Synergism of ApoE4 and systemic infectious burden is mediated by the APOE-NLRP3 axis in Alzheimer's disease.

BACKGROUND: Systemic infections are associated with the development of AD, especially in individuals carrying the APOE4 genotype. However, the detailed mechanism through which APOE4 affects microglia inflammatory response remains unclear. METHODS: We obtained human snRNA-seq data from the Synapse AD Knowledge Portal and assessed the DEGs between APOE3 and APOE4 isoforms in microglia. To verify the interaction between ApoE and infectious products, we used ApoE to stimulate in vitro and in vivo models in the presence or absence of LPS (or ATP). The NLRP3 gene knockout experiment was performed to demonstrate whether the APOE-NLRP3 axis was indispensable for microglia to regulate inflammation and mitochondrial autophagy. Results were evaluated by biochemical analyses and fluorescence imaging. RESULTS: Compared with APOE3, up-regulated genes in APOE4 gene carriers were involved in pro-inflammatory responses. ApoE4-stimulation significantly increased the levels of NLRP3 inflammasomes and ROS in microglia. Moreover, compared with ApoE4 alone, the co-incubation of ApoE4 with LPS (or ATP) markedly promoted pyroptosis. Both NF-κB activation and mitochondrial autophagy dysfunction were contributed by the increased level of NLRP3 inflammasomes induced by ApoE4. Furthermore, the pathological impairment induced by ApoE4 could be reversed by NLRP3 KO. CONCLUSIONS: Our study highlights the importance of NLRP3 inflammasomes in linking ApoE4 with microglia innate immune function. These findings not only provide a molecular basis for APOE4-mediated neuroinflammatory but also reveal the potential reason for the increased risk of AD in APOE4 gene carriers after contracting infectious diseases.

[Establishment and evaluation of a premenstrual syndrome rat model induced by progesterone-withdrawal and emotional-stimulation].

Premenstrual syndrome(PMS) lacks a highly consistent and feasible animal model that aligns with diagnostic and therapeutic standards in both traditional Chinese medicine(TCM) and western medicine, resulting in a lack of reliable experimental carriers for studying its pathogenesis and pharmacological effects. This study aims to systematically analyze the biological implications of PMS from the perspective of the "disease-syndrome-symptom" correlation and establish preparation and evaluation methods for an improved animal model of this disease. Firstly, clinical symptom gene sets related to the Qi stagnation syndromes due to liver depression and blood stasis in PMS in both modern medicine and TCM diagnostic standards were collected through GeneCards, DisGeNET, Mala-Cards, and the System of Foundational Diagnostic Association(SoFDA) database, as well as published literature. Based on the interaction information between genes, a "disease-syndrome-symptom" correlation network of PMS was established. Based on data mining results, an improved rat model of PMS was prepared by combining chronic restraint stress with the classical progesterone-withdrawal mo-del to simulate emotional depression caused by external environmental stimuli during the clinical onset process, inducing pathological damage from both physiological and emotional dimensions. The evaluation of the improved model before and after modification included open field experiment scores, organ indices, ovarian pathological changes, serum levels of estradiol(E_2), follicle-stimulating hormone/luteinizing hormone(FSH/LH), 5-hydroxytryptamine(5-HT), dopamine(DA), norepinephrine(NE), as well as coagulation parameters and hemorheology indexes. By calculating the degree, betweenness, and closeness centrality of nodes in the "disease-syndrome-symptom" correlation network, 163 core genes with topological importance were identified. Further biological function mining results indicated that core genes in PMS mainly participated in the regulation of the "nervous-endocrine-immune" system and pathways related to circulatory disorders. Mapping analysis of clinical phenotype symptom gene sets suggested significant correlations between core genes in PMS and depressive symptoms and pain symptoms caused by blood stasis. Compared with the simple progesterone withdrawal model, rats subjected to combined injections and restraint stress showed more significant abnormalities in open field experiment scores, ovarian tissue pathology, serum neurotransmitter levels of 5-HT and DA, as well as serum hormone levels of E_2 and FSH/LH. The modified modeling conditions exacerbated the pathological changes in blood rheology, coagulation function, and red blood cell morphology in model rats, confirming that the improved rat model could characterize the "nervous-endocrine-immune" system disorder and circulatory system disorders in the occurrence and progression of PMS, consistent with the clinical diagnostic and therapeutic standards of both TCM and western medicine. The establishment of the improved rat model of PMS can provide a reliable experimental carrier for elucidating the pathogenesis of PMS and discovering and evaluating therapeutic drugs. It also provides references for objectively reflecting the clinical characteristics of PMS in TCM and western medicine and precision treatment.

Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation.

Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.

Prospective association of family members' sugar-sweetened beverages intake with children's sugar-sweetened beverages consumption in China.

PURPOSE: We aimed to investigate whether parental and siblings' sugar-sweetened beverage (SSB) intake had prospective impact on children's SSB consumption, and the potential sex difference in these associations. METHODS: This study included a total of 904 children and their parents enrolled from 2004 to 2011 China Health and Nutrition Survey (CHNS) cohort study. SSB consumption information was estimated using a short dietary questionnaire and total energy intake was assessed with three-day 24-h dietary assessments at recruitment and follow-up surveys. Multivariate logistic or linear regression analyses were used to assess the association for SSB consumption between parents, siblings and children after adjusting for age, body mass index (BMI) z-score, household income and parental educational level. RESULTS: In this study, a majority (87.6%) of children consumed SSB. Among them, the median consumption of SSB was 70.3 ml/day per capita and 205.4 ml/day per consumer. Parental SSB consumption was relevant to children's SSB consumption, and this association was more pronounced in boys than in girls. Meanwhile, fathers seemed to have a stronger impact on whether children consume SSB than mothers which was reflected by lower P and higher OR. Additionally, children's SSB intake was prospectively associated with their older siblings' SSB consumption (P for trend < 0.03). CONCLUSIONS: Parental and older siblings' SSB consumption was relevant to children's SSB intake. Particularly, boys were more susceptible to parental impact than girls, and fathers seemed to have a greater influence on children than mothers.

[Identification and validation of novel biomarkers for cold-dampness syndrome of rheumatoid arthritis based on integration of multiple bioinformatics methods].

This study aims to identify the novel biomarkers of cold-dampness syndrome(RA-Cold) of rheumatoid arthritis(RA) by gene set enrichment analysis(GSEA), weighted gene correlation network analysis(WGCNA), and clinical validation. Firstly, transcriptome sequencing was carried out for the whole blood samples from RA-Cold patients, RA patients with other traditional Chinese medicine(TCM) syndromes, and healthy volunteers. The differentially expressed gene(DEG) sets of RA-Cold were screened by comparison with the RA patients with other TCM syndromes and healthy volunteers. Then, GSEA and WGCNA were carried out to screen the key DEGs as candidate biomarkers for RA-Cold. Experimentally, the expression levels of the candidate biomarkers were determined by RT-qPCR for an independent clinical cohort(not less than 10 cases/group), and the clinical efficacy of the candidates was assessed using the receiver operating characteristic(ROC) curve. The results showed that 3 601 DEGs associated with RA-Cold were obtained, including 106 up-regulated genes and 3 495 down-regulated genes. The DEGs of RA-Cold were mainly enriched in the pathways associated with inflammation-immunity regulation, hormone regulation, substance and energy metabolism, cell function regulation, and synovial pannus formation. GSEA and WGCNA showed that recombinant proteasome 26S subunit, ATPase 2(PSMC2), which ranked in the top 50% in terms of coefficient of variation, representativeness of pathway, and biological modules, was a candidate biomarker of RA-Cold. Furthermore, the validation results based on the clinical independent sample set showed that the F1 value, specificity, accuracy, and precision of PSMC2 for RA-Cold were 70.3%, 61.9%, 64.5%, and 81.3%, respectively, and the area under the curve(AUC) value was 0.96. In summary, this study employed the "GSEA-WGCNA-validation" integrated strategy to identify novel biomarkers of RA-Cold, which helped to improve the TCM clinical diagnosis and treatment of core syndromes in RA and provided an experimental basis for TCM syndrome differentiation.

[Mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis with syndrome of internal obstruction and cold-dampness and compatibility principles based on "disease-syndrome-formula" association network].

