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Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1β, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1β. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1β cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1β cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1β axis in the microglia.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 μg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 μg/mL). The EC50 was 2.05 μg/mL (95% CI: 1.85–2.19 μg/mL) in PD group, much lower than the 2.72 μg/mL (95% CI: 2.53–2.88 μg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.)

Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1[beta], which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1[beta]. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasingthe number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL- 1[beta] cleavage were well inhibited by resveratrol dosedependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1[beta] cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1[beta] axis in the microglia.

Background： Endometriosis （EMs） is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance ofectopic endometriotic lesions. Transtbrming growth factor-beta I （TGF-β1） plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions. Methods： Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA （mRNA） and protein expression levels ofTGF-β1, vascular endothelial growth fhctor （VEGF）, and hypoxia-inducible fhctor-Ic~ （HIF-β1） were measured. A DuaI-Luciferase Reporter Assay was used to examine the effect ofTGF-[31 and hypoxia on a VEGF promoter construct. Student＇s t-test was pertbrmed/br comparison among groups （one-sided or two-sided） and a value ofP 〈 0.05 was considered statistically significant. Results： TGF-β1, VEGF, HIF-β1 mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue （t = 2.16, P = 0.042）. EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein （t = 6.84, P - 0.023）. VEGF mRNA levels increased 12.5% in response to TGF-β1, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production （87.5% increases） of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 （2.6-fold, t = 6.08, P = 0.032） or hypoxia （11.2-fold, t = 32.70, P 〈 0.001 ）, whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect （ 18.5-fold, t = 33.50, P 〈 0.001 ）. Conclusions： The data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-[31 and hypoxia is taking place at the transcriptional level.

Time-reversal invariant topological insulator is widely recognized as one of the fundamental discoveries in condensed matter physics, for which the most fascinating hallmark is perhaps a spin-based topological protection, the absence of scattering of conduction electrons with certain spins on matter surface. Recently, it has created a paradigm shift for topological insulators, from electronics to photonics, phononics and mechanics as well, bringing about not only involved new physics but also potential applications in robust wave transport. Despite the growing interests in topologically protected acoustic wave transport, T -invariant acoustic topological insulator has not yet been achieved. Here we report experimental demonstration of anomalous Floquet topological insulator for sound: a strongly coupled metamaterial ring lattice that supports one-way propagation of pseudo-spin-dependent edge states under T -symmetry. We also demonstrate the formation of pseudo-spin-dependent interface states due to lattice dislocations and investigate the properties of pass band and band gap states. Topological protected acoustic wave propagation has been predicted, but yet awaits for experimental demonstration. Here, Peng et al . report one-way propagation of pseudo-spin-dependent edge states for sound, analogous to Floquet topological insulator in solid state.

The Schrödinger equation is a fundamental equation to describe the wave function of a quantum-mechanical system. The similar forms between the Schrödinger equation and the paraxial wave equation allow a paradigm shift from the quantum mechanics to classical fields, opening up a plethora of interesting phenomena including the optical super-oscillatory behavior. Here, we propose an ultrasonic meta-lens for generating super-oscillation acoustic wave-packets with different spatial momenta and then superimposing them to a diffraction-limit-broken spot, visually represented by the ring-shaped trapping of tiny particles. Moreover, based on the focused super-oscillation packets, we experimentally verify proof-of-concept super-resolution ultrasound imaging, opening up the arena of super-oscillation ultrasonics for advanced acoustic imaging, biomedical applications, and versatile far-field ultrasound control. Here, the authors propose an ultrasonic meta-lens for generating super-oscillation wave packets with different spatial momenta and then superimposing them to a diffraction-limit-broken spot. They experimentally verify super-resolution ultrasound imaging of subwavelength objects.

This study evaluates changes in cross-national disparities in the burden of severe periodontitis between 1990 and 2021. All data on severe periodontitis used in this study were derived from the 2021 Global Burden of Disease (GBD) study. Annual years lived with disability (YLDs) and their estimated annual percentage changes (EAPCs) were calculated and stratified by year, age, geographical region, and socio-demographic index (SDI) at global, regional, and national levels. Decomposition analysis assessed the contributions of demographic and epidemiological factors to the evolving burden of severe periodontitis. A frontier analysis identified areas for improvement and disparities among countries based on development levels. Distributional inequalities were measured using the slope index of inequality (SII) and concentration index. The autoregressive integrated moving average model (ARIMA) was used to project the disease burden up to 2036. In 2021, there were 6,903.28 thousand YLDs (95% uncertainty interval [UI]: 2,772.28−14,106.18 thousand) attributed to severe periodontitis globally. Between 1990 and 2021, the global age-standardized rate (ASR) of YLDs showed a stable trend, increasing slightly from 79.62 (95% UI: 31.46–169.62) to 80.89 (95% UI: 32.47–165.37) with an EAPC of 0.08% (95% confidence interval [CI]: −0.03 to 0.18). Population growth accounted for 66.73% of the global increase in YLDs. SII values rose from 12.72 (95% CI: 1.92–23.52) in 1990 to 44.99 (95% CI: 31.14–58.85) in 2021, while the concentration index decreased from 0.05 (95% CI: −0.04 to 0.13) in 1990 to 0.035 (95% CI: −0.06 to 0.13). According to the forecasts, the global ASR of YLDs for severe periodontitis is projected to show a slight decline over the next 15 years. Significant potential exists for reducing the burden of severe periodontitis across countries, irrespective of their development levels. Severe periodontitis remains a significant global health challenge, with substantial cross-country disparities that persist despite overall stable trends in global YLDs. Targeted interventions and policies are urgently needed to address these disparities, focusing on improving oral health outcomes across all countries, regardless of their socio-demographic development levels.

