Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells.

BACKGROUND: Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action. METHOD: An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action. RESULTS: Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD. CONCLUSION: This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.

Dynamic interfacial electrostatic energy harvesting via a single wire.

Spontaneously occurred electrostatic breakdown releases enormous energy, but harnessing the energy remains a notable challenge due to its irregularity and instantaneity. Here, we propose a revolutionary method that effectively harvests the energy of dynamic interfacial electrostatic breakdown by simply imbedding a conductive wire (diameter, 25 micrometers) beneath dielectric materials to regulate the originally chaotic and distributed electrostatic energy resulted from contact electrification into aggregation, effectively transforming mechanical energy into electricity. A point-charge physical model is proposed to explain the power generation process and output characteristics, guide structural design, and enhance output performance. Furthermore, a quantified triboelectric series including 72 dielectric material pairs is established for materials choice and optimization. In addition, a high voltage of over 10 kilovolts is achieved using polytetrafluoroethylene and polyethylene terephthalate. This work opens a door for effectively using electrostatic energy, offering promising applications ranging from novel high-voltage power sources, smart clothing, and internet of things.

[Outcomes of idiopathic pulmonary fibrosis patients with high body mass index undergoing extracorporeal membrane oxygenation support].

OBJECTIVE: To evaluate the extracorporeal membrane oxygenation (ECMO) related outcomes during hospitalization during the intensive care unit (ICU) in idiopathic pulmonary fibrosis (IPF) patients with high body mass index (BMI, > 25 kg/m2) undergoing lung transplantation with ECMO support. METHODS: A retrospective observational study was conducted. IPF patients who received ECMO during lung transplantation admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from 2019 to 2020 were enrolled. Preoperative indicators including, demographics, comorbidities, arterial blood gas, and laboratory indicators; intraoperative indicators, such as lung lobe volume reduction, surgical type, surgical time, cold ischemia time, blood loss and transfusion volume; immediate indicators upon admission to the ICU, such as blood gas analysis and laboratory indicators; ECMO related outcomes, such as ECMO mode, ECMO support time, ECMO related complications (bleeding at the catheterization site, intraductal thrombosis, lower limb ischemia), and the length of ICU stay, duration of mechanical ventilation, and 30-day survival rate were collected. According to BMI, patients were divided into three groups: light weight group (BMI < 18.5 kg/m2), normal weight group (BMI 18.5-24.9 kg/m2), and overweight group (BMI ≥ 25.0 kg/m2). Mainly to compare the relevant outcomes of ECMO among patients during ICU. RESULTS: A total of 114 IPF patients who received ECMO support during lung transplantation were collected, including 23 cases in the light weight group, 63 cases in the normal weight group, and 28 cases in the overweight group. Compared with patients with underweight and normal weight, overweight patients were more likely to have hypertension (46.4% vs. 8.7%, 23.8%, P < 0.01) and coronary heart disease (32.1% vs. 4.3%, 20.6%, P < 0.05) before surgery, which was consistent with international guidelines for obesity. Other clinical data (preoperative, intraoperative, ICU characteristics) showed no statistically significant differences and were comparable. There was no statistically significant difference in terms of ECMO related outcomes, such as ECMO related complications [veno-venous (V-V) mode: 78.3%, 77.8%, 78.6%, veno-arterial (V-A) mode: 21.7%, 22.2%, 21.4%], ECMO support time (hours: 61.70±20.03, 44.57±5.76, 41.77±7.26), ECMO related complications (bleeding at the catheterization site: 4.3%, 7.9%, 14.3%; intraductal thrombosis: 8.7%, 12.7%, 17.9%; lower limb ischemia: 8.7%, 12.7%, 14.3%), and the length of ICU stay (days: 11±3, 7±1, 9±1), duration of mechanical ventilation [days: 2 (2, 11), 2 (2, 6), 3 (2, 8)] among the light weight group, normal weight group, and overweight group (all P > 0.05). Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 30-day cumulative survival rate among the three groups (Log-Rank test: χ 2 = 0.919, P = 0.632). CONCLUSIONS: High BMI does not worsen ECMO-related outcomes or adversely affect early prognosis in IPF patients undergoing lung transplantation. BMI as a single parameter should not be a contraindication for the use of ECMO in lung transplantation surgery for IPF patients.