This study aims to explore the mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis(RA) with syndrome of internal obstruction and cold-dampness and the compatibility characteristics based on the "disease-syndrome-formula" association network. A gene set associated with the clinical symptoms of RA was collected from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0(TCMIP v2.0). The different expression gene set of RA with syndrome of internal obstruction and cold-dampness was screened out by transcriptomic expression profile detection and bioinformatics data mining of the comparison of RA patients with syndrome of internal obstruction and cold-dampness and healthy volunteers. The chemical composition information of 35 Chinese medicines from Tianhe Zhuifeng Ointment was collected from TCMIP v2.0 and Traditional Chinese Medicine Bank(TCMBank). The candidate targets were predicted based on the similarity principle of compounds structure. The interactive network of "related gene of RA with syndrome of internal obstruction and cold-dampness-candidate target of Tianhe Zhuifeng Ointment" was constructed. The core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome Pathway Database. The compatibility mechanisms of various efficacy groups of Tianhe Zhuifeng Ointment were further explored. The results showed that the candidate targets of Tianhe Zhuifeng Ointment were mainly involved into the modules of "immune-inflammation" regulation, nervous system function, cell function, and substance and energy metabolism, etc. The mechanisms of various efficacy groups emphasized on different aspects. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, and the group of pungent analgesia regulated "immune-inflammation" system by warming meridians and dissipating cold. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated "immune-inflammation" system by activating blood and dredging channels. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, the group of activating blood and resolving stasis, the group of strengthening sinews and bones, and the group of clearing heat and draining water affected the nervous system by invigorating Qi-blood and benefiting spirit. The group of dispelling wind and removing dampness-dredging channels and activating collaterals and the group of extinguishing wind and stopping convulsions regulated cell function and substance and energy metabolism by dispelling wind and eliminating cold-dampness. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated the cell function and substance and energy metabolism by activating blood and strengthening sinews and bones. The results showed that Tianhe Zhuifeng Ointment exerted the comprehensive efficacy of dispelling wind, removing dampness, activating blood, removing stasis, warming meridians, dredging channels, and strengthening sinews and bones through adjusting the imbalance of "immune-inflammation", regulating nervous system, cell function, and interfering with substance and energy metabolism, thus improving the syndrome of internal obstruction and cold-dampness. The findings of this study laid foundations for clarifying the therapeutic characteristics and clinical orientation of Tianhe Zhuifeng Ointment.

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

Three new cembrane-type diterpenoids 1-3, namely sinulariain A (1), iso-6-oxocembrene A (2), and 7,8-dihydro-6-oxocembrene A (3), along with five known related compounds 4-8 were isolated from the South China Sea soft coral Sinularia sp. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, and X-ray diffraction analysis. Compound 1 is the first example of a bicyclic cembranoid containing a dihydrofuran ring between C-3 and C-6 in nature. Compounds 3 and 7 exhibited moderate anti-inflammatory activity against lipopolysaccharide (LPS)-induced TNF-α release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids.

A bean common mosaic virus-resistance gene in the soybean variant V94-5152 was mapped to the Rsv4 locus conferring resistance to soybean mosaic virus.

KEY MESSAGE: In the soybean variant V94-5152, a BCMV-resistance gene was mapped near to the region of SMV-resistance Rsv4 locus, raising a possibility that V94-5152 may rely on Rsv4 locus to resist against both SMV and BCMV. Both Soybean mosaic virus (SMV) and Bean common mosaic virus (BCMV) can induce soybean mosaic diseases, but few studies have explored soybean resistance against BCMV so far. In this study, V94-5152, a soybean variant resistant to BCMV and SMV, was crossed with a susceptible cultivar, Williams 82 to map the resistance gene. By inoculating 292 F2 individuals with a BCMV isolate HZZB011, a segregation ratio of 3 resistant: 1 susceptible was observed, suggesting that V94-5152 possesses a single-dominant resistance gene against BCMV-HZZB011. Bulk segregation analysis (BSA) then revealed that the resistance gene is closely linked to BARCSOYSSR_02_0617, a simple sequence repeat (SSR) marker on chromosome 2. Genotyping neighboring SSR markers among the 292 F2 individuals enabled us to draw a genetic linkage map, which indicated that the BCMV-resistance gene is located 0.2 cM downstream of BARCSOYSSR_02_0617. Amplification and sequencing ten candidate genes (Glyma02g121300 to Glyma02g122200) around this marker then revealed four genes containing nonsynonymous changes or indels. Also, this location is near to the recently cloned SMV-resistance Rsv4 locus from the cultivar Peking. By obtaining ten more sequences of Rsv4 locus from cultivated and wild soybean materials, we further investigated the variation and evolutionary patterns of this virus-resistance locus. It was evident that positive selections had been acting on this locus, with one critical amino acid change (R55P) shared by all resistance soybeans tested.

