetic correlation, pleiotropic loci and causal relationship of smoking with eBMD, leveraging summary statistics of the hitherto largest genome-wide association studies conducted in European ancestry for smoking initiation (Nsmoker = 1 175 108, Nnonsmoker = 1 493 921), heaviness (cigarettes per day, N = 618 489), cessation (Ncurrent smoker = 304 244, Nformer smoker = 843 028), and eBMD (N = 426 824). A significant negative global genetic correlation was found for smoking cessation and eBMD (${r}_g$ = -0.051, P = 0.01), while we failed to identify a significant global genetic correlation of smoking initiation or heaviness with eBMD. Partitioning the whole genome into independent blocks, we observed 6 significant shared local signals for smoking and eBMD, with 22q13.1 showing the strongest regional genetic correlation. Such a genetic overlap was further supported by 71 pleiotropic loci identified in the cross-trait meta-analysis. Mendelian randomization identified no causal effect of smoking initiation (beta = -0.003 g/cm2, 95% CI = -0.033 to 0.027) or heaviness (beta = -0.017 g/cm2, 95% CI = -0.072 to 0.038) on eBMD, but a putative causal effect of genetic predisposition to being a current smoker was associated with a lower eBMD compared to former smokers (beta = -0.100 g/cm2, 95% CI = -0.181 to -0.018). Our study demonstrates a pronounced biological pleiotropy as well as a putative causal link between current smoking status and eBMD, providing novel insights into the primary prevention and modifiable intervention of osteoporosis by advocating individuals to avoid, reduce or quit smoking as early as possible.

We conducted a comprehensive genome-wide cross-trait analysis to investigate the shared genetic basis and causal relationship underlying smoking and osteoporosis. Our findings revealed that smoking and eBMD are inherently linked through biological pleiotropy. Importantly, our study discovered that quitting smoking significantly reduced the risk of lower eBMD. We recommend individuals to avoid, reduce, or quit smoking as early as possible to protect bone health.

Overexpression of macrophage migration inhibitory factor protects against pressure overload-induced cardiac hypertrophy through regulating the miR-29b-3p/HBP1 axis.

Cardiac hypertrophy is an adaptive response to stressors such as high cardiac workload, which might lead to abnormal cardiac function and heart failure. Previous studies have indicated that macrophage migration inhibitory factor (MIF) might play a protective role in cardiac hypertrophy. Here, we aimed to illustrate the mechanism of MIF in protecting against pressure overload-induced cardiac hypertrophy. Transverse aortic constriction (TAC) mouse model was established and we found that overexpression of MIF protected against pressure overload-induced cardiac hypotrophy in TAC treated mice, as evidenced by significantly decreased the heart weight. In addition, transthoracic echocardiography showed that overexpression of MIF restored ejection fraction in TAC-treated mice. While TAC treatment resulted in a much larger cardiomyocyte size in mice, MIF overexpression notably decreased the cardiomyocyte size. Next, we demonstrated that MIF overexpression promoted the expression of miR-29b-3p which further downregulated the expression of its downstream target HMG box protein 1 (HBP1). Overexpression of HBP1 reversed the effect of MIF in alleviating Ang-II induced oxidative stress in cardiomyocytes. In conclusion, our findings suggest that MIF could attenuate pressure overload-induced cardiac hypertrophy through regulating the miR-29b-3p/HBP1 axis.

The relationship between dietary intake of ω-3 and ω-6 fatty acids and frailty risk in middle-aged and elderly individuals: a cross-sectional study from NHANES.

Background: Frailty is a complex clinical syndrome characterized by a decline in the functioning of multiple body systems and reduced adaptability to external stressors. Dietary ω-3 fatty acids are considered beneficial dietary nutrients for preventing frailty due to their anti-inflammatory and immune-regulating properties. However, previous research has yielded conflicting results, and the association between ω-6 fatty acids, the ω-6: ω-3 ratio, and frailty remains unclear. This study aims to explore the relationship between these factors using the National Health and Nutrition Examination Survey (NHANES) database. Materials and methods: Specialized weighted complex survey design analysis software was employed to analyze data from the 2005-2014 NHANES, which included 12,315 participants. Multivariate logistic regression models and restricted cubic splines (RCS) were utilized to assess the relationship between omega intake and frailty risk in all participants. Additionally, a nomogram model for predicting frailty risk was developed based on risk factors. The reliability of the clinical model was determined by the area under the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Results: In dietary ω-3 intake, compared to the T1 group (≤1.175 g/d), the T3 group's intake level (>2.050 g/d) was associated with approximately 17% reduction in frailty risk in model 3, after rigorous covariate adjustments (odds ratio (OR) = 0.83, 95% confidence interval (CI): (0.70, 0.99)). In dietary ω-6 intake, the T2 group's intake level (>11.423, ≤19.160 g/d) was associated with a 14% reduction in frailty risk compared to the T1 group (≤11.423 g/d) (OR: 0.86, 95% CI: 0.75, 1.00, p = 0.044). RCS results indicated a non-linear association between ω-3 and ω-6 intake and frailty risk. Both ROC and DCA curves demonstrated the stability of the constructed model and the effectiveness of an omega-rich diet in reducing frailty risk. However, we did not find a significant association between the ω-6: ω-3 ratio and frailty. Conclusion: This study provides support for the notion that a high intake of ω-3 and a moderate intake of ω-6 may contribute to reducing frailty risk in middle-aged and elderly individuals.

Manipulation of magnetic beads for actively capturing Vibrio parahaemolyticus and nucleic acid based on microfluidic system.

Rapid biological detection of pathogen micro-organisms has attracted much attention for practical biomedical applications. Despite the development in this field, it is still challenging to achieve simple and rapid biological detection using the microfluidic method. Herein, we propose a novel strategy of biological detection that combines precise detection control of the capillary microfluidic chip and versatile manipulation of magnetic beads. The microfluidic chip was fabricated via laser cutting, which utilized capillary pressure to realize rapid passive injection of liquid samples. Under an external magnetic field, the aptamer-modified magnetic beads were actuated to mix with Vibrio parahaemolyticus (V. parahaemolyticus) and its nucleic acid in the capillary microfluidic chip for rapid selective capture and detection, which could be achieved within 40 min. The experimental results demonstrated that V. parahaemolyticus could be captured using on-chip immunomagnetic beads with a high efficiency and significantly enhanced detection value. Due to these superior performances, the capillary microfluidic system, based on the manipulation of magnetic beads, demonstrated great potential for automatic biological detection.

Discovery of novel biphenyl derivatives as androgen receptor degraders for the treatment of enzalutamide-resistant prostate cancer.

Second-generation AR antagonists, such as enzalutamide, are the primary therapeutic agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery and optimization of a series of biphenyl derivatives as androgen receptor antagonists and degraders. These biphenyl derivatives exhibited potent antiproliferative activity against LNCaP and 22Rv1 cells. Our discoveries enrich the diversity of small molecule AR degraders and offer insights for the development of novel AR degraders for the treatment of enzalutamide-resistant prostate cancer.