[Comparative analysis of plastomes of Rubus chingii and R. chingii var. suavissimus].

Rubus chingii and R. chingii var. suavissimus are unique dual-purpose plant resources, with significant nutraceutical, pharmaceutical, and economic value, as well as promising prospects for further development. To investigate the genetic structure and evolutionary characteristics of these two varieties, this study conducted plastome sequencing using the Illumina HiSeq XTen sequencing platform. Subsequently, the study performed assembly, annotation, and characterization of the genomes, followed by a comparative plastome and phylogenetic analysis using bioinformatics techniques. The results revealed that the plastomes of R. chingii and R. chingii var. suavissimus exhibited a tetrad structure, comprising a large single-copy region(LSC), a small single-copy region(SSC), and two inverted repeat regions(IRs). The study identified a total of 56 simple sequence repeats(SSRs) after comparative analysis, predominantly consisting of A and T. Furthermore, the structure of the IR boundary genes in both varieties was found to be highly conserved, with only minor nucleotide variations. Additionally, the study identified three highly variable regions: rps16-trnQ-psbK, trnR-atpA, and trnT-trnL, which held promise as potential identification marks for further development and utilization. Phylogenetic analysis results obtained by the maximum likelihood and Bayesian inference methods demonstrated a close clustering of R. chingii and R. chingii var. suavissimus(100% support), with their closest relatives being R. trianthus. This study, focusing on plastome-level genetic distinctions between these two varieties, lays a foundation for future species protection, development, and utilization.

Shizukaol C alleviates trimethylamine oxide-induced inflammation through activating Keap1-Nrf2-GSTpi pathway in vascular smooth muscle cell.

BACKGROUND: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. PURPOSE: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. METHODS: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. RESULTS: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. CONCLUSION: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.

Integration of metabolomics and transcriptomics to reveal the mechanism of Gerberae piloselloidis herba in alleviating bronchial asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Gerberae Piloselloides Herba (GPH) is derived from Gerbera piloselloides (Linn.) Cass. It is a commonly used traditional medicine in China, featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial and anti-tumor. It is often used as an effective treatment for cough and sore throat as well as bronchial asthma (BA) in China. It was demonstrated in our previous studies that GPH exerted significant effects on the treatment of BA, but its underlying mechanism remains unclear. AIM OF THE STUDY: This study was aimed at revealing the mechanism through which GPH protects against BA. MATERIALS AND METHODS: The protective effect of GPH against BA was evaluated in a mouse model of BA induced by ovalbumin. Through integrated metabolomics and transcriptomics analysis, the most critical pathways were discovered. The effects of GPH in regulating these pathways was verified through molecular biology experiments and molecular docking. RESULTS: GPH have anti-BA effects. In plasma and lung tissue, 5 and 17 differentially expressed metabolites (DEMs), respectively, showed a reversed tendency in the GPH group compared with the model group; apart from gamma-aminobutyric acid and butyrylcarnitine, these DEMs might aid in BA diagnosis. The DEMs were involved primarily in the regulation of lipid metabolism, followed by glucose metabolism and amino acid metabolism. Transcriptomic analysis indicated that GPH modulated 268 differentially expressed genes (DEGs). Integration analysis of metabolomics and transcriptomics revealed that GPH might regulate the PPAR signaling pathway, thus affecting the expression of key gene targets such as Cyp4a12a, Cyp4a12b, Adh7, Acaa1b and Gpat2; controlling fatty acid degradation, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and other lipid metabolic pathways; and ameliorating BA. This possibility was confirmed through reverse-transcription quantitative polymerase chain reaction, western blotting, immunofluorescence and molecular docking. CONCLUSION: GPH was found to activate the PPAR signaling pathway, decrease the levels of Cyp4a12a and Cyp4a12b, and increase the levels of Adh7, Acaa1b and Gpat2, thereby regulating lipid metabolism disorder, decreasing the generation of inflammatory mediators and limiting lung injury.

