[Application of the holism of body-qi-spirit in needle knife treatment for cervical vertigo].

This paper introduces Professor WANG Haidong's approach to treat cervical vertigo with needle knife based on the holism of body-qi-spirit. Professor WANG Haidong, considering the etiology and pathogenesis of cervical vertigo, starting from the holism of body-qi-spirit, based on the anatomical structure, employs the "seven-neck points" technique to improve local blood supply and address the physical issue; guided by the Jingjin theory, he utilizes the "knot releasing technique" to disperse knots and relax sinews, thereby regulating qi. In addition, he uses the "bone puncturing technique at governor vessel" to uplift yang-qi and nourish the brain, thereby nurturing the spirit.

CXCR4 influences PUFA desaturation and oxidative stress injury in experimental prostatitis mice by activating Fads2 via PPARγ.

Chronic prostatitis-induced excessive inflammation and oxidative stress (OS) damage substantially affect men's quality of life. However, its treatment remains a major clinical challenge. Therefore, the identification of drugs that can decrease chronic prostatitis and oxidative stress targets is urgent and essential. CXCR4 is a classic chemokine receptor that is crucially associated with the occurrence and development of inflammation. This investigation aimed to elucidate how CXCR4 affects prostatitis regression and progression. The effect of CXCR4 on chronic prostatitis was evaluated by HE staining, immunohistochemistry, immunofluorescence, PCR, and TUNEL analyses. Furthermore, CXCR4 influence on metabolism was also evaluated by monitoring body weight, body temperature, food intake, and LC/MS. Additionally, chromatin immunoprecipitation, Western blot, and double luciferase reporter gene assays were carried out to elucidate the mechanism by which CXCR4 modulates Fads2 transcription by PPARγ. Lastly, ROS, DHE, mito-tracker, and ATP were utilized to validate the α-linolenic acid's protective effect against OS in prostate epithelial cells. It was revealed that the inhibition of CXCR4 can effectively alleviate prostatitis in mice. Furthermore, downregulating CXCR4 expression can markedly reduce the inflammatory cell infiltration in mouse prostates, decrease the elevated levels of DNA damage markers,MDA and 4-HNE, and mitigate apoptosis of prostatic epithelial cells. Moreover, treatment of CXCR4 knockdown mice with a PPARγ inhibitor revealed different degrees of changes in the above phenotypes. Mechanistically, the PPARγ protein translocates to the nucleus and serves as a transcription factor to regulate Fads2 expression, thereby altering PUFA metabolism. Additionally, in vitro experiments indicated that α-linolenic acid can effectively alleviate OS damage and RWPE-1 cell apoptosis by protecting mitochondrial function and enhancing the antioxidant capacity of prostatic epithelial cells. In conclusion, reducing the levels of CXCR4 can alleviate inflammation and OS damage in chronic prostatitis.

Continuous flow delivery system for the perfusion of scaffold-based 3D cultures.

The paper-based culture platform developed by Whitesides readily incorporates tissue-like structures into laboratories with established workflows that rely on monolayer cultures. Cell-laden hydrogels are deposited in these porous scaffolds with micropipettes; these scaffolds support the thin gel slabs, allowing them to be evaluated individually or stacked into thick constructs. The paper-based culture platform has inspired many basic and translational studies, each exploring how readily accessible materials can generate complex structures that mimic aspects of tissues in vivo. Many of these examples have relied on static culture conditions, which result in diffusion-limited environments and cells experiencing pericellular hypoxia. Perfusion-based systems can alleviate pericellular hypoxia and other cell stresses by continually exposing the cells to fresh medium. These perfusion systems are common in microfluidic and organ-on-chip devices supporting cells as monolayer cultures or as 3D constructs. Here, we introduce a continuous flow delivery system, which uses parts readily produced with 3D printing to provide a self-contained culture platform in which cells in paper or other scaffolds are exposed to fresh (flowing) medium. We demonstrate the utility of this device with examples of cells maintained in single cell-laden scaffolds, stacks of cell-laden scaffolds, and scaffolds that contain monolayers of endothelial cells. These demonstrations highlight some possible experimental questions that can be enabled with readily accessible culture materials and a perfusion-based device that can be readily fabricated.

Brain Nucleic Acid Delivery and Genome Editing via Focused Ultrasound-Mediated Blood-Brain Barrier Opening and Long-Circulating Nanoparticles.

