Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AMB) is a herb with wide application in traditional Chinese medicine, exerting a wealth of pharmacological effects. AMB has been proven to have an evident therapeutic effect on ischemic cerebrovascular diseases, including cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism underlying AMB in CIRI remains unclear. AIM OF THE STUDY: This study aimed to investigate the potential role of AMB in CIRI through a comprehensive approach of network pharmacology and in vivo experimental research. METHODS: The intersection genes of drugs and diseases were obtained through analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network was created through the string website. Meanwhile, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out using R studio, and thereafter the key genes were screened. Then, the molecular docking prediction was made between the main active ingredients and target genes, and hub genes with high binding energy were obtained. In addition, molecular dynamic (MD) simulation was used to validate the result of molecular docking. Based on the results of network pharmacology, we used animal experiments to verify the predicted hub genes. First, the rat middle cerebral artery occlusion and reperfusion (MACO/R) model was established and the effective dose of AMB in CIRI was determined by behavioral detection and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Then the target proteins corresponding to the hub genes were measured by Western blot. Moreover, the level of neuronal death was measured using hematoxylin and eosin (HE) and Nissl staining. RESULTS: Based on the analysis of the TCMSP database and GEO database, a total of 62 intersection target genes of diseases and drugs were obtained. The KEGG enrichment analysis showed that the therapeutic effect of AMB on CIRI might be realized through the advanced glycation endproduct-the receptor of advanced glycation endproduct (AGE-RAGE) signaling pathway in diabetic complications, nuclear factor kappa-B (NF-κB) signaling pathway and other pathways. Molecular docking results showed that the active ingredients of AMB had good binding potential with hub genes that included Prkcb, Ikbkb, Gsk3b, Fos and Rela. Animal experiments showed that AWE (60 g/kg) could alleviate CIRI by regulating the phosphorylation of PKCß, IKKß, GSK3ß, c-Fos and NF-κB p65 proteins. CONCLUSION: AMB exerts multi-target and multi-pathway effects against CIRI, and the underlying mechanism may be related to anti-apoptosis, anti-inflammation, anti-oxidative stress and inhibiting calcium overload.

Characterization of phosphate solubilizing bacteria in the sediments of eutrophic lakes and their potential for cyanobacterial recruitment.

Microbes may induce endogenous phosphorus (P) migration from lacustrine sediment. This study focused on the role of phosphate-solubilizing bacteria (PSB) disturbance in affecting the sediment P release and further contributing to cyanobacterial recruitment in Meiliang Bay, Lake Taihu. Gluconic acid was the main mechanism of phosphate solubilizing by PSB. The dominant PSB (Burkholderia) isolated from eutrophic lake sediments was used as a representative to investigate the effects of disturbance on endogenous P release using diffusive gradients in thin films (DGT) and high-resolution dialysis (HR-Peeper). The results show that soluble reactive phosphorus (SRP) and iron (Fe (II)) concentrations could reach 0.51 mg L-1 and 33.56 mg L-1 in pore water, respectively. And the sediment DGT-P and DGT-Fe were relatively reduced by PSB. Subsequent the chlorophyll a (Chl a) concentrations reached peaks of 344.8 µg L-1 in overlying water. The abundance of the dominant PSB (Burkholderia-Caballeronia-Paraburkholderia) were significantly associated with Chl a (P < 0.05) and algal effective state phosphorus (AAP) (P < 0.05), respectively. PSB mainly regulates AAP leaching to pore water and then diffusing across the sediment-water interface to the overlying water, producing the effect of cyanobacteria recruitment. The results provide new insights into early management of cyanobacterial resuscitation in a large eutrophic lake.

Machine learning facilitated the conceptual design of an alum dosing system for phosphorus removal in a wastewater treatment plant.

Wastewater treatment plants (WWTPs) face challenges in controlling total phosphorus (TP), given more stringent regulations on TP discharging. In particular, WWTPs that operate at a small scale lack resources for real-time monitoring of effluent quality. This study aimed to develop a conceptual alum dosing system for reducing TP concentration, leveraging machine learning (ML) techniques and data from a full-scale WWTP containing incomplete TP information. The proposed system comprises two ML models in series: an Alert model based on LightGBM with an accuracy of 0.92, and a Dosage model employing a voting algorithm through combining three ML algorithms (LightGBM, SGD, and SVC) with an accuracy of 0.76. The proposed system has demonstrated the potential to ensure that 88.1% of the effluent remains below the TP discharge limit, which outperforms traditional dosing methods and could reduce overdosing from 61.3 to 12.1%. Furthermore, the SHapley Additive exPlanations (SHAP) analysis revealed that incorporating the output features from the previous cycle and utilizing the results of the Alert model as the input features for dosage prediction could be an effective method for data with limited information. The findings of this study have practical applications in improving the efficiency and effectiveness of TP control in small-scale WWTPs, providing a valuable solution for complying with stringent regulations and enhancing environmental sustainability.

Study on the management efficiency of lanthanum/iron co-modified attapulgite on sediment phosphorus load.

