Pectin demethylation-mediated cell wall Na+ retention positively regulates salt stress tolerance in oilseed rape.

KEY MESSAGE: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes.

Nickel uptake in leafy greens from contaminated soil: an investigation into phytoavailability and health risk assessment using in vitro digestion model.

Nickel (Ni) is a toxic metal that not only pollutes the environment but also causes harmful impacts on plant growth and human health. Therefore, it is crucial to assess the relationship between the phytoavailability of Ni in soil and its accumulation in edible and non-edible parts of vegetables. A pot experiment was conducted to investigate Ni uptake in three different leafy vegetables, spinach (Spinacia oleracea L.), lettuce (Lactuca sativa L.), and fenugreek (Trigonella foenum-graecum L.), grown in soil artificially contaminated with Ni at three different treatment levels (100 mg kg-1, 200 mg kg-1, and 300 mg kg-1). The potential dietary toxicity of these vegetables in humans was examined by using an in vitro digestion model. The lowest and highest chlorophyll contents were detected in lettuce at 300 mg kg-1 of Ni concentration and in control plants of spinach. Their values were 34.16 ± 3.01 (SPAD unit) and 53 ± 3.7673 (SPAD unit), respectively. Among the three vegetables, lettuce and spinach at 300 mg kg-1 exhibited the highest accumulation of Ni, with 43 mg kg-1 in edible parts and 182 mg kg-1 in non-edible parts. Furthermore, health risk index (HRI) values were found to be > 1 for lettuce and fenugreek at Ni concentrations of 200 and 300 mg kg-1 for both children and adults. The average bioaccessibility of Ni in lettuce, fenugreek, and spinach during the gastrointestinal phase was 32-23%, 24-10%, and 45-37%, respectively, at a Ni concentration of 300 mg kg-1. All three vegetables grown on Ni-contaminated soil may potentially contribute to food chain toxicity. The HRI values being > 1 suggest that these vegetables are unsafe for consumption. Monitoring of Ni concentration in leafy vegetables is essential to minimize human health risks associated with food chain contamination.

Selenium inhibits ferroptosis in hyperglycemic cerebral ischemia/reperfusion injury by stimulating the Hippo pathway.

Hyperglycemia can exacerbate cerebral ischemia/reperfusion (I/R) injury, and the mechanism involves oxidative stress, apoptosis, autophagy and mitochondrial function. Our previous research showed that selenium (Se) could alleviate this injury. The aim of this study was to examine how selenium alleviates hyperglycemia-mediated exacerbation of cerebral I/R injury by regulating ferroptosis. Middle cerebral artery occlusion (MCAO) and reperfusion models were established in rats under hyperglycemic conditions. An in vitro model of hyperglycemic cerebral I/R injury was created with oxygen-glucose deprivation and reoxygenation (OGD/R) and high glucose was employed. The results showed that hyperglycemia exacerbated cerebral I/R injury, and sodium selenite pretreatment decreased infarct volume, edema and neuronal damage in the cortical penumbra. Moreover, sodium selenite pretreatment increased the survival rate of HT22 cells under OGD/R and high glucose conditions. Pretreatment with sodium selenite reduced the hyperglycemia mediated enhancement of ferroptosis. Furthermore, we observed that pretreatment with sodium selenite increased YAP and TAZ levels in the cytoplasm while decreasing YAP and TAZ levels in the nucleus. The Hippo pathway inhibitor XMU-MP-1 eliminated the inhibitory effect of sodium selenite on ferroptosis. The findings suggest that pretreatment with sodium selenite can regulate ferroptosis by activating the Hippo pathway, and minimize hyperglycemia-mediated exacerbation of cerebral I/R injury.

Fine-Scale analysis of both wild and cultivated horned galls provides insight into their quality differentiation.

