The plastid-localized lipoamide dehydrogenase 1 is crucial for redox homeostasis, tolerance to arsenic stress and fatty acid biosynthesis in rice.

Soil contamination with arsenic (As) can cause phytotoxicity and reduce crop yield. The mechanisms of As toxicity and tolerance are not fully understood. In this study, we used a forward genetics approach to isolate a rice mutant, ahs1, that exhibits hypersensitivity to both arsenate and arsenite. Through genomic resequencing and complementation tests, we identified OsLPD1 as the causal gene, which encodes a putative lipoamide dehydrogenase. OsLPD1 was expressed in the outer cell layer of roots, root meristem cells, and in the mesophyll and vascular tissues of leaves. Subcellular localization and immunoblot analysis demonstrated that OsLPD1 is localized in the stroma of plastids. In vitro assays showed that OsLPD1 exhibited lipoamide dehydrogenase (LPD) activity, which was strongly inhibited by arsenite, but not by arsenate. The ahs1 and OsLPD1 knockout mutants exhibited significantly reduced NADH/NAD+ and GSH/GSSG ratios, along with increased levels of reactive oxygen species and greater oxidative stress in the roots compared with wild-type (WT) plants under As treatment. Additionally, loss-of-function of OsLPD1 also resulted in decreased fatty acid concentrations in rice grain. Taken together, our finding reveals that OsLPD1 plays an important role for maintaining redox homeostasis, conferring tolerance to arsenic stress, and regulating fatty acid biosynthesis in rice.

ETPNav: Evolving Topological Planning for Vision-Language Navigation in Continuous Environments.

Vision-language navigation is a task that requires an agent to follow instructions to navigate in environments. It becomes increasingly crucial in the field of embodied AI, with potential applications in autonomous navigation, search and rescue, and human-robot interaction. In this paper, we propose to address a more practical yet challenging counterpart setting - vision-language navigation in continuous environments (VLN-CE). To develop a robust VLN-CE agent, we propose a new navigation framework, ETPNav, which focuses on two critical skills: 1) the capability to abstract environments and generate long-range navigation plans, and 2) the ability of obstacle-avoiding control in continuous environments. ETPNav performs online topological mapping of environments by self-organizing predicted waypoints along a traversed path, without prior environmental experience. It privileges the agent to break down the navigation procedure into high-level planning and low-level control. Concurrently, ETPNav utilizes a transformer-based cross-modal planner to generate navigation plans based on topological maps and instructions. The plan is then performed through an obstacle-avoiding controller that leverages a trial-and-error heuristic to prevent navigation from getting stuck in obstacles. Experimental results demonstrate the effectiveness of the proposed method. ETPNav yields more than 10% and 20% improvements over prior state-of-the-art on R2R-CE and RxR-CE datasets, respectively. Our code is available at https://github.com/MarSaKi/ETPNav.

Using an In Vivo Mouse Model to Determine the Exclusion Criteria of Preexisting Anti-AAV9 Neutralizing Antibody Titer of Pompe Disease Patients in Clinical Trials.

The efficacy of adeno-associated virus (AAV)-based gene therapy is dependent on effective viral transduction, which might be inhibited by preexisting immunity to AAV acquired from infection or maternal delivery. Anti-AAV neutralizing Abs (NAbs) titer is usually measured by in vitro assay and used for patient enroll; however, this assay could not evaluate NAbs' impacts on AAV pharmacology and potential harm in vivo. Here, we infused a mouse anti-AAV9 monoclonal antibody into Balb/C mice 2 h before receiving 1.2 × 1014 or 3 × 1013 vg/kg of rAAV9-coGAA by tail vein, a drug for our ongoing clinical trials for Pompe disease. The pharmacokinetics, pharmacodynamics, and cellular responses combined with in vitro NAb assay validated the different impacts of preexisting NAbs at different levels in vivo. Sustained GAA expression in the heart, liver, diaphragm, and quadriceps were observed. The presence of high-level NAb, a titer about 1:1000, accelerated vector clearance in blood and completely blocked transduction. The AAV-specific T cell responses tended to increase when the titer of NAb exceeded 1:200. A low-level NAbs, near 1:100, had no effect on transduction in the heart and liver as well as cellular responses, but decreased transduction in muscles slightly. Therefore, we propose to preclude patients with NAb titers > 1:100 from rAAV9-coGAA clinical trials.

