Based on polydopamine-coated metal organic framework multifunctional nanoplatform for enhanced photothermal/sonodynamicand treatment combined with checkpoint blockade therapy.

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.

Metabolomics signature of blood pressure salt sensitivity and its link to cardiovascular disease: A dietary salt-intervention trial.

Individuals with a high degree of salt sensitivity (SS) have a greater risk of cardiovascular disease (CVD), but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear. This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs, based on the MetaSalt study, which was a dietary salt-intervention trial conducted at four centers in China in 2019. A total of 528 participants were recruited and underwent 3 days of baseline observations, a 10-day low-salt intervention, and a 10-day high-salt intervention. Plasma untargeted metabolomics, lipidomics, and BP measurements were scheduled at each stage. Participants were grouped into extreme SS, moderate SS, and salt-resistant (SR) individuals according to their BP responses to salt. Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness. Mendelian randomization (MR) analyses were applied to establish the causal pathways among the SS-related metabolites, BP, and CVDs. Among the 713 metabolites, 467 were significantly changed after the high-salt intervention. Among them, the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups. Of the remaining nonsalt-related metabolites, the baseline levels of 11 metabolites were related to SS. These 41 metabolites explained 23% of the variance in SS. Moreover, SS and its metabolomics signature were positively correlated with arterial stiffness. MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP, indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause. Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs. This study provides insight into understanding the biology and targets of SS and its role in CVDs.

Dietary intake changes the associations between long-term exposure to fine particulate matter and the surrogate indicators of insulin resistance.

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 µg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction < 0.0028). For instance, among participants with a healthy diet, TyG increased by 0.11 % (95 % CI: 0.08 %, 0.15 %) per 10 µg/m3 PM2.5 increment, significantly lower than the association observed in those with an unhealthy diet. The findings of this study emphasize the potential of a healthy diet to mitigate these associations, highlighting the urgency for improving air quality and implementing dietary interventions among susceptible populations in China.

Isolation, identification, and optimization of conditions for the degradation of four sulfonamide antibiotics and their metabolic pathways in Pseudomonas stutzeri strain DLY-21.

Overuse of sulfonamides in aquaculture and agriculture leads to residual drugs that cause serious pollution of the environment. However, the residues of sulfonamides in the environment are not unique, and the existing microbial degradation technology has a relatively low degradation rate of sulfonamides. Therefore, in this study, a Pseudomonas stutzeri strain (DLY-21) with the ability to degrade four common SAs was screened and isolated from aerobic compost. Under optimal conditions, the DLY-21 strain degraded four sulfonamides simultaneously within 48 h, and the degradation rates were all over 90%, with the average degradation rates of SAs being sulfoxide (SDM) ≈ sulfachloropyridazine (SCP) > sulfa quinoxaline (SQ) > sulfadiazine (SQ). In addition, the main compounds of the strain DLY-21-degrading SAs were identified by LC-MS analysis. On this basis, four detailed reaction pathways for SA degradation were deduced. This is the first report of the use of a P. stutzeri strain to degrade four sulfonamide antibiotics (SQ, SDM, SCP, and SM1), which can improve the removal efficiency of sulfonamide antibiotic pollutants and thus ameliorate environmental pollution. The results showed that DLY-21 had a good degradation effect on four SAs (SQ, SDM, SCP, and SM1).

Intrarenal pressure detection during flexible ureteroscopy with fiber optic pressure sensor system in porcine model.

To validate the feasibility of a fiber-optic pressure sensor-based pressure measurement device for monitoring intrarenal pressure and to analyze the effects of ureteral acess sheath (UAS) type, surgical location, perfusion flow rate, and measurement location on intrarenal pressure (IRP). The measurement deviations and response times to transient pressure changes were compared between a fiber-optic pressure sensing device and a urodynamic device IRP in an in vitro porcine kidney and in a water tank. Finally, pressure measurements were performed in anesthetized female pigs using fiber-optic pressure sensing device with different UAS, different perfusion flow rates, and different surgical positions at different renal calyces and ureteropelvic junctions (UPJ). According to our operation, the result is fiber optic pressure sensing devices are highly accurate and sensitive. Under the same conditions, IRP varied among different renal calyces and UPJ (P < 0.05). IRP was lowest at 50 ml/min and highest at 150 ml/min (P < 0.05). Surgical position had a significant effect on IRP (P < 0.05). 12/14 Fr UAS had a lower IRP than 11/13 Fr UAS. Therefore fiber optic pressure sensing devices are more advantageous for IRP measurements. In ureteroscopy, the type of ureteral sheath, the surgical position, the perfusion flow rate, and the location of the measurement all affect the intrarenal pressure value.

