Epidemiological characteristics of community-acquired pneumonia and effects from the COVID-19 pandemic in Shenzhen of China.

OBJECTIVE: This study aimed to observe the impact of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of non-COVID-19 community-acquired pneumonia (CAP) in Shenzhen of China, offering new ideas for evaluating the effects of non-pharmaceutical interventions. METHODS: A retrospective analysis was conducted of inpatients with pneumonia from 2017 to 2021. Epidemiological characteristics of CAP and effects from the COVID-19 pandemic were analyzed by the basic characteristics, time distribution, etiology and disease burden. RESULTS: There were a total of 5746 CAP inpatient cases included from 2017 to 2021. The number of CAP hospitalizations decreased during the pandemic from 2020 to 2021, with seasonal variations of being higher in spring and winter and lower in summer and autumn, whereas it was prevalent throughout the year prior to the pandemic. The children group decreased significantly during the pandemic, with a 15% decrease in the share of CAP inpatients. The detection rates of bacteria and mycoplasma decreased in CAP patients, while the detection rate of the virus increased, and the number of moderate and severe cases reduced more than that of the mild. CONCLUSION: Non-pharmaceutical interventions from COVID-19 have led to a decrease in the number of CAP inpatients, especially for children, with a specific seasonal prevalence in spring and winter, when the prevention interventions should be strengthened further for adults during the pandemic.

Dynamic Alteration Profile and New Role of RNA m6A Methylation in Replicative and H2O2-Induced Premature Senescence of Human Embryonic Lung Fibroblasts.

N6-methyladenosine (m6A) methylation is one of the most common RNA modifications, regulating RNA fate at the posttranscriptional level, and is closely related to cellular senescence. Both models of replicative and premature senescence induced by hydrogen peroxide (H2O2) were used to detect m6A regulation during the senescence of human embryonic lung fibroblasts (HEFs). The ROS level accumulated gradually with senescence, leading to normal replicative senescence. H2O2-treated cells had dramatically increased ROS level, inducing the onset of acute premature senescence. Compared with replicative senescence, ROS changed the expression profiles for m6A-related enzymes and binding proteins, including higher levels of METTL3, METTL14, WTAP, KIAA1429, and FTO, and lower levels of METTL16, ALKBH5, YTHDC1, and YTHDF1/2/3 in the premature senescence persistence group, respectively. Meanwhile, senescent cells decreased total m6A content and RNA methylation enzymes activity, regardless of replicative or premature senescence. Moreover, specific m6A methylation levels regulated the expression of SIRT3, IRS2, and E2F3 between replicative and premature senescence separately. Taken together, differential m6A epitranscription microenvironment and the targeted genes can be used as epigenetic biomarkers to cell senescence and the related diseases, offering new clues for the prevention and intervention of cellular senescence.

Novel Roles of RNA m6A Methylation Regulators in the Occurrence of Alzheimer's Disease and the Subtype Classification.

Alzheimer's disease (AD) is one of the most common forms of dementia, closely related to epigenetic factors. N6-methyladenosine (m6A) is the most abundant RNA modification, affecting the pathogenesis and development of neurodegenerative diseases. This study was the first exploration of the combined role of 25 common m6A RNA methylation regulators in AD through the integrated bioinformatics approaches. The 14 m6A regulators related to AD were selected by analyzing differences between AD patients and normal controls. Based on the selected m6A regulators, AD patients could be well classified into two m6A models using consensus clustering. The two clusters of patients had different immune profiles, and m6A regulators were associated with the components of immune cells. Additionally, there were 19 key AD genes obtained by screening differential genes through weighted gene co-expression network and least absolute shrinkage and selection operator regression analysis, which were highly associated with important m6A regulators during the occurrence of AD. More interestingly, NOTCH2 and NME1 could be potential targets for m6A regulation of AD. Taken together, these findings indicate that dysregulation of m6A methylation affects the occurrence of AD and is vital for the subtype classification and immune infiltration of AD.