We introduce a two-pronged strategy comprising focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening and long-circulating biodegradable nanoparticles (NPs) for systemic delivery of nucleic acids to the brain. Biodegradable poly(ß-amino ester) polymer-based NPs were engineered to stably package various types of nucleic acid payloads and enable prolonged systemic circulation while retaining excellent serum stability. FUS was applied to a predetermined coordinate within the brain to transiently open the BBB, thereby allowing the systemically administered long-circulating NPs to traverse the BBB and accumulate in the FUS-treated brain region, where plasmid DNA or mRNA payloads produced reporter proteins in astrocytes and neurons. In contrast, poorly circulating and/or serum-unstable NPs, including the lipid NP analogous to a platform used in clinic, were unable to provide efficient nucleic acid delivery to the brain regardless of the BBB-opening FUS. The marriage of FUS-mediated BBB opening and the long-circulating NPs engineered to copackage mRNA encoding CRISPR-associated protein 9 and single-guide RNA resulted in genome editing in astrocytes and neurons precisely in the FUS-treated brain region. The combined delivery strategy provides a versatile means to achieve efficient and site-specific therapeutic nucleic acid delivery to and genome editing in the brain via a systemic route.

atRA Attenuates High Salt-Driven EAE Mainly Through Suppressing Th17-Like Regulatory T Cell Response Mediated by the Inhibition of IL-23R Signaling Pathway.

High salt diet (HSD) is implicated in numerous disorders, which boosts Th17 cell development and weakens immunosuppressive function of regulatory T cells (Treg cells) Treg cells, leading to the exacerbation of EAE. However, little is known regarding the harness of excessive proinflammatory responses evoked by HSD. Here we show that atRA, a key vitamin A metabolite with multifaceted immunoregulatory properties has the potential in inhibiting the proinflammatory reaction of high salt. Treatment with atRA in vivo elicited the Treg generation in cervical and axillary lymph nodes (CALs), and in CNS of experimental autoimmune encephalomyelitis (EAE). Meanwhile, the proportion of Th17-like Treg cells (RORγt-positive or GM-CSF-positive Treg cells) decreased in CALs. atRA also inhibited IL-17A expression in CD4+ effector T cells. In-vitro mechanistic studies showed that atRA inhibit IL-23R but not SGK1 expression in Treg cells and this results in maintained immunosuppressive function of Treg cells even in the presence of IL-6 and high salt. Furthermore, treatment of EAE with anti-IL-23R mAb attenuated HSD-provoked EAE progress. This was associated with a reduction in the number of CNS-infiltrating Th17 cells and an increase of CAL-Treg cells. Mechanically, treatment with atRA significantly promoted LP-CD103+CD11c+ dendritic cells, a subgroup of cells most closely involved in endogenous retinoic acid metabolism, and enhanced intestinal Aldh1a1 and Rdh10 expression from HSD-fed EAE mice. Interestingly, anti-IL-23R mAb administration also reduced IL-23R expression in Treg cells, along with the increased proportion of LP-CD103+CD11c+ dendritic cells and Rdh10 mRNA expression. In conclusion, administration of atRA might be a way to combat the proinflammatory effects of HSD. Meanwhile, systematic inhibition of IL-23R also had a moderate therapeutic potential in inhibiting inflammatory effects of high salt, which may serve as a basis for the identification of novel therapeutic strategies against HSD-driven autoimmune disorders.

Supported gel slab scaffolds as a three-dimensional cell-based assay platform.

Cell-based assays are heavily relied on in the drug discovery pipeline, quickly pairing down large compound libraries to a manageable number of drug candidates for further characterization and evaluation. Monolayer cultures in which cells are deposited onto the bottom of well plates are the workhorse of many of these screens despite continued evidence of their inability to predict in vivo responses. Three-dimensional (3D) culture platforms can generate tissue-like environments with more representative cellular phenotypes than monolayers but have proven challenging to incorporate into already-developed workflows. Scaffold-based approaches are a tractable means of generating tissue-like environments, supporting cell-laden gels whose preparation is analogous to depositing cells in a well plate. Here, we describe supported gel slab (SGS) scaffolds prepared from commercially available materials, an adhesive spray, and a laser cutter. These cell-containing scaffolds can readily fit into well plates, providing a format compatible with current liquid handlers and analytical instrumentation. The scaffolds enable the evaluation of cellular responses in individual or stacked structures, which contain extracellular matrix-rich microenvironments. With a series of demonstrations, we highlight the utility of the readily assembled SGS scaffolds to quantify cellular responses. These readouts include confocal microscopy, quantifying cellular invasion in Transwell-like and stacked formats, generating multilayered spheroid-on-demand structures capable of providing spatially resolved maps of drug responses, and identifying potential chemotherapies in a screening application.