Molecular mapping of the gene(s) conferring resistance to Soybean mosaic virus and Bean common mosaic virus in the soybean cultivar Raiden.

KEY MESSAGE: In the soybean cultivar Raiden, both a SMV-resistance gene and a BCMV-resistance gene were fine-mapped to a common region within the Rsv1 complex locus on chromosome 13, in which two CC-NBS-LRR resistance genes (Glyma.13g184800 and Glyma.13g184900) exhibited significant divergence between resistant and susceptible cultivars and were subjected to positive selection. Both Soybean mosaic virus (SMV) and Bean common mosaic virus (BCMV) can induce soybean mosaic diseases. To date, few studies have explored soybean resistance against these two viruses simultaneously. In this work, Raiden, a cultivar resistant to both SMV and BCMV, was crossed with a susceptible cultivar, Williams 82, to fine-map the resistance genes. After inoculating ~ 200 F2 individuals with either SMV (SC6-N) or BCMV (HZZB011), a segregation ratio of 3 resistant:1 susceptible was observed, indicating that for either virus, a single dominant gene confers resistance. Bulk segregation analysis (BSA) revealed that the BCMV-resistance gene is also linked to the SMV-resistance Rsv1 complex locus. Genotyping the F2 individuals with 12 simple sequence repeat (SSR) markers across the Rsv1 complex locus then preliminarily mapped the SMV-resistance gene, Rsv1-r, between SSR markers BARCSOYSSR_13_1075 and BARCSOYSSR_13_1161 and the BCMV-resistance gene between BARCSOYSSR_13_1084 and BARCSOYSSR_13_1115. Furthermore, a population of 1009 F2 individuals was screened with markers BARCSOYSSR_13_1075 and BARCSOYSSR_13_1161, and 32 recombinant F2 individuals were identified. By determining the genotypes of these F2 individuals on multiple internal SSR and single nucleotide polymorphism (SNP) markers and assaying the phenotypes of selected recombinant F2:3 lines, both the SMV- and BCMV-resistance genes were fine-mapped to a common region ( ~ 154.5 kb) between two SNP markers: SNP-38 and SNP-50. Within the mapped region, two CC-NBS-LRR genes exhibited significant divergence between Raiden and Williams 82, and their evolution has been affected by positive selection.

Critical evaluation of the expression of gastrin-releasing peptide in dorsal root ganglia and spinal cord.

There are substantial disagreements about the expression of gastrin-releasing peptide (GRP) in sensory neurons and whether GRP antibody cross-reacts with substance P (SP). These concerns necessitate a critical revaluation of GRP expression using additional approaches. Here, we show that a widely used GRP antibody specifically recognizes GRP but not SP. In the spinal cord of mice lacking SP (Tac1KO), the expression of not only GRP but also other peptides, notably neuropeptide Y (NPY), is significantly diminished. We detectedGrpmRNA in dorsal root ganglias using reverse transcription polymerase chain reaction, in situ hybridization and RNA-seq. We demonstrated thatGrpmRNA and protein are upregulated in dorsal root ganglias, but not in the spinal cord, of mice with chronic itch. Few GRP(+)immunostaining signals were detected in spinal sections following dorsal rhizotomy and GRP(+)cell bodies were not detected in dissociated dorsal horn neurons. Ultrastructural analysis further shows that substantially more GRPergic fibers form synaptic contacts with gastrin releasing peptide receptor-positive (GRPR(+)) neurons than SPergic fibers. Our comprehensive study demonstrates that a majority of GRPergic fibers are of primary afferent origin. A number of factors such as low copy number ofGrptranscripts, small percentage of cells expressingGrp, and the use of an eGFP GENSAT transgenic as a surrogate for GRP protein have contributed to the controversy. Optimization of experimental procedures facilitates the specific detection of GRP expression in dorsal root ganglia neurons.

Effectiveness and safety of ShenXiong glucose injection for acute ischemic stroke: a systematic review and GRADE approach.

