More and more focus has been placed on the processes by which viruses interact with bacteria to influence the biogeochemical cycles. The intricacy of soil matrix and the incompleteness of databases, ...however, constrains the investigation on the mechanisms of soil viruses exerting ecological functions. The modification of ICTV classification system in 2021 was also a huge shock to the results of the existing studies on virome. We used viral metagenomes combined with soil properties to investigate the viral community composition and auxiliary metabolic genes (AMGs) profiles of various lifestyles in soils of Mount Everest at different altitudes. Viral lifestyles and soil nutrient levels were found to significantly influence the diversity and composition of viral communities. Temperate virus lifestyle dominated in high-altitude soils with lower level of nutrients because of its stronger survival adaptability, and the structural and functional diversity of viral communities was positively correlated with the contents of nutrients (total carbon and total nitrogen). The primary types of AMGs carried by temperate and virulent viruses differed, while a variety of genes involved in carbon metabolism highlighted the potential importance of viruses in the soil carbon cycle of Mount Everest. Moreover, the abundance of AMGs encoding carbohydrate-active enzymes had a significant and positive correlation with soil C/N ratio. Overall, these findings provide a context for further exploration on the regulatory mechanisms of viruses in carbon cycle via interactions with microorganisms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•We evaluated the effect of prenatal phthalate exposure on children cognitive development by repeated measure analysis.•The first trimester might be the most critical period of cognitive development ...in term of exposure to phthalate.•VCI and VSI might be more susceptible to phthalates exposure than other domains.•A gender-specific effect may exist between prenatal phthalates exposure and IQ.
Phthalates are a group of heavily produced endocrine disruptors that are widely used in personal care products, food packaging, building materials, and medical device. Few epidemiological studies have examined the effect of repeated prenatal exposure to multiple phthalates on preschooler cognitive development.
This study aimed to examine the association between prenatal phthalate exposure measured at multiple time points and the intelligent quotient (IQ) scores of preschoolers, and to further identify the critical windows and specific intelligence domains in which phthalate exposure would affect preschooler cognitive development.
The current study was based on the Ma’anshan Birth Cohort (MABC) study. Seven phthalate metabolites were measured in 2128 maternal urine samples collected during the first, second, and third trimesters of pregnancy. The IQ score of preschool-aged children were assessed with the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth edition (WPPSI-Ⅳ CN). Linear mixed models (LMMs) were used to assess the longitudinal effects of repeated prenatal phthalate exposure on children’s IQ score. Multiple linear regression models were fitted to determine whether critical window phthalate exposure would affect cognitive development of children.
Overall, the repeated measures analysis indicated that the verbal comprehension index (VCI), visual space index (VSI) and full-scale intelligence quotient (FSIQ) decreased by 0.30 (95% CI: −0.60, 0; p = 0.05), 0.32 (95% CI: −0.62, −0.01; p = 0.04), and 0.31 (95% CI:-0.57, −0.04; p = 0.02) points, respectively, with each ln-transformed increase in the metabolite concentration of MBP. The fluid reasoning index (FRI) and processing speed index (PSI) increased by 0.30 (95% CI: 0.07, 0.54; p = 0.01) and 0.28 (95% CI: 0.06, 0.51; p = 0.01) points, respectively, with each ln-concentration increase in MEP. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. In the first trimester, each ln-transformed MBP increase was associated with reductions in VCI, VSI and FSIQ of 0.56 (95% CI:-1.09, −0.02; p = 0.04), 0.60 (95% CI:-1.15, −0.05; p = 0.03) and 0.49 (95% CI:-0.97, −0.01; p = 0.04) points, respectively. In the third trimester, we observed that only MBzP exposure was associated with an increase in VCI (β: 0.48, 95% CI: 0.03, 0.92; p = 0.04). The gender-stratified analyses revealed that boys drove these associations.
Our results suggest that prenatal phthalate exposure impairs the cognitive development of preschoolers. The first trimester of pregnancy might be the most vulnerable period in terms of neurotoxicitydue to phthalate exposure. These findings warrant further confirmation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To build a predictive scoring model based on simple immune and inflammatory parameters to predict postoperative survival in patients with breast cancer.
We used a brand-new immuno-inflammatory ...index-pan-immune-inflammation value (PIV)-to retrospectively evaluate the relationship between PIV and overall survival (OS), and based on the results of Cox regression analysis, we established a simple scoring prediction model based on several independent prognostic parameters. The predictive accuracy of the model was evaluated and independently validated.