Ferric citrate enhanced bioreduction of Cr(VI) by Bacillus cereus RCr in aqueous solutions: reduction performance and mechanisms.

The bioreduction characteristics and mechanisms of Cr(VI) onto Bacillus cereus RCr enhanced by ferric citrate were investigated. The optimum conditions were initial pH 9, temperature 40 °C, inoculation amount 4%, and glucose 3 g/L, respectively. The addition of 1.5 g/L ferric citrate increased the average reduction rate from 120.43 to 220.61 mg/(L∙h) compared with the control (without ferric citrate). The binding capacity of Cr(III) on the cell surface increased to 21%, in which the precipitates were mainly CrO(OH), Cr2O3, and FeCr2O4. Cell membrane was the main site of reduction, related important functional groups: - COOH, C-H, - NH2, C = C, and P-O. Fe(III) increased the yield of NADH and cytochrome c by approximately 48.51% and 68.63%, which significantly facilitated the electron generation and electron transfer, thus increasing the amount of electrons in the bioreduction of heavy metals by an average of 110%. Among the electrons obtained by Cr(VI), the proportion of indirect reduction mediated by Fe(III)/Fe(II) shuttle was 62% on average, whereas direct reduction mediated by reductase was 38%. These results may provide insights into the bioreduction process by bacteria enhanced by Fe(III) for detoxification of heavy metals with multiple valences, as an important step towards improving microbial remediation.

Nanoarchitectonics of ultrafine molybdenum carbide nanocrystals into three-dimensional nitrogen-doped carbon framework for capacitive deionization.

Molybdenum carbide (MoC) has emerged as a promising material for capacitive deionization (CDI), but the poor electrochemical kinetics in conventional MoC owing to the bulk structure and low electric conductivity limit its CDI performance. To address this challenge, herein, we develop a novel strategy to synthesize ultrafine MoC nanocrystals that are embedded within a three-dimensional nitrogen-doped carbon framework (NC/MoC). This synthesis method involves the space-confined pyrolysis of molybdate precursors within metal-organic frameworks (MOFs). In this process, molybdates are confined into the MOF crystalline structure, where MOFs provide a confined reactor and carbon source. The resulting NC/MoC with the uniformly distributed MoC nanocrystals provides sufficient active sites for the electrosorption of salt ions, while the MOF-derived NC matrix facilitates charge transfer and provides the space-confined effect for preventing the possible aggregations of MoC nanocrystals during the CDI process. The NC/MoC exhibits an impressive salt adsorption capacity (SAC, 84.2 mg g-1, 1.2 V), rapid desalination rate, and high cycling stability (91.4% SAC retention after 200 cycles), better than those of most previously reported carbon-based CDI materials. Besides, the possible mechanisms are systematically investigated by ex situ characterization and density functional theory calculations. This study opens up new avenues for the construction of metal carbide-based nanocrystals for CDI and other electrochemical applications.

Miniaturized Multi-Cantilever MEMS Resonators with Low Motional Impedance.

Microelectromechanical system (MEMS) cantilever resonators suffer from high motional impedance (Rm). This paper investigates the use of mechanically coupled multi-cantilever piezoelectric MEMS resonators in the resolution of this issue. A double-sided actuating design, which utilizes a resonator with a 2.5 µm thick AlN film as the passive layer, is employed to reduce Rm. The results of experimental and finite element analysis (FEA) show agreement regarding single- to sextuple-cantilever resonators. Compared with a standalone cantilever resonator, the multi-cantilever resonator significantly reduces Rm; meanwhile, the high quality factor (Q) and effective electromechanical coupling coefficient (Kteff2) are maintained. The 30 µm wide quadruple-cantilever resonator achieves a resonance frequency (fs) of 55.8 kHz, a Q value of 10,300, and a series impedance (Rs) as low as 28.6 kΩ at a pressure of 0.02 Pa; meanwhile, the smaller size of this resonator compared to the existing multi-cantilever resonators is preserved. This represents a significant advancement in MEMS resonators for miniaturized ultra-low-power oscillator applications.