Time-concentration-dependent profile of histone modifications on human hepatocytes treated by trichloroacetic acid.

Trichloroacetic acid (TCA) is a common non-volatile by-product of chlorination disinfection for drinking water. It is necessary to know the epigenetic toxicity and mechanisms for establishing safe exposure limit for environmental TCA exposure. This study explored the histone modification variations of TCA-treated human hepatocytes L-02 at different time and concentrations. TCA (0.1 mM, 0.3 mM and 0.9 mM) had an inhibitory effect on the growth of L-02 cells, with no significant changes in morphology. Treated with TCA for 24 h and 48 h, L-02 cells showed decreased mRNA and protein level of histone deacetylases (HDACs), but increased after 72 h. The downregulation of HDACs in early stage of TCA exposure might be one of the important reasons for the increase of H3K9ac level. These changes of histone modification may serve as early epigenetic biomarkers for TCA exposure and the related diseases, offering the safe environmental exposure concentration reference.

Dispersive liquid-liquid microextraction based on a new hydrophobic deep eutectic solvent for the determination of phenolic compounds in environmental water samples.

Dispersive liquid-liquid microextraction has garnered increasing attention in sample preparation due to its rapid and efficient extraction process. In this study, a new terpineol-based hydrophobic deep eutectic solvent was firstly synthesized by mixing α-terpineol with 1-octanoic acid, and then applied to analysis of phenols from water samples by dispersive liquid-liquid microextraction combined with high-performance liquid chromatography and diode array detection. Infrared spectroscopy indicated that hydrogen bonding was responsible for the formation of deep eutectic solvent between α-terpineol and 1-octanoic acid. After optimization of several parameters, such as the type and volume of deep eutectic solvent and the disperser, pH and ionic strength of sample solution, the developed method exhibited excellent extraction performance to the phenols with the enrichment factors from 27 to 32. Good linearity was acquired ranging from 5 to 5000 µg/L, and detection of limits of the proposed method for the phenols ranged from 0.15 to 0.38 µg/L. The recoveries measured by spiked samples at three concentration levels ranged from 81.6 to 99.3%, and precision was found with intra- and inter-day relative standard deviations less than 8.7 and 9.2%, respectively. Finally, the proposed method was successfully applied to the determination of the phenols in environmental water samples.

An Epidemiological Retrospective and Predictive Analysis of Rubella in Beijing, Haidian District of China.

BACKGROUND: This study is aimed to investigate the epidemiological characteristics of rubella in Beijing, Haidian District of China, from 2005 to 2020, providing scientific basis for controlling rubella and the congenital rubella syndrome. METHODS: Data were collected via the legal infectious disease report cards from medical institutions in Haidian, 2005-2020. The descriptive epidemiological methods plus statistical analysis were used to analyze the distribution of rubella in terms of population, time and region. RESULTS: In total, there were 994 cases of rubella in Beijing, Haidian District, with an average incidence of 1.81/100 000. In 2007, it was hit by rubella with the highest incidence up to 8.37/100 000, in the past 16 years. The peak incident of rubella was in spring (March to May). The majority of rubella patients were students and employees (70.1%) who are infected mainly due to the gathering. The majority of patients aged 15-29 years (63.4%). And the male-to-female ratio was 1.45 : 1. Rubella had a feature of spatial aggregation and appeared in all the regions in Haidian. According to Joinpoint regression model, rubella would still exist in the next 3 years with 2-5 new cases per year. CONCLUSIONS: Rubella showed a downshift trend from 2008 to 2014, then a sporadic distribution till 2020 in Haidian. Not completely eliminated yet, it is quite impending to improve people's awareness of preventing rubella and their health literacy mentally and physically in the whole population by means of the policy issuing from government.

Nitric oxide alleviates salt stress in seed germination and early seedling growth of pakchoi (Brassica chinensis L.) by enhancing physiological and biochemical parameters.