A total of 1,312 patients were included for analysis. PIV was calculated as follows: neutrophil count (10
/L) × platelet count (10
/L) × monocyte count (10
/L)/lymphocyte count (10
/L). According to the best cutoff value of PIV, we divided the patients into two different subgroups, high PIV (PIV > 310.2) and low PIV (PIV ≤ 310.2), associated with significantly different survival outcomes (3-year OS, 80.26% vs. 86.29%, respectively; 5-year OS, 62.5% vs. 71.55%, respectively). Six independent prognostic factors were identified and used to build the scoring system, which performed well with a concordance index (C-index) of 0.759 (95% CI: 0.715-0.802); the calibration plot showed good calibration.
We have established and verified a simple scoring system for predicting prognosis, which can predict the survival of patients with operable breast cancer. This system can help clinicians implement targeted and individualized treatment strategies.
Two complete chloroplast genome sequences of Asteropyrum, as well as those of 25 other species from Ranunculaceae, were assembled using both Illumina and Sanger sequencing methods to address the ...structural variation of the cp genome and the controversial systematic position of the genus. Synteny and plastome structure were compared across the family. The cp genomes of the only two subspecies of Asteropyrum were found to be differentiated with marked sequence variation and different inverted repeat-single copy (IR-SC) borders. The plastomes of both subspecies contains 112 genes. However, the IR region of subspecies peltatum carries 27 genes, whereas that of subspecies cavaleriei has only 25 genes. Gene inversions, transpositions, and IR expansion-contraction were very commonly detected in Ranunculaceae. The plastome of Asteropyrum has the longest IR regions in the family, but has no gene inversions or transpositions. Non-coding regions of the cp genome were not ideal markers for inferring the generic relationships of the family, but they may be applied to interpret species relationship within the genus. Plastid phylogenomic analysis using complete cp genome with Bayesian method and partitioned modeling obtained a fully resolved phylogenetic framework for Ranunculaceae. Asteropyrum was detected to be sister to Caltha, and diverged early from subfamily Ranunculoideae.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Gynostemma pentaphyllum has been used as traditional medicine for many diseases, including metabolic syndrome (Mets), aging, diabetes, neurodegenerative diseases in China, some East Asian and ...Southeast Asian countries. It was shown that G. pentaphyllum and gypenosides had anti-obesity and cholesterol-lowering effects too. However, its main active ingredients are still unclear.
The objective of this study was to compare the effects of gypenosides before and after heat-processing on high fat obese mice, and to analyze the function of G. pentaphyllum saponin via network pharmacology and molecular docking.
The leaves of G. pentaphyllum were heat processed at 120 °C for 3 h to obtain heat-processed G. pentaphyllum. Gypenosides (Gyp) and heat-processed gypenosides (HGyp) were prepared by resin HP-20 chromatography and analyzed using LC-MS from the extracts of G. pentaphyllum before and after heat-processing, respectively. Obesity model was made with high fat diet (HFD). Gyp and HGyp were administrated at 100 mg/kg for 12 weeks in HFD obese mice and the body weight, energy intake, and levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) were compared. HGyp was administrated at a dose of 50,100,200 mg/kg for 12 weeks in HFD obese mice and the perirenal adipose, epididymal adipose, abdominal adipose, shoulder brown adipose, inguinal adipose were measured. Moreover, the potential targets, hub genes and pathways of damulin A, damulin B, gypenoside L, gypenoside LI for treating Mets were screened out via network pharmacology. According to the results of network pharmacology, core targets of treating Mets were docking with damulin A, gypenoside L, damulin B, gypenoside LI via molecular docking.
HGyp showed stronger effects on body weight loss and lipid-lowering in obese mice than Gyp. The contents of gypenoside L, gypenoside LI, damulin A and damulin B of G. pentaphyllum were increased by heat-processing. HGyp significantly decreased the body weight, calorie intake, and levels of TC, TG, LDL, HDL on the obese mice. It up-regulated PPARα and PPARγ in the liver tissues. HGyp reduced significantly the size of adipocytes in inguinal, abdominal, epididymal adipose and increased the proportion of interscapular brown fat. Network pharmacology results showed that 21 potential targets and 12 related-pathways were screened out. HMGCR, ACE, LIPC, LIPG, PPARα PPARδ, PPARγ were the core targets of HGyp against lipid metabolism by molecular docking. The putative functional targets of HGyp may be modulated by AGE-RAGE, TNF, glycerolipid metabolism, lipid and atherosclerosis, cholesterol metabolism, PPAR, fat digestion and absorption, cell adhesion molecules signaling pathway.
Gyp and HGyp are valuable for inhibition obesity, lipid-lowering, metabolic regulation. Especially, the effect of HGyp is better than that of Gyp.