Background and objective: Andrographis paniculata (AP) is a traditionally used herbaceous plant, whose main active constituent is andrographolide. Andrographolide derivative medications and herbal preparations of AP are often used to treat respiratory tract infections. This study aims to systematically evaluate the safety of andrographolide derivative medications and herbal preparations of AP based on clinical studies. Methods: English and Chinese databases were searched for all types of clinical studies that reported adverse drug reactions (ADRs) and adverse events (AEs) of andrographolide derivative medications and herbal preparations of AP. The ADRs and AEs were classified according to manifestations, and graded according to severity. Single-rate meta-analysis was performed for ADR incidence using R software. Results: A total of 262 studies were included, including 125 randomized controlled trials, 23 non-randomized controlled trials, 6 case series, and 108 case reports. In 9490 participants using andrographolide derivative injections, 383 (4.04%) reported ADRs. Meta-analysis showed that the ADR incidence of three most frequently used injections of andrographolide derivatives (andrographolide sulfonate, potassium sodium dehydroandrographolide succinate, and potassium dehydroandrographolide succinate) were 5.48% [95% CI (4.47%, 6.72%)], 3.69% [95% CI (2.59%, 4.94%)] and 5.33% [95% CI (3.68%, 7.72%)], respectively, which may be slightly higher than the actual ADR incidence, because only studies that reported the occurrence of ADRs or AEs were included, but studies without ADR and AE were not included. The ADRs of andrographolide derivative injections were mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Fifty-five patients experienced life-threatening anaphylactic shock, three patients died, and the causation attributed to the andrographolide derivative injection. Other ADRs were mild, moderate or medically significant. Nine herbal preparations of AP were tested in 10 studies, and the reported ADRs were mainly mild to moderate gastrointestinal, skin and subcutaneous tissue disorders. Except for five patients using andrographolide derivative injections eventually died, most of the ADRs were alleviated after drug withdrawal and symptomatic treatment. Conclusions: The ADRs of andrographolide derivative medications are few, but can be life-threatening, mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Injections of andrographolide derivatives should be used with caution. Herbal preparations of AP are essentially safe. Systematic Review Registration : [website], identifier [registration number]

Tendinopathy is a complex multifaceted tendinopathy often associated with overuse and with its high prevalence resulting in significant health care costs. At present, the pathogenesis and effective treatment of tendinopathy are still not sufficiently elucidated. The purpose of this research is to intensely explore the genes, functional pathways, and immune infiltration characteristics of the occurrence and development of tendinopathy. The gene expression profile of GSE106292, GSE26051 and GSE167226 are downloaded from GEO (NCBI comprehensive gene expression database) and analyzed by WGCNA software bag using R software, GSE26051, GSE167226 data set is combined to screen the differential gene analysis. We subsequently performed gene enrichment analysis of Gene Ontology (GO) and \"Kyoto Encyclopedia of Genes and Genomes\" (KEGG), and immune cell infiltration analysis. By constructing the LASSO regression model, Support vector machine (SVM-REF) and Gaussian mixture model (GMMs) algorithms are used to screen, to identify early diagnostic genes. We have obtained a total of 171 DEGs through WGCNA analysis and differentially expressed genes (DEGs) screening. By GO and KEGG enrichment analysis, it is found that these dysregulated genes were related to mTOR, HIF-1, MAPK, NF-κB and VEGF signaling pathways. Immune infiltration analysis showed that M1 macrophages, activated mast cells and activated NK cells had infiltration significance. After analysis of THE LASSO SVM-REF and GMMs algorithms, we found that the gene MACROD1 may be a gene for early diagnosis. We identified the potential of tendon disease early diagnosis way and immune gene regulation MACROD1 key infiltration characteristics based on comprehensive bioinformatics analysis. These hub genes and functional pathways may as early biomarkers of tendon injuries and molecular therapy level target is used to guide drug and basic research.

Plant calcium-dependent protein kinases (CDPKs) were reported to play important roles in plant resistance to abiotic stress. Foxtail millet cultivation \"H138\" was used for RNA-seq analysis. The data from drought-induced transcriptomic sequences of foxtail millet showed that CDPKs were up- or down-regulated by drought to different degrees. In this study, 29 foxtail millet CDPKs were classified into four subgroups. These genes were unevenly distributed on nine foxtail millet chromosomes, and chromosomes 2, 3, and 9 contained the most SiCDPK members. Analysis of putative -acting elements showed that most foxtail millet CDPK genes contained the ABRE, LTR, HSE, MYB, MYC, DRE, CGTCA-motif, and TGACG-motif -acting elements, which could be activated by abiotic stresses. Real-time PCR analysis indicated that 29 SiCDPK genes experienced different degrees of induction under drought and ABA stresses. had the highest expression levels at 6 and 12 h of drought treatment and was chosen for further analysis. SiCDPK24 localized to the cell membrane and the nucleus of mesophyll protoplasts. Western blot analysis showed that SiCDPK24 protein had autophosphorylation activity. Overexpression of in enhanced drought resistance and improved the survival rate under drought stress. It also activated the expressions of nine stress-related genes, namely , , , , , , , , and . These genes are involved in resistance to abiotic stresses in . These results indicate that foxtail millet CDPK genes play important roles in resisting drought stress.