The germination and seedling vigor of crops is negatively affected by soil salinity. Nitric oxide (NO) has emerged as a key molecule involved in many physiological events in plants. The objective of present study was to evaluate the impact of exogenous sodium nitroprusside (SNP, a NO donor) at different concentrations on the seed germination and early seedling growth characteristics of pakchoi (Brassica chinensis L.) under NaCl stress. 100 mM NaCl stress markedly inhibited the seed germination potential, germination index, vitality index and growth of radicles and plumules. SNP pretreatment attenuated the salt stress effects in a dose-dependent manner, as indicated by enhancing the characteristics of seed germination and early seedling growth parameters, and the mitigating effect was most pronounced at 10 µM SNP. Efficient antioxidant systems were activated by SNP pre-treatment, and which effectively increased the activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX), and reduced contents of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and the production rate of superoxide anion radical (O2·-) in radicles and plumules, thereby preventing oxidative damage from NaCl stress. SNP pre-treatment also increased the contents of proline and soluble sugar in radicles and plumules under NaCl stress. In addition, SNP pre-treatment significantly increased the K+ contents and decreased Na+ contents in radicles and plumules, resulting in the increased level of K+/Na+ ratio. Our results demonstrated that SNP application on pakchoi seeds may be a good option to improve seed germination and seedling growth under NaCl stress by modulating the physiological responses resulting in better seed germination and seedling growth.

Phytotoxicity Assessment of Copper Oxide Nanoparticles on the Germination, Early Seedling Growth, and Physiological Responses in Oryza sativa L.

The increasing utilization of copper oxide nanoparticles (CuO NPs) and their release into the environment has made it imperative to elucidate their impact on the ecological system including plants. However, their potential toxic impact and mechanisms on plant growth are still unclear. The aim of this study was to investigate the effects of CuO NPs and released Cu ions on seed germination and early seedling growth, as well as physiological and biochemical parameters of Oryza sativa. The results showed that CuO NPs at high concentration significantly inhibited seed germination and early seedling growth. The toxicity of CuO NPs originated from the particulate NPs rather than the released Cu2+. The phytotoxicity of CuO NPs to rice seed germination and seedling growth probably induced by high Cu accumulation along with the lignification and oxidative damage. The work presented here will increase our knowledge of phytotoxicity of CuO NPs.

Porous Gold Nanoshells on Functional NH2 -MOFs: Facile Synthesis and Designable Platforms for Cancer Multiple Therapy.

AuroShell nanoparticles (sealed gold nanoshell on silica) are the only inorganic materials that are approved for clinical trial for photothermal ablation of solid tumors. Based on that, porous gold nanoshell structures are thus critical for cancer multiple theranostics in the future owing to their inherent cargo-loading ability. Nevertheless, adjusting the diverse experimental parameters of the reported procedures to obtain porous gold nanoshell structures is challenging. Herein, a series of amino-functionalized porous metal-organic frameworks (NH2 -MOFs) nanoparticles are uncovered as superior templates for porous gold nanoshell deposition (NH2 -MOFs@Aushell ) by means of a more facile and general one-step method, which combines the enriched functionalities of NH2 -MOFs with those of porous gold nanoshells. Moreover, in order to illustrate the promising applications of this method in biomedicine, platinum nanozymes-encapsulated NH2 -MOFs are further designed with porous gold nanoshell coating and photosensitizer chlorin e6 (Ce6)-loaded nanoparticles with continuous O2 -evolving ability (Pt@UiO-66-NH2 @Aushell -Ce6). The combination of photodynamic and photothermal therapy is then carried out both in vitro and in vivo, achieving excellent synergistic therapeutic outcomes. Therefore, this work not only presents a facile strategy to fabricate functionalized porous gold nanoshell structures, but also illustrates an excellent synergistic tumor therapy strategy.

Regulatory role of Piezo1 channel in endothelium-dependent hyperpolarization-mediated vasorelaxation of small resistance vessels and its anti-inflammatory action.