BACKGROUND: Galla chinensis is a traditional Chinese medicine (TCM) produced due to the interaction between the Fordinae aphids and the Rhus plant species. Horned galls with high tannin content are the most widely cultivated gall type, and Wufeng county of Hubei province in China is the center of cultivation. However, long-term artificial cultivation and domestication of horned galls to meet the increasing production demand have led to quality degradation. Understanding the reasons underlying quality degradation is urgent for horned gall production and application. The present study used a combination of metabolic, genetic, and ecological analyses to investigate the quality and genetic differentiation of the horned galls under long-term domestication as well as the potential relationships between them. RESULTS: Analysis of gallic acid content and other three phenotypic traits (fresh weight, gall size, and wall thickness) revealed quality differentiation of horned galls collected from five locations in Wufeng, in which the cultivated samples from Wang Jiaping (WJP) showed the highest degradation. Genetic differentiation between the cultivated and wild Rhus chinensis trees in WJP, and between WJP and the other populations was detected based on SSR molecular markers, however, no significant difference in genetic structure was seen for the aphid populations. Among the various ecological factors examined, temperature was identified as the primary one affecting the quality of horned galls. CONCLUSIONS: Both genetic and ecological factors caused quality differentiation of horned galls. The collection of diverse germplasm of host trees and aphids will help reduce the quality degradation of horned galls in Wufeng.

The Main Medicinal Plants in Arid Regions of Uzbekistan and Their Traditional Use in Folk Medicine.

Seventy percent of the territory of Uzbekistan consists of arid regions. This situation is considered very favorable for plants adapted to a desert climate. Medicinal plants distributed in the arid regions of Uzbekistan have not been studied much. Medicinal plants are considered inexpensive, yet are vital for the lives of local residents. They play a very important role in the traditional healing of ailments. To determine the current state of medicinal plants and enhance their subsequent protection and sustainable use, it is necessary to obtain annual information on the state of their distribution, their population size, and the impact of negative factors on their populations. Based on our field studies, which were conducted during the period from 2012 to 2022 in the arid regions of Uzbekistan, we updated the checklists of the main medicinal plants used in these regions. A total of 529 medicinal species belonging to 70 families and 269 genera were identified in the study region. Several species, including Peganum harmala L., Capparis spinosa L., Ferula foetida (Bunge) Regel, Glycyrrhiza glabra L., Alhagi pseudalhagi (M. Bieb.) Desv. ex Wangerin, Lagochilus inebrians Bunge, Xanthium strumarium L., Silybum marianum (L.) Gaertn., Onopordum acanthium L., Ziziphora tenuior L., and Cichorium intybus L., are spread over large areas and have been used regularly by the locals since ancient times. These species are common in saline and degraded soils in arid regions of Uzbekistan. Semi-structured interviews were conducted with tabibs (traditional doctors), elders, herders, and residents with experience in traditional healing using medicinal plants. The medicinal value of most plants was based on the interviews with representatives of the local population, which were useful for understanding traditional healing skills and customer service skills.

Natural compound So-2 suppresses triple-negative breast cancer through inducing ferroptosis via downregulating transcription factor E2F7.

Triple-negative breast cancer (TNBC), accounting for about 15∼18% of all breast cancers, is notorious for its poor prognosis, high rate of relapse and short overall survival. Because of lacking effective therapeutic targets or drugs, treatment of TNBC in clinical encounters great obstacle. Siegesbeckiaorientalis L. have been used as a traditional Chinese medicine "Xi-Xian-Cao" for centuries with multiple medicinal benefits including cancerous treatment. We have reported the isolation of twenty-seven germacranolides including So-2 from the aerial parts of S. orientalis with potent cytotoxicity against breast cancer cells. The studyaims to verified the anti-TNBC function of the natural compound So-2 both in vitro and vivo and uncover the underlying mechanism. The results showed that So-2 caused cell cycle arrest and suppress TNBC cell proliferation and migration. Also, So-2 was first identified to be a bona fide ferroptosis inducer in TNBC cells. So-2 effectively suppressed tumor growth of TNBC by using an orthotopic transplantation tumor model. We also characterized the oncogenic role of the transcription factor E2F7 in TNBC. E2F7 was demonstrated to be involved in the ferroptosis-inducing and tumor suppression effect of So-2. Altogether, So-2 exhibits inhibitory effect on TNBC both in vitro and vivo by inducing TNBC ferroptosis via downregulating the expression of E2F7. These findings provide valuable insight into the pathogenesis of TNBC. The natural compound So-2, isolated from Chinese traditional medicine, might be a prospective drug candidate in TNBC therapy.

Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Impact of climate change on the geographical distribution and niche dynamics of Gastrodia elata.

