Effects of Mesenchymal Stem Cells-Derived Extracellular Vesicles on Inhibition of Hepatic Fibrosis by Delivering miR-200a.

BACKGROUND: Hepatic fibrosis (HF) is a common pathological feature of chronic hepatic diseases. We aimed to illuminate the significance of amniotic mesenchymal stem cells (AMSCs)-derived extracellular vesicles (AMSCs-EVs) in HF. METHODS: Human AMSCs-EVs were isolated and identified. HF mice were constructed and treated with EVs. The fibrosis was observed by staining experiments and Western blot (WB) assay. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and hepatic hydroxyproline (Hyp) were detected to confirm liver function. For the in vitro experiments, human hepatic stellate cells were induced with transforming growth factor-ß and treated with EVs. To measure the degree of HF, the expression of alpha-smooth muscle actin (α-SMA) and Collagen I was detected by WB assay, and cell proliferation was detected by cell counting kit 8 assay. The levels of miR-200a, Zinc finger E-box binding homeobox 1 (ZEB1), and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) were detected by WB and real-time quantitative polymerase chain reaction. The binding of ZEB1 to PIK3R3 and miR-200a to ZEB1 was analyzed by chromatin immunoprecipitation and dual luciferase assays to validate their relationships. RESULTS: Human AMSCs and AMSCs-EVs were obtained. Serum ALT, AST, TBIL, and hepatic Hyp were increased, implying the fibrosis degree was aggravated in HF mice, which was decreased again after EV treatment. EVs inhibited HF degree by reducing α-SMA and Collagen I and promoting cell proliferation. AMSCs-EVs delivered miR-200a into hepatocytes, which up-regulated miR-200a expression, inhibited ZEB1 expression, and reduced its enrichment on the PIK3R3 promoter, therefore inhibiting PIK3R3 expression and alleviating HF. Overexpression of ZEB1 or PIK3R3 attenuated the anti-fibrotic effect of AMSCs-EVs. CONCLUSION: Human AMSCs-derived EVs mediated miR-200a delivery and inhibition of intracellular ZEB1/PIK3R3 axis to exert anti-fibrosis effects.

Injectable isoniazid-loaded bone cement based on hydrazone bonds achieving long-term release and decent mechanical properties.

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

Analysis of widely targeted metabolites of quinoa sprouts (Chenopodium quinoa Willd.) under saline-alkali stress provides new insights into nutritional value.

Quinoa sprouts are a green vegetable rich in bioactive chemicals, which have multiple health benefits. However, there is limited information on the overall metabolic profiles of quinoa sprouts and the metabolite changes caused by saline-alkali stress. Here, a UHPLC-MS/MS-based widely targeted metabolomics technique was performed to comprehensively evaluate the metabolic profiles of quinoa sprouts and characterize its metabolic response to saline-alkali stress. A total of 930 metabolites were identified of which 232 showed significant response to saline-alkali stress. The contents of lipids and amino acids were significantly increased, while the contents of flavonoids and phenolic acids were significantly reduced under saline-alkali stress. Moreover, the antioxidant activities of quinoa sprouts were significantly affected by saline-alkali stress. The enrichment analysis of the differentially accumulated metabolites revealed that flavonoid, amino acid and carbohydrate biosynthesis/metabolism pathways responded to saline-alkali stress. This study provided an important theoretical basis for evaluating the nutritional value of quinoa sprouts and the changes in metabolites in response to saline-alkali stress.

Investigating the in vitro antibacterial efficacy of composite bone cement incorporating natural product-based monomers and gentamicin.

OBJECTIVE: The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). METHODS: Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. RESULTS: The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). CONCLUSION: In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.

Novel drimane-type sesquiterpenoids and nucleosides from the Helicoma septoconstrictum suppress the growth of ovarian cancer cells.

Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1-6), were isolated from the fungus Helicoma septoconstrictum. Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC50 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3's phosphorylation. These findings offered crucial support for development of H. septoconstrictum and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals.

Hematological and Neurological Expressed 1 Promotes Tumor Progression Through mTOR Signaling in Ovarian Cancer.