AIMS: Although endothelial Piezo1 channel is known to induce NO-mediated vasorelaxation of conduit vessels, it remains largely unknown if it can induce endothelial-dependent hyperpolarization (EDH)-mediated vasorelaxation of resistance vessels. Therefore, the present study aims to investigate Piezo1/EDH-mediated vasorelaxation in health and its involvement in ulcerative colitis (UC) and sepsis, two intractable and deadly inflammatory diseases. MAIN METHODS: The tension of the second-order branch of mouse mesenteric artery was measured via the Danish DMT600M microvascular measurement system. The changes in cytoplasmic calcium ([Ca2+]cyt) signaling in vascular endothelial cells were detected by fluorescent calcium assay, and the membrane potential changes were monitored by patch clamp. Experimental murine models of UC and sepsis were induced by dextran sulfate sodium (DSS) and lipopolysaccharides (LPS), respectively. KEY FINDINGS: A selective activator of Piezo1 channel, Yoda1, dose-dependently induced vasorelaxation of the second-order branch of mouse mesenteric artery in an endothelium-dependent manner. The endothelial Piezo1 channel mediated the vasorelaxation through EDH mechanism by a functional coupling of Piezo1 and TRPV4 channels. Their function and coupling were verified by [Ca2+]cyt imaging and patch clamp study in single endothelial cells. Moreover, while ACh-induced vasorelaxation played a major role in health, it was significantly impaired in the pathogenesis of UC and sepsis; however, Piezo1/EDH-mediated vasorelaxation remained intact. Finally, Piezo1/EDH-mediated vasorelaxation recovered ACh-induced vasorelaxation impaired in UC and sepsis. SIGNIFICANCE: Piezo1/TRPV4/EDH-mediated vasorelaxation rescues the impaired ACh-induced vasorelaxation to likely recover hemoperfusion to organs, leading to organ protection against UC and sepsis. Our study not only suggests that endothelial Piezo1, TRPV4 and KCa channels are the potential therapeutic targets, but also implies that Piezo1 activators may benefit to prevent/treat UC and sepsis.

Zinc-sensing receptor activation induces endothelium-dependent hyperpolarization-mediated vasorelaxation of arterioles.

BACKGROUND: The micronutrient zinc (Zn2+) is critical for cell function as intracellular signaling and endogenous ligand for Zn2+ sensing receptor (ZnR). Although cytosolic Zn2+ (cyt) signaling in the vascular system was studied previously, role of the ZnR has not been explored in vascular physiology. METHODS: ZnR-mediated relaxation response of human submucosal arterioles and the mesenteric arterioles from wide-type (WT), ZnR-/- and TRPV4-/- mice were determined by a Mulvany-style wire myograph. The perfused vessel density (PVD) of mouse mesenteric arterioles was also measured in in vivo study. The expression of ZnR in arterioles and vascular endothelial cells (VEC) were examined by immunofluorescence staining, and its function was characterized in VEC by Ca2+ imaging and patch clamp study. RESULTS: ZnR expression was detected on human submucosal arterioles, murine mesenteric arterioles and VEC but not in ZnR-/- mice. ZnR activation predominately induced endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation of arterioles in vitro and in vivo via Ca2+ signaling, which is totally different from endothelium-dependent vasorelaxation via Zn2+ (cyt) signaling reported previously. Furthermore, ZnR-induced vasorelaxation via EDH was significantly impaired in ZnR-/- and TRPV4-/- mice. Mechanistically, ZnR induced endothelium-dependent vasorelaxation predominately via PLC/IP3/IP3R and TRPV4/SOCE. The role of ZnR in regulating Ca2+ signaling and ion channels on VEC was verified by Ca2+ imaging and patch clamp techniques. CONCLUSION: ZnR activation induces endothelium-dependent vasorelaxation of resistance vessels predominately via TRPV4/Ca2+/EDH pathway. We therefore not only provide new insights into physiological role of ZnR in vascular system but also may pave a potential pathway for developing Zn2+-based treatments for vascular disease.

A simple method for estimating the coarse lateral root biomass of shrubs using ground-penetrating radar: Validation by Caragana microphylla Lam. in Inner Mongolia.