Antibacterial Activity of Plants in Cirsium: A Comprehensive Review.

As ethnic medicine, the whole grass of plants in Cirsium was used as antimicrobial. This review focuses on the antimicrobial activity of plants in Cirsium, including antimicrobial components, against different types of microbes and bacteriostatic mechanism. The results showed that the main antimicrobial activity components in Cirsium plants were flavonoids, triterpenoids and phenolic acids, and the antimicrobial ability varied according to the species and the content of chemicals. Among them, phenolic acids showed a strong antibacterial ability against Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium. The antibacterial mechanisms include: (1) damaging the cell membrane, cell walls, mitochondria and nucleus of bacteria; (2) inhibiting the synthesis of proteins and nucleic acids; (3) suppressing the synthesis of enzymes for tricarboxylic acid cycle pathways and glycolysis, and then killing the bacteria via inhibition of energy production. Totally, most research results on antimicrobial activity of Cirsium plants are reported based on in vitro assays. The evidence from clinical data and comprehensive evaluation are needed.

Saikosaponin F ameliorates depression-associated dry eye disease by inhibiting TRIM8-induced TAK1 ubiquitination.

AIMS: Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye disease often occurs together with depression. The aim of this study is to investigate whether SsF can improve depression-associated dry eye disease and explore the underlying mechanism. METHODS: Behavioral test was used to verify the effect of SsF on CUMS-induced depression-like behaviors in mice. Corneal fluorescein staining, phenol red cotton thread test and periodic acid-Schiff (PAS) staining were used to observe the effect of SsF on depression-associated dry eye disease. Western blot (WB) was performed to observe the expression of TAK1 protein and key proteins of NF-κB and MAPK (P38) inflammatory pathways in the hippocampus and cornea. Immunohistochemical staining was used to observe the expression of microglia, and immunoprecipitation was used to observe K63-linked TAK1 ubiquitination. Subsequently, we constructed a viral vector sh-TAK1 to silence TAK1 protein to verify whether SsF exerted its therapeutic effect based on TAK1. The expression of inflammatory factors such as IL-1ß, TNF-α and IL-18 in hippocampus and cornea were detected by ELISA. Overexpression of TRIM8 (OE-TRIM8) by viral vector was used to verify whether SsF improved depression-associated dry eye disease based on TRIM8. RESULTS: SsF treatment significantly improved the depression-like behavior, increased tear production and restored corneal injury in depression-related dry eye model mice. SsF treatment downregulated TAK1 expression and TRIM8-induced K63-linked TAK1 polyubiquitination, while inhibiting the activation of NF-κB and MAPK (P38) inflammatory pathways and microglial expression. In addition, selective inhibition of TAK1 expression ameliorated depression-associated dry eye disease, while overexpression of TRIM8 attenuated the therapeutic effect of SsF on depression-associated dry eye disease. CONCLUSION: SsF inhibited the polyubiquitination of TAK1 by acting on TRIM8, resulting in the downregulation of TAK1 expression, inhibition of inflammatory response, and improvement of CUMS-induced depression-associated dry eye disease.

Tet1/DLL3/Notch1 signal pathway affects hippocampal neurogenesis and regulates depression-like behaviour in mice.

Ten-eleven translocation protein 1 (Tet1) is associated with the regulation of depression-like behaviour in mice. However, the mechanism by which Tet1 affects neurogenesis in mice to regulate depression-like behaviours remains unclear. In this study, the chronic social defeat stress (CSDS) paradigm was constructed by overexpressing Tet1 protein in the mouse hippocampus, and 5-ethynyl-2'-deoxyuridine (EdU, 50 mg/kg) was injected on the seventh day to explore the mechanism of the regulation of the Tet1/Delta-like protein 3 (DLL3)/Notch1 protein pathway in mice hippocampal neurogenesis and its influence on depression-like behaviour. Following CSDS, the expression level of Tet1 decreased significantly. Moreover, due to the downregulation of Tet1 protein, the maintenance of the DNA methylation and demethylation balance was affected, resulting in a significant increase in the methylation levels of Notch1 and DLL3 and a significant decrease in the protein expression levels of DLL3, Notch1, and brain-derived neurotrophic factor (BDNF). At the same time, the proliferation and differentiation of neurones were affected, which was related to a significant decrease in the number of EdU+, doublecortin (DCX)+, and Ki67+ cells in the hippocampus of the CSDS model mice. When the Tet1 protein was overexpressed in the mouse hippocampus, DLL3 and Notch1 protein expression levels were upregulated, promoting hippocampal neurogenesis and alleviating depression-like behaviour in mice. These findings suggest that regulation of the hippocampal Tet1/DLL3/Notch1 protein pathway to influence neurogenesis may be a therapeutic strategy for depression.

Saikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activation.

Saikosaponin-d (SSd) is a triterpene saponin from the roots of Bupleurum chinese. Recent studies have revealed its antidepressant activity, but its mechanism involved is unclear. This study's objective was to ascertain how SSd may reduce depression in depressed mice subjected to chronic unpredictable animal stress (CUMS) and to investigate the mechanisms underlying these effects. Models of CUMS depression were established and different groups were treated with SSd and escitalopram. After the last day of administration of the treatment, behavioral tests were performed. ELISA was used to measure the expression of IL-1ß, TNF-α, and IL-18, and western blot was used to measure the presence of proteins associated with NLRP3. Hippocampal neuronal damage was observed using Nissl staining, and NLRP3 ubiquitination assay was performed by immunoprecipitation and gene silencing. An inflammatory cell model was constructed by treating BV2 cells with lipopolysaccharides (LPS) and adenosine triphosphate (ATP) to verify the ubiquitination modification of NLRP3 by SSd. Behavioral tests demonstrated that SSd effectively alleviated depression-like symptoms. SSd should substantially limit the degrees of proteins associated with NLRP3, as properly as limit the harm to hippocampal neurons. Gene silencing results showed that SSd regulates NLRP3 through the E3 ubiquitin ligase MARCHF7. In vitro, SSd remarkably increased the protein expression of K48-linked ubiquitin in inflammatory BV2 cells, while decreasing the protein levels of NLRP3. Our findings suggest that SSd has antidepressant effects in CUMS mice by promoting ubiquitination of NLRP3 to inhibit inflammasome activation and improve the inflammatory state.

SNHG16/miR-205/HDAC5 is involved in the progression of renal fibrosis.

Renal interstitial fibrosis (RIF) represents an irreversible and progressive pathological manifestation of chronic renal disease, which ultimately leads to end-stage renal disease. Long noncoding RNAs (lncRNAs) have been suggested to be involved in the progression of RIF. Small nucleolar RNA host gene 16 (SNHG16), a member of lncRNAs, has been found to be involved in the progression of pulmonary fibrosis. This paper first researched the effect of SNHG16 on renal fibrosis. We established a unilateral ureteral obstruction (UUO)-induced mouse RIF model by ligation of the left ureter to evaluate the biological function of SNHG16 in RIF. As a result, SNHG16 was upregulated in UUO-induced renal fibrotic tissues. Knockdown of SNHG16 inhibited RIF and reduced alpha-smooth muscle actin (α-SMA), fibronectin, and college IV expression. miR-205 was a target of SNHG16, and downregulated in UUO-induced renal fibrotic tissues. Inhibition of miR-205 promoted RIF and increased the expression of α-SMA, college IV, and fibronectin. Overexpression of SNHG16 promoted the UUO-induced RIF, but miR-205 abrogated this effect of SNHG16. Histone deacetylase 5 (HDAC5) showed high expression in UUO-induced renal fibrotic tissues. Knockdown of HDAC5 significantly reduced α-SMA, fibronectin, and college IV expression in renal tissues of UUO-induced mice. Inhibition of miR-205 promoted HDAC5 expression, but knockdown of SNHG16 inhibited HDAC5 expression in renal tissues of UUO-induced mice. In conclusion, SHNG16 is highly expressed in renal fibrotic tissues of UUO-induced mice. Knockdown of SHNG16 may prevent UUO-induced RIF by indirectly upregulating HDAC5 via targeting miR-205. SHNG16 may be novel target for treating renal fibrosis.