Effects of pyriproxyfen on development and hormone of the aphis, Aphis craccivora (Hemiptera: Aphididae).

Pyriproxyfen (PPF) has been shown to affect the pupal stage and ecdysone levels in holometabolous insects, such as silkworms and mealworms. It remains unknown whether it affects hemimetabolous insects with their hormone levels in insects lacking a pupal stage. In this laboratory study, bioassays were conducted to investigate the effects of varying doses of PPF on Aphis craccivora Koch (Hemiptera: Aphididae). Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the types and titers of juvenile hormone (JH) and 20-hydroxyecdysone (20E). Additionally, the effects of PPF on A. craccivora reproduction and molting, as well as its influence on relevant gene expression, were examined. The results revealed LC50 and LC90 values of 3.84 and 7.49 mg/l for PPF, respectively, after 48 h of exposure. The results demonstrated a significant reduction in the titer of JH III and a significant increase in the titer of 20E following treatment with PPF. However, there was no significant decrease observed in the titer of JH III skipped bisepoxide (JH SB3). A sublethal concentration of PPF was found to inhibit Krüppel homolog 1 (kr-h1) gene expression and reduce aphid reproduction, but it did not significantly impact ecdysone receptor expression and aphid molting. The results of this study demonstrate that PPF exhibits a lethal effect on aphids, thereby providing an effective means of control. Additionally, sublethal concentrations of PPF have been found to inhibit the JH in aphids, resulting in a decline in their reproductive ability and achieving the desired control objectives.

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma.

PURPOSE: This study aimed to construct an m6A and cuproptosis-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using the information acquired from The Cancer Genome Atlas (TCGA) database. METHODS: First, the co-expression analysis was performed to identify lncRNAs linked with N6-methyladenosine (m6A) and cuproptosis in ccRCC. Then, a model encompassing four candidate lncRNAs was constructed via univariate, least absolute shrinkage together with selection operator (LASSO), and multivariate regression analyses. Furthermore, Kaplan-Meier, principal component, functional enrichment annotation, and nomogram analyses were performed to develop a risk model that could effectively assess medical outcomes for ccRCC cases. Moreover, the cellular function of NFE4 in Caki-1/OS-RC-2 cultures was elucidated through CCK-8/EdU assessments and Transwell experiments. Dataset outcomes indicated that NFE4 can have possible implications in m6A and cuproptosis, and may promote ccRCC progression. RESULTS: We constructed a panel of m6A and cuproptosis-related lncRNAs to construct a prognostic prediction model. The Kaplan-Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. Furthermore, the m6A and cuproptosis-related lncRNA model indicated higher diagnostic efficiency than other clinical features. Moreover, the NFE4 function analysis indicated a gene associated with m6A and cuproptosis-related lncRNAs in ccRCC. It was also revealed that the proliferation and migration of Caki-1 /OS-RC-2 cells were inhibited in the NFE4 knockdown group. CONCLUSION: Overall, this study indicated that NFE4 and our constructed risk signature could predict outcomes and have potential clinical value.

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01).

Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer. Methods: and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR). Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). Trial registration: This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

Comparative transcriptome analysis provides insights into the resistance regulation mechanism and inhibitory effect of fungicide phenamacril in Fusarium asiaticum.

