[Spatiotemporal Pattern and Influencing Factors of Thermal Environment Based on SEM Model: A Case Study in Xi'an Metropolitan Area].

The urban thermal environment is an important indicator for evaluating the ecological environment of a city. It directly affects the health of residents and the sustainable development of the urban economy. However, there is currently a lack of analysis on the impact pathways of the thermal environment considering both natural and human factors. Based on the MODIS MYD11A2 land surface temperature data, meteorological data, and human activity data of Xi'an metropolitan area in 2020, ArcGIS spatial geostatistical analysis was used to study the temporal and spatial distribution pattern of the thermal environment in different seasons, and redundancy analysis was utilized to select the main factors affecting the thermal environment. Then, structural equation modeling was used to quantify the direct and indirect effects of the dominant factors on the urban thermal environment. The results showed that:① The surface temperature in the Xi'an urban area showed a spatial pattern of higher temperatures in the north and lower temperatures in the south, with a decrease in temperature from the city center to the surrounding areas. The most severe heat environment pollution occurred in the summer. ② The redundancy analysis (RDA) results indicated that the main factors that affected the thermal environment were air temperature, impermeable surfaces, vegetation, and precipitation. ③ The results of the structural equation modeling (SEM) indicated that meteorological, surface, and anthropogenic factors affected the urban thermal environment mainly through direct pathways, which were much more important than all indirect pathways. Factors such as temperature, impervious surfaces, and point of interest density had a significant positive effect on the thermal environment (0.10 and 0.33). On the other hand, factors such as water bodies, precipitation, and vegetation had a significant negative effect on the thermal environment (-0.29 and -0.25). Human activities had a greater direct impact on nocturnal surface temperatures than surface and meteorological factors. Increasing economic efficiency is beneficial for mitigating the urban heat island effect. The results of the study can provide a reference for studying local climate change in urban heat islands and for the construction of green and ecologically livable urban environments.

Development of a chloroplast expression system for Dunaliella salina.

Dunaliella salina is an innovative expression system due to its distinct advantages such as high salt tolerance, low susceptibility to contamination, and the absence of the cell wall. While nuclear transformation has been extensively studied, research on D. salina chloroplast transformation remains in the preliminary stages. In this study, we established an efficient chloroplast expression system for D. salina using Golden Gate assembly. We developed a D. salina toolkit comprising essential components such as chloroplast-specific promoters, terminators, homologous fragments, and various vectors. We confirmed its functionality by expressing the EGFP protein. Moreover, we detailed the methodology of the entire construction process. This expression system enables the specific targeting of foreign genes through simple homologous recombination, resulting in stable expression in chloroplasts. The toolkit achieved a relatively high transformation efficiency within a shorter experimental cycle. Consequently, the construction and utilization of this toolkit have the potential to enhance the efficiency of transgenic engineering in D. salina and advance the development of microalgal biofactories.

Experimental Virtual Distillation of Entanglement and Coherence.

Noise is, in general, inevitable and detrimental to practical and useful quantum communication and computation. Under the resource theory framework, resource distillation serves as a generic tool to overcome the effect of noise. Yet, conventional resource distillation protocols generally require operations on multiple copies of resource states, and strong limitations exist that restrict their practical utilities. Recently, by relaxing the setting of resource distillation to only approximating the measurement statistics instead of the quantum state, a resource-frugal protocol, "virtual resource distillation," is proposed, which allows more effective distillation of noisy resources. Here, we report its experimental implementation on a photonic quantum system for the distillation of quantum coherence (up to dimension four) and bipartite entanglement. We show the virtual distillation of the maximal superposed state of dimension four from the state of dimension two, an impossible task in conventional coherence distillation. Furthermore, we demonstrate the virtual distillation of entanglement with operations acting only on a single copy of the noisy Einstein-Podolsky-Rosen (EPR) pair and showcase the quantum teleportation task using the virtually distilled EPR pair with a significantly improved fidelity of the teleported state. These results illustrate the feasibility of the virtual resource distillation method and pave the way for accurate manipulation of quantum resources with noisy quantum hardware.

A cross-sectional analysis of the relationship between the non-high density to high density lipoprotein cholesterol ratio (NHHR) and kidney stone risk in American adults.