Saikosaponin a activates tet1/dll3/notch1 signalling and promotes hippocampal neurogenesis to improve depression-like behavior in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri, also named "Chaihu" in Chinese, is a substance derived from the dry roots of Bupleurum chinense DC. [Apiaceae] and Bupleurum scorzonerifolium Willd. [Apiaceae]. Radix Bupleuri was initially recorded as a medicinal herb in Shen Nong Ben Cao Jing, the earliest monograph concerning traditional Chinese medicine (TCM). Ever since, Radix Bupleuri has been broadly used to alleviate exterior syndrome, disperse heat, modulate the liver-qi, and elevate yang-qi in TCM. Radix Bupleuri has also been utilized as an important component in Xiaoyaosan, a classical formula for relieving depression, which was originated from the famous Chinese medical book called "Tai Ping Hui Min He Ji Ju Fang" in Song Dynasty. Currently, many valuable pharmacological effects of Radix Bupleuri have been explored, such as antidepressant, neuroprotective activities, antiinflammation, anticancer, immunoregulation, etc. Former studies have illustrated that Saikosaponin A (SSa), one of the primary active components of Radix Bupleuri, possesses potential antidepressant properties. However, the underlying mechanisms still remain unknown. AIM OF THE STUDY: We used a chronic social defeat stress (CSDS) mouse model to explore the ameliorative effects and potential mechanisms of SSa in depressive disorder in vivo. MATERIALS AND METHODS: The CSDS mouse model was established and mice underwent behavioral studies using assays such as the social interaction test (SIT), sucrose preference test (SPT), forced-swim test (FST), tail suspension test (TST), and open field test (OFT). Western blotting, immunofluorescence, and Golgi staining were performed to investigate signaling pathway activity, and alterations in synaptic spines in the hippocampus. To model the anticipated interaction between SSa and Tet1, molecular docking and microscale thermophoresis (MST) techniques were employed. Finally, sh-RNA Tet1 was employed for validation via lentiviral transfection in CSDS mice to confirm the requirement of Tet1 for SSA efficacy. RESULTS: SSa dramatically reduced depressed symptoms, boosted the expression of Tet1, Notch, DLL3, and BDNF, encouraged hippocampus development, and enhanced the dendritic spine density of hippocampal neurons. In contrast, Tet1 knockdown in CSDS mice dampened the beneficial effects of SSa on depressive symptoms. CONCLUSIONS: Therefore, our results suggest that SSa significantly activates the Tet1/Notch/DLL3 signaling pathways and promotes hippocampal neurogenesis to exert antidepressant effects in the CSDS mouse model in vivo. The present results also provide new insight into the importance of the Tet1/DLL3/Notch pathways as potential targets for novel antidepressant development.

The nomogram for the prediction of overall survival after surgery in patients in early-stage NSCLC based on SEER database and external validation cohort.

BACKGROUND & AIMS: Currently, there is a lack of effective tools for predicting the prognostic outcome of early-stage lung cancer after surgery. We aim to create a nomogram model to help clinicians assess the risk of postoperative recurrence or metastasis. MATERIALS AND METHODS: This work obtained 16,459 NSCLC patients based on SEER database from 2010 to 2015. In addition, we also enrolled 385 NSCLC patients (2017/01-2019/06) into external validation cohort at Tianjin Medical University General Hospital. Univariable as well as multivariable Cox regression was carried out for identifying factors independently predicting OS. In addition, we built a nomogram by incorporating the above prognostic factors for the prediction of OS. RESULTS: Tumor size was positively correlated with the risk of poor differentiation. Advanced age, male and adenocarcinoma patients were factors independently predicting poor prognosis. The risk of white race is higher, followed by Black race, Asians and Indians, which is consistent with previous study. Chemotherapy is negatively related to prognostic outcome in patients of Stage IA NSCLC and positively related to that in those of Stage IB NSCLC. Lymph node dissection can reduce the postoperative mortality of patients. AUCs of the nomograms for 1, 2, and 3-year OS was 0.705, 0.712, and 0.714 for training cohort, while those were 0.684, 0.688, and 0.688 for validation cohort. CONCLUSIONS: The nomogram could be used as a tool to predict the postoperative prognosis of patients with Stage I non-small cell lung cancer.