Overlapping Pattern of the Four Individual Components of Dyslipidemia in Adults: Analysis of Nationally Representative Data.

Background/Objectives: Dyslipidemia is a well-established risk factor for cardiovascular disease (CVD). However, among available drug treatments, only those targeted at lowering LDL-C and consequently TC have demonstrated efficacy in preventing CVD. This is to say that the benefit for those with isolated high TG or low HDL-C is limited. The objective of this study is to examine the overlapping pattern of the four dyslipidemia components in US adult populations, which is important for quantifying the proportion of those who are less likely to benefit from lipid-lowering drugs and for a more precise use of the drug. Methods: A total of 7822 participants aged over 20 with abnormalities in any of the four lipid parameters, excluding those on lipid-lowering medications, were included from the National Health and Nutrition Examination Survey (NHANES) cycles spanning 1999-2000 through 2017-2018. The proportions of different combinations of them were calculated and presented using area-proportional Euler plots. Results: High TC, high LDL-C, high TG, and low HDL-C were seen in 32.8% (95% CI: 31.3%-34.2%), 28.1% (95% CI: 26.6%-29.6%), 26.7% (95% CI: 25.4%-28.0%), and 65.9% (95% CI: 64.0%-67.7%) of the people with dyslipidemia, respectively. The proportions of dyslipidemia cases attributable to "high LDL-C or high TC" (irrespective of HDL-C and TG levels), "normal LDL-C, normal TC, but high TG" (irrespective of HDL-C level), and "normal LDL-C, normal TC, normal TG, but low HDL-C" (i.e., isolated low HDL-C) accounted for 37.5% (95% CI: 35.9%-39.1%), 18.3% (95% CI: 17.2%-19.4%), and 44.2% (95% CI: 42.5%-46.0%), respectively. Conclusions: Some two-thirds of those with dyslipidemia had low HDL-C or high TG but normal LDL-C and normal TC. As these people are less likely to benefit from currently available drug treatments in terms of CVD prevention, it is important to identify other effective strategies or interventions targeted at them in order to achieve more precise and cost-effective management of dyslipidemia.

FedKG: A Knowledge Distillation-Based Federated Graph Method for Social Bot Detection.

Malicious social bots pose a serious threat to social network security by spreading false information and guiding bad opinions in social networks. The singularity and scarcity of single organization data and the high cost of labeling social bots have given rise to the construction of federated models that combine federated learning with social bot detection. In this paper, we first combine the federated learning framework with the Relational Graph Convolutional Neural Network (RGCN) model to achieve federated social bot detection. A class-level cross entropy loss function is applied in the local model training to mitigate the effects of the class imbalance problem in local data. To address the data heterogeneity issue from multiple participants, we optimize the classical federated learning algorithm by applying knowledge distillation methods. Specifically, we adjust the client-side and server-side models separately: training a global generator to generate pseudo-samples based on the local data distribution knowledge to correct the optimization direction of client-side classification models, and integrating client-side classification models' knowledge on the server side to guide the training of the global classification model. We conduct extensive experiments on widely used datasets, and the results demonstrate the effectiveness of our approach in social bot detection in heterogeneous data scenarios. Compared to baseline methods, our approach achieves a nearly 3-10% improvement in detection accuracy when the data heterogeneity is larger. Additionally, our method achieves the specified accuracy with minimal communication rounds.

Tailoring the peroxidase-like properties of Mo atom nanoclusters/N-MXene nanozymes for sensitive colorimetric detection of glutathione.