The potential increases in carbon stocks in arid regions due to recent shrub encroachment have attracted extensive interest among both ecologists and carbon policy analysts. Quantifying the shrub root biomass amount in these ecosystems is essential to understanding the ecological changes occurring. In this paper, we proposed a simple nondestructive method for estimating the coarse lateral root biomass of shrubs based on the root counts obtained from ground-penetrating radar (GPR) radargrams. Root data were gathered via field experiments using GPR with antenna center frequencies of 900 MHz and 400 MHz. Five Caragana microphylla Lam. shrubs of different sizes were selected for measuring objects, and a total of 40 GPR survey lines were established for GPR data acquisition. The soil profile wall excavation method was used to obtain the total root biomass from each radargram. A model for estimating the root biomass was built by establishing the relationship between the root biomass in each profile and the root counts interpreted from the radargrams. According to the mathematical relationship between the root diameter and root biomass, the proxy root radius was derived, which could explain the rationality of the proposed model from the biological mechanism. The established model provided high confidence in estimating the root dry biomass using the GPR data obtained at the two antenna frequencies (R2= 0.73 for 900 MHz and R2= 0.71 for 400 MHz). The leave-one-out cross-validation results showed that the model exhibits satisfactory performance. This study expands the application of geophysical methods in root research and offers a new simplified method for estimating the root biomass from GPR data under field conditions.

2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation.

BACKGROUND & AIMS: 2'-Fucosyllactose (2'-FL), the primary constituent of human milk oligosaccharides, has been identified as a potential regulator of inflammation in inflammatory bowel disease. Despite this recognition, the specific mechanisms through which 2'-FL alleviates ulcerative colitis (UC) remain ambiguous. This study seeks to investigate the potential anti-inflammatory properties of 2'-FL concerning intestinal inflammation and uncover the associated mechanisms. METHODS: C57BL/6J mice were orally administered a daily dose of 500 mg/kg 2'-FL for 11 consecutive days, followed by the induction of colitis using 3 % (wt/vol) dextran sulfate sodium (DSS) for the final 6 days. Subsequently, a comprehensive range of techniques, including an Acyl-biotin exchange assay, fluorescein-isothiocyanate-labeled dextran assay, histopathology, ELISA, quantitative real-time PCR, Western blot, immunofluorescence staining, immunohistochemistry staining, Alcian blue-periodic acid schiff staining, TdT-mediated dUTP nick end labeling, transmission electron microscopy, iTRAQ quantitative proteomics, bioinformatics analysis, and the generation of signal transducer and activator of transcription 3 (STAT3) knockout mice, were employed to explore the relevant molecular mechanisms. RESULTS: Administration of 2'-FL significantly ameliorated DSS-induced colitis in mice and enhanced the integrity of the intestinal mucosal barrier. 2'-FL downregulated the phosphorylation of STAT3 and inhibited STAT3-related signaling pathways in colon tissues, which, in turn, reduced inflammatory responses. Interestingly, knockdown of STAT3 attenuated the protective effects of 2'-FL, highlighting that 2'-FL-mediated inflammatory attenuation is dependent on STAT3 expression. Additionally, 2'-FL could influence STAT3 activation by modulating the palmitoylation and depalmitoylation of STAT3. CONCLUSIONS: 2'-FL promotes the recovery of the intestinal mucosal barrier and suppresses inflammation in ulcerative colitis by inhibiting the palmitoylation and phosphorylation of STAT3.

Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis.

The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.

Sorption of chloramphenicol on pond sediments and the effect of coexistence Cu(II).

The sorption of chloramphenicol on four types of sediment and the effect of coexistence Cu(II) on the sorption were studied. Sorption isotherms and thermodynamic analysis were employed to dispose the experimental sorption data. Experimental results showed that organic matter was the dominant parameter and the coexistence of heavy metal Cu(II) could promote the sorption of chloramphenicol on four tested sediments. The adsorption parameter analysis showed sorption of chloramphenicol on the sediment was not pure distributional effects, not a strong interaction between molecule and surface, but other weak interactions. Thermodynamic parameters values such as ΔG, ΔH and ΔS were all below zero, which indicated that the sorption was a spontaneous and exothermal process.