BACKGROUND: Recent interest in the Non-High Density to High Density Lipoprotein Cholesterol ratio (NHHR) has emerged due to its potential role in metabolic disorders. However, the connection between NHHR and the development of kidney stones still lacks clarity. The primary goal of this research is to explore how NHHR correlates with kidney stone incidence. METHODS: An analysis was conducted on the data collected by the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, focusing on adults over 20 years diagnosed with kidney stones and those with available NHHR values. Employing weighted logistic regression and Restricted Cubic Spline (RCS) models, NHHR levels' correlation with kidney stone risk was examined. Extensive subgroup analyses were conducted for enhanced reliability of the findings. RESULTS: The findings indicate a heightened kidney stone risk for those at the highest NHHR levels relative to those at the lowest (reference group). A notable non-linear correlation of NHHR with kidney stone incidence has been observed, with a significant P-value (< 0.001), consistent across various subgroups. CONCLUSION: A clear link exists between high NHHR levels and increased kidney stone risk in the American adult population. This study highlights NHHR's significance as a potential indicator in kidney stone formation.

In Situ Electrochemical Rapid Induction of Highly Active γ-NiOOH Species for Industrial Anion Exchange Membrane Water Electrolyzer.

Limited by the strong oxidation environment and sluggish reconstruction process in oxygen evolution reaction (OER), designing rapid self-reconstruction with high activity and stability electrocatalysts is crucial to promoting anion exchange membrane (AEM) water electrolyzer. Herein, trace Fe/S-modified Ni oxyhydroxide (Fe/S-NiOOH/NF) nanowires are constructed via a simple in situ electrochemical oxidation strategy based on precipitation-dissolution equilibrium. In situ characterization techniques reveal that the successful introduction of Fe and S leads to lattice disorder and boosts favorable hydroxyl capture, accelerating the formation of highly active γ-NiOOH. The Density Functional Theory (DFT) calculations have also verified that the incorporation of Fe and S optimizes the electrons redistribution and the d-band center, decreasing the energy barrier of the rate-determining step (*O→*OOH). Benefited from the unique electronic structure and intermediate adsorption, the Fe/S-NiOOH/NF catalyst only requires the overpotential of 345 mV to reach the industrial current density of 1000 mA cm-2 for 120 h. Meanwhile, assembled AEM water electrolyzer (Fe/S-NiOOH//Pt/C-60 °C) can deliver 1000 mA cm-2 at a cell voltage of 2.24 V, operating at the average energy efficiency of 71% for 100 h. In summary, this work presents a rapid self-reconstruction strategy for high-performance AEM electrocatalysts for future hydrogen economy.

Association between kidney stones and life's essential 8: a population-based study.

BACKGROUND: Kidney stones exhibit a robust correlation with cardiovascular disease (CVD). The objective of this research is to investigate the correlation between kidney stones and Life's Essential 8 (LE8), a newly updated assessment of cardiovascular health (CVH), among adults in the United States. METHODS: In this study, which analyzed data from the 2007-2018 National Health and Nutrition Examination Survey, we employed LE8 scores (ranging from 0 to 100) as the independent variable, classifying them into low, moderate, and high CVH categories. The research examined the relationship between LE8 scores and kidney stones by using multivariate logistic regression and restricted cubic spline models, with kidney stones as the dependent variable. RESULTS: Out of the 14,117 participants in this research, the weighted mean LE8 score was 69.70 ± 0.27. After accounting for confounding factors, there was an inverse association between higher LE8 scores and the likelihood of developing kidney stones (OR of 0.81 per 10-point increase, with a 95% confidence interval of 0.77-0.85), demonstrating a non-linear dose-response pattern. Similar patterns were observed for health behaviors, health factor scores, and kidney stones. Stratified analyses demonstrated a stable negative correlation between LE8 scores and kidney stones across different subgroups. CONCLUSION: LE8 and its subscale scores exhibited a robust and inverse correlation with the occurrence of kidney stones. Encouraging adherence to optimal CVH levels has the potential to serve as an effective strategy in preventing and minimizing the occurrence of kidney stones.

[Natural 5α-reductase inhibitors in treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia(BPH) is a common disease of the male urinary system, and its incidence rate in China is increasing. However, the mechanism underlying the pathogenesis of BPH remains unclear. Some studies demonstrated that the incidence of BPH was related to the change in the levels of steroid hormones. Too high content of dihydrotestosterone(DHT) in the body may cause BPH and other related diseases. Testosterone(T) is converted to DHT by 5α-reductase(SRD5A). By inhibiting the activity of this enzyme, the production of DHT can be reduced, and then the incidence of BPH can be lowered. Therefore, it has drawn great attention to screen and discover safer and more effective 5α-reductase inhibitors from natural medicines to treat prostatic hyperplasia without affecting the physiological function of men. This review summarizes the characteristics and tissue distribution of 5α-reductase, the discovery of 5α-reductase inhibitors in traditional Chinese medicine and natural medicines, 5α-reductase inhibitors commonly used in clinical practice and their side effects, as well as the animal models of prostatic hyperplasia and common detection indicators, aiming to provide a reference for more in-depth understanding and research about BPH and development of drugs.

