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.

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.

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.

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.

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.

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.

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.

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.

Optimized O(α_{s}

The failure of observing the e^{+}e^{-}→J/ψJ/ψ events at B factories to date is often attributed to the significant negative order-α_{s} correction. In this work we compute the O(α_{s}^{2}) correction to this process for the first time. The magnitude of the next-to-next-to-leading order (NNLO) perturbative correction is substantially negative so that the standard nonrelativistic QCD prediction would suffer from an unphysical, negative cross section. This dilemma may be traced in the fact that the bulk contribution of the fixed-order radiative corrections stems from the perturbative corrections to the J/ψ decay constant. We thus implement an improved nonrelativistic QCD factorization framework, by decomposing the amplitude into the photon-fragmentation piece and the nonfragmentation piece. With the measured J/ψ decay constant as input, which amounts to resumming a specific class of radiative and relativistic corrections to all orders, the fragmentation-induced production rate can be predicted accurately and serves a benchmark prediction. The nonfragmentation type of the amplitude is then computed through NNLO in α_{s} and at lowest order in velocity. Both the O(α_{s}) and O(α_{s}^{2}) corrections in the interference term become positive and exhibit a decent convergence behavior. Our finest prediction is σ(e^{+}e^{-}→J/ψJ/ψ)=2.13_{-0.06}^{+0.30} fb at sqrt[s]=10.58 GeV. With the projected integrated luminosity of 50 ab^{-1}, the prospect to observe this exclusive process at Belle 2 experiment appears to be bright.

F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice.

BACKGROUND: Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice. RESULTS: Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1ß (IL-1ß), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor ß (TGF-ß) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). CONCLUSION: Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile.

Distribution and risk assessment of antibiotics under water level fluctuation in the riparian zone of the Hanjiang River.

The riparian zone (RZ) is an important region connecting surface water and groundwater, and it has widely been acknowledged for its pollutant buffering capacity. However, the decontaminating effect of RZ on trace organic compounds such as antibiotics has received little attention. This study explored the distribution of 21 antibiotics and 4 sulfonamide metabolites in river water and groundwater in the lower reaches of the Hanjiang River. The diffusion and exchange of contaminants between the river and riverbanks under the influence of water conservancy projects (Xinglong Dam and the Yangtze-Hanjiang Water Diversion Project) were investigated. Macrolide antibiotics were prevalent in river water (62.5-100%) and groundwater samples (42.9-80.4%). Ofloxacin and chlortetracycline were detected with the highest concentrations in river water (12.2 ng L-1) and groundwater (9.3 ng L-1) respectively. Higher levels of antibiotics were observed in spring and winter than in other seasons. The river-groundwater interaction has a certain interception effect on antibiotics, especially near riverbanks. Redox sensitive element Fe2+ showed significantly positive correlations with some tetracycline and macrolide antibiotics (p < 0.05), and thus the migration mechanism between Fe2+ and antibiotics under the condition of redox change should be investigated further. Environmental risks posed by antibiotics were assessed for algae, daphnids, and fish in surface water and groundwater. Only clarithromycin and chlortetracycline presented a medium risk to algae (0.1 < RQ < 1), and the rest presented low risk (RQ < 0.1). Nevertheless, the risk range may be further extended by interactions between groundwater and surface water. Accurate understanding of antibiotic transport in RZ is critical for developing management strategies aimed at reducing the pollution load on the watershed.

DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants.

BACKGROUND: Two variants in the gene encoding apolipoprotein L1 (APOL1) that are highly associated with African ancestry are major contributors to the large racial disparity in rates of human kidney disease. We previously demonstrated that recruitment of APOL1 risk variants G1 and G2 from the endoplasmic reticulum to lipid droplets leads to reduced APOL1-mediated cytotoxicity in human podocytes. METHODS: We used CRISPR-Cas9 gene editing of induced pluripotent stem cells to develop human-derived APOL1G0/G0 and APOL1G2/G2 kidney organoids on an isogenic background, and performed bulk RNA sequencing of organoids before and after treatment with IFN-γ. We examined the number and distribution of lipid droplets in response to treatment with inhibitors of diacylglycerol O-acyltransferases 1 and 2 (DGAT1 and DGAT2) in kidney cells and organoids. RESULTS: APOL1 was highly upregulated in response to IFN-γ in human kidney organoids, with greater increases in organoids of high-risk G1 and G2 genotypes compared with wild-type (G0) organoids. RNA sequencing of organoids revealed that high-risk APOL1G2/G2 organoids exhibited downregulation of a number of genes involved in lipogenesis and lipid droplet biogenesis, as well as upregulation of genes involved in fatty acid oxidation. There were fewer lipid droplets in unstimulated high-risk APOL1G2/G2 kidney organoids than in wild-type APOL1G0/G0 organoids. Whereas DGAT1 inhibition reduced kidney organoid lipid droplet number, DGAT2 inhibition unexpectedly increased organoid lipid droplet number. DGAT2 inhibition promoted the recruitment of APOL1 to lipid droplets, with associated reduction in cytotoxicity. CONCLUSIONS: Lipogenesis and lipid droplet formation are important modulators of APOL1-associated cytotoxicity. Inhibition of DGAT2 may offer a potential therapeutic strategy to attenuate cytotoxic effects of APOL1 risk variants.