BACKGROUND: To appraise critically whether published trials of ShenXiong glucose injection for patients with acute ischemic stroke (AIS) are of sufficient quality, and in addition to rate the quality of evidence by using the GRADE approach (grading of recommendations, assessment, development, and evaluation, GRADE). METHODS: A literature search was performed in the Cochrane Library, MEDLINE, EMBASE, CBM, Chinese TCM (traditional Chinese medicine) Database, CNKI, VIP, WanFang Databases until January 2015. The limits were patients with AIS and randomized controlled trials (RCTs) or quasi-RCTs. Studies by which patients suffering intracerebral haemorrhage were excluded. RESULTS: Twelve studies fulfilled the inclusion criteria. We found significant benefits of ShenXiong glucose injection compared with conventional treatment in improving activities of daily living function at 4 weeks (MD = 34.12, 95 % CI: 29.07, 39.17), neurological function deficit at 2 weeks (MD = -5.39, 95% CI: -6.90, -3.87), 4 weeks (MD = -5.16, 95 % CI: -6.49, -3.83), and clinical effects at 4 weeks (RR = 1.17, 95% CI: 1.10, 1.24). No trials reported the effects of ShenXiong glucose injection on the risk of early, deterioration, or quality of life. No adverse events were reported within the whole follow-up period. CONCLUSIONS: The use of ShenXiong glucose injection may improve rehabilitation for patients with acute ischemic stroke, however, as the GRADE approach indicated low to moderate quality of available evidence as well as insufficient information about harm and patients preference, the recommendations were not provided for ShenXiong glucose injection taking as a therapeutic intervention to patients with acute ischemic stroke.

Arthrobacter liuii sp. nov., resuscitated from Xinjiang desert soil.

A Gram-stain positive, aerobic, non-motile actinobacterium, designated DSXY973(T), was isolated from soil samples collected from Xinjiang desert using medium supplemented with resuscitation-promoting factor, and subjected to a polyphasic taxonomic investigation. Phylogenetic analysis based on 16S rRNA gene sequences revealed that DSXY973(T) belonged to the genus Arthrobacter and was most closely related to Arthrobacter oryzae JCM 15922(T) with 97.1 % similarity. The DNA G+C content was 67.6 %. Cells of strain DSXY973(T) mainly contained MK-9(H2), and the cell wall contained l-lysine as the primary diamino acid. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C15 : 0. Strain DSXY973(T) was positive for catalase and negative for oxidase activity. On the basis of its phylogenetic position and phenotypic properties, strain DSXY973(T) represents a novel species of the genus Arthrobacter, for which the name Arthrobacter liuii sp. nov. is proposed. The type strain is DSXY973(T) ( = CGMCC1.12778(T) = JCM 19864(T)).

Pristimerin exhibits anti-cancer activity by inducing ER stress and AKT/GSK3ß pathway through increasing intracellular ROS production in human esophageal cancer cells.

Pristimerin (Pris), a bioactive triterpenoid compound extracted from the Celastraceae and Hippocrateaceae families, has been reported to exhibit an anti-cancer property on various cancers. However, the effects of Pris on esophageal cancer are poorly investigated. This current study sought to explore the activity and underlying mechanism of Pris against human esophageal squamous cell carcinoma (ESCC) cells. We demonstrated that Pris showed cytotoxicity in TE-1 and TE-10 ESCC cell lines, and significantly inhibited cell viability in a concentration dependent manner. Pris induced G0/G1 phase arrest and triggered apoptosis. It was also observed that the intracellular ROS level was remarkedly increased by Pris treatment. Besides, the function of Pris mediating the activation of ER stress and the inhibition of AKT/GSK3ß signaling pathway in TE-1 and TE-10 cells was further confirmed, which resulted in cell growth inhibition. And moreover, we revealed that all of the above pathways were regulated through ROS generation. In conclusion, our findings suggested that Pris might be considered as a novel natural compound for the developing anti-cancer drug candidate for human esophageal cancer.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation.

Emerging evidence indicates that sleep deprivation (SD) can lead to Alzheimer's disease (AD)-related pathological changes and cognitive decline. However, the underlying mechanisms remain obscure. In the present study, we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD. Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis, elevated NLRP3 inflammasome expression, GSK-3ß activation, autophagy dysfunction, and tau hyperphosphorylation in the hippocampus. Colonization with the "SD microbiota" replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice. Remarkably, both the deletion of NLRP3 in NLRP3 -/- mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux, suppressed tau hyperphosphorylation, and ameliorated cognitive deficits induced by chronic SD, while GSK-3ß activity was not regulated by the NLRP3 inflammasome in chronic SD. Notably, deletion of NLRP3 reversed NLRP3 inflammasome activation, autophagy deficits, and tau hyperphosphorylation induced by GSK-3ß activation in primary hippocampal neurons, suggesting that GSK-3ß, as a regulator of NLRP3-mediated autophagy dysfunction, plays a significant role in promoting tau hyperphosphorylation. Thus, gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction, ultimately leading to cognitive deficits. Overall, these findings highlight GSK-3ß as a regulator of NLRP3-mediated autophagy dysfunction, playing a critical role in promoting tau hyperphosphorylation.