An Umbrella Insight into the Phytochemistry Features and Biological Activities of Corn Silk: A Narrative Review.

Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.

Nutrition therapy in critically ill patients with severe acute pancreatitis.

A significant proportion of patients (10%-20%) with acute pancreatitis develop severe acute pancreatitis characterized by pancreatic necrosis, systemic inflammation, and organ failure, commonly requiring intensive care unit (ICU) admission. In this specific population, nutrition therapy is more challenging than that in the general ICU population, primarily because of inevitable gastrointestinal involvement by pancreatic inflammation. In this review, we discussed several key aspects of nutrition therapy in this population, including key pathophysiology that may impede nutrition therapy, the timing and implementation of enteral nutrition and parenteral nutrition, the importance of specific nutrient supplements, and the long-term outcomes that may be addressed by nutrition therapy.

Four new glycosides isolated from Gerbera delavayi Franch.

Phytochemical investigation of the whole plant of Gerbera delavayi afforded four new glycosides including three coumarin glycosides, Gerbelavinside A (1), Gerbelavinside B (2) and Gerbelavinside C (3) and one acetophenone glycoside, Gerbelavinside F (4). The structures of isolated compounds were elucidated by analysis of 1D and 2D NMR, HR-ESI-MS, acid hydrolysis, as well as comparing with the literature. The isolated compounds were examined the effects of nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells, and Gerbelavinside C presented a certain inhibitory activity.

Effect of Vitamin E on Diabetic Nephropathy: A Meta-Analysis.

Background: Diabetes nephropathy has always been one of the main causes of chronic kidney disease and end-stage kidney disease (ESRD), and diabetes nephropathy accounts for about 40% of ESRD cases. Vitamin E can effectively reduce urinary microalbumin, urinary albumin excretion rate and serum nitric oxide level in patients with type 2 diabetes nephropathy. Methods: The computer retrieves four databases to obtain controlled trials on the effects of vitamin E in patients with diabetic nephropathy. After a rigorous literature quality evaluation, data analysis was performed using Stata software. Study Design Type Published controlled trials on the effects of vitamin E in patients with diabetic nephropathy. However, the animal trials were excluded. The intervention group received vitamin E in the treatment of patients with diabetic nephropathy, and the control group received a placebo in the treatment of patients with diabetic nephropathy. Outcome indicators patients with diabetic nephropathy; According to research, the assessment tools for the effects of vitamin E in patients with diabetic nephropathy are: (1) HbA1c (Glycated hemoglobin,%); (2) EGFR (mL/min 1.73 m2); (3) Serum creatinine (µmol/L); (4) Urea (mmol/L); (5) Systolic BP (mmHg); (6) Diastolic BP (mmHg). Results: 5 studies were ultimately included in this meta-analysis. 5 studies reported the glycosylated hemoglobin (HbA1c) of the test group and the control group, which was significantly lower (SMD: -0.17; 95% Cl: -0.26,-0.07; P < .01) than the control group. Meta-analysis showed that the Serum creatinine of the test group was also significantly lower (SMD: -11.20; 95% Cl: -12.89,-9.51; P < .01) than the control group. EGFR of the test group had no significant statistical significance (SMD: -0.90; 95% Cl: -13.30,11.49; P = .886) than the control group. Meta-analysis showed that the urea of the test group had no significant statistical significance(SMD: -0.57; 95% Cl: -1.58,0.45; P = .275). The systolic BP (SMD: -3.95; 95% Cl: -9.79,1.88; P = .184) and Diastolic BP (SMD: 0.26; 95% Cl: -0.75,1.27; P = .617) are also consistent with the group. Conclusion: The results of this study suggest that vitamin E may be effective on in patients with diabetic nephropathy, as evidenced by HbA1c and Serum creatinine, and the above conclusions need to be verified by more high-quality studies.

Breast Imaging Patient Demographics at a Major Comprehensive Cancer Center Before and During the COVID-19 Pandemic.