Modulating SARS-CoV-2 Spike Protein Reactivity through Moderate Electric Fields: A Pathway to Innovative Therapies.

In the quest for effective COVID-19 treatments and vaccines, traditional biochemical methods have been paramount, yet the challenge of accommodating diverse viral mutants persists. Recent simulations propose an innovative physical strategy involving an external electric field applied to the SARS-CoV-2 spike protein, demonstrating a reduced viral binding potential. However, limited empirical knowledge exists regarding the characteristics of the spike protein after E-field treatment. Our study addresses this gap by employing diverse analytical techniques to elucidate the impact of low/moderate E-field intensity on the binding of the SARS-CoV-2 spike protein to the ACE2 receptor. Through comprehensive analysis, we unveil a substantial reduction in the spike protein binding capacity validated via enzyme-linked immunosorbent assay and quartz crystal microbalance experiments. Remarkably, the E-field exposure induces significant protein structure rearrangement, leading to an enhanced negative surface zeta potential confirmed by dynamic light scattering. Circular dichroism spectroscopy corroborates these structural changes, showing alterations in the secondary protein structures. This study provides insights into SARS-CoV-2 spike protein modification under an E-field pulse, potentially paving the way for nonbiochemical strategies to mitigate viral reactivity and opening avenues for innovative therapeutic and preventive approaches against COVID-19 and its evolving variants.

A DFT study towards dynamic structures of iron and iron carbide and their effects on the activity of the Fischer-Tropsch process.

The Fe-based Fischer-Tropsch synthesis (FTS) catalyst shows a rich phase chemistry under pre-treatment and FTS conditions. The exact structural composition of the active site, whether iron or iron carbide (FeCx), is still controversial. Aiming to obtain an insight into the active sites and their role in affecting FTS activity, the swarm intelligence algorithm is implemented to search for the most stable Fe(100), Fe(110), Fe(210) surfaces with different carbon ratios. Then, ab initio atomistic thermodynamics and Wulffman construction were employed to evaluate the stability of these surfaces at different chemical potentials of carbon. Their FTS reactivity and selectivity were later assessed by semi-quantitative micro-kinetic equations. The results show that stability, reactivity, and selectivity of the iron are all affected by the carbonization process when the carbon ratio increases. Formation of the carbide, a rather natural process under experimental conditions, would moderately increase the turnover frequency (TOF), but both iron and iron carbide are active to the reaction.

Exploration and analysis of differentially expressed genes in Epstein–Barr virus negative and positive plasmablastic lymphoma

Objectives Plasmablastic lymphoma (PBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) often associated with Epstein–Barr virus (EBV) infection. Despite recent advances in treatment, PBL still has a poor prognosis. EBV is listed as one of the human tumor viruses that may cause cancer, and is closely related to the occurrence of some nasopharyngeal carcinoma (NPC), lymphoma and 10% of gastric cancer (GC). It is very important to explore the differentially expressed genes (DEGs) between EBV-positive and EBV-negative PBL. Through bioinformatics analysis of DEGs between EBV-positive PBL and EBV-negative PBL, we gain a deeper understanding of the pathogenesis of EBV-positive PBL. Methods We selected the GSE102203 data set, and screened the DEGs between EBV-positive PBL and EBV-negative PBL. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied. The protein–protein interaction (PPI) network was constructed, and screened for the hub genes. Finally, Gene Set Enrichment Analysis (GSEA) was performed. Results In EBV-positive PBL, the immune-related pathway is upregulated and Cluster of differentiation 27 (CD27) and programmed cell death-ligand 1 (PD-L1) are hub genes. Conclusions In EBV-positive PBL, EBV may affect tumorigenesis through activation of immune-related pathways and upregulation of CD27, PD-L1. Immune checkpoint blockers of CD70/CD27 and programmed cell death 1 (PD-1)/PD-L1 pathways may be one of the effective strategies for the treatment of EBV-positive PBL (AU)

Rice roots avoid asymmetric heavy metal and salinity stress via an RBOH-ROS-auxin signaling cascade.