Ovarian cancer (OV) is a highly aggressive malignancy with poor prognosis due to recurrence and drug resistance. Therefore, it is imperative to investigate the key molecular mechanisms underlying OV progression in order to develop promising diagnostic and therapeutic interventions. Although the importance of hematological and neurological expressed 1 (HN1) protein in hemopoietic cell and neurological development has been well-established, its function in cancer, particularly in OV, remains uncertain. In this study, we compared the expression of HN1 in ovarian cancers and para-tumor tissues and predicted potential related signaling pathways through enrichment analysis. In order to confirm the role of HN1 in vitro and vivo, we carried out a variety of experiments including bioinformation analysis, colony formation, flow cytometry analysis, and subcutaneous tumor models. The results demonstrated that HN1 was upregulated in OV and was negatively associated with clinical prognosis. Moreover, we observed that HN1 enhances cell proliferation, migration, and drug resistance, while suppressing apoptosis in OV cells. Notably, we discovered that HN1 functions as a novel regulator of mTOR pathways. Our findings suggest that HN1-mediated mTOR regulation facilitates OV advancement and targeting HN1 could provide a promising therapeutic approach for clinical OV treatment.

Gossypol Acetic Acid alleviates the Ferroptosis of Chondrocytes in Osteoarthritis by Inhibiting GPX4 Methylation.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, usually accompanied by degeneration of the articular cartilage, fibrosis, bone hyperplasia around the joint, and damage to the entire articular surface. Gossypol is a natural phenolic compound isolated from the seed of cotton plants, and gossypol acetic acid (GAA) is a medicinal form of Gossypol. Recently, various biological activities of GAA, including anti-inflammatory and anti-tumor effects, have been widely reported. However, its effect on chondrocytes in OA has yet to be determined. METHODS: In this study, we investigated the effect of GAA on ferroptosis in OA chondrocytes. The effect of GAA on the cell viability and cytotoxicity of chondrocytes in rat cells was investigated using CCK8. Western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescence staining were used to elucidate the molecular mechanisms and signaling pathways of GAA inhibition of ferroptosis in OA chondrocytes. The effect of GAA on reactive oxygen species (ROS) production and lipid peroxidation levels in chondrocytes was examined using dihydroethidium (DHE) staining and fluorescent dye BODIPY581/591 C11. in vivo, micro-CT imaging, hematoxylin and eosin staining, Safranin O-Fast staining, and immunohistochemistry were performed to evaluate the effects of GAA on OA cartilage. RESULTS: The results showed that GAA treatment regulated the expression of chondrocyte extracellular matrix (ECM) related factors, including ADAMTS5, MMP13, SOX9, Aggrecan, and COL1A2 and reduced the ROS and lipid peroxidation levels. Besides, Erastin could reverse the effects of GAA on chondrocytes. Similar to GAA, 5-AZA caused the reduction of ROS and lipid peroxidation levels and reversed the effect of IL-1ß on the expression of ECM-related factors in OA chondrocytes. The above results clarified that GAA alleviated the ferroptosis of chondrocytes in OA by inhibiting GPX4 methylation. CONCLUSION: Our findings revealed that GAA might be developed as a drug for treating OA clinically.

Propofol inhibits the proliferation, invasion, migration, and angiogenesis of oral squamous cell carcinoma through circ_0008898-mediated pathway.

Propofol has been shown to inhibit oral squamous cell carcinoma (OSCC) progression. However, it is not clear whether propofol mediates OSCC progression through regulating circular RNA (circRNA) network. Quantitative real-time PCR was used to detect circ_0008898, miR-545-3p, and CT10 regulator of kinase-like protein (CRKL) expression. Cell functions were determined using CCK8 assay, Edu staining, MTT assay, transwell assay, wound healing assay, tube formation assay, and flow cytometry. Protein levels were examined by western blot analysis. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Our data showed that propofol repressed OSCC cell proliferation, invasion, migration, angiogenesis, and promoted apoptosis. circ_0008898 was highly expressed in OSCC, and its expression could be decreased by propofol. circ_0008898 silencing aggravated the suppressive effect of propofol on OSCC progression. In the mechanism, circ_0008898 could target miR-545-3p to positively regulate CRKL. MiR-545-3p inhibitor abolished the regulation of circ_0008898 silencing on propofol-mediated OSCC cell progression. MiR-545-3p inhibited the progression of propofol-treated OSCC cells, and this effect was reversed by CRKL overexpression. Also, circ_0008898 knockdown reduced OSCC tumor growth by regulating miR-545-3p/CRKL. In conclusion, propofol suppressed OSCC progression, which was achieved through regulating the circ_0008898/miR-545-3p/CRKL axis.

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria.

Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.