Although nanozyme engineering has made tremendous progress, there is a huge gap between them and natural enzymes due to the enormous challenge of precisely adjusting the geometric and electronic structure of active sites. Considering that intentionally adjusting the metal-carrier interactions may bring the promising catalytic activity, in this work, a novel Mo atom nanocluster is successfully synthesized using nitrogen-doped Mxene (MoACs/N-MXene) nanozymes as carriers. The constructed MoACs/N-MXene displays excellent peroxidase-like catalytic activity and kinetics, outweighing its N-MXene and Mo nanoparticles (NPs)-MXene references and natural horse radish peroxidase. This work not only reports a successful example of MoACs/N-MXene nanozyme as a guide for achieving peroxidase-mimic performance of nanozymes for colorimetric glutathione sensing at 0.29 µM, but also expands the application prospects of two-dimensional MXene nanosheets by reasonably introducing metal atomic clusters and nonmetal atom doping and exploring related nanozyme properties.

Platinum single atom on CsPbBr3 nanocrystals as electrocatalyst boosts electrochemical sensing of ascorbic acid.

Monitoring ascorbic acid (AA) levels in human body can provide valuable clues for disease diagnosis. Anchoring noble metal single atoms on perovskite substrate is a promising strategy to design electrocatalysts with outstanding electrocatalytic performance. Herein, we design an electrochemical method for detecting AA by utilizing Pt single atoms-doped CsPbBr3 nanocrystals (Pt SA/CsPbBr3 NCs) fixed on a glassy carbon electrode as an electrochemical catalyst. The uncharged 3,5,3',5'-tetramethylbenzidine (TMB) undergoes oxidation to form the positively charged oxidized TMB (oxTMB) owing to the exceptional electrochemical catalytic performance of Pt SA/CsPbBr3 NCs. Subsequently, the target AA reduces oxTMB to TMB, which is then electrocatalytically oxidized to oxTMB, producing significant oxidation current. In this way, such characteristic provides a sensitive electrochemical strategy for AA detection, achieving a concentration range of 50-fold with the detection limit of 0.0369 µM. The developed electrochemical method also successfully generates accurate detection response of AA in complex sample media (urine). Overall, this approach is expected to offer a novel way for early disease diagnosis.

Deregulation of immune response contributing to fulminant hepatitis in HEV infected pregnant women.

Hepatitis E virus (HEV) infection in pregnant women is associated with a wide spectrum of adverse consequences for both mother and fetus. The high mortality in this population appears to be associated with hormonal changes and consequent immunological changes. This study conducted an analysis of immune responses in pregnant women infected with HEV manifesting varying severity. Data mining analysis of the GSE79197 was utilized to examine differentially biological functions in pregnant women with HEV infection (P-HEV) versus without HEV infection (P-nHEV), P-HEV progressing to ALF (P-ALF) versus P-HEV, and P-HEV versus non-pregnant women with HEV infection (nP-HEV). We found cellular response to interleukin and immune response-regulating signalings were activated in P-HEV compared with P-nHEV. However, there was a significant decrease of immune responses, such as T cell activation, leukocyte cell-cell adhesion, regulation of lymphocyte activation, and immune response-regulating signaling pathway in P-ALF patient than P-HEV patient. Compared with nP-HEV, MHC protein complex binding function was inhibited in P-HEV. Further microRNA enrichment analysis showed that MAPK and T cell receptor signaling pathways were inhibited in P-HEV compared with nP-HEV. In summary, immune responses were activated during HEV infection while being suppressed when developing ALF during pregnancy, heightening the importance of immune mediation in the pathogenesis of severe outcome in HEV infected pregnant women.

Spontaneously established reverse electric field to enhance the performance of triboelectric nanogenerators via improving Coulombic efficiency.

Mechanical energy harvesting using triboelectric nanogenerators is a highly desirable and sustainable method for the reliable power supply of widely distributed electronics in the new era; however, its practical viability is seriously challenged by the limited performance because of the inevitable side-discharge and low Coulombic-efficiency issues arising from electrostatic breakdown. Here, we report an important progress on these fundamental problems that the spontaneously established reverse electric field between the electrode and triboelectric layer can restrict the side-discharge problem in triboelectric nanogenerators. The demonstration employed by direct-current triboelectric nanogenerators leads to a high Coulombic efficiency (increased from 28.2% to 94.8%) and substantial enhancement of output power. More importantly, we demonstrate this strategy is universal for other mode triboelectric nanogenerators, and a record-high average power density of 6.15 W m-2 Hz-1 is realized. Furthermore, Coulombic efficiency is verified as a new figure-of-merit to quantitatively evaluate the practical performance of triboelectric nanogenerators.