Screening of potential biomarkers in propofol-induced neurotoxicity via bioinformatics prediction and experimental verification.

OBJECTIVES: To identify hub genes and biological processes of propofol-induced neurotoxicity and promote the development of pediatric anesthesiology. METHODS: We downloaded the GSE106799 dataset from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, then Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment analyses were performed on all DEGs. We identified potential ferroptosis genes in the pathogenesis of propofol-induced neurotoxicity. A key module was obtained after performing weighted gene co-expression network analysis (WGCNA) on the GSE106799 dataset. Hub genes were identified after the least absolute shrinkage and selection operator (LASSO) regression analysis of the intersection of DEGs and genes from the key module. We established a competing endogenous RNA network and predicted potential drugs according to the hub genes. Total RNA and proteins were extracted for real-time quantitative polymerase chain reaction and Western blotting, respectively. RESULTS: A total of 112 DEGs, including 76 upregulated and 36 downregulated ones were screened out. Propofol-induced neurotoxicity involved processes such as nervous system development, activation of JAK/STAT and MAPK signaling pathways, vascular regeneration, and oxidative stress. The results of WGCNA suggested that the tan module was the most strongly associated with propofol-induced neurotoxicity. We identified 4 hub genes (EGR4, HAO1, ITK and GM14446) after LASSO regression analysis. Animal experiments demonstrated that propofol caused overexpression of the protein levels of HAO1, ITK and inflammatory factors in the brain, as well as the mRNA levels of HAO1, ITK and GM14446. Propofol inhibited expression of EGR4 at mRNA and protein levels. CONCLUSIONS: Previous studies have demonstrated that EGR4, HAO1, ITK and GM14446 play a role in intellectual development, neuroinflammation and neuronal differentiation. These hub genes may help us to find new preventive and therapeutic targets for propofol-induced neurotoxicity.

CO2 Photoreduction Over Semiconducting 2D Materials with Supported Single Atoms: Recent Progress and Challenges.

In the face of the growing energy crisis and environmental challenges, substantial efforts are now directed toward sustainable clean energy as a replacement for traditional fossil fuels. CO2 photoreduction into value-added chemicals and fuels is widely recognized as a promising approach to mitigate current energy and environmental concerns. Photocatalysts comprising single atoms (SAs) supported on two-dimensional (2D) semiconducting materials (SAs-2DSemi) have emerged as a novel frontier due to the combined merits of SA catalysts and 2D materials. In this study, we review advancements in metal SAs confined on 2DSemi substrates, categorized into four groups: (1) metal oxide-based, (2) g-C3N4-based, (3) emerging, and (4) hybridized 2DSemi, for photocatalytic CO2 conversion over the past few years. With a particular focus on highlighting the distinct advantages of SAs-2DSemi, we delve into the synthesis of state-of-the-art catalysts, their catalytic performances, and mechanistic elucidation facilitated by experimental characterizations and theoretical calculations. Following this, we outline the challenges in this field and offer perspectives on harnessing the potential of SAs-2DSemi as promising photocatalysts. This comprehensive review aims to provide valuable insights for the future development of 2D photocatalytic materials involving SAs for CO2 reduction.

Enhancing the prediction of symptomatic radiation pneumonitis for locally advanced non-small-cell lung cancer by combining 3D deep learning-derived imaging features with dose-volume metrics: a two-center study.

OBJECTIVE: This study aims to examine the ability of deep learning (DL)-derived imaging features for the prediction of radiation pneumonitis (RP) in locally advanced non-small-cell lung cancer (LA-NSCLC) patients. MATERIALS AND METHODS: The study cohort consisted of 90 patients from the Fudan University Shanghai Cancer Center and 59 patients from the Affiliated Hospital of Jiangnan University. Occurrences of RP were used as the endpoint event. A total of 512 3D DL-derived features were extracted from two regions of interest (lung-PTV and PTV-GTV) delineated on the pre-radiotherapy planning CT. Feature selection was done using LASSO regression, and the classification models were built using the multilayered perceptron method. Performances of the developed models were evaluated by receiver operating characteristic curve analysis. In addition, the developed models were supplemented with clinical variables and dose-volume metrics of relevance to search for increased predictive value. RESULTS: The predictive model using DL features derived from lung-PTV outperformed the one based on features extracted from PTV-GTV, with AUCs of 0.921 and 0.892, respectively, in the internal test dataset. Furthermore, incorporating the dose-volume metric V30Gy into the predictive model using features from lung-PTV resulted in an improvement of AUCs from 0.835 to 0.881 for the training data and from 0.690 to 0.746 for the validation data, respectively (DeLong p < 0.05). CONCLUSION: Imaging features extracted from pre-radiotherapy planning CT using 3D DL networks could predict radiation pneumonitis and may be of clinical value for risk stratification and toxicity management in LA-NSCLC patients. CLINICAL RELEVANCE STATEMENT: Integrating DL-derived features with dose-volume metrics provides a promising noninvasive method to predict radiation pneumonitis in LA-NSCLC lung cancer radiotherapy, thus improving individualized treatment and patient outcomes.