Root developmental plasticity is crucial for plants to adapt to a changing soil environment, where nutrients and abiotic stress factors are distributed heterogeneously. How plant roots sense and avoid heterogeneous abiotic stress in soil remains unclear. Here, we show that, in response to asymmetric stress of heavy metals (cadmium, copper, or lead) and salt, rice roots rapidly proliferate lateral roots (LRs) in the stress-free area, thereby remodeling root architecture to avoid localized stress. Imaging and quantitative analyses of reactive oxygen species (ROS) showed that asymmetric stress induces a ROS burst in the tips of the exposed roots and simultaneously triggers rapid systemic ROS signaling to the unexposed roots. Addition of a ROS scavenger to either the stressed or stress-free area abolished systemic ROS signaling and LR proliferation induced by asymmetric stress. Asymmetric stress also enhanced cytosolic calcium (Ca2+) signaling; blocking Ca2+signaling inhibited systemic ROS propagation and LR branching in the stress-free area. We identified two plasma-membrane-localized respiratory burst oxidase homologs, OsRBOHA and OsRBOHI, as key players in systemic ROS signaling under asymmetric stress. Expression of OsRBOHA and OsRBOHI in roots was upregulated by Cd stress, and knockout of either gene reduced systemic ROS signaling and LR proliferation under asymmetric stress. Furthermore, we demonstrated that auxin signaling and cell wall remodeling act downstream of the systemic ROS signaling to promote LR development. Collectively, our study reveals an RBOH-ROS-auxin signaling cascade that enables rice roots to avoid localized stress of heavy metals and salt and provides new insight into root system plasticity in heterogenous soil.

Revealing the Adsorption Mechanisms of Methanol on Lithium-Doped Porous Carbon through Experimental and Theoretical Calculations.

Previous reports have shown that it is difficult to improve the methanol adsorption performance of nitrogen and oxygen groups due to their low polarity. Here, we first prepared porous carbon with a high specific surface area and large pore volume using benzimidazole as a carbon precursor and KOH as an activating agent. Then, we improved the surface polarity of the porous carbon by doping with Lithium (Li) to enhance the methanol adsorption performance. The results showed that the methanol adsorption capacity of Li-doped porous carbon reached 35.4 mmol g-1, which increased by 57% compared to undoped porous carbon. Molecular simulation results showed that Li doping not only improved the methanol adsorption performance at low pressure, but also at relatively high pressure. This is mainly because Li-modified porous carbon has higher surface polarity than nitrogen and oxygen-modified surfaces, which can generate stronger electrostatic interactions. Furthermore, through density functional theory (DFT) calculations, we determined the adsorption energy, adsorption distance, and charge transfer between Li atom and methanol. Our results demonstrate that Li doping enhances the adsorption energy, reduces the adsorption distance, and increases the charge transfer in porous carbon. The mechanism of methanol adsorption by Li groups was revealed through experimental and theoretical calculations, providing a theoretical basis for the design and preparation of methanol adsorbents.

Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression.

The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.

Astragaloside IV ameliorates peritoneal fibrosis by promoting PGC-1α to reduce apoptosis in vitro and in vivo.

Prolonged exposure of the peritoneum to high glucose dialysate leads to the development of peritoneal fibrosis (PF), and apoptosis of peritoneal mesothelial cells (PMCs) is a major cause of PF. The aim of this study is to investigate whether Astragaloside IV could protect PMCs from apoptosis and alleviate PF. PMCs and rats PF models were induced by high glucose peritoneal fluid. We examined the pathology of rat peritoneal tissue by HE staining, the thickness of rat peritoneal tissue by Masson's staining, the number of mitochondria and oxidative stress levels in peritoneal tissue by JC-1 and DHE fluorescence staining, and mitochondria-related proteins and apoptosis-related proteins such as PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 were measured. We used hoechst staining and flow cytometry to assess the apoptotic rate of PMCs in the PF model, and further validated the observed changes in the expressions of PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 in PMCs. We further incubated PMCs with MG-132 (proteasome inhibitor) and Cyclohexylamine (protein synthesis inhibitor). The results demonstrated that Astragaloside IV increased the expression of PGC-1α by reducing the ubiquitination of PGC-1α. It was further found that the protective effects of Astragaloside IV on PMCs were blocked when PGC-1α was inhibited. In conclusion, Astragaloside IV effectively alleviated PF both in vitro and in vivo, possibly by promoting PGC-1α to enhance mitochondrial synthesis to reduce apoptotic effects.