Long-term exposure to ambient ozone and adult-onset asthma: A prospective cohort study.

BACKGROUND: The association between long-term exposure to ozone (O3) and adult-onset asthma (AOA) remains inconclusive, and analysis of causality is lacking. OBJECTIVES: To examine the causal association between long-term O3 exposure and AOA. METHODS: A prospective cohort study of 362,098 participants was conducted using the UK Biobank study. Incident cases of AOA were identified using health administrative data of the National Health Services. O3 exposure at participants' residential addresses was estimated by a spatio-temporal model. Instrumental variable (IV) modelling was used to analyze the causal association between O3 exposure and AOA, by incorporating wind speed and planetary boundary layer height as IVs into time-dependent Cox model. Negative control outcome (accidental injury) was also used to additionally evaluate unmeasured confounding. RESULTS: During a mean follow-up of 11.38 years, a total of 10,973 incident AOA cases were identified. A U-shaped concentration-response relationship was observed between O3 exposure and AOA in the traditional Cox models with HR of 0.916 (95% CI: 0.888, 0.945) for O3 at low levels (<38.17 ppb), and 1.204 (95% CI: 1.168, 1.242) for O3 at high levels (≥38.17 ppb). However, in the IV analysis we only found a statistically significant association between high-level O3 exposure and AOA risk, but not for low-level O3 exposure. No significant associations between O3 exposure and accidental injury were observed. CONCLUSION: Our findings suggest a potential causal relationship between long-term exposure to high-level ambient O3 and increased risks of AOA.

A Dual-Mode Triboelectric Nanogenerator for Efficiently Harvesting Droplet Energy.

Triboelectric nanogenerator (TENG) is a promising solution to harvest the low-frequency, low-actuation-force, and high-entropy droplet energy. Conventional attempts mainly focus on maximizing electrostatic energy harvest on the liquid-solid surface, but enormous kinetic energy of droplet hitting the substrate is directly dissipated, limiting the output performance. Here, a dual-mode TENG (DM-TENG) is proposed to efficiently harvest both electrostatic energy at liquid-solid surface from a droplet TENG (D-TENG) and elastic potential energy of the vibrated cantilever from a contact-separation TENG (CS-TENG). Triggered by small droplets, the flexible cantilever beam, rather than conventional stiff ones, can easily vibrate multiple times with large amplitude, enabling frequency multiplication of CS-TENG and producing amplified output charges. Combining with the top electrode design to sufficiently utilize charges at liquid-solid interface, a record-high output charge of 158 nC is realized by single droplet. The energy conversion efficiency of DM-TENG is 2.66-fold of D-TENG. An array system with the specially designed power management circuit is also demonstrated for building self-powered system, offering promising applications for efficiently harvesting raindrop energy.

A High-Voltage-Specialized Direct-Current Triboelectric Nanogenerator for Air Purification.

Human health and the environment face significant challenges of air pollution, which is predominantly caused by PM2.5 or PM10 particles. Existing control methods often require elevated energy consumption or bulky high-voltage electrical equipment. To overcome these limitations, a self-powered, convenient, and compact direct current high-voltage triboelectric nanogenerator based on triboelectrification and electrostatic breakdown effects is proposed. By optimizing the structure-design of the direct current triboelectric nanogenerator and corresponding output voltage, it can easily achieve an output voltage of over 3 kV with a high charge density of 320 µC m-2 . A power management circuit is designed to overcome the influence of third domain self-breakdown, optimize 92.5% amplitude of voltage shake, and raise 5% charge utilization ratio. With a device size as tiny as 2.25 cm3 , it can continuously drive carbon nanowires to generate negative ions that settle dust within 300 s. This compact, simple, efficient, and safe high-voltage direct current triboelectric nanogenerator represents a promising sustainable solution. It offers efficient dust mitigation, fostering cleaner environments, and enhancing overall health.

New multi-source waste co-incineration and clustering park operating model for small- and medium-sized city: A case study in China.