Attapulgite co-modified by lanthanum-iron (MT-LHMT) was used to study its effectiveness and mechanism in controlling phosphorus release from sediments. MT-LHMT has high adsorption capacity for phosphate and the maximum adsorption capacity of MT-LHMT to phosphate can reach 75.79 mg/g. The mechanism mainly involved electrostatic action, surface precipitation and ligand exchange between MT-LHMT bonded hydroxyl and phosphate to form La-O-P and Fe-O-P inner-sphere complexes. MT-LHMT has excellent adsorption performance in the pH range of 3-8. In addition to HCO3-, CO32- and HA- had a negative effect on the phosphorus removal of MT-LHMT, while NO3-, Cl-, SO42-, K+, Ca2+ and Mg2+ had a positive or no effect on phosphorus removal. MT-LHMT significantly reduced the risk of phosphorus release from overlying water in different dose effects and covering methods, as well as the unstable inactivation of flowing phosphorus, sediment dissolved reactive phosphorus (DRP) and available phosphorus with medium diffusion gradient in thin film in the sediment-water interface (Labile-PDGT). The MT-LHMT capping wrapped with fabric can reduce the risk of nitrogen release from sediment to overlying water more than only MT-LHMT capping. The results of this study showed that the MT-LHMT capping wrapped with fabric has high potential and can be used as an active capping material to manage the nitrogen and phosphorus load in surface water.

Xiao-Yao-San Formula Improves Cognitive Ability by Protecting the Hippocampal Neurons in Ovariectomized Rats.

Xiao-Yao-San (XYS) decoction is a traditional Chinese medicine formula. This study aimed to investigate the effect of XYS on cognitive abilities and its underlying mechanism in ovariectomized rats. Female Sprague-Dawley rats were ovariectomized and treated with XYS (3 g/kg or 9 g/kg) by gavage, with subcutaneous injection of 17-ß estradiol (E2, 2 µg/kg) as a positive drug control and gavage of 1 ml saline (0.9%) as a placebo control. After 6 weeks of treatment, rats were examined using the Morris water maze test. The estradiol level in the serum and hippocampus was measured by ELISA. Golgi staining was performed to observe neuronal morphology in the hippocampus. Apoptosis of hippocampal cells was observed by TUNEL staining. The protein content of N-methyl-D-aspartate receptor (NMDAR) 2A and 2B in the hippocampal CA1 region was determined by Western blot and immunohistochemistry. Expression of estrogen receptor (ER) and PI3K signaling was detected by Western blot. Compared with the sham group, both learning and memory were impaired in ovariectomized rats. Rats treated with E2 or high-dose XYS showed better learning and memory compared with the saline-treated rats. High-dose XYS significantly reduced escape latency in the spatial acquisition trial; meanwhile, the cross times and duration in the probe quadrant were increased in the spatial probe trial. High-dose XYS promoted the de novo synthesis of E2 content in the hippocampus but had no significant effect on the serum E2 level. Golgi staining indicated that high-dose XYS could increase the branch number and density of dendritic spines in the hippocampal CA1 area. TUNEL staining showed that high-dose XYS alleviated ovariectomy-induced neuronal apoptosis. The expression level of NMDAR2A and NMDAR2B in hippocampal CA1 was upregulated by XYS treatment. The beneficial effect of XYS was through activating ERα-PI3K signaling. In conclusion, high-dose XYS treatment can improve the cognitive abilities of ovariectomized rats by protecting the hippocampal neurons and restoring the hippocampal E2 level.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.

Bacterial Acid Resistance Toward Organic Weak Acid Revealed by RNA-Seq Transcriptomic Analysis in Acetobacter pasteurianus.

Under extreme acidic environments, bacteria exploit several acid resistance (AR) mechanisms for enhancing their survival, which is concerned with several aspects, such as issues in human health and fermentation for acidic products. Currently, knowledge of bacterial AR mainly comes from the strong acid (such as hydrochloric acid) stresses, whereas AR mechanisms against organic weak acids (such as acetic acid), which are indeed encountered by bacteria, are less understood. Acetic acid bacteria (AAB), with the ability to produce acetic acid up to 20 g/100 mL, possess outstanding acetic acid tolerance, which is conferred by their unique AR mechanisms, including pyrroloquinoline quinine-dependent alcohol dehydrogenase, acetic acid assimilation and molecular chaperons. The distinguished AR of AAB toward acetic acid may provide a paradigm for research in bacterial AR against weak organic acids. In order to understand AAB's AR mechanism more holistically, omics approaches have been employed in the corresponding field. However, the currently reported transcriptomic study was processed under a low-acidity (1 g/100 mL) environment, which could not reflect the general conditions that AAB are usually faced with. This study performed RNA-Seq transcriptomic analysis investigating AR mechanisms in Acetobacter pasteurianus CGMCC 1.41, a widely used vinegar-brewing AAB strain, at different stages of fermentation, namely, under different acetic acid concentrations (from 0.6 to 6.03 g/100 mL). The results demonstrated the even and clustered genomic distribution of up- and down-regulated genes, respectively. Difference in AR between AAB and other microorganisms was supported by the down-regulation of urea degradation and trehalose synthesis-related genes in response to acetic acid. Detailed analysis reflected the role of ethanol respiration as the main energy source and the limited effect of acetic acid assimilation on AR during fermentation as well as the competition between ethanol respiratory chain and NADH, succinate dehydrogenase-based common respiratory chain. Molecular chaperons contribute to AR, too, but their regulatory mechanisms require further investigation. Moreover, pathways of glucose catabolism and fatty acid biosynthesis are also related to AR. Finally, 2-methylcitrate cycle was proposed as an AR mechanism in AAB for the first time. This study provides new insight into AR mechanisms of AAB, and it also indicates the existence of numerous undiscovered AR mechanisms.