Effect of bolus materials on dose deposition in deep tissues during electron beam radiotherapy.

Several materials are utilized in the production of bolus, which is essential for superficial tumor radiotherapy. This research aimed to compare the variations in dose deposition in deep tissues during electron beam radiotherapy when employing different bolus materials. Specifically, the study developed general superficial tumor models (S-T models) and postoperative breast cancer models (P-B models). Each model comprised a bolus made of water, polylactic acid (PLA), polystyrene, silica-gel or glycerol. Geant4 was employed to simulate the transportation of electron beams within the studied models, enabling the acquisition of dose distributions along the central axis of the field. A comparison was conducted to assess the dose distributions in deep tissues. In regions where the percentage depth dose (PDD) decreases rapidly, the relative doses (RDs) in the S-T models with silica-gel bolus exhibited the highest values. Subsequently, RDs for PLA, glycerol and polystyrene boluses followed in descending order. Notably, the RDs for glycerol and polystyrene boluses were consistently below 1. Within the P-B models, RDs for all four bolus materials are consistently below 1. Among them, the smallest RDs are observed with the glycerol bolus, followed by silica-gel, PLA and polystyrene bolus in ascending order. As PDDs are ~1-3% or smaller, the differences in RDs diminish rapidly until are only around 10%. For the S-T and P-B models, polystyrene and glycerol are the most suitable bolus materials, respectively. The choice of appropriate bolus materials, tailored to the specific treatment scenario, holds significant importance in safeguarding deep tissues during radiotherapy.

A review of modulation strategies for improving the catalytic performance of transition metal sulfide self-supported electrodes for the hydrogen evolution reaction.

Electrocatalytic water splitting is considered to be one of the most promising technologies for large-scale sustained production of H2. Developing non-noble metal-based electrocatalytic materials with low cost, high activity and long life is the key to electrolysis of water. Transition metal sulfides (TMSs) with good electrical conductivity and a tunable electronic structure are potential candidates that are expected to replace noble metal electrocatalysts. In addition, self-supported electrodes have fast electron transfer and mass transport, resulting in enhanced kinetics and stability. In this paper, TMS self-supported electrocatalysts are taken as examples and their recent progress as hydrogen evolution reaction (HER) electrocatalysts is reviewed. The HER mechanism is first introduced. Then, based on optimizing the active sites, electrical conductivity, electronic structure and adsorption/dissociation energies of water and intermediates of the electrocatalysts, the article focuses on summarizing five modulation strategies to improve the activity and stability of TMS self-supported electrode electrocatalysts in recent years. Finally, the challenges and opportunities for the future development of TMS self-supported electrodes in the field of electrocatalytic water splitting are presented.

Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation.

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

Enhanced Spin-Polarized Electric Field Modulating p-Band Center on Ni-Doped CdS for Boosting Photocatalytic Hydrogen Evolution.

It is a challenge to regulate charge separation dynamics and redox reaction kinetics at the atomic level to synergistically boost photocatalytic hydrogen (H2 ) evolution. Herein, a robust Ni-doped CdS (Ni-CdS) photocatalyst is synthesized by incorporating highly dispersed Ni atoms into the CdS lattice in substitution for Cd atoms. Combined characterizations with theoretical analysis indicate that local lattice distortion and S-vacancy of Ni-CdS induced by Ni incorporation lead to an increased dipole moment and enhanced spin-polarized electric field, which promotes the separation and transfer of photoinduced carriers. In this contribution, charge redistribution caused by enhanced internal electric field results in the downshift of the S p-band center, which is conducive to the desorption of intermediate H* for boosting the H2 evolution reaction. Accordingly, the Ni-CdS photocatalyst shows a remarkably improved photocatalytic performance with an H2 evolution rate of 20.28 mmol g-1  h-1 under visible-light irradiation, which is 5.58 times higher than that of pristine CdS. This work supplied an insightful understanding that the enhanced polarization electric field governs the p-band center for efficient photocatalytic H2 evolution activity.