Background: Gastrodia elata is widely used in China as a valuable herbal medicine. Owing to its high medicinal and nutrient value, wild resources of G. elata have been overexploited and its native areas have been severely damaged. Understanding the impacts of climate change on the distribution of this endangered species is important for the conservation and sustainable use of G. elata. Methods: We used the optimized maximum entropy model to simulate the potential distribution of G. elata under contemporary and future time periods (1970-2000, 2050s, 2070s, and 2090s) and different climate change scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). Under these conditions, we investigated the key environmental factors influencing the distribution of G. elata as well as the spatial and temporal characteristics of its niche dynamics. Results: With high Maxent model accuracy (AUCmean = 0.947 ± 0.012, and the Kappa value is 0.817), our analysis revealed that annual precipitation, altitude, and mean temperature of driest quarter are the most important environmental factors influencing the distribution of G. elata. Under current bioclimatic conditions, the potentially suitable area for G. elata in China is 71.98 × 104 km2, while the highly suitable region for G. elata growth is 7.28 × 104 km2. Our models for three future periods under four climate change scenarios indicate that G. elata can maintain stable distributions in southern Shaanxi, southwestern Hubei, and around the Sichuan basin, as these areas are highly suitable for its growth. However, the center of the highly suitable areas of G. elata shift depending on different climatic scenarios. The values of niche overlap for G. elata show a decreasing trend over the forecasted periods, of which the niche overlap under the SSP3-7.0 scenario shows the greatest decrease. Discussions: Under the condition of global climate change in the future, our study provides basic reference data for the conservation and sustainable utilization of the valuable and endangered medicinal plant G. elata. It is important to carefully choose the protection area of G. elata wild resources according the suitable area conditions modeled. Moreover, these findings will be valuable for providing insights into the breeding and artificial cultivation of this plant, including the selection of suitable areas for planting.

Genome-wide analysis of bHLH gene family in Coptis chinensis provides insights into the regulatory role in benzylisoquinoline alkaloid biosynthesis.

Coptis chinensis Franch is a perennial species with high medical value. The rhizome of C. chinensis is a traditional Chinese medicine widely used for more than 2000 years in China. Its principal active ingredients are benzylisoquinoline alkaloids (BIAs). The basic helix-loop-helix (bHLH) transcription factors play an important regulatory role in the biosynthesis of plant secondary metabolites. However, the bHLH genes in C. chinensis have not been described, and little is known about their roles in alkaloid biosynthesis. In this study, a total of 143 CcbHLH genes (CcbHLHs) were identified and unevenly distributed on nine chromosomes. Phylogenetic analysis divided the 143 CcbHLH proteins into 26 subfamilies by comparison with Arabidopsis thaliana bHLH proteins. The majority CcbHLHs in each subgroup had similar gene structures and conserved motifs. Furthermore, the physicochemical properties, conserved motif, intron/exon composition, and cis-acting elements of CcbHLHs were analyzed. Transcriptome analysis revealed that 30 CcbHLHs were significantly expressed in the rhizomes of C. chinensis. Co-expression analysis revealed that 11 CcbHLHs were highly positively correlated with contents of various alkaloids of C. chinensis. Moreover, yeast one-hybrid experiments verified that CcbHLH001 and CcbHLH0002 could interact with the promoters of berberine biosynthesis pathway genes CcBBE and CcCAS, suggesting their regulatory roles in BIA biosynthesis. This study provides comprehensive insights into the bHLH gene family in C. chinensis and will support in-depth functional characterization of CcbHLHs involved in the regulation of protoberberine-type alkaloid biosynthesis.

Blapstin, a Diapause-Specific Peptide-Like Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera, Has Antifungal Function.