The CaSR/TRPV4 coupling mediates pro-inflammatory macrophage function.

AIM: Although calcium-sensing receptor (CaSR) and transient receptor potential vanilloid 4 (TRPV4) channels are functionally expressed on macrophages, it is unclear if they work coordinately to mediate macrophage function. The present study investigates whether CaSR couples to TRPV4 channels and mediates macrophage polarization via Ca2+ signaling. METHODS: The role of CaSR/TRPV4/Ca2+ signaling was assessed in lipopolysaccharide (LPS)-treated peritoneal macrophages (PMs) from wild-type (WT) and TRPV4 knockout (TRPV4 KO) mice. The expression and function of CaSR and TRPV4 in PMs were analyzed by immunofluorescence and digital Ca2+ imaging. The correlation factors of M1 polarization, CCR7, IL-1ß, and TNFα were detected using q-PCR, western blot, and ELISA. RESULTS: We found that PMs expressed CaSR and TRPV4, and CaSR activation-induced marked Ca2+ signaling predominately through extracellular Ca2+ entry, which was inhibited by selective pharmacological blockers of CaSR and TRPV4 channels. The CaSR activation-induced Ca2+ signaling was significantly attenuated in PMs from TRPV4 KO mice compared to those from WT mice. Moreover, the CaSR activation-induced Ca2+ entry via TRPV4 channels was inhibited by blocking phospholipases A2 (PLA2)/cytochromeP450 (CYP450) and phospholipase C (PLC)/Protein kinase C (PKC) pathways. Finally, CaSR activation promoted the expression and release of M1-associated cytokines IL-1ß and TNFɑ, which were attenuated in PMs from TRPV4 KO mice. CONCLUSION: We reveal a novel coupling of the CaSR and TRPV4 channels via PLA2/CYP450 and PLC/PKC pathways, promoting a Ca2+ -dependent M1 macrophage polarization. Modulation of this coupling and downstream pathways may become a potential strategy for the prevention/treatment of immune-related disease.

Cl- induces endothelium-dependent mesenteric arteriolar vasorelaxation through the NKCC1/TRPV4/NCX axis.

AIMS: Although absorbed NaCl increases intestinal blood flow to facilitate absorption and transportation, it is unclear if it can directly mediate mesenteric arterial relaxation. We aimed to investigate and test our hypothesis that Cl- induces mesenteric arterial vasorelaxation via endothelium-dependent hyperpolarization (EDH). MAIN METHODS: We used wire myograph to study NaCl-induced vasorelaxation of mesenteric arteries isolated from mice. Cl-, Ca2+ and K+ imaging was performed in human vascular endothelial cells pre-treated with pharmacological agents. KEY FINDINGS: The Cl- concentration-dependently induced vasorelaxation of mesenteric arteries likely through EDH. The Cl--induced vasorelaxation was attenuated in TRPV4 KO mice and inhibited by selective blockers of Na+-K+-2Cl- cotransporter 1 (NKCC1) (bumetanide, 10 µM), transient receptor potential vanilloid 4 (TRPV4) (RN-1734, 40 µM), and small conductance Ca2+-activated K+ channels (SKCa) (apamin, 3 µM)/ intermediate conductance Ca2+-activated K+ channels (IKCa) (TRAM-34, 10 µM) and myoendothelial gap junction (18α-glycyrrhetinic acid, 10 µM), but enhanced by a selective activator of IKCa/SKCa (SKA-31, 0.3 µM). Cl- decreased intracellular K+ concentrations in endothelial cells, which was reversed by apamin (200 nM) plus TRAM-34 (500 nM). Extracellular Cl- raised intracellular Cl- concentrations in endothelial cells, which was attenuated by bumetanide (10 µM). Finally, Cl- induced a transient Ca2+ signaling via TRPV4 in endothelial cells, which became sustained when the Ca2+ exit mode of Na+-Ca2+ exchanger (NCX) was blocked. SIGNIFICANCE: Cl- induces a pure EDH-mediated vasorelaxation of mesenteric arteries through activation of endothelial NKCC1/TRPV4/NCX axis. We have provided a novel insight into the role of Cl--induced vasorelaxation via EDH mechanism.