Geographical discrimination of Flos Trollii by GC-MS and UHPLC-HRMS-based untargeted metabolomics combined with chemometrics.

For centuries, Flos Trollii has been consumed as functional tea and a folk medicine in China's north and northwest zones. The quality of Flos Trollii highly depends on the producing zones. Unfortunately, few studies have been reported on the geographical discrimination of Flos Trollii. This work comprehensively investigated Flos Trollii compounds with an integration strategy combining gas chromatography-mass spectrometry (GC-MS) and ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) with chemometrics to explore the differences between Flos Trollii obtained from various origins of China. About 71 volatile and 22 involatile markers were identified with GC-MS and UHPLC-HRMS, respectively. Geographical discrimination models were synthetically investigated based on the identified markers. The results indicated that the UHPLC-HRMS coupled with the fisher discrimination model provided the best prediction capability (>97%). This study provides a new solution for Flos Trollii discrimination.

[Research status of Bovis Calculus and relevant Chinese patent medicines based on bibliometric analysis].

With scarce resources, natural Bovis Calculus is expensive and hard to meet clinical demand. At the moment, four kinds of Bovis Calculus are available on the market: the natural product, in vitro cultured product, synthesized product, and the product formed in cow after manual intervention. In this study, papers on the four kinds of Bovis Calculus products and relevant Chinese patent medicines were searched from Web of Science, PubMed, and China National Knowledge Infrastructure(CNKI). CiteSpace, citexs AI, and CNKI were employed for bibliometric analysis and knowledge map analysis. On this basis, the status, trend, and focuses of research on Bovis Calculus and relevant Chinese patent medicines were summarized. The results suggested overall slow development in the research on Bovis Calculus and relevant Chinese patent medicines with three typical growth stages. It is consistent with the development of Bovis Calculus substitutes and the national policy for the development of traditional Chinese medicine. At the moment, the research on Bovis Calculus and relevant Chinese patent medicines has been on the rise. In recent years, there has been an explosion of research on them, particularly the quality control of Bovis Calculus and the Chinese patent medicines, the pharmacological efficacy of Chinese patent medicines, such as Angong Niuhuang Pills, and the comparison of the quality of various Bovis Calculus products. However, there is a paucity of research on the pharmacological efficacy and the mechanism of Bovis Calculus. This medicinal and the relevant Chinese patent medicines have been studied from diverse perspectives and China becomes outstanding in this research field. However, it is still necessary to reveal the chemical composition, pharmacological efficacy, and mechanism through multi-dimensional deep research.

Antimicrobial activity in Asterceae: The selected genera characterization and against multidrug resistance bacteria.

Plants from the Asteraceae family are widely used as ethno medicines to treatment parasitic, malaria, hematemesis, pruritus, pyretic, anthelmintic, wound healing. The aim of this review is to provide an overview of Asteraceae plants antimicrobial activity. The most relevant results from the published studies are summarized and discussed. The species in genus of Artemisia, Echinacea, Centaurea, Baccharis, and Calendula showed antimicrobial activity. Most of these species are usually used as ethno medicines to treat infection, inflammation, and parasitics. The effective part or component for antimicrobial was essential oil and crude extract, and essential oil attracted more attention. It was also reported that nanoparticles coated with crude extract were effective against multidrug resistant bacteria. For multidrug resistant bacteria study, the species in Armtemisia were the most investigated, and Staphylococcus aureus and Escherichia coli were the most studied multidrug resistant strains. The antimicrobial activity was evaluated mainly based on the results of minimum inhibitory concentration (MIC). Few reports have been reported on minimum bactericide concentration (MBC) and its antibacterial mechanisms. According to the reported study results, some plants in Asteraceae have the potential to be developed as bacteriostatic agents and against multidrug resistant bacteria. However, most studies are still in vitro, further clinical and applied studies are needed.