Drug resistance against bacteria and fungi has become common in recent years, and it is urgent to discover novel antimicrobial peptides to manage this problem. Many antimicrobial peptides from insects have been reported to have antifungal activity and are candidate molecules in the treatment of human diseases. In the present study, we characterized an antifungal peptide named blapstin that was isolated from the Chinese medicinal beetle Blaps rhynchopetera used in folk medicine. The complete coding sequence was cloned from the cDNA library prepared from the midgut of B. rhynchopetera. It is a 41-amino-acid diapause-specific peptide (DSP)-like peptide stabilized by three disulfide bridges and shows antifungal activity against Candida albicans and Trichophyton rubrum with MICs of 7 µM and 5.3 µM, respectively. The C. albicans and T. rubrum treated with blapstin showed irregular and shrunken cell membranes. In addition, blapstin inhibited the activity of C. albicans biofilm and showed little hemolytic or toxic activity on human cells and it is highly expressed in the fat body, followed by the hemolymph, midgut, muscle, and defensive glands. These results indicate that blapstin may help insects fight against fungi and showed a potential application in the development of antifungal reagents. IMPORTANCE Candida albicans is one of the conditional pathogenic fungi causing severe nosocomial infections. Trichophyton rubrum and other skin fungi are the main pathogens of superficial cutaneous fungal diseases, especially in children and the elderly. At present, antibiotics such as amphotericin B, ketoconazole, and fluconazole are the main drugs for the clinical treatment of C. albicans and T. rubrum infections. However, these drugs have certain acute toxicity. Long-term use can increase kidney damage and other side effects. Therefore, obtaining broad-spectrum antifungal drugs with high efficiency and low toxicity for the treatment of C. albicans and T. rubrum infections is a top priority. Blapstin is an antifungal peptide which shows activity against C. albicans and T. rubrum. The discovery of blapstin provides a novel clue for our understanding of the innate immunity of Blaps rhynchopetera and provides a template for designing antifungal drugs.

Comparative analysis of complete Artemisia subgenus Seriphidium (Asteraceae: Anthemideae) chloroplast genomes: insights into structural divergence and phylogenetic relationships.

BACKGROUND: Artemisia subg. Seriphidium, one of the most species-diverse groups within Artemisia, grows mainly in arid or semi-arid regions in temperate climates. Some members have considerable medicinal, ecological, and economic value. Previous studies on this subgenus have been limited by a dearth of genetic information and inadequate sampling, hampering our understanding of their phylogenetics and evolutionary history. We therefore sequenced and compared the chloroplast genomes of this subgenus, and evaluated their phylogenetic relationships. RESULTS: We newly sequenced 18 chloroplast genomes of 16 subg. Seriphidium species and compared them with one previously published taxon. The chloroplast genomes, at 150,586-151,256 bp in length, comprised 133 genes, including 87 protein-coding genes, 37 tRNA genes, 8 rRNA genes, and one pseudogene, with GC content of 37.40-37.46%. Comparative analysis showed that genomic structures and gene order were relatively conserved, with only some variation in IR borders. A total of 2203 repeats (1385 SSRs and 818 LDRs) and 8 highly variable loci (trnK - rps16, trnE - ropB, trnT, ndhC - trnV, ndhF, rpl32 - trnL, ndhG - ndhI and ycf1) were detected in subg. Seriphidium chloroplast genomes. Phylogenetic analysis of the whole chloroplast genomes based on maximum likelihood and Bayesian inference analyses resolved subg. Seriphidium as polyphyletic, and segregated into two main clades, with the monospecific sect. Minchunensa embedded within sect. Seriphidium, suggesting that the whole chloroplast genomes can be used as molecular markers to infer the interspecific relationship of subg. Seriphidium taxa. CONCLUSION: Our findings reveal inconsistencies between the molecular phylogeny and traditional taxonomy of the subg. Seriphidium and provide new insights into the evolutionary development of this complex taxon. Meanwhile, the whole chloroplast genomes with sufficiently polymorphic can be used as superbarcodes to resolve interspecific relationships in subg. Seriphidium.