Estrogen receptor subtype mediated anti-inflammation and vasorelaxation via genomic and nongenomic actions in septic mice.

Aim: Sepsis is a life-threatening disease with high mortality worldwide. Septic females have lower severity and mortality than the males, suggesting estrogen exerts a protective action, but nothing is known about the role of vascular endothelial estrogen receptor subtypes in this process. In the present study, we aimed to study the estrogen receptors on mesenteric arterioles in normal and sepsis mice and to elucidate the underlying mechanisms. Methods: Sepsis was induced in mice by intraperitoneal injection of LPS. The changes in the expression and release of the serum and cell supernatant proinflammatory cytokines, including TNF-α, IL-1ß and IL-6, were measured by qPCR and ELISA, and the functions of multiple organs were analyzed. The functional activities of mouse mesenteric arterioles were determined by a Mulvany-style wire myograph. The expression of phospholipase C (PLC) and inositol 1,4,5-trisphosphate receptor (IP3R) in endothelial cells were examined by Western blot and their functions were characterized by cell Ca2+ imaging. Results: Septic female mice had higher survival rate than the male mice, and pretreatment with E2 for 5 days significantly improved the survival rate and inhibited proinflammatory cytokines in septic male mice. E2 ameliorated pulmonary, intestinal, hepatic and renal multiple organ injuries in septic male mice; and ER subtypes inhibited proinflammatory cytokines in endothelial cells via PLC/IP3R/Ca2+ pathway. E2/ER subtypes immediately induced endothelial-derived hyperpolarization (EDH)-mediated vasorelaxation via PLC/IP3R/Ca2+ pathway, which was more impaired in septic male mice. E2/ER subtypes could rescue the impaired acetylcholine (ACh)-induced EDH-mediated vasorelaxation in septic male mice. Conclusions: E2 through ER subtypes mediates anti-inflammation and vasorelaxation via genomic and nongenomic actions in sepsis. Mechanistically, activation of endothelial ER subtypes reduces proinflammatory cytokines and induces EDH-mediated vasorelaxation via PLC/IP3R/Ca2+ pathway, leading to amelioration of sepsis-induced organ injury and survival rate.

Spatial-temporal characteristics of geological disaster resilience in poverty and disaster-prone areas in China: a case study of Ganzi Prefecture.

Under the tremendous challenges of frequent disasters, disaster resilience is imperative for risk reduction and sustainable management in poverty and disaster-prone areas. Ganzi Prefecture has a complicated topography and vulnerable ecosystems. Geological disasters have historically been the most serious risks in the region. To fully understand the potential risks and strengthen resilience, the study investigates the resilience level of 18 counties in Ganzi. Firstly, the paper develops a multidimensional index system based on the Baseline Resilience Indicators for Communities (BRIC) framework. And the entropy weighting method is used to calculate Ganzi's disaster resilience level from the aspects of "society-economy-infrastructure-environment." Then, the study uses exploratory spatial data (ESDA) to analyze the spatial-temporal evolution of disaster resilience. Finally, Geodetector is used to investigate the main driving factors of disaster resilience and their interactions. The results indicated that Ganzi's disaster resilience had maintained an upward trend from 2011 to 2019, with significant spatial divergence, which shows high resilience in the southeast and low resilience in the northwest. The economic indicator is the driving factor in the spatial difference of disaster resilience, and the interaction factor has a significantly stronger explanatory power for resilience. Therefore, the government should strengthen ecotourism development to help alleviate poverty in special industries and promote synergistic regional development.