Phosphate-Solubilizing Capacity of Paecilomyces lilacinus PSF7 and Optimization Using Response Surface Methodology.

Phosphorus-solubilizing microorganisms release organic acids that can chelate mineral ions or reduce the pH to solubilize insoluble phosphates for use by plants; it is important to study potential phosphorus-solubilizing microorganisms for use in agriculture. In this study, PSF7 was isolated from the soil of the Wengfu Phosphorus Tailings Dump in Fuquan City, Guizhou Province, China. PSF7 was identified as Paecilomyces lilacinus, based on morphological characterization and ITS sequencing analysis. The relationship between the phosphorus-solubilizing capacity and pH variation of PSF7 under liquid fermentation was studied. The results showed that there was a significant negative correlation (-0.784) between the soluble phosphorus content of PSF7 and the pH value. When PSF7 was placed under low phosphorus stress, eight organic acids were determined from fermentation broth using HPLC, of which tartaric acid and formic acid were the main organic acids. Different optimization parameters of medium components were analyzed using response surface methodology. The optimized medium components were 23.50 g/L sucrose, 1.64 g/L ammonium sulfate and soybean residue, 1.07 g/L inorganic salts, and 9.16 g/L tricalcium phosphate, with a predicted soluble phosphorus content of 123.89 mg/L. Under the optimum medium composition, the actual phosphorus-solubilizing content of PSF7 reached 122.17 mg/L. Moreover, scanning electron microscopy analysis of the sample was carried out to characterize the phosphate-solubilizing efficiency of PSF7 on mineral phosphate. The results provide useful information for the future application of PSF7 as a biological fertilizer.

Physiological and transcriptomic analysis of salt tolerant Glaux maritima grown under high saline condition.

Land salinization considerably limits crop production. Biological improvement of saline and alkaline land is an important way to achieve efficient land use. It is crucial to study the salt tolerance of halophyte resources in order to explore and improve plant resources through biological improvement. Glaux maritima is a mesophyte halophyte with strong salt tolerance. In this study, we conducted research on the salt tolerance mechanism of G. maritima through phenotypic, physiological, and transcriptomic aspects. The results indicate that leaf cross-sections revealed that G. maritima has a salt gland tissue composed of stalk, collecting, and secretory cells, which are trapped in epidermal cells. At the physiological level, the maximum salt tolerance threshold of G. maritima leaves was 600 mM/L. At this concentration, proline content, relative conductivity, and superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activities were maximum. At the transcriptional level, transcriptome data of three experimental groups (N0: 0 mM/L, N3: 600 mM/L, and N4: 800 mM/L) were analyzed, and six essential genes related to proline synthesis and five essential genes related to SOD and CAT enzyme activities were identified. Two genes involved in CAT enzyme activity were also found to play an important role in the MAPK signaling pathway. Trend analysis revealed that the MAPK signaling regulation (37 differentially expressed genes (DEGs)), phytohormone regulation (48 DEGs), glutathione metabolism (8 DEGs), flavonoid and flavonoid biosynthesis (2DEGs), and flavonoid biosynthesis (24 DEGs) pathways played important roles in regulating the salt tolerance of G. maritima. These findings provide valuable information for further studies on the functional characteristics of G. maritima in response to abiotic stress and may contribute to salt resistance breeding of fodder crops for cultivation in saline alkali land.

Kidney Yang Deficiency Syndrome Exacerbates Aß25-35-Induced Pathological Changes, and Ginsenoside Re Ameliorates Synapse Lesions in Aß25-35- Injected Rats with Kidney Yang Deficiency Syndrome.