Antitumor mechanism of kangliu pill on gliomas in mice through PI3K-Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gliomas are common malignant intracranial tumors that have worse prognosis and pose a serious threat to human health. The Kangliu pill (KLP) is an innovative herbal compound from Xuanwu Hospital of Capital Medical University that has been clinically used for the treatment of gliomas for more than 40 years, and is one of the few drugs for primary treatment of this disorder. But the fundamental molecular mechanisms and pathways of KLP are not clear. AIM OF THE STUDY: To investigate the therapeutic mechanism of KLP in the treatment of gliomas. MATERIALS AND METHODS: An in situ xenograft model of red fluorescent protein-labeled human glioma cell line (U87-RFP) in BALB/c-nu mouse was established, and the therapeutic effect of KLP on gliomas was assessed by tumor weights and fluorescence areas. A quantitative proteomics approach using tandem mass tags combined with liquid chromatography-tandem mass spectrometry was performed to explore differentially expressed proteins (DEPs) in glioma tissues, and bioinformatics analyses including Gene Ontology analysis, pathway analysis, and network analysis were performed to analyze the proteins involved in the network therapeutic mechanisms responsible for key metabolic pathways. Cytological experiments corroborated the above analysis results. RESULTS: Network pharmacology approach screened 246 bioactive compounds contained in KLP, targeting 724 proteins and 173 potential targets of KLP for glioma treatment. The important targets obtained after visualizing the PPI network were AKT1, INS, GAPDH, SRC, TP53, etc. The KEGG enrichment results showed that 9 proteins were related to cancer, including Pathways in cancer, PI3K/AKT signaling pathway, etc. KLP had antitumor activity in gliomas, which reduced tumor weights and fluorescence areas. A number of DEPs possibly associated with gliomas were identified through quantitative proteomic techniques. Among these DEPs, 50 (25 upregulated and 25 downregulated) were identified that might be associated with KLP action. Bioinformatics showed that these 50 DEPs were mainly focused on focal adhesion, extracellular matrix (ECM)-receptor interactions, and the PI3K-Akt signaling pathway. Cytological experiments revealed that KLP significantly inhibited the proliferation and promoted apoptosis of U87-MG human glioma cells, and its mechanism was through the inhibition of PI3K/AKT signaling pathway. CONCLUSION: Therapeutic effect of KLP was regulation of multiple pathways in the treatment of gliomas. In specific, it interacts through the PI3K-Akt signaling pathway. This work may contribute proteomic insights for further research on the medical treatment of glioma using KLP.

Traditional Chinese medicine decoctions and Chinese patent medicines for the treatment of depression: Efficacies and mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is a major mental disorder and it is currently recognized as the second-leading cause of disability worldwide. However, the therapeutic effect of antidepressants remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely used for centuries, including commonly-used complementary and alternative medical therapies for depression. Recent clinical trials have been carried out to assess the efficacy and safety of TCM, and to explore the mechanisms of action in relation to the treatment of depression. AIM OF THE STUDY: To summarize frequently used TCM decoctions and Chinese patent medicines (CPM) for treating depression, review their clinical therapeutic effects in treating depressive disorders, consider their possible mechanisms, and characterize the relationships between their efficacy and mechanisms. MATERIALS AND METHODS: We performed a computerized literature search using the electronic databases such as PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases, with the keywords "depression", "traditional Chinese medicine decoction", "Chinese patent medicine", "application", "mechanism", and their combinations, from January 1, 2000 to August 8, 2022 (inclusive). RESULTS: A total of 51 papers were identified. We reviewed studies on six each TCM decoctions and CPMs, which demonstrated their significant clinical efficacy for treating depression and examined their mechanisms of action. The anti-depressive effects were related to: 1) increased monoamine neurotransmitter levels, 2) inhibiting hyperactivity of the hypothalamic-pituitary-adrenal axis, 3) regulating hippocampal neurons and neurotrophic factors, 4) regulating immune cytokines, 5) counteracting excitatory amino acid toxicity, and 6) regulating microbe-gut-brain axis function. CONCLUSION: TCM plays an increasingly important role in the management of depression by enhancing the therapeutic effects and alleviating the side effects of antidepressant chemicals.

Enhanced electroencephalography effective connectivity in frontal low-gamma band correlates of emotional regulation after mindfulness training.

Practicing mindfulness, focusing attention on the internal and external experiences occurring in the present moment with open and nonjudgement stance, can lead to the development of emotional regulation skills. Yet, the effective connectivity of brain regions during mindfulness has been largely unexplored. Studies have shown that mindfulness practice promotes functional connectivity in practitioners, potentially due to improved emotional regulation abilities and increased connectivity in the lateral prefrontal areas. To examine the changes in effective connectivity due to mindfulness training, we analyzed electroencephalogram (EEG) signals taken before and after mindfulness training, focusing on training-related effective connectivity changes in the frontal area. The mindfulness training group participated in an 8-week mindfulness-based stress reduction (MBSR) program. The control group did not take part. Regardless of the specific mindfulness practice used, low-gamma band effective connectivity increased globally after the mindfulness training. High-beta band effective connectivity increased globally only during Breathing. Moreover, relatively higher outgoing effective connectivity strength was seen during Resting and Breathing and Body-scan. By analyzing the changes in outgoing and incoming connectivity edges, both F7 and F8 exhibited strong parietal connectivity during Resting and Breathing. Multiple regression analysis revealed that the changes in effective connectivity of the right lateral prefrontal area predicted mindfulness and emotional regulation abilities. These results partially support the theory that the lateral prefrontal areas have top-down modulatory control, as these areas have high outflow effective connectivity, implying that mindfulness training cultivates better emotional regulation.