With improvements in urban waste management to promote sustainable development, an increasing number of waste types need to be sorted and treated separately. Due to the relatively low amount of waste generated in small- and medium-sized cities, separate treatment facilities for each waste type lack scale, waste is treated at a high cost and low efficiency. Therefore, industrial symbiosis principles are suggested to be used to guide collaborative waste treatment system of multi-source solid wastes, and co-incineration is the most commonly used technology. Most existing studies have focused on co-incineration of one certain waste type (such as sludge or medical waste) with municipal solid waste (MSW), but the systematic design and the comprehensive benefits on a whole city and park level have not been widely studied. Taking the actual operation of a multi-source waste co-incineration park in south-central China as an example, this study conducted a detailed analysis of the waste-energy-water metabolism process of MSW, sludge, food waste, and medical waste co-incineration. The environmental and economic benefits were evaluated and compared with the single decentralized waste treatment mode. The results showed that the multi-source waste co-incineration and clustering park operating model was comprehensively superior to the single treatment mode, greenhouse gases and human toxicity indicators were decreased by 11.87% and 295.74%, respectively, and the internal rate of return of the project was increased by 29.35%. This mainly benefits from the synergy of technical system and the economies of scale. Finally, this research proposed policy suggestions from systematic planning and design, technical route selection, and an innovative management mode in view of the potential challenges.

Causal association between long-term exposure to air pollution and incident Parkinson's disease.

Epidemiological evidence for long-term air pollution exposure and Parkinson's disease (PD) is controversial, and analysis of causality is limited. We identified 293,888 participants who were free of PD at baseline in the UK Biobank (2006-2010). Time-varying air pollution [fine particulate (PM2.5) and ozone (O3)] exposures were estimated using spatio-temporal models. Incident cases of PD were identified using validated algorithms. Four methods were used to investigate the associations between air pollution and PD, including (1) standard time-varying Cox proportional-hazard model; (2) Cox models weighted by generalized propensity score (GPS) and inverse-probability weights (IPW); (3) instrumental variable (IV) analysis; and (4) negative control outcome analysis. During a median of 11.6 years of follow-up, 1822 incident PD cases were identified. Based on standard Cox regression, the hazard ratios (95% confidence interval) for a 1 µg/m3 or ppb increase in PM2.5 and O3 were 1.23 (1.17, 1.30) and 1.02 (0.98, 1.05), respectively. Consistent results were found in models weighted by GPS and IPW, and in IV analysis. There were no significant associations between air pollution and negative control outcomes. This study provides evidence to support a causal association between PM2.5 exposure and PD. Mitigation of air pollution could be a protective measure against PD.

Tailored Polypyrrole Nanofibers as Ion-to-Electron Transduction Membranes for Wearable K+ Sensors.

Conductive polymers are recognized as ideal candidates for the development of noninvasive and wearable sensors for real-time monitoring of potassium ions (K+) in sweat to ensure the health of life. However, the low ion-to-electron transduction efficiency and limited active surface area hamper the development of high-performance sensors for low-concentration K+ detection in the sweat. Herein, a wearable K+ sensor is developed by tailoring the nanostructure of polypyrrole (PPy), serving as an ion-to-electron transduction layer, for accurately and stably tracing the K+ fluctuation in human sweat. The PPy nanostructures can be tailored from nanospheres to nanofibers by controlling the supramolecular assembly process during PPy polymerization. Resultantly, the ion-to-electron transduction efficiency (17-fold increase in conductivity) and active surface area (1.3-fold enhancement) are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofibers-based K+ sensor achieved a high sensitivity of 62 mV decade-1, good selectivity, and solid stability. After being integrated with a temperature sensor, the manufactured wearable sensor realized accurate monitoring of K+ fluctuation in the human sweat.

Prevalence of and factors associated with potentially redundant randomized controlled trials: a cross-sectional study.