OBJECTIVE: The coronavirus disease of 2019 (COVID-19) pandemic disproportionately affected certain vulnerable communities. The purpose of our study was to determine how COVID-19 affected the socioeconomic demographics of breast imaging patients at a major comprehensive cancer center. METHODS: This retrospective cohort study compared female patients who underwent screening mammograms, diagnostic mammograms, breast ultrasound, or breast MRI during the following time periods: prepandemic (February 1, 2018, through February 29, 2020), acute pandemic (March 1, 2020, through June 30, 2020), subacute pandemic (August 1, 2020, through December 31, 2020), and chronic pandemic (January 1, 2021, through June 30, 2022). Statistics were performed using the generalized estimating equations approach. RESULTS: A total of 74,398 female patients (mean age, 55.6 ± 12.4 years) underwent 238,776 total breast imaging examinations. For screening mammograms, Hispanics represented 27.1% (9,197 of 33,960) of patients in the prepandemic time period compared with 16.7% (604 of 3,621) in the acute pandemic time period, 18.7% (1,835 of 9,830) in the subacute pandemic time period, and 24.3% (7,492 of 30,869) in the chronic pandemic time period (all P < .0001). Self-pay patients saw similar declines for screening mammograms during the same time periods: 21.7% (7,375 of 33,960), 7.9% (286 of 3,621), 9.5% (933 of 9,830), and 17.4% (5,357 of 30,869), respectively (all P < .0001, compared with the prepandemic time period). Similarly dramatic trends were not observed for race or other imaging examinations. DISCUSSION: At our cancer center, Hispanics and self-pay patients were disproportionately affected by the COVID-19 pandemic. Strategies to improve health inequities are needed.

Efficacy and Adverse Effects of Atrasentan in Patients with Diabetic Nephropathy: A Meta-Analysis.

Background: About 30% of Type 1 diabetes (T1DM) patients and 40% of Type 2 diabetes (T2DM) patients were diagnosed with diabetic nephropathy, which has also greatly affected the global end-stage renal disease (ESRD) outcome. Atrasentan is a selective endothelin receptor type A (ETA) antagonist initially studied for the potential treatment of cancer. However, the role of Atrasentan was not sure in the DM. Methods: The machine searches eight databases to find studies examining the impact of Atrasentan in people with diabetic nephropathy both domestically and overseas. Type of Study Design RCTs have been published on Atrasentan's effects in patients with chronic kidney disease.Utilizing RevMan 5.3 software, data analysis was carried out following a thorough assessment of the quality of the literature. Results: This meta-analysis has included 4 papers for statistics. They were all regarded as being random controlled trials. According to 4 studies, the test group's urinary albumin/creatinine ratio (UACR) was significantly lower than the control group's (standardized mean difference (SMD): -222.47; 95% confidence interval (CI): -367.57, -77.38; P < .01), as were the test group's prevalence of cardiovascular disease (OR: 0.83; 95% CI: 0.73, 0.95; P < .01) and adverse reactions (OR: 1.00; 95% CI: 1.00). Conclusion: Atrasentan improves the UACR in individuals with chronic kidney disease as compared to the control category. However, these findings need to be confirmed by more high-quality research. Further studies could focus on the effect of the Atrasentan on the diabetic nephropathy management,which will shed light on the treatment of diabetic nephropathy.

Analysis of compatibility mechanism of shenxiong glucose injection after multiple dosing based on differences of PK-PD correlation and cytochrome P450 enzyme.