Effects and mechanisms of Xiaochaihu Tang against liver fibrosis: An integration of network pharmacology, molecular docking and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a potentially harmful chronic liver disease caused by various etiologies. There is currently no specific drug for liver fibrosis. Xiaochaihu Tang (XCHT) is a traditional formula combined of seven herbs, which was first recorded in the Treatise on Febrile Diseases in Han Dynasty of ancient China. It is widely used in clinic to hepatic protection, analgesic, antipyretic and anti-inflammatory treatment. And it has been recommended for treating chronic hepatitis and chronic cholecystitis in the latest guidelines for the diagnosis and treatment of liver fibrosis with integrated traditional and western medicine. However, the underlying regulatory mechanisms remain elusive. AIM OF THE STUDY: This study aims to explore the therapeutic effects of XCHT on liver fibrosis and its underlying molecular mechanisms from the perspective of network pharmacology and experimental research. MATERIALS AND METHODS: Carbon tetrachloride (CCl4) induced and bile duct ligation (BDL) induced liver fibrosis models in mice were established to evaluate the anti-fibrosis effects of XCHT in vivo. Potential anti-fibrosis targets of XCHT were screened via network establishment. The underlying mechanisms were uncovered through GO and pathway enrichment analysis. Then, the core targets were identified from protein-protein interaction network by means of the Cytohubba plug-in of Cytoscape. Furthermore, two effective monomer components of XCHT were recognized by molecular docking. Moreover, the predicted components and pathways were verified by in vitro experiments. RESULTS: When treated with XCHT, liver fibrosis was alleviated in both mice models, showing as the improvement of liver function, the protection of hepatocytes, the inhibition of HSC activation and the reduction of hepatic collagen accumulation. 540 monomer components, 300 therapeutic targets, 109 signaling pathways, 246 GO biological processes, 77 GO cellular components, 107 GO molecular functions items and core targets were identified by network analysis. Then, 6-gingerol and baicalein were identified as the core components of anti-fibrosis effects of XCHT via leptin or Nrf2 signaling pathway. Furthermore, the experiment in vitro also validated the results. CONCLUSIONS: Our study suggests XCHT could alleviate liver fibrosis through multi-targets and multi-pathways; 6-gingerol and baicalein are its core components which may play an important role via leptin or Nrf2 signaling pathway.

Characteristics of Vaginal Microbiome in Reproductive-Age Females with HPV Infection in Xinjiang, China.

Objective: We investigated the characteristics of vaginal microbiome in reproductive-age females with HPV infection in Xinjiang, China. Methods: A total of 135 females of reproductive age were enrolled. There were 43 healthy HPV-negative females in control group (N group), 58 HPV-positive females in nonlesion group (P1 group), and 34 HPV-positive females in low-grade squamous intraepithelial lesion group (P2 group). DNA was extracted from the vaginal secretions, and V3-V4 regions of bacterial 16S rDNA were amplified and sequenced by NovaSeq. QIIME2 and R software were used to perform diversity analysis of bacteria. PICRUSt2 was used to predict the function of the vaginal microbiota. Results: Lactobacillus was the main genus of vaginal microbiota in asymptomatic reproductive-age females with or without HPV in Xinjiang. The diversity of vaginal microbiota in the P1 group was significantly higher than that in the N group, and the proportion of Gardnerella increased significantly. The vaginal microbiota structure of the P2 group was different from the N group, characterized by the decrease of Lactobacillus crispatus and the increase of Shuttleworthia. The function of the inordinate microbiome may play a role in accelerating HPV replication and integration. Conclusion: The structure of vaginal microbiota alters under persistent HPV infection in asymptomatic females of reproductive age in Xinjiang. The Gardnerella increase is associated with increased susceptibility to HPV infection, and Lactobacillus iners predominance and Shuttleworthia presence may be a signature of HPV infection with low-grade squamous intraepithelial lesion.

Ecological Responses of Maize Rhizosphere to Antibiotics Entering the Agricultural System in an Area with High Arsenicals Geological Background.