OBJECTIVES: To investigate the prevalence of meta-analyses containing potentially redundant randomized controlled trials (RCTs) and the factors associated with the presence of redundancy. STUDY DESIGN AND SETTING: This is a cross-sectional study, based on a random sample of references (n = 4500) that were published during 2020 and 2021, indexed in PubMed, Embase, or the Cochrane Database of Systematic Reviews, and retrieved through comprehensive searches using terms about systematic reviews and meta-analysis. From each systematic review, one meta-analysis fulfilling all the following criteria, if available, was included in this study: (1) assessing the effect of the intervention on a primary outcome of the systematic review; (2) combining RCTs only. The primary outcome was prevalence of meta-analyses containing potentially redundant RCTs. Potentially redundant RCTs referred to the trials that started 1 year after the overall effect estimate from cumulative meta-analysis had been statistically robust, as determined by trial sequential analysis when appropriate. The number of potentially redundant trials (if any) in each eligible meta-analysis and the number of participants involved in those trials were documented and contrasted across groups. Logistic regression analysis was conducted to explore the factors associated with presence of potential redundancy. RESULTS: Of the 448 eligible meta-analyses, 57 (12.7%, 95% confidence interval (CI) 9.8-16.2%) contained potentially redundant RCTs. When limited to the 333 low-heterogeneity meta-analyses, the prevalence was 17.1% (95% CI 13.5-21.5%). The total number of potentially redundant RCTs was 295 (involving 85,385 participants), accounting for 38.5% of the RCTs (and 30.3% of the participants) included in the 57 meta-analyses. In these meta-analyses, the median number of potentially redundant RCTs and the participants involved were 2 (range: 1-50) and 352 (range: 17-26997), respectively. Potentially redundant RCTs were more likely to be present in the meta-analyses evaluating pharmaceutical intervention (odds ratio [OR] 2.31, 95% CI 1.16-4.49), assessing efficacy outcomes (OR 7.25, 95% CI 0.85-61.87), containing more than 5 RCTs (OR 6.47, 95% CI 3.22-12.99), or with the earliest RCT reporting statistically significant effect estimate (OR 5.30, 95% CI 2.64-10.64). CONCLUSION: This study found that 12.7% to 17.1% of recently published meta-analyses contained potentially redundant RCTs, highlighting the importance of conducting or examining systematic reviews of existing evidence to justify new RCTs. More importantly, the study identified some scenarios in which redundancy was more likely to occur and thus has implications for trialists, funding agencies, ethics committees, and journal editors.

[Characteristics of Vertical Distribution and Environmental Factors of Antibiotics in Quaternary Sedimentary Column in Urban Areas].

Antibiotics easily remain in sediments after migrating from the surface to the subsurface due to water-rock interactions, posing a risk of secondary release to groundwater. To investigate the vertical distribution characteristics and environmental impact factors of antibiotics, five 30 m quaternary sediment columns were drilled and stratified near the hospital, and five major classes of antibiotics and sulfonamide metabolites were tested and analyzed. The results showed that:① the antibiotic content in the sediments ranged from 3.05 to 107.03 µg·kg-1, and all of the target antibiotics were detected except lomefloxacin, of which ofloxacin and oxytetracycline were the most important antibiotics in the study area. ② The antibiotics did not show a strict downward trend in the vertical direction but varied with the lithological stratification. ③ Antibiotics were primarily deposited in the clay layer and varied with the fluctuation of the groundwater level. ④ The results of redundancy analysis between antibiotics and environmental factors suggested that pH and TOC controlled the fate and transformation of antibiotics through influencing the adsorption of antibiotics by sediments. The risk of antibiotic contamination from hospital wastewater seepage into the subsurface environment should be taken seriously.

Hyperhenrones: Prenylated α-pyrones with anti-inflammatory activity from Hypericum henryi.

Fourteen previously undescribed α-pyrone derivatives (1-14) together with four known analogs (15-18) were isolated from a traditional Chinese medicinal plant Hypericum henryi. Compounds (+)/(-)-1, 2, and 3 share a rare 6/6/4/6/6 polycyclic skeleton. Compound 14 was the first example of a 7,7-dimethyl-pyran-4-one moiety. Their structures were elucidated using comprehensive spectroscopic analyses and electronic circular dichroism calculations. The anti-inflammatory activities of 1-18 were screened in lipopolysaccharide-induced RAW264.7 cells. Among them, compounds 14, (+)-18, and (-)-18 exhibited inhibitory effects against nitric oxide production in LPS-induced RAW264.7 cells. Additionally, compound 14 suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-induced RAW264.7 cells. Furthermore, preliminary mechanism studies indicated that compound 14 suppressed the phosphorylation and degradation of the inhibitor of NF-κB, and this led to the inhibition of NF-κB activation.