Fusarium asiaticum is a destructive phytopathogenic fungus that causes Fusarium head blight of wheat (FHB), leading to serious yield and economic losses to cereal crops worldwide. Our previous studies indicated that target-site mutations (K216R/E, S217P/L, or E420K/G/D) of Type I myosin FaMyo5 conferred high resistance to phenamacril. Here, we first constructed one sensitive strain H1S and three point mutation resistant strains HA, HC and H1R. Then we conducted comparative transcriptome analysis of these F. asiaticum strains after 1 and 10 µg·mL-1 phenamacril treatment. Results indicated that 2135 genes were differentially expressed (DEGs) among the sensitive and resistant strains. The DEGs encoding ammonium transporter MEP1/MEP2, nitrate reductase, copper amine oxidase 1, 4-aminobutyrate aminotransferase, amino-acid permease inda1, succinate-semialdehyde dehydrogenase, 2, 3-dihydroxybenzoic acid decarboxylase, etc., were significantly up-regulated in all the phenamacril-resistant strains. Compared to the control group, a total of 1778 and 2097 DEGs were identified in these strains after 1 and 10 µg·mL-1 phenamacril treatment, respectively. These DEGs involved in 4-aminobutyrate aminotransferase, chitin synthase 1, multiprotein-bridging factor 1, transcriptional regulatory protein pro-1, amino-acid permease inda1, ATP-dependent RNA helicase DED1, acetyl-coenzyme A synthetase, sarcoplasmic/endoplasmic reticulum calcium ATPase 2, etc., showed significantly down-regulated expression in phenamacril-sensitive strain but not in resistant strains after phenamacril treatment. In addition, cyanide hydratase, mating-type protein MAT-1, putative purine nucleoside permease, plasma membrane protein yro2, etc., showed significantly co-down-regulated expression in all the strains after phenamacril treatment. Taken together, This study provides deep insights into the resistance regulation mechanism and the inhibitory effect of fungicide phenamacril and these new annotated proteins or enzymes are worth for the discovery of new fungicide targets.

A multilayer network model of interaction between rumor propagation and media influence.

Rumors spread among the crowd have an impact on media influence, while media influence also has an impact on rumor dissemination. This article constructs a two-layer rumor media interaction network model, in which the rumors spread in the crowd are described using the susceptibility-apathy-propagation-recovery model, and the media influence is described using the corresponding flow model. The rationality of the model is studied, and then a detailed analysis of the model is conducted. In the simulation section, we undertake a sensitivity analysis of the crucial parameters within our model, focusing particularly on their impact on the basic reproduction number. According to data simulation analysis, the following conclusion can be drawn: First, when the media unilaterally influences the crowd and does not accept feedback from the crowd, the influence of the media will decrease to zero over time, which has a negative effect on the spread of rumors among the crowd (the degree of rumor dissemination decreases). Second, when the media does not affect the audience and accepts feedback from the audience, this state is similar to the media collecting information stage, which is to accept rumors from the audience but temporarily not disclose their thoughts. At this time, both the media influence and the spread of rumors in the audience will decrease. Finally, the model is validated using an actual dataset of rumors. The simulation results show an R-squared value of 0.9606, indicating that the proposed model can accurately simulate rumor propagation in real social networks.

Identify CTBP1-DT as an immunological biomarker that promotes lipid synthesis and apoptosis resistance in KIRC.

Recently, mounting evidence has highlighted the essential function of the C-terminal binding protein-1 divergent transcript (CTBP1-DT) in malignancies. However, its role in kidney renal clear cell carcinoma (KIRC) remains largely unknown. Our study aimed to identify the potential function of CTBP1-DT in KIRC. RT-qPCR, Kaplan-Meier survival analysis, Cox regression analysis, and nomogram analysis were utilized to determine the expression and effects of CTBP1-DT on survival. The subcellular localization of CTBP1-DT was determined using RNA fluorescence in situ hybridization (FISH). To investigate the functions of CTBP1-DT in regulating KIRC cell proliferation, migration, invasion, lipid synthesis, and apoptosis, we conducted CCK8, EdU, Transwell, and Oil Red O staining and cell apoptosis staining assays. The relationships between CTBP1-DT and the tumor microenvironment were investigated with multiple bioinformatics analysis algorithms and databases, including CYBERSORT, TIMER2, Spearman correlation test, tumor mutation burden (TMB), microsatellite instability (MSI), and immunophenoscore (IPS). According to our results, CTBP1-DT is a lncRNA located in the nucleus that is significantly upregulated in KIRC and is correlated with better clinical outcomes. Downregulating CTBP1-DT inhibited cell viability, migration, invasion, and lipid synthesis but triggered cell apoptosis. Additionally, we explored the potential effect of CTBP1-DT in regulating immune cell infiltration in KIRC and other malignancies. Furthermore, CTBP1-DT could be used to predict the effectiveness of targeted drugs and immune checkpoint inhibitors. In conclusion, we identified CTBP1-DT as a potential immunological biomarker and discovered the potential role of CTBP1-DT in regulating lipid synthesis and apoptosis resistance.