Metal(loid)s can promote the spread and enrichment of antibiotic resistance in the environmental ecosystem through a co-selection effect. Little is known about the ecological effects of entering antibiotics into the environment with long-term metal(loid)s' resistance profiles. Here, cow manure containing oxytetracycline (OTC) or sulfadiazine (SA) at four concentrations (0 (as control), 1, 10, and 100 mg/kg) was loaded to a maize cropping system in an area with high a arsenicals geological background. Results showed that exogenous antibiotics entering significantly changed the nutrient conditions, such as the concentration of nitrate nitrogen, ammonium nitrogen, and available phosphorus in the maize rhizosphere soil, while total arsenic and metals did not display any differences in antibiotic treatments compared with control. Antibiotics exposure significantly influenced nitrate and nitrite reductase activities to reflect the inhibition of denitrification rates but did not affect the soil urease and acid phosphatase activities. OTC treatment also did not change soil dehydrogenase activities, while SA treatment posed promotion effects, showing a tendency to increase with exposure concentration. Both the tested antibiotics (OTC and SA) decreased the concentration of arsenite and arsenate in rhizosphere soil, but the inhibition effects of the former were higher than that of the latter. Moreover, antibiotic treatment impacted arsenite and arsenate levels in maize root tissue, with positive effects on arsenite and negative effects on arsenate. As a result, both OTC and SA treatments significantly increased bioconcentration factors and showed a tendency to first increase and then decrease with increasing concentration. In addition, the treatments decreased translocation capacity of arsenic from roots to shoots and showed a tendency to increase translocation factors with increasing concentration. Microbial communities with arsenic-resistance profiles may also be resistant to antibiotics entering.

The regulatory network of potential transcription factors and MiRNAs of mitochondria-related genes for sarcopenia.

Background: Mitochondrial dysfunction is a significant contributor to sarcopenia, but the mechanism remains unclear. Methods: In the present study, we downloaded GSE117525 and GSE8479 datasets from Gene Expression Omnibus (GEO), then the weighted correlation network analysis (WGCNA) was used to construct scale-free co-expression networks respectively. The key genes of aging muscle were obtained by overlapping key modules of two networks. Receiver operating characteristic (ROC) curve was drawn to explore the diagnostic efficacy of key genes. Finally, a transcription factor-key gene network was constructed based on ChEA3 platform and hTFtarget database, and a miRNA-key gene network was constructed using starBase and the multimiR R package. Results: The most positively or negatively correlated modules of the two datasets were identified, and genes related to oxidative phosphorylation and mitochondrial ribosomal proteins were identified as key genes. The diagnostic values were confirmed with ROC curves by self-verification (GSE117525 and GSE8479) and external verification (GSE47881). Then, Yin Yang 1 (YY1) was identified as the most important transcription factor of the transcription factor-key gene network. In addition, miRNAs related to key genes were also predicted. Conclusion: The findings of the present study provide a novel insight into the pathological mechanism of sarcopenia.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Association between polyunsaturated fatty acid intake and infertility among American women aged 20-44 years.

Background: Infertility is a nationwide public health priority in the U.S. However, few studies have investigated the effects of dietary intake of polyunsaturated fatty acids (PUFAs) on female infertility. This study explored the association between PUFA intake and risk of infertility. Methods: A total of 1,785 women aged 20-44 years from three National Health and Nutrition Examination Survey cycles (2013-2018) were included in this cross-sectional study. The intake of PUFAs was obtained from a 24-h dietary interview on two separate days with a 3-10-day interval, and nutrient residue models were used. Fertility status was assessed by positive response to two relative questions via a questionnaire. Logistic regression models were used and some covariates were adjusted. Results: Among all the participants, 340 (19.05%) women suffered from infertility. The intake of docosahexaenoic acid (DHA) (OR = 0.998, 95% CI 0.998, 0.009) was slightly related to the risk of infertility. In contrast, women with higher α-linolenic acid (ALA) (OR = 1.416, 95% CI 1.138, 1.763) and linoleic acid (LA) intake (OR = 1.020, 95% CI 1.002, 1.038) presented with a relatively higher risk of primary infertility. Furthermore, in 20-34-year-old women, higher omega-6/omega-3 was significant associated with the risk of infertility (OR = 1.002, 95%CI 1.000, 1.005). Conclusions: Our results suggest that PUFA intake is only slightly associated with infertility. The higher the DHA intake, the lower the risk of infertility regardless of age. In women with primary infertility, ALA and LA has negative effect.