A Conway-Maxwell-Poisson-Binomial AR(1) Model for Bounded Time Series Data.

Binomial autoregressive models are frequently used for modeling bounded time series counts. However, they are not well developed for more complex bounded time series counts of the occurrence of n exchangeable and dependent units, which are becoming increasingly common in practice. To fill this gap, this paper first constructs an exchangeable Conway-Maxwell-Poisson-binomial (CMPB) thinning operator and then establishes the Conway-Maxwell-Poisson-binomial AR (CMPBAR) model. We establish its stationarity and ergodicity, discuss the conditional maximum likelihood (CML) estimate of the model's parameters, and establish the asymptotic normality of the CML estimator. In a simulation study, the boxplots illustrate that the CML estimator is consistent and the qqplots show the asymptotic normality of the CML estimator. In the real data example, our model takes a smaller AIC and BIC than its main competitors.

Screening of differentially expressed microRNAs and target genes in two potato varieties under nitrogen stress.

BACKGROUND: A reasonable supply of nitrogen (N) fertilizer is essential for obtaining high-quality, high-level, and stable potato yields, and an improvement in the N utilization efficiency can effectively reduce N fertilizer use. It is important to use accurate, straightforward, and efficient transgenic breeding techniques for the identification of genes that can improve nitrogen use efficiency, thus enabling us to achieve the ultimate goal of breeding N-efficient potato varieties. In recent years, some of the mechanisms of miRNAs have been elucidated via the analysis of the correlation between the expression levels of potato miRNA target genes and regulated genes under conditions of stress, but the role of miRNAs in the inhibition/expression of key genes regulating N metabolism under N stress is still unclear. Our study aimed to identify the role played by specific enzymes and miRNAs in the responses of plants to N stress. RESULTS: The roots and leaves of the N-efficient potato variety, Yanshu4 ("Y"), and N-inefficient potato variety, Atlantic ("D"), were collected at the seedling and budding stages after they were exposed to different N fertilizer treatments. The miRNAs expressed differentially under the two types of N stress and their corresponding target genes were first predicted using miRNA and degradome analysis. Then, quantitative polymerase chain reaction (qRT-PCR) was performed to verify the expression of differential miRNAs that were closely related to N metabolism. Finally, the shearing relationship between stu-miR396-5p and its target gene StNiR was determined by analyzing luciferase activity levels. The results showed that NiR activity increased significantly with an increase in the applied N levels from the seedling stage to the budding stage, and NiR responded significantly to different N treatments. miRNA sequencing enabled us to predict 48 families with conserved miRNAs that were mainly involved in N metabolism, carbon metabolism, and amino acid biosynthesis. The differences in the expression of the following miRNAs were identified via screening (high expression levels and P < 0.05): stu-miR396-5p, stu-miR408b-3p_R-1, stu-miR3627-3p, stu-miR482a-3p, stu-miR8036-3p, stu-miR482a-5p, stu-miR827-5p, stu-miR156a_L-1, stu-miR827-3p, stu-miR172b-5p, stu-miR6022-p3_7, stu-miR398a-5p, and stu-miR166c-5p_L-3. Degradome analysis showed that most miRNAs had many-to-many relationships with target genes. The main target genes involved in N metabolism were NiR, NiR1, NRT2.5, and NRT2.7. qRT-PCR analysis showed that there were significant differences in the expression levels of stu-miR396-5p, stu-miR8036-3p, and stu-miR482a-3p in the leaves and roots of the Yanshu4 and Atlantic varieties at the seedling and budding stages under conditions that involved no N and excessive N application; the expression of these miRNAs was induced in response to N stress. The correlation between the differential expression of stu-miR396-5p and its corresponding target gene NiR was further verified by determining the luciferase activity level and was found to be strongly negative. CONCLUSION: The activity of NiR was significantly positively correlated with N application from the seedling to the budding stage. Differential miRNAs and target genes showed a many-to-many relationship with each other. The expression of stu-miR396-5p, stu-miR482a-3p, and stu-miR8036-3p in the roots and leaves of the Yanshu4 and Atlantic varieties at the seedling and budding stages was notably different under two types of N stress. Under two types of N stress, stu-miR396-5p was down-regulated in Yanshu4 in the seedling-stage and shoot-stage roots, and up-regulated in seedling-stage roots and shoot-stage leaves; stu-miR482a-3p was up-regulated in the seedling and shoot stages. The expression of stu-miR8036-3p was up-regulated in the leaves and roots at the seedling and budding stages, and down-regulated in roots under both types of N stress. The gene expressing the key enzyme involved in N metabolism, StNiR, and the stu-miR396-5p luciferase assay reporter gene had a strong regulatory relationship with each other. This study provides candidate miRNAs related to nitrogen metabolism and highlights that differential miRNAs play a key role in nitrogen stress in potato, providing insights for future research on miRNAs and their target genes in nitrogen metabolic pathways and breeding nitrogen-efficient potatoes.