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•Gypenosides reduced the body weight, calorie intake, and the contents of TC, TG, LDL of high-fat diet induced mice.•They up-regulated PPARα and PPARγ in the liver tissues.•The targets and pathways of gypenosides on metabolic syndrome were analyzed via network pharmacology and molecular docking.•HMGCR, ACE, LIPC, LIPG, PPARα, PPARδ, PPARγ were the core targets of heat-processed gypenosides against lipid metabolism.•The targets may be modulated by the signaling pathways of AGE-RAGE, glycerolipid metabolism, cholesterol metabolism etc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lung cancer is the chief reason of cancer death worldwide, and non-small cell lung cancer (NSCLC) make up the majority of lung cancers. Gypenosides are the main active constituents from Gynostemma ...pentaphyllum. Previous studies showed that they were used to remedy many cancers. The effect of gypenosides on NSCLC has never been studied from the perspective of network pharmacology and metabolomics. The mechanism is still not clear and remains to be explored.
To explore the anti-NSCLC activity and mechanism of gypenosides in A549 cells.
Gypenosides of G. pentaphyllum were detected by HPLC-MS. The cytotoxicity was detected by MTT assay. The migration, cell cycle and apoptosis of gypenosides were studied by wound healing assay, JC-1 assay and flow cytometry. The mechanism of gypenosides on NSCLC was studied by metabolomics and network pharmacology. Some key proteins and pathways were further confirmed by Western blot.
Eleven gypenosides were detected by HPLC-MS. Gypenosides could suppress the proliferation of A549 cells, inhibit the migration of A549 cells, induce apoptosis and arrest cell cycle in G0/G1 phase. Metabolomics and network pharmacology approach revealed that gypenosides might affect 17 metabolite related proteins by acting on 9 candidate targets (STAT3, VEGFA, EGFR, MMP9, IL2, TYMS, FGF2, HPSE, LGALS3), thus resulting in the changes of two metabolites (uridine 5′-monophosphate, D-4′-Phosphopantothenate) and two metabolic pathways (pyrimidine metabolism; pantothenate and CoA biosynthesis). Western blotting indicated that gypenosides might inhibit A549 cells through MMP9, STAT3 and TYMS to indirectly affect the pathways of pyrimidine metabolism, pantothenate and CoA biosynthesis.
This study revealed that metabolomics combined with network pharmacology was conducive to understand the anti-NSCLC mechanism of gypenosides.
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•Effect of gypenosides against A549 cells was analyzed by metabolomics and network pharmacology.•Gypenosides affected 9 candidate targets and acted on 17 metabolite-related proteins.•Gypenosides might inhibit A549 cells through MMP9, STAT3 and TYMS to indirectly affect 2 metabolites and 2 pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gynostemma pentaphyllum (Thunb.) Makino, a traditional medicine in China, has been widely used for the treatment of various diseases. Gypenoside LI (Gyp LI) is a major constituent from steamed G. ...pentaphyllum. Previous studies have shown that gypnenoside LI possess inhibitory effect on the growth of many cancer cells. However, its pharmacological effect in breast cancer and the mechanism have not been reported yet.
To investigate the anti-breast cancer activity of gypenoside LI and underlying mechanisms of gypenoside LI in MDA-MB-231 and MCF-7 cells.
The cytotoxicity of gypenoside LI was determined by MTT, colony-formation and three-dimensional spheroid assay. The migration, cell apoptosis and the cell cycle were investigated through cell morphology observation, flow cytometry analysis and key proteins detection. The anticancer mechanisms of gypenoside LI were detected by RNA sequencing (RNA-seq) and Gene Set Enrichment Analysis (GSEA) transcriptome analysis.
Gypenoside LI inhibited cell proliferation, migration, induced cell apoptosis and cell cycle arrest. Gypenoside LI arrested cell cycle at G0/G1 phase by regulating E2F1. It also inhibited tumor proliferation by regulating the expression of ERCC6L. Interestingly, we found that E2F1 siRNA also down-regulated the expression of ERCC6L. Gypenoside LI showed potential anti-breast cancer cells activity, especially on triple-negative breast cancer cells.
These data indicate that gypenoside LI could inhibit human breast cancer cells through inhibiting proliferation and migration, inducing apoptosis, arresting cell cycle at G0/G1 phase by regulating E2F1. It could be used as potential multi-target chemopreventive agents for cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•A dual bacterial consortium for erythromycin degradation is constructed.•Proposal of a new erythromycin biodegradation pathway.•The rare erythromycin esterase gene ereD is found in ...strain ERY-6B.•Efficient adsorption of modified coconut shell activated carbon for erythromycin.•96% of erythromycin is removed by immobilized cells within 24 h.