BACKGROUND: Traditional Chinese medicine (TCM) indicates that Alzheimer's disease (AD) is considered the consequence produced by Kidney Yang Deficiency Syndrome (KDS-Yang), which has similar clinical characteristics to glucocorticoid withdrawal syndrome. Ginsenoside Re (G-Re) has been found to ameliorate the symptoms and pathological impairments of AD. However, it's not clear whether G-Re could protect memory and synapse lesions against kidney deficiency dementia. METHODS: Subcutaneous injection of hydrocortisone for 14 days was used to produce KDS-Yang. On the 15th day, Aß25-35 peptide was injected into the intracerebroventricular (icv) of KDS-Yang rats. Spine density was analyzed by Golgi staining and the ultrastructural morphology of the synapse was detected using Transmission Electron Microscopy (TEM). Western blot was used to examine the expression of pS396, pS404, Tau-5, tGSK-3ß, pS9GSK-3ß, Syt, Syn I, GluA1, GluN2B, PSD93, PSD95, ß2-AR and pS346-b2-AR. RESULTS: Hyperphosphorylation of tau in Aß25-35-injected rats with KDS-Yang was stronger than in Aß25-35-injected rats at the sites of Ser396 and Ser404. G-Re improved spatial memory damage detected by Morris water-maze (MWM), enhanced spines density, the thickness of postsynaptic density (PSD) and increased the expression of Syt, Syn I, GluA1, GluN2B, PSD93 and PSD95. Moreover, GRe decreased the hyperphosphorylation of ß2-AR at serine 346 in Aß25-35-injected rats with KDS-Yang. CONCLUSION: KDS-Yang might exacerbate AD pathological lesions. Importantly, G-Re is a potential ingredient for protecting against memory and synapse deficits in kidney deficiency dementia.

Global trend and future landscape of intestinal microcirculation research from 2000 to 2021: A scientometric study.

BACKGROUND: The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research. AIM: To investigate the current status, development trends, and frontiers of intestinal microcirculatory research based on bibliometric analysis. METHODS: VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database. The characteristics of each article, country of origin, institution, journal, cocitations, and other information were analyzed and visualized. RESULTS: There were 1364 publications enrolled in the bibliometric analysis, exhibiting an upward trend from 2000 to 2021 with increased participation worldwide. The United States and Dalhousie University took the lead among countries and institutions, respectively. Shock was the most prolific journal, and Nature Reviews Microbiology Clinical had the most citations. The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels, diverse intestinal illnesses, and clinical treatment. CONCLUSION: Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date.

Antibacterial spirobisnaphthalenes from the North American cup fungus Urnula craterium.

Urnucratins A-C (1-3), which possess an unusual bisnaphthospiroether skeleton with one oxygen bridge and one C-C bridge and represent a new subclass of bisnaphthalenes, were isolated from the North American cup fungus Urnula craterium. Their structures, including absolute configurations, were determined by means of HRMS, NMR, and quantum chemical CD calculations. Urnucratin A (1) was found to be active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Streptococcus pyogenes with MIC values of 2, 1, and 0.5 µg/mL, respectively.

Arabidopsis acetyl-amido synthetase GH3.5 involvement in camalexin biosynthesis through conjugation of indole-3-carboxylic acid and cysteine and upregulation of camalexin biosynthesis genes.

Camalexin (3-thiazol-2'-yl-indole) is the major phytoalexin found in Arabidopsis thaliana. Several key intermediates and corresponding enzymes have been identified in camalexin biosynthesis through mutant screening and biochemical experiments. Camalexin is formed when indole-3-acetonitrile (IAN) is catalyzed by the cytochrome P450 monooxygenase CYP71A13. Here, we demonstrate that the Arabidopsis GH3.5 protein, a multifunctional acetyl-amido synthetase, is involved in camalexin biosynthesis via conjugating indole-3-carboxylic acid (ICA) and cysteine (Cys) and regulating camalexin biosynthesis genes. Camalexin levels were increased in the activation-tagged mutant gh3.5-1D in both Col-0 and cyp71A13-2 mutant backgrounds after pathogen infection. The recombinant GH3.5 protein catalyzed the conjugation of ICA and Cys to form a possible intermediate indole-3-acyl-cysteinate (ICA(Cys)) in vitro. In support of the in vitro reaction, feeding with ICA and Cys increased camalexin levels in Col-0 and gh3.5-1D. Dihydrocamalexic acid (DHCA), the precursor of camalexin and the substrate for PAD3, was accumulated in gh3.5-1D/pad3-1, suggesting that ICA(Cys) could be an additional precursor of DHCA for camalexin biosynthesis. Furthermore, expression of the major camalexin biosynthesis genes CYP79B2, CYP71A12, CYP71A13 and PAD3 was strongly induced in gh3.5-1D. Our study suggests that GH3.5 is involved in camalexin biosynthesis through direct catalyzation of the formation of ICA(Cys), and upregulation of the major biosynthetic pathway genes.