Shenxiong glucose injection (SGI) containing a water extract from the roots of Danshen and Ligustrazine hydrochloride, is the main drug used for the prevention and treatment of acute myocardial ischemia (AMI) in China. Based on the characteristics of drug clinical applications, this study aims to uncover the compatibility mechanism of SGI by investigating pharmacokinetic (PK) and pharmacodynamic (PD) differences between Danshen glucose injection (DGI), Ligustrazine glucose injection (LGI) and SGI groups after multiple dosing during the pathological state from the perspective of metabolic enzymes. Compared to the LGI group, the absorption (Cmax) and exposure (AUC) of ligustrazine increased significantly, and the protein expression of CYP1A2, CYP2C11 and CYP3A2 in the SGI group decreased significantly. Furthermore, the PK and PD experimental data for Danshen and ligustrazine in AMI rats were fitted to obtain a PK-PD binding model with three components. PK-PD parameter analysis showed that in the SGI group the IC50 values of ligustrazine and danshensu on AST, CK-MB, cTn-I and the IC50 values of rosmarinic acid on AST and CK-MB were lower than the DGI or LGI group. It is speculated that Danshen inhibited CYP1A2, CYP2C11 and CYP3A2 mediating the metabolism of ligustrazine and decreased the expression of these three isozymes, which further affected the in vivo process of ligustrazine. Moreover, the combination of Danshen and ligustrazine could have better regulating effect on AST, CK-MB and cTn-I. This preliminary study has provided a scientific basis for understanding the compatibility mechanism of SGI from the viewpoint of the regulation of CYP enzymes in the PK-PD model.

[Research progress in microevolutionary process of excellent traits and quality of Dao-di herbs].

Dao-di herbs are the treasure of Chinese materia medica and one of the characteristic research objects of traditional Chinese medicine(TCM). Probing into the microevolution of Dao-di herbs can help to reveal their biological essence and quality formation mechanisms. The progress in molecular biology and omics provides the possibility to elucidate the phylogenetic and quality forming characteristics of Dao-di herbs at the molecular level. In particular, genomics serves as a powerful tool to decipher the genetic origins of Dao-di herbs, and molecular markers have been widely used in the research on the genetic diversity and population structure of Dao-di herbs. Focusing on the excellent traits and quality of Dao-di herbs, this paper reviews the studies about the microevolution process of quality formation mechanisms of Dao-di herbs with the application of molecular markers and omics, aiming to underpin the protection and utilization of TCM resources.

Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Biancaea decapetala (Roth) O.Deg. extract exerts an anti-inflammatory effect by regulating the TNF/Akt/NF-κB pathway.

BACKGROUND: Biancaea decapetala (Roth) O.Deg. (Fabaceae) is used to treat colds, fever, and rheumatic pain caused by inflammation. However, the mechanism underlying its anti-inflammatory properties remains unclear. PURPOSE: This study aimed to evaluate the anti-inflammatory activity of Biancaea decapetala extract (BDE) in vitro and in vivo and explore the possible underlying mechanism and potential targets. METHODS: The release of nitric oxide (NO) and inflammatory cytokines in LPS-stimulated RAW264.7 cells and rats were measured using Griess reagent and enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was employed to examine the pathology of animal tissues. Transcriptome analysis was performed to screen the pathways related to BDE-mediated inhibition of inflammation, and the expression of related proteins was measured using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, ELISA, and immunofluorescence methods. Surface Plasmon Resonance (SPR) and the Drug Affinity Reaction Target Stability (DARTS) method were used to verify whether BDE binds to TNF-α target protein, while a L929 cell model and NF-κB gene reporter systematic method were used to investigate the inhibitory effect of BDE on the activity of TNF-α protein. RESULTS: BDE inhibited the expression of TNF-α, IL-1ß, IL-6, and NO in RAW264.7 cells and rats, and improved the pathological changes in lung tissue. RNA-seq showed that BDE may regulate the TNF/Akt/NF-κB pathway to inhibit inflammation onset. BDE significantly downregulated the mRNA expression of TNF-α, IL-6, IL-1ß, and that of relevant proteins, including TNF-α, p-p65, p-Akt, p-IκBα. Furthermore, BDE inhibited the nuclear translocation of NF-κB (p65) and the activation of the Akt pathway by SC79. The L929 cell model, luciferase reporter gene analysis, DARTS, and SPR experiments showed that BDE may bind to TNF-α and inhibit the TNF-α-NF-κB pathway. CONCLUSION: BDE may target TNF-α to inhibit the TNF/Akt/NF-κB pathway, thereby attenuating inflammation. These findings reveal the anti-inflammatory effects and mechanisms of BDE and provide a theoretical basis for the further development and utilization of BDE.