Machine Learning Revealed a Novel Ferroptosis-Based Classification for Diagnosis in Antiretroviral Therapy-Treated HIV Patients with Defective Immune Recovery.

Despite virological suppression, the CD4+ T lymphocytes are not restored in some HIV-infected patients after antiretroviral therapy. These individuals are known as immune non-responders (INRs). INRs are at high risk of developing AIDS and non-AIDS-related events and have a shorter life expectancy. Hence, it is vital to identify INRs early and prevent their complications, but there are still no specific diagnostic indicators or models. Ferroptosis has lately been reported as a type of programmed cell death, which plays an indispensable part in diverse diseases. However, its particular regulatory mechanisms remain unclear and its function in the pathogenic process of defective immunological recovery is still unknown. Blood is mainly used for rapid diagnosis because it enables quick testing. To investigate the role of ferroptosis-related genes (FRGs) in early detection of INRs, we scrutinized Gene Expression Omnibus datasets of peripheral blood samples to estimate their effectiveness. To our knowledge, for the first time, gene expression data were utilized in this study to discover six FRGs that were explicitly expressed in peripheral blood from INRs. Later on, multiple machine-supervised learning algorithms were employed, and a superlative diagnostic model for INRs was built with the random forest algorithm, which displayed satisfactory diagnostic efficiency in the training cohort (area under the curve [AUC] = 0.99) and one external validation cohort (AUC = 0.727). Our findings suggest that FRGs are implicated in the development of defective immune recovery, presenting a potential route for early detection and potential biological targets for the most effective treatment of defective immune recovery.

Genetic Predisposition, Sedentary Behavior, and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

PURPOSE: Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST) and to further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. METHODS: This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. RESULTS: During a median follow-up of 11.60 yr, 1156 CAD events were documented. Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95% confidence interval [CI] = 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h·d -1 ), those with high genetic risk and high ST (≥10 h·d -1 ) had the highest CAD risk, with the hazard ratio (HR) and 95% CI of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with HR (95% CI) values of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST ( Ptrend = 0.024). CONCLUSIONS: Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

Effect of Pulmonary Rehabilitation Exercise on Lung Volume and Respiratory Muscle Recovery in Lung Cancer Patients Undergoing Lobectomy.

Objective: This work assessed the impact of drug therapy combined with pulmonary rehabilitation exercise training on specific lung function and respiratory parameters of lung cancer (LC) patients after thoracoscopic lobectomy. Methods: 88 LC patients who had undergone thoracoscopic lobectomy were selected based on their surgical indications and health condition. The study aimed to explore methods to assist patients in their postoperative recovery; therefore, patients meeting the surgical criteria were chosen to ensure the internal validity and external applicability of the results. Meanwhile, these 88 LC patients undergoing thoracoscopic lobectomy were randomly allocated into an experimental group (EG, 44 cases) and a control group (CG, 44 cases). The EG received inhalation therapy with albuterol sulfate nebulizer solution and personalized pulmonary rehabilitation exercise training, while the CG received nebulized treatment alone. The study lasted for three months. The pulmonary rehabilitation program included regular physical exercises, including respiratory training and physical fitness training, among other activities. Results: After pulmonary lobectomy surgery, both groups of patients showed a significant decrease in (1) forced vital capacity (FVC), (2) forced expiratory volume in 1 second (FEV1), (3) maximum voluntary ventilation (MVV), and (4) peak expiratory flow (PEF). However, the values of FVC, FEV1, MVV, and PEF in the EG were significantly higher than those in the CG (P < .05). Furthermore, both groups demonstrated significant improvements in the 6-minute walk test (6MWT) results after lung lobectomy; however, the 6MWT results in the EG also significantly increased (P < .05). In terms of dyspnea index (DI), after lung lobectomy, the DI for both groups of patients significantly increased, but the DI in the EG was significantly lower than that in the CG (P < .05). Conclusions: The combined application of drug therapy and pulmonary rehabilitation exercise training contributed to promoting cardiopulmonary function and respiratory muscle recovery in LC patients after thoracoscopic lobectomy. This was crucial for improving the quality of life of patients, as enhanced cardiopulmonary function and respiratory muscle recovery can alleviate postoperative respiratory difficulties, increase the physical stamina and activity levels of patients. This may help reduce the risk of postoperative complications, shorten hospital stays, and potentially improve long-term survival rates. Consequently, these results could have a positive impact on the development of postoperative care and treatment strategies. However, this work was subjected to several limitations, including a relatively short duration, necessitating longer-term follow-up to assess long-term effects. Additionally, the sample size was relatively small, and further large-scale research was needed to validate these findings.

Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.

Promoting Electromagnetic Wave Absorption Performance by Integrating MoS2@Gd2O3/MXene Multiple Hetero-Interfaces in Wood-Derived Carbon Aerogels.

Multi-component composite materials with a magnetic-dielectric synergistic effect exhibit satisfactory electromagnetic wave absorption performance. However, the effective construction of the structure for these multi-component materials to fully exploit the advantages of each component remains a challenge. Inspired by natural biomass, this study utilizes wood as the raw material and successfully prepares high-performance MoS2@Gd2O3/Mxene loaded porous carbon aerogel (MGMCA) composite material through a one-pot hydrothermal method and carbonization treatment process. With a delicate structural design, the MGMCA is endowed with abundant heterogeneous interface structures, favorable impedance matching characteristics, and a magnetic-dielectric synergistic system, thus demonstrating multiple electromagnetic wave loss mechanisms. Benefiting from these advantages, the obtained MGMCA exhibits outstanding electromagnetic wave absorption performance, with a minimum reflection loss of -57.5 dB at an ultra-thin thickness of only 1.9 mm. This research proposes a reliable strategy for the design of multi-component composite materials, providing valuable insight for the design of biomass-based materials as electromagnetic wave absorbers.

Pollinator sharing and hybridization in a pair of dioecious figs sheds light on the pathways to speciation.

The dynamics and processes underlying the codiversification of plant-pollinator interactions are of great interest to researchers of biodiversity and evolution. Cospeciation is generally considered a key process driving the diversity of figs and their pollinating wasps. Groups of closely related figs pollinated by separate wasps occur frequently and represent excellent opportunities to study ongoing diversification in this textbook mutualism. We study two closely related sympatric dioecious figs (Ficus heterostyla and Ficus squamosa) in Xishuangbanna, southwest China, and aim to document what is likely to be the final stages of speciation between these species using a combination of trait data and experimental manipulation. Volatile profiles at the receptive phase, crucial for attracting pollinators, were analyzed. In total, 37 and 29 volatile compounds were identified from receptive F. heterostyla and F. squamosa figs, respectively. Despite significant interspecific dissimilarity, 25 compounds were shared. Ovipositor lengths lie well within range required for access to heterospecific ovules, facilitating hybridization. Cross introduction of wasps into figs was conducted and hybrid seeds were generated for all donor/recipient combinations. F. heterostyla wasps produce adult offspring in F. squamosa figs. While F. squamosa wasps induce gall development in F. heterostyla figs and their offspring fail to mature in synchrony with their novel host. We record limited geographic barriers, minimal volatile dissimilarity, compatible morphology, complementary reproductive phenologies, and the production of hybrid seeds and wasp offspring. These findings suggest ongoing wasp specialization and reproductive isolation, potentially applicable to other related fig species.

Involvement of RFC3 in tamoxifen resistance in ER-positive breast cancer through the cell cycle.

Since the establishment of the molecular subtyping system, ER positive breast cancer was considered to be the most prevalent type of breast cancer, and endocrine therapy was a very important solution. However, numerous studies have shown that the cell cycle plays a key role in the progression and metastasis of breast cancer. The present study showed that RFC3 was involved in the cell cycle through DNA replication. Furthermore, RFC3 expression was significantly higher in breast cancer-resistant cells than in parental cells, which correlated with the cell cycle. We confirmed these results by established drug-resistant cell lines for breast cancer, raw letter analysis and immunohistochemical analysis of primary and recurrent tissues from three ER+ breast cancers. In addition, analysis of the results through an online database revealed that RFC3 expression was significantly associated with poor prognosis in ER+ breast cancer. We also demonstrated that in ER positive breast cancer-resistant cells, knockdown of RFC3 blocked the S-phase of cells and significantly attenuated cell proliferation, migration and invasion. Furthermore, RFC3 overexpression in ER positive breast cancer cells enhanced cell proliferation, migration and invasion. Taking all these findings into account, we could conclude that RFC3 was involved in endocrine resistance in breast cancer through the cell cycle. Thus, RFC3 may be a target to address endocrine therapy resistance in ER positive breast cancer and may be an independent prognostic factor in ER positive breast cancer.