Recruitment of APOL1 kidney disease risk variants to lipid droplets attenuates cell toxicity.

Two coding variants in the apolipoprotein L1 (APOL1) gene (termed G1 and G2) are strongly associated with increased risk of nondiabetic kidney disease in people of recent African ancestry. The mechanisms by which the risk variants cause kidney damage, although not well-understood, are believed to involve injury to glomerular podocytes. The intracellular localization and function of APOL1 in podocytes remain unclear, with recent studies suggesting possible roles in the endoplasmic reticulum (ER), mitochondria, endosomes, lysosomes, and autophagosomes. Here, we demonstrate that APOL1 also localizes to intracellular lipid droplets (LDs). While a large fraction of risk variant APOL1 (G1 and G2) localizes to the ER, a significant proportion of wild-type APOL1 (G0) localizes to LDs. APOL1 transiently interacts with numerous organelles, including the ER, mitochondria, and endosomes. Treatment of cells that promote LD formation with oleic acid shifted the localization of G1 and G2 from the ER to LDs, with accompanying reduction of autophagic flux and cytotoxicity. Coexpression of G0 APOL1 with risk variant APOL1 enabled recruitment of G1 and G2 from the ER to LDs, accompanied by reduced cell death. The ability of G0 APOL1 to recruit risk variant APOL1 to LDs may help explain the recessive pattern of kidney disease inheritance. These studies establish APOL1 as a bona fide LD-associated protein, and reveal that recruitment of risk variant APOL1 to LDs reduces cell toxicity, autophagic flux, and cell death. Thus, interventions that divert APOL1 risk variants to LDs may serve as a novel therapeutic strategy to alleviate their cytotoxic effects.

Benzophenone Rhamnosides and Chromones from Hypericum seniawinii Maxim.

Two new benzophenone glycosides, hypersens A and B, along with four known compounds, (S)-(+)-5,7-dihydroxy-2-(1-methylpropyl) chromone (3), 5,7-dihydroxy-2-isopropylchromone (4), urachromone B (5), and 3-8'' bisapigenin (6), were isolated from Hypericum seniawinii. The structures of new compounds (1 and 2) were elucidated according to comprehensive spectroscopic data analyses. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations. All isolated compounds were evaluated for their neuroprotective effect using corticosterone-induced PC12 cell injury. In addition, compounds 1-6 were evaluated for their anti-inflammatory activity in lipopolysaccharide-induced RAW 264.7 cells. Compound 6 was a biflavonoid and significantly inhibited the production of nitric oxide with an IC50 value of 11.48 ± 1.23 µM.

MiR-506-3p Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells via Targeting KLF4.

BACKGROUND: The dysregulation of proliferation and migration of vascular smooth muscle cells (VSMCs) is one of the major causes of atherosclerosis (AS). Accumulating studies confirm that Kruppel-like factor 4 (KLF4) can regulate the proliferation and differentiation of VSMCs through multiple signaling pathways. However, the mechanism of KLF4 dysregulation remains unknown. METHODS: Apolipoprotein E-knockout (ApoE-/-) mice and human VSMCs were used to establish AS animal model and cell model, respectively. qRT-PCR was employed to determine the expressions of miR-506-3p and KLF4. Cell Counting Kit -8, Transwell, TUNEL assays, and flow cytometry were performed to measure the proliferation, migration, and apoptosis of VSMCs. The upstream miRNAs of KLF4 were predicted by microT, miRanda, miRmap, and TargetScan databases. The interaction between KLF4 and miR-506-3p was confirmed using qRT-PCR, Western blot, and luciferase reporter gene assay. RESULTS: KLF4 expression was significantly decreased in the VSMCs of ApoE-/- mice fed with high-fat diet and in human VSMCs treated with oxidized low-density lipoprotein in time-dependent and dose-dependent manners. The transfection of miR-506-3p mimics or KLF4 shRNA promoted the proliferation and migration of VSMCs but inhibited the apoptosis while miR-506-3p inhibitors and pcDNA3.1-KLF4 exerted opposite effects. Additionally, KLF4 was confirmed as a target gene of miR-506-3p and could be negatively regulated by miR-506-3p. CONCLUSION: MiR-506-3p can promote the proliferation and migration of VSMCs via targeting KLF4, which can probably contribute to the pathogenesis of AS.