Prognostic Value of Elevated Plasma Galectin-3 for Renal Adverse Events in Dialysis Patients: A Systematic Review and Meta-Analysis.

Context: In prognostic research, Galectin-3 (Gal-3) has gained recognition in renal fibrosis and nephrosis for its characteristics of promoting inflammation and fibrosis. High levels of Gal-3 may function as a predictor of adverse outcomes for patients with end-stage renal disease (ESRD). Objective: The review intended to systematically examine the significance of Gal-3 in the forecast of adverse outcomes for dialysis patients, using a method of evidence-based medicine. Design: The research team performed a systematic narrative review and meta-analysis by searching the Excerpta Medica Database (EMBASE) and the PubMed, Cochrane, and Web of Science databases for pertinent studies published before June 1, 2022. The search contained both meshes and free terms, such as Galectin 3, Gal-3, renal dialysis, hemodialysis, peritoneal dialysis, HD, and PD. Setting: The review took place at First People's Hospital of Linping District in Hangzhou, China. Outcome Measures: The research team used the Newcastle-Ottawa Scale (NOS) for assessment of the quality of the included research. The team created two reports to assess the value of Gal-3 in prediction of risk: (1) one for studies using continuous variables and (2) one for studies using categorical variables, dividing patients into high- and low-level Gal-3 groups with a cut-off value of Gal-3, being Gal-3 < 10.5 ng/mL for the lower tertile, and Gal-3 ≥ 13.4 ng/mL for the higher tertile. The team performed the meta-analysis using Stata 15.0, analyzed publication bias using Egger's test and directly showed it in a funnel plot. Results: The search found 1061 publications, with eight studies with 5194 participants being included in the current review. For the continuous variables, Gal-3 was associated with all-cause risk of death-Hazard ratio (HR) 1.06, 95%CI 1.01-1.12, and P = .024-and cardiovascular (CV) events-HR 1.13, 95%CI 1.07-1.203, and P = .000, but no significant correlation existed between Gal-3 and risk of CV mortality-HR 1.07, 95%CI 0.99-1.16, and P = .091. For the categorical variables, a high level of Gal-3 was correlated with a high risk of dying, from all causes-HR 2.05, 95%CI 1.50-2.80, and P = .000. Conclusions: Clinicians can use Gal-3 as a standalone forecaster of all-cause mortality and CV events for hemodialysis patients because correlates with these outcomes. Further research is necessary to determine its predictive value for CV mortality. Investigators need to perform further research with a large sample size on the predictive value of Gal-3 for dialysis patients, particularly PD patients, from a variety of ethnic backgrounds to improve the precise treatment for high-risk patients.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Lateral hypothalamic orexin neurons mediate electroacupuncture-induced anxiolytic effects in a rat model of post-traumatic stress disorder.