Global analysis of iron metabolism-related genes identifies potential mechanisms of gliomagenesis and reveals novel targets.

AIMS: This study aimed to investigate key regulators of aberrant iron metabolism in gliomas, and evaluate their effect on biological functions and clinical translational relevance. METHODS: We used transcriptomic data from multiple cross-platform glioma cohorts to identify key iron metabolism-related genes (IMRGs) based on a series of bioinformatic and machine learning methods. The associations between IMRGs and prognosis, mesenchymal phenotype, and genomic alterations were analyzed in silico. The performance of the IMRGs-based signature in predicting temozolomide (TMZ) treatment sensitivity was evaluated. In vitro and in vivo experiments were used to explore the biological functions of these key IMRGs. RESULTS: HMOX1, LTF, and STEAP3 were identified as the most essential IMRGs in gliomas. The expression levels of these genes were strongly related to clinicopathological and molecular features. The robust IMRG-based gene signature could be used for prognosis prediction. These genes facilitate mesenchymal transformation, driver gene mutations, and oncogenic alterations in gliomas. The gene signature was also associated with TMZ resistance. HMOX1, LTF, and STEAP3 knockdown in glioma cells significantly reduced cell proliferation, colony formation, migration, and malignant invasion. CONCLUSION: The study presented a comprehensive view of key regulators underpinning iron metabolism in gliomas and provided new insights into novel therapeutic approaches.

The promoting effect and mechanism of MAD2L2 on stemness maintenance and malignant progression in glioma.

BACKGROUND: Glioblastoma, the most common primary malignant tumor of the brain, is associated with poor prognosis. Glioblastoma cells exhibit high proliferative and invasive properties, and glioblastoma stem cells (GSCs) have been shown to play a crucial role in the malignant behavior of glioblastoma cells. This study aims to investigate the molecular mechanisms involved in GSCs maintenance and malignant progression. METHODS: Bioinformatics analysis was performed based on data from public databases to explore the expression profile of Mitotic arrest deficient 2 like 2 (MAD2L2) and its potential function in glioma. The impact of MAD2L2 on glioblastoma cell behaviors was assessed through cell viability assays (CCK8), colony formation assays, 5-Ethynyl-2'-deoxyuridine (EDU) incorporation assays, scratch assays, and transwell migration/invasion assays. The findings from in vitro experiments were further validated in vivo using xenograft tumor model. GSCs were isolated from the U87 and LN229 cell lines through flow cytometry and the stemness characteristics were verified by immunofluorescence staining. The sphere-forming ability of GSCs was examined using the stem cell sphere formation assay. Bioinformatics methods were conducted to identified the potential downstream target genes of MAD2L2, followed by in vitro experimental validation. Furthermore, potential upstream transcription factors that regulate MAD2L2 expression were confirmed through chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The MAD2L2 exhibited high expression in glioblastoma samples and showed significant correlation with patient prognosis. In vitro and in vivo experiments confirmed that silencing of MAD2L2 led to decreased proliferation, invasion, and migration capabilities of glioblastoma cells, while decreasing stemness characteristics of glioblastoma stem cells. Conversely, overexpression of MAD2L2 enhanced these malignant behaviors. Further investigation revealed that MYC proto-oncogene (c-MYC) mediated the functional role of MAD2L2 in glioblastoma, which was further validated through a rescue experiment. Moreover, using dual-luciferase reporter gene assays and ChIP assays determined that the upstream transcription factor E2F-1 regulated the expression of MAD2L2. CONCLUSION: Our study elucidated the role of MAD2L2 in maintaining glioblastoma stemness and promoting malignant behaviors through the regulation of c-MYC, suggesting its potential as a therapeutic target.