Isoliquiritigenin reduces experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) lead to severe irritation and impaired sperm quality in males. However, current therapeutic options often fail to achieve satisfactory effects. Consequently, the investigation of novel treatment strategies or remedies holds substantial clinical importance. As a flavonoid monomer, isoliquiritigenin (ISL) has been shown to possess anti-inflammatory activity, especially in several chronic nonspecific-inflammatory conditions. Thus, an exploration of the possible anti-inflammatory effects of ISL on CP/CPPS, a chronic aseptic inflammation of the prostate, has significant potential. METHODS: An experimental autoimmune prostatitis (EAP) model was used for the evaluation of the anti-inflammatory effects of ISL. It was found that ISL treatment could reduce the secretion and invasion of pro-inflammatory cytokines in prostate tissue. In EAP mice, ISL treatment also reduced oxidative stress (OS) and activation of the NLRP3 inflammasome. In vitro, ISL upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibited NLRP3 inflammasome activation in RAW264.7 macrophages exposed to lipopolysaccharide (LPS). RESULTS: Treatment with ISL treatment relieved prostate inflammation and pelvic pain in EAP mice. Both in vivo and in vitro, ISL treatment activated Nrf2/HO-1 signaling, which in turn inhibited oxidative stress and activation of the NLRP3 inflammasome. Blockade of Nrf2/HO-1 signaling abolished the inhibitory effects of ISL on oxidative stress and NLRP3 inflammasome activation. CONCLUSIONS: Isoliquiritigenin reduced experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.

Inhaled endotoxin induces a systemic neutrophil response without affecting cardiovascular measures in a randomized cross-over exposure study.

OBJECTIVE: The gram-negative bacterial cell wall component endotoxin (lipopolysaccharide, LPS) is a key component of particulate matter (PM). PM exposure is associated with cardiovascular morbidity and mortality. However, the contribution of individual components of PM to acute and chronic cardiovascular measures is not clear. This study examines whether systemic inflammation induced by LPS inhalation causes acute changes in cardiovascular physiology measures. MATERIALS AND METHODS: In this double blinded, placebo-controlled crossover study, fifteen adult volunteers underwent inhalation exposure to 20,000 EU Clinical Center Reference Endotoxin (CCRE). Peripheral blood and induced sputum neutrophils were obtained at baseline and six hours post-exposure. Blood pressure, measures of left ventricular function (ejection fraction (LVEF) and global longitudinal strain (LVGLS)), and indices of endothelial function (flow mediated dilation (FMD) and velocity time integral during hyperemia (VTIhyp)) were measured before and after treatment. Wilcoxon sign-rank tests and linear mixed models were used for statistical analysis. RESULTS: In comparison with normal saline, LPS inhalation resulted in significant increases in peripheral blood and sputum neutrophils but was not associated with significant alterations in blood pressure, LVGLS, LVEF, FMD, or VTIhyp. DISCUSSION AND CONCLUSIONS: In healthy adults, systemic inflammation after LPS inhalation was not associated with acute changes in cardiovascular physiology. Larger studies are needed to investigate the effects of other PM components on inflammation induced cardiovascular dysfunction.

A prognostic prediction model for ovarian cancer using a cross-modal view correlation discovery network.

Ovarian cancer is a tumor with different clinicopathological and molecular features, and the vast majority of patients have local or extensive spread at the time of diagnosis. Early diagnosis and prognostic prediction of patients can contribute to the understanding of the underlying pathogenesis of ovarian cancer and the improvement of therapeutic outcomes. The occurrence of ovarian cancer is influenced by multiple complex mechanisms, including the genome, transcriptome and proteome. Different types of omics analysis help predict the survival rate of ovarian cancer patients. Multi-omics data of ovarian cancer exhibit high-dimensional heterogeneity, and existing methods for integrating multi-omics data have not taken into account the variability and inter-correlation between different omics data. In this paper, we propose a deep learning model, MDCADON, which utilizes multi-omics data and cross-modal view correlation discovery network. We introduce random forest into LASSO regression for feature selection on mRNA expression, DNA methylation, miRNA expression and copy number variation (CNV), aiming to select important features highly correlated with ovarian cancer prognosis. A multi-modal deep neural network is used to comprehensively learn feature representations of each omics data and clinical data, and cross-modal view correlation discovery network is employed to construct the multi-omics discovery tensor, exploring the inter-relationships between different omics data. The experimental results demonstrate that MDCADON is superior to the existing methods in predicting ovarian cancer prognosis, which enables survival analysis for patients and facilitates the determination of follow-up treatment plans. Finally, we perform Gene Ontology (GO) term analysis and biological pathway analysis on the genes identified by MDCADON, revealing the underlying mechanisms of ovarian cancer and providing certain support for guiding ovarian cancer treatments.