The lateral hypothalamus' orexinergic system has been associated with anxiety-related behaviors, and electroacupuncture (EA) modifies orexin neurons to control the anti-anxiety process. However, in a rat model of post-traumatic stress disorder (PTSD), the important role of LH orexin neurons (OXNs) in the anxiolytic effects induced by EA has not been explored. In this study, rats underwent modified single prolonged stress (MSPS) for seven days before developing EA. The rats were then subjected to elevated plus maze (EPM) and open field (OFT) tests, and western blot and c-Fos/orexin double labeling investigations were carried out to determine the functional activation of LH orexinergic neurons. Compared to MSPS model rats, it has been demonstrated that EA stimulation enhanced the amount of time spent in the central zone (TSCZ) in OFT and the amount of time spent in the open arm (TSOA) in EPM in MSPS model rats (P < 0.01). After behavioral testing, MSPS model rats had decreased activated c-Fos positive OXNs. Still, EA in SPS rats increased that number and elevated orexin type 1 receptors (OXR1) protein expression in the LH. Furthermore, after administering SB334867 (an OXR1 antagonist) to MSPS model rats, the effects of EA therapy on anxiety-like behaviors (ALBs) were significantly diminished. Additionally, when low-dose orexin-A (LORXA) was administered intracerebroventricularly together with EA stimulation in MSPS rats, the anxiolytic effects of the stimulation were substantially enhanced (P < 0.05). The results of this study reveal the mechanisms by which acupuncture may reduce PTSD and advance our understanding of the function of LH orexin signaling in EA's anxiolytic effects.

[Qualitative and quantitative study of constituents in Lysionoti Herba based on UHPLC-Q-Exactive Orbitrap HRMS and HPLC-UV].

Ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HRMS) was employed to systematically analyze the chemical constituents in Lysionoti Herba, and high perfor-mance liquid chromatography-ultraviolet(HPLC-UV) to determine the content of main compounds. A Synergi~(TM) Hydro-RP 100 Å colu-mn(2 mm×100 mm, 2.5 µm) was used for gradient elution with acetonitrile-0.1% aqueous formic acid as the mobile phase at a flow rate of 0.2 mL·min~(-1) and a column temperature of 40 ℃. MS and MS/MS were conducted with electrospray ionization(ESI) in both positive and negative modes. The chemical components in Lysionoti Herba were identified by comparison with the retention time and mass spectra of reference compounds and the relevant mass spectral data reported in MS databases and relevant literature. Furthermore, the content of five constituents(neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin) in different Lysiono-ti Herba samples was simultaneously determined by HPLC-UV at the wavelength of 330 nm. A total of 84 compounds were identified in Lysionoti Herba, including 27 flavonoids, 20 phenylethanoid glycosides, 5 amino acids, 18 organic acids, 1 alkaloid, 6 nucleosides, and 7 others. The content of neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin showed good linear relationship(r>0.999) with the peak area within certain concentration ranges, which were 3.22-102.90, 12.84-410.82, 31.63-1 012.01, 25.00-800.11, and 4.08-130.51 µg·mL~(-1), respectively. The instrument precision, method repeatability, and solution stability all met requirement, and the average recovery rate was 97.31%-100.2%, with RSD ranging from 0.95% to 2.4%. The content of the five components varied among different Lysionoti Herba samples collected from different regions of Guizhou, and the average content of forsythoside B was the highest. The established qualitative method can rapidly and efficiently identify the chemical components of Lysionoti Herba, and the developed HPLC-UV method can simultaneously determine the content of five components in a simple, ra-pid, and accurate manner, providing a scientific basis for the quality evaluation of Lysionoti Herba.

Metabolomics Analysis of Electroacupuncture Pretreatment Induced Neuroprotection on Mice with Ischemic Stroke.

The brain metabolic changes caused by the interruption of blood supply are the initial factors of brain injury in ischemic stroke. Electroacupuncture (EA) pretreatment has been shown to protect against ischemic stroke, but whether its neuroprotective mechanism involves metabolic regulation remains unclear. Based on our finding that EA pretreatment significantly alleviated ischemic brain injury in mice by reducing neuronal injury and death, we performed a gas chromatography-time of flight mass spectrometry (GC-TOF/MS) to investigate the metabolic changes in the ischemic brain and whether EA pretreatment influenced these changes. First, we found that some glycolytic metabolites in the normal brain tissues were reduced by EA pretreatment, which may lay the foundation of neuroprotection for EA pretreatment against ischemic stroke. Then, 6[Formula: see text]h of cerebral ischemia-induced brain metabolic changes, especially the enhanced glycolysis, were partially reversed by EA pretreatment, which was manifested by the brain levels of 11 of 35 up-regulated metabolites and 18 of 27 down-regulated metabolites caused by cerebral ischemia significantly decreasing and increasing, respectively, due to EA pretreatment. A further pathway analysis showed that these 11 and 18 markedly changed metabolites were mainly involved in starch and sucrose metabolism, purine metabolism, aspartate metabolism, and the citric acid cycle. Additionally, we found that EA pretreatment raised the levels of neuroprotective metabolites in both normal and ischemic brain tissues. In conclusion, our study revealed that EA pretreatment may attenuate the ischemic brain injury by inhibiting glycolysis and increasing the levels of some neuroprotective metabolites.