UBD modifies APOL1-induced kidney disease risk.

People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene APOL1 termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, most individuals with a high-risk APOL1 genotype do not develop overt kidney disease, prompting interest in identifying those factors that interact with APOL1 We performed an admixture mapping study to identify genetic modifiers of APOL1-associated kidney disease. Individuals with two APOL1 risk alleles and focal segmental glomerulosclerosis (FSGS) have significantly increased African ancestry at the UBD (also known as FAT10) locus. UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation. African ancestry at the UBD locus correlates with lower levels of UBD expression. In cell-based experiments, the disease-associated APOL1 alleles (known as G1 and G2) lead to increased abundance of UBD mRNA but to decreased levels of UBD protein. UBD gene expression inversely correlates with G1 and G2 APOL1-mediated cell toxicity, as well as with levels of G1 and G2 APOL1 protein in cells. These studies support a model whereby inflammatory stimuli up-regulate both UBD and APOL1, which interact in a functionally important manner. UBD appears to mitigate APOL1-mediated toxicity by targeting it for destruction. Thus, genetically encoded differences in UBD and UBD expression appear to modify the APOL1-associated kidney phenotype.

Kidney Disease-Associated APOL1 Variants Have Dose-Dependent, Dominant Toxic Gain-of-Function.

BACKGROUND: Two coding renal risk variants (RRVs) of the APOL1 gene (G1 and G2) are associated with large increases in CKD rates among populations of recent African descent, but the underlying molecular mechanisms are unknown. Mammalian cell culture models are widely used to study cytotoxicity of RRVs, but results have been contradictory. It remains unclear whether cytotoxicity is RRV-dependent or driven solely by variant-independent overexpression. It is also unknown whether expression of the reference APOL1 allele, the wild-type G0, could prevent cytotoxicity of RRVs. METHODS: We generated tetracycline-inducible APOL1 expression in human embryonic kidney HEK293 cells and examined the effects of increased expression of APOL1 (G0, G1, G2, G0G0, G0G1, or G0G2) on known cytotoxicity phenotypes, including reduced viability, increased swelling, potassium loss, aberrant protein phosphorylation, and dysregulated energy metabolism. Furthermore, whole-genome transcriptome analysis examined deregulated canonical pathways. RESULTS: At moderate expression, RRVs but not G0 caused cytotoxicity in a dose-dependent manner that coexpression of G0 did not reduce. RRVs also have dominant effects on canonical pathways relevant for the cellular stress response. CONCLUSIONS: In HEK293 cells, RRVs exhibit a dominant toxic gain-of-function phenotype that worsens with increasing expression. These observations suggest that high steady-state levels of RRVs may underlie cellular injury in APOL1 nephropathy, and that interventions that reduce RRV expression in kidney compartments may mitigate APOL1 nephropathy.

Synthesis of Novel Arginine-Based Flame Retardant and Its Application in Lyocell Fabric.

Lyocell fabrics are widely applied in textiles, however, its high flammability increases the risk of fire. Therefore, to resolve the issue, a novel biomass-based flame retardant with phosphorus and nitrogen elements was designed and synthesized by the reaction of arginine with phosphoric acid and urea. It was then grafted onto the lyocell fabric by a dip-dry-cure technique to prepare durable flame-retardant lyocell fabric (FR-lyocell). X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR) analysis demonstrated that the flame retardant was successfully introduced into the lyocell sample. Thermogravimetric (TG) and Raman analyses confirmed that the modified lyocell fabric featured excellent thermal stability and significantly increased char residue. Vertical combustion results indicated that FR-lyocell before and after washing formed a complete and dense char layer. Thermogravimetric Fourier-transform infrared (TG-FTIR) analysis suggested that incombustible substances (such as H2O and CO2) were produced and played a significant fire retarding role in the gas phase. The cone calorimeter test corroborated that the peak of heat release rate (PHRR) and total heat release (THR) declined by 89.4% and 56.4%, respectively. These results indicated that the flame retardancy of the lyocell fabric was observably ameliorated.