One-Shot Single-Cell Proteome and Metabolome Analysis Strategy for the Same Single Cell.

Characterizing the profiles of proteome and metabolome at the single-cell level is of great significance in single-cell multiomic studies. Herein, we proposed a novel strategy called one-shot single-cell proteome and metabolome analysis (scPMA) to acquire the proteome and metabolome information in a single-cell individual in one injection of LC-MS/MS analysis. Based on the scPMA strategy, a total workflow was developed to achieve the single-cell capture, nanoliter-scale sample pretreatment, one-shot LC injection and separation of the enzyme-digested peptides and metabolites, and dual-zone MS/MS detection for proteome and metabolome profiling. Benefiting from the scPMA strategy, we realized dual-omic analysis of single tumor cells, including A549, HeLa, and HepG2 cells with 816, 578, and 293 protein groups and 72, 91, and 148 metabolites quantified on average. A single-cell perspective experiment for investigating the doxorubicin-induced antitumor effects in both the proteome and metabolome aspects was also performed.

Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell.

The shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a mammalian cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 2449-3500, 2278-3257 and 1621-2904 protein groups are quantified in single A549 cells (n = 37), HeLa cells (n = 44) and U2OS cells (n = 27) under the DIA (MBR) mode, respectively. Benefiting from the flexible cell picking-up ability, we study HeLa cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight.

T-type voltage-gated channels, Na+/Ca2+-exchanger, and calpain-2 promote photoreceptor cell death in inherited retinal degeneration.

Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, a connection between excessive Ca2+ influx and photoreceptor loss has yet to be proven.Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca2+-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca2+-chelator BAPTA-AM or inhibitors of different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and - 2 were monitored, cell death was assessed via the TUNEL assay.While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca2+-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors.These results suggest that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca2+-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. Video Abstract.

Hedysarumqilianshanense sp. nov. (Fabaceae, Hedysareae), a new species from the Qilianshan Mountains in Gansu, China.

Hedysarumqilianshanensesp. nov. (Fabaceae, Hedysareae) is described and illustrated from the Qilianshan Mountains in Gansu, China. This new species is similar to H.przewalskii, but can be distinguished by its corolla being light purple to purple, standard 15-19 mm long, wings 14-16 mm long, keels 16-19 mm long, and the ovary and legume being glabrous. The new species can be easily distinguished from H.neglectum Ledeb. by its bract being shorter than the pedicel, and the ovary and legume being glabrous. Phylogenetic tree based on the nuclear ITS and ETS sequences shows that H.qilianshanense is sister to H.przewalskii, while the tree based on the plastid psbA-trnH, trnC-petN, trnL-F, trnS-G and petN-psbM sequences shows H.qilianshanense as sister to a clade consisting of H.hedysaroides, H.inundatum, H.americanum and H.neglectum. The new species is a diploid with the chromosome number 2n = 14. Based on morphological, phylogenetic and karyotypic evidence, the new species may originate from an ancient homoploid hybrid speciation event.

Diaporaustalides A-L, Austalide Meroterpenoids from a Plant Endophytic Diaporthe sp.

Twelve new austalide meroterpenoids (1-12) were isolated from the endophytic fungus Diaporthe sp. XC1211. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1, 3, 4, and 6 were established by single-crystal X-ray diffraction, whereas those for the others were established by experimental electronic circular dichroism (ECD) data analysis. Compounds 1-12 represent a rare class of austalides with a 24α-CH3. Compounds 2 and 5 demonstrated potent proliferation inhibitory effects against LPS-induced B cells with IC50 values of 6.7 (SI = 3.6) and 3.8 (SI > 13) µM, respectively. Compounds 2 and 5 decreased the secretion of IL-6 in LPS-induced B cells in a dose-dependent manner.

Urinary biomarkers of exposure to organophosphate, pyrethroid, neonicotinoid insecticides and oxidative stress: A repeated measurement analysis among pregnant women.