Tumor Microenvironment-Responsive Nanoherb Delivery System for Synergistically Inhibition of Cancer Stem Cells.

Multidrug resistance in cancer stem cells (CSCs) is a major barrier to chemotherapy; hence, developing CSC-specific targeted nanocarriers for efficient drug delivery is critical. In this study, monodisperse hollow-structured MnO2 (H-MnO2) with a mesoporous shell was created for efficient targeted drug delivery. An effective therapeutic compound isoliquiritigenin (ISL) was confirmed to inhibit the lung cancer stem-cell phenotype by natural compound screening based on integrated microfluidic devices. The resultant H-MnO2 showed a high drug-loading content of the potent CSC-targeting compound ISL and near-infrared fluorescent dye indocyanine green (ICG). In addition, H-MnO2 was successively modified with hyaluronic acid (HA) to enhance targeting CSCs with high CD44 expression levels. The H-MnO2@(ICG + ISL)@HA nanocomposites displayed promising chemotherapeutic and photothermal treatment capabilities, as well as NIR-triggered drug release, which showed excellent CSC-killing effects and tumor inhibition efficacy. Meanwhile, the development of the tumor was effectively restrained by NIR-triggered phototherapy and prominent chemotherapy without obvious side effects after tail vein injection of the nanocomposites in vivo. In summary, the prepared nanocomposites accomplished synergistic cancer therapy that targets CSCs, offering a versatile platform for lung cancer diagnosis and treatment.

Mechanism for the restoration of degraded typical steppe by nitrogen and phosphorus co-addition.

The reduction of soil nutrient content is one of the major reasons caused grassland degradation in China. Nutrient addition is thus considered as an effective measure for the restoration of degraded grasslands. However, over-fertilization can lead to decrease in plant diversity. To clarify the appropriate amount of nutrient addition and the underlying mechanism that promotes grassland restoration, we set up a nitrogen and phosphorus co-addition experiment in a degraded typical steppe of Inner Mongolia, and examined the responses at community, functional group and species levels to nutrient addition. The results showed that nutrient addition enhanced biomass while did not reduce species richness at the community level. The biomass showed a saturation response with the increases of nutrient addition, which approached saturation under the 12.0 g N·m-2, 3.8 g P·m-2 treatment. Species richness increased significantly under the lower nutrient treatments (N <9.6 g·m-2, P < 3.0 g·m-2) compared with the control, while the two high nutrient treatments did not alter species richness. At the functional group level, biomass and abundance of perennial rhizome grasses increased significantly with the increases of nutrient addition levels. Biomass and density of annuals increased significantly under high nutrient addition levels. However, the abundance and biomass of perennial bunchgrasses and perennial forbs were rarely affected. At the species level, six target species responded differently to nutrient addition. Biomass of Leymus chinensis was significantly increased due to the increase of population density and individual biomass. Biomass of Stipa grandis, Agropyron cristatum and Cleistogenes squarrosa change little. Biomass of Potentilla acaulis and Carex korshinskyi were reduced due to the decreases in individual biomass and population density, respectively. As a measure of restoring degraded grassland, nutrient addition could significantly increase biomass and species diversity, decrease biomass of the degradation indicator species, and increase biomass of perennial rhizomes grasses.