Electronic Structure Regulated Nickel-Cobalt Bimetal Phosphide Nanoneedles for Efficient Overall Water Splitting.

Transition metal phosphides (TMPs) have been widely studied for water decomposition for their monocatalytic property for anodic or cathodic reactions. However, their bifunctional catalytic activity still remains a major challenge. Herein, hexagonal nickel-cobalt bimetallic phosphide nanoneedles with 1-3 µm length and 15-30 nm diameter supported on NF (NixCo2-xP NDs/NF) with adjusted electron structure have been successfully prepared. The overall alkaline water electrolyzer composed of the optimal anode (Ni0.67Co1.33P NDs/NF) and cathode (Ni1.01Co0.99P NDs/NF) provide 100 mA cm-2 at 1.62 V. Gibbs Free Energy for reaction paths proves that the active site in the hydrogen evolution reaction (HER) is Ni and the oxygen evolution reaction (OER) is Co in NixCo2-xP, respectively. In the HER process, Co-doping can result in an apparent accumulation of charge around Ni active sites in favor of promoting HER activity of Ni sites, and ΔGH* of 0.19 eV is achieved. In the OER process, the abundant electron transfer around Co-active sites results in the excellent ability to adsorb and desorb *O and *OOH intermediates and an effectively reduced ∆GRDS of 0.37 eV. This research explains the regulation of electronic structure change on the active sites of bimetallic materials and provides an effective way to design a stable and effective electrocatalytic decomposition of alkaline water.

HIF-2α/LINC02609/APOL1-mediated lipid storage promotes endoplasmic reticulum homeostasis and regulates tumor progression in clear-cell renal cell carcinoma.

BACKGROUND: The VHL-HIF pathway and lipid droplet accumulation are the main characteristics of clear cell renal cell carcinoma (ccRCC). However, the connection between the two features is largely unknown. METHODS: We used transcriptional sequencing and TCGA database analysis to identify APOL1 as a novel therapeutic target for ccRCC. The oncogenic functions of APOL1 were investigated by cell proliferation, colony formation, migration and invasion assays in ccRCC cells in vitro and xenografts derived from ccRCC cells in vivo. Oil red O staining and quantification were used to detect lipid droplets. Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assays were carried out to identify HIF-2α bound to the promoter of APOL1 and lncRNA LINC02609. RNA-FISH and luciferase reporter assays were performed to determine that LncRNA LINC02609 functions as a competing endogenous RNA to regulate APOL1 expression by sponging miR-149-5p. FINDINGS: RNA-seq data revealed that HIF2α can regulate APOL1 and lncRNA LINC02609 expression. We also found that HIF-2α can bind to the promoter of APOL1 and lncRNA LINC02609 and transcriptionally regulate their expression directly. We further demonstrated that LncRNA LINC02609 functions as a competing endogenous RNA to regulate APOL1 expression by sponging miR-149-5p in ccRCC. Mechanistically, APOL1-dependent lipid storage is required for endoplasmic reticulum (ER) homeostasis and cell viability and metastasis in ccRCC. We also showed that high APOL1 expression correlated with worse clinical outcomes, and knockdown of APOL1 inhibited tumor cell lipid droplet formation, proliferation, metastasis and xenograft tumor formation abilities. Together, our studies identify that HIF2α can regulate the expression of the lipid metabolism related gene APOL1 by direct and indirect means, which are essential for ccRCC tumorigenesis. INTERPRETATION: Based on the experimental data, in ccRCC, the HIF-2α/LINC02609/APOL1 axis can regulate the expression of APOL1, thus interfering with lipid storage, promoting endoplasmic reticulum homeostasis and regulating tumor progression in ccRCC. Together, our findings provide potential biomarkers and novel therapeutic targets for future studies in ccRCC.