Exposure to insecticides may be associated with increased oxidative stress (OS), but few studies have assessed the associations of OS biomarkers (OSBs) with exposure to multiple insecticides and their mixture, especially in pregnant women who are a vulnerable population. In the present study, 1,094 Chinese pregnant women were recruited and a total of 3,282 urine samples were collected at their three trimesters to measure eight metabolites of organophosphates, three metabolites of pyrethroids, nine typical neonicotinoids/their metabolites, and three OSBs of DNA damage (8-OHdG), RNA damage (8-OHG), and lipid peroxidation (HNE-MA). Among the twenty target insecticide metabolites, sixteen of them were frequently detected; thirteen of them were detected in over 86% of all the urine samples except for imidacloprid (IMI, detection frequency: 72.9%), desnitro-imidacloprid (DN-IMI, 70.0%), and clothianidin (CLO, 79.6%). The reproducibility of their concentrations across the three trimesters was poor to fair (intraclass correlation coefficients <0.50). Multiparity and warm season were related to higher urinary levels of some insecticide metabolites, while higher education level and inadequate weight gain during pregnancy were significantly associated with lower concentrations of certain insecticide metabolites. Linear mixed model analyses suggested that almost all the frequently detected insecticide metabolites [other than 3-phenoxybenzoic acid (3-PBA)] were significantly associated with elevated levels of the three OSBs (8-OHdG, 8-OHG, and HNE-MA), where the percent change (Δ%) ranged 8.10-36.0% for 8-OHdG, 8.49-34.7% for 8-OHG, and 5.92-182% for HNE-MA, respectively, with each interquartile ratio (IQR)-fold increase in the concentrations of the individual exposure biomarkers. Weighted quantile sum models demonstrated that the insecticide metabolite mixture was positively associated with the three OSBs. Overall, urinary desmethyl-clothianidin (DM-CLO) and 3,5,6-trichloro-2-pyridinol (TCPy) were the top insecticide exposure biomarkers contributing to the association with 8-OHdG and 8-OHG levels, while PNP contributed the most to the association with HNE-MA levels. These findings suggested that gestational exposure to organophosphates, pyrethroids, neonicotinoids, their transformation products, and their mixture may increase oxidative damage to lipids, RNA, and DNA during pregnancy.

Simultaneous deep transcriptome and proteome profiling in a single mouse oocyte.

Although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing, and mass spectrometry technology to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level, providing an important resource for understanding the relationship between transcription and translation in cells. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19,948 genes and 2,663 protein groups in single mouse oocytes. In particular, we analyzed the correlation of individual RNA and protein pairs, as well as the meiosis regulatory network with unprecedented depth, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, which could be productive for exploring transcriptional and translational regulatory features during oocyte meiosis.

Associations of Trimester-Specific Exposure to Perchlorate, Thiocyanate, and Nitrate with Childhood Neurodevelopment: A Birth Cohort Study in China.

Studies about the impacts of maternal exposure to perchlorate, thiocyanate, and nitrate on offspring neurodevelopment are scarce. Based on a birth cohort in China, 1,028 mothers provided urine samples at three trimesters for determination of the three target analytes, and their offspring neurodevelopment was evaluated at 2 years old. Associations of maternal exposure to the three chemicals with offspring neurodevelopment were estimated using three statistical methods. Trimester-specific analyses using generalized estimating equation models showed that double increment of thiocyanate and nitrate during the first trimester was associated with 1.56 (95% CI: -2.82, -0.30) and 1.22 (-2.40, -0.03) point decreases in the offspring mental development index (MDI), respectively. Weighted quantile sum (WQS) regression analyses showed that the mixture exposure at the first and second trimesters was negatively associated with the offspring MDI (ß = -2.39, 95% CI: -3.85, -0.93; ß = -1.75, 95% CI: -3.04, -0.47, respectively) and thiocyanate contributed the most to the association (65.0 and 91.6%, respectively). Bayesian kernel machine regression analyses suggested an inverted U-shape relationship of maternal urinary thiocyanate with the offspring MDI. These findings suggested that prenatal exposure to the three chemicals (at current levels), especially thiocyanate and nitrate, may impair neurodevelopment. Early pregnancy seems to be the sensitive window.

Association of Prenatal Exposure to Organophosphate, Pyrethroid, and Neonicotinoid Insecticides with Child Neurodevelopment at 2 Years of Age: A Prospective Cohort Study.

BACKGROUND: Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown. OBJECTIVES: We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure. METHODS: Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (N=1,041). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined. RESULTS: Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): -5.59, -0.74] and 3.06 points (95% CI: -5.45, -0.68) respectively in boys' MDI scores. Each 1-unit increase in that of trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: -3.89, -0.58) in boys' MDI scores and 1.90 points (95% CI: -3.16, -0.64) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: -5.47, -0.57) in MDI scores among the boys, and trans-DCCA contributed the most to the association (18%). CONCLUSIONS: Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097.

Sociodemographic features associated with the MoCA, SPPB, and GDS scores in a community-dwelling elderly population.