Removing erythromycin from the environment is a major challenge. In this study, a dual microbial consortium (Delftia acidovorans ERY-6A and Chryseobacterium indologenes ERY-6B) capable of degrading erythromycin was isolated, and the erythromycin biodegradation products were studied. Coconut shell activated carbon was modified and its adsorption characteristics and erythromycin removal efficiency of the immobilized cells were studied. It was indicated that alkali-modified and water-modified coconut shell activated carbon and the dual bacterial system had excellent erythromycin removal ability. The dual bacterial system follows a new biodegradation pathway to degrade erythromycin. The immobilized cells removed 95% of erythromycin at a concentration of 100 mg L−1 within 24 h through pore adsorption, surface complexation, hydrogen bonding, and biodegradation. This study provides a new erythromycin removal agent and for the first time describes the genomic information of erythromycin-degrading bacteria, providing new clues regarding bacterial cooperation and efficient erythromycin removal.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Gypenosides from heat-processed Gynostemma pentaphyllum has the effect of reduced lipids and lost weight in obese mice with high-fat diet.•Lipomics revealed that gypenosides in heat-processed ...Gynostemma pentaphyllum significantly attenuated liver metabolites in hyperlipidemic mice, especially ceramide and lysophosphatidylcholine.•The liver participates in the regulation of lipid metabolism by heat-processed Gynostemma pentaphyllum saponin. The mechanism may be related to lipid synthesis, catabolism and metabolism.
In traditional Chinese medicine, Gynostemma pentaphyllum (G. pentaphyllum) is widely used to treat conditions associated with hyperlipidemia, and its therapeutic potential has been demonstrated in numerous studies. However, the mechanism of lipid metabolism in hyperlipidemic by G. pentaphyllum, especially heat-processed G. pentaphyllum is not yet clear.
The aim of this study was to investigate the therapeutic mechanism of gypenosides from heat-processed G. pentaphyllum (HGyp) in hyperlipidemic mice by means of a lipidomics.
The content of the major components of HGyp was determined by ultra-performance liquid chromatography-electrospray ionization ion trap mass spectrometry (UPLC-ESI-MS). An animal model of hyperlipidaemia was constructed using C57BL/6J mice fed with high-fat diet. HGyp was also administered at doses of 50, 100 and 200 mg/kg, all for 12 weeks. Serum parameters were measured, histological sections were prepared and liver lipidome analysis using UPLC-MS coupled with multivariate statistical analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyze the genes and proteins associated with lipid lowering in HGyp.
HGyp reduced body weight, serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) and hepatic lipid accumulation in hyperlipidemic obese mice. To explore specific changes in lipid metabolism in relation to HGyp administration, lipid analysis of the liver was performed. Orthogonal partial least squares discriminant analysis (OPLS-DA) score plots showed that HGyp altered lipid metabolism in HFD mice. In particular, fatty acids (FA), triglycerides (DG), TG and ceramides (CER) were significantly altered. Eleven lipids were identified as potential lipid biomarkers, namely TG (18:2/20:5/18:2), TG (18:2/18:3/20:4), DG (18:3/20:0/0:0), Cer (d18:1/19:0), Cer (d16:1/23:0), Ceramide (d18:1/9Z-18:1), PS (19:0/18:3), PS (20:2/0:0), LysoPC (22:5), LysoPE (0:0/18:0), PE (24:0/16:1). Western blot and qRT-PCR analysis showed that these metabolic improvements played a role by down-regulating genes and proteins related to fat production (SREBP1, ACC1, SCD1), up-regulating genes and proteins related to lipid oxidation (CPTA1, PPARα) and lipid transport decomposition in the bile acid pathway (LXRα, PPARγ, FXR, BSEP).
The lipid-lowering effect of gypenosides from heat-processed G. pentaphyllum is regulate lipid homeostasis and metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Glucose metabolic disorders (GMD) can promote insulin resistance (IR) and diabetes, and damage liver and kidney.
Gynostemma pentaphyllum
is commonly used in the clinical treatment of diabetes, but ...the research on its main active constituents and GMD has not been reported yet. This study explores the therapeutic potential of gypenosides of heat-processed
Gynostemma pentaphyllum
(HGyp) on high-fat diet-induced GMD in mice. HGyp was administered at different doses for 12 weeks. The investigation encompassed an array of parameters, including body weight, blood lipids, blood glucose, and liver tissue components. Metabolomic and network analyses were conducted to uncover potential targets and pathways associated with HGyp treatment. The results revealed that HGyp alleviated GMD by reducing body weight, blood glucose, and improving blood lipids levels, while increasing liver glycogen and antioxidant enzyme levels. Additionally, HGyp exhibited protective effects on liver and kidney health by reducing tissue damage. Fourteen blood components were detected by LC-MS. Metabolomic and network analyses indicated the potential engagement of the AGE-RAGE signaling pathway in the therapeutic effects of HGyp.Furthermore, Western blot and ELISA assays confirmed that HGyp upregulated GLO1 and GLUT4 while down-regulating AGEs and RAGE expression in liver tissue. In light of these findings, HGyp demonstrates promise as a potential therapeutic candidate for combating GMD, warranting further exploration in the development of therapeutic strategies or functional products.
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