BACKGROUND: An accurate evaluation of cognitive function, physical health, and psychological health is fundamental for assessing health problems in the elderly population, and it is important to identify the necessity of early therapeutic intervention. The objective of this study was to evaluate the states of mental and physical functions and to investigate the relationships between sociodemographic features and these functions in a community-dwelling elderly population. METHODS: This community-based cross-sectional study was conducted in a suburban district of Shanghai, China. A total of 1025 participants aged 60-89 years underwent investigations of demographic and lifestyle features and a multidimensional geriatric evaluation comprising the Montreal Cognitive Assessment (MoCA), Short Physical Performance Battery (SPPB), and Geriatric Depression Scale (GDS). RESULTS: The results of the multivariate linear regression models demonstrated that the MoCA and SPPB scores decreased with advancing age (all P < 0.01). However, the GDS score did not exhibit an age-related decrease (P = 0.09). Both sex and living alone influenced the MoCA score (P < 0.01 and P = 0.04, respectively), SPPB score (P < 0.01 and P = 0.04, respectively), and GDS score (P < 0.01 and P < 0.01, respectively). A higher education level was related to better MoCA and SPPB scores (all P < 0.01). Furthermore, age and sex had interactive effects on the MoCA score (P = 0.03) and SPPB score (P < 0.01). The kernel-weighted local polynomial smoothing curves exhibited similar trends. CONCLUSIONS: It is imperative to develop a more sensitive evaluation of physical function, and to encourage various intellectually and emotionally stimulating social activity strategies to promote healthy aging, especially in elderly women and those living alone who have a low education level.

Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity characterized by intrahepatic ectopic steatosis. As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle, the incidence of NAFLD has surpassed that of viral hepatitis, making it the most common cause of chronic liver disease globally. Huangqin decoction (HQD), a Chinese medicinal formulation that has been used clinically for thousands of years, has beneficial outcomes in patients with liver diseases, including NAFLD. However, the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood. AIM: To evaluate the ameliorative effects of HQD in NAFLD, with a focus on lipid metabolism and insulin resistance, and to elucidate the underlying mechanism of action. METHODS: High-fat diet-induced NAFLD rats and palmitic acid (PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action. Phytochemicals in HQD were analyzed by high-performance liquid chromatography (HPLC) to identify the key components. RESULTS: Ten primary chemical components of HQD were identified by HPLC analysis. In vivo, HQD effectively prevented rats from gaining body and liver weight, improved the liver index, ameliorated hepatic histological aberrations, decreased transaminase and lipid profile disorders, and reduced the levels of pro-inflammatory factors and insulin resistance. In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation, inflammation, and insulin resistance in HepG2 cells. In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathway-modulated lipogenesis and inflammation, contributing to its beneficial actions, which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD. CONCLUSION: In summary, our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.

Dexmedetomidine abates myocardial ischemia reperfusion injury through inhibition of pyroptosis via regulation of miR-665/MEF2D/Nrf2 axis.

The current study intended to delve into the mechanisms of dexmedetomidine (Dex) in regulating myocardial pyroptosis against myocardial ischemia/reperfusion injury (MIRI). The rat MIRI models were induced by ligation/release of the coronary artery in vivo and Langendorff perfusion ex vivo. Hemodynamic parameters, infarction sizes, and histopathological changes were assessed to understand the effects of Dex on MIRI. We explored the mechanisms through functional experiments on an H9c2 cell hypoxia/reoxygenation (H/R) model. Cell viability and apoptosis were evaluated using cell counting kit 8 (CCK-8) and AV/PI dual staining respectively. The expressions of miR-665 and MEF2D mRNA were detected by qRT-PCR. Western blot was employed to determine the expression levels of pyroptosis- and signaling pathway- related proteins. The interplays between miR-665 and MEF2D were validated by Dual-luciferase reporter assays. Our findings indicated that Dex preconditioning dramatically attenuated hemodynamic derangements, infarct size, and histopathological damage in rats undergoing MIRI. Dex markedly augmented cell viability, while suppressing cell apoptosis and expressions of NLRP3, cleaved-caspase-1, ASC, GSDMD, IL-1ß, and IL-18 in H9c2 cells subjected to H/R injury. MiR-665 was significantly upregulated, MEF2D and Nrf2 downregulated following H/R, whereas Dex preconditioning reversed these changes. MEF2D was validated to be a target gene of miR-665. Overexpression of miR-665 decreased the expression of MEF2D and blunted the protective effects of Dex in H9c2 cells. Moreover, the functional rescue experiment further verified that Dex regulated MEF2D/Nrf2 pathway via miR-665. In conclusion, Dex mitigates MIRI through inhibiting pyroptosis via regulating miR-665/MEF2D/Nrf2 axis.