Comamonas-dominant microbial community in carbon poor aquitard sediments revealed by metagenomic-based growth rate investigation.

The microbiological ecology of a low-nutrient shallow aquifer with high arsenic content in the Yinchuan Plain was investigated in this study. Amplicon sequencing data from five samples (depths: 1.5 m, 3.5 m, 11.2 m, 19.3 m, and 25.5 m) revealed diverse and adaptable microbial community. Among the microbial community, Comamonas was the most prominent, accounting for 10.52 % of the total. This genus displayed high growth rates, with a maximum growth rate of 12.06 d-1 and a corresponding doubling time of 1.38 days, as determined through an analysis of codon usage bias. Functional annotation of Metagenome-Assembled Genomes (MAGs) for samples at 1.5 m and 11.2 m depths revealed Comamonas' metabolic versatility, including various carbon pathways, assimilative sulfate reduction (ASR), and dissimilatory reduction to ammonium (DNRA). The TPM (Transcripts Per Kilobase of exon model per Million mapped reads) of MAGs at 11.2 m sample was 15.7 and 12.3. The presence of arsenic resistance genes in Comamonas aligns with sediment arsenic levels (65.8 mg/kg for 1.5 m depth, 32.8 mg/kg for 11.2 m depth). This study highlights the role of Comamonas as a 'generalist' bacteria in challenging oligotrophic sediments, emphasizing the significance of such organisms in community stability and ecological functions. ENVIRONMENTAL IMPLICATION: Low-biomass limits the microbial activity and biogeochemical study in oligotrophic environments, which is the typical condition for underground aquatic ecosystems. Facilitated by growth rate estimation, our research focuses on active functional microorganisms and their biogeochemical metabolic in oligotrophic aquifer sediments, revealing their impact on the environment and response to arsenic threats. Findings illuminate the metabolic advantage of a 'generalist life-style' in carbon-scarce environments and contribute to a broader understanding of bacterial ecosystems and environmental impacts in oligotrophic aquifer sediments worldwide.

Comparison of surgical and endovascular left subclavian artery revascularization during thoracic aortic endovascular repair: a systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to incorporate data from the latest clinical studies and compare the safety and efficacy of surgical left subclavian artery (LSA) revascularization and endovascular LSA revascularization during thoracic endovascular aortic repair (TEVAR). Methods: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the PROSPERO database on 16 April 2023 (CRD42023414579). The Embase, MEDLINE (PubMed), and the Cochrane Library databases were searched from January 2000 to May 2023. Results: A total of 14 retrospective cohort studies with a total of 1,695 patients, were included for review. The peri-operative stroke rates of the surgical and endovascular LSA revascularization groups were 3.8% and 2.6%, respectively (P = 0.97). The peri-operative technical success rates for the surgical and endovascular LSA revascularization groups were 95.6% and 93.0%, respectively (P = 0.24). The peri-operative spinal cord ischemia rates were 1.6% (n = 18) and 1.9% (n = 7) in the surgical and endovascular LSA revascularization groups, respectively (P = 0.90). The peri-operative type Ⅰ endoleak rates for the surgical and endovascular LSA revascularization groups were 6.6% and 23.2%, respectively (P = 0.25). The subgroup analysis showed that the incidence of peri-operative type I endoleak in the parallel stent group was significantly higher than that in the surgical LSA revascularization group (P < 0.0001). The peri-operative left upper limb ischemia rates for the surgical and endovascular LSA revascularization groups were 1.2% and 0.6%, respectively (P = 0.96). The peri-operative mortality rates of the surgical and endovascular LSA revascularization groups were 2.0% and 2.0%, respectively (P = 0.88). Conclusion: There was no significant difference in the terms of short-term outcomes when comparing the two revascularization techniques. The quality of evidence assessed by GRADE scale was low to very-low. Surgical and endovascular LSA revascularization during TEVAR were both safe and effective. Compared with surgical LSA revascularization techniques, parallel stent revascularization of LSA significantly increased the rate of type I endoleak.

Silencing METTL14 alleviates liver injury in non-alcoholic fatty liver disease by regulating mitochondrial homeostasis.

Mitochondrial dysfunction is an important pathogenic factor in non-alcoholic fatty liver disease (NAFLD). Methyltransferase-like 14 (METTL14) has been implicated in mitochondrial fission processes. This research aimed to investigate the mechanism of METTL14 in the mitochondrial function of NAFLD. We first established NAFLD mouse models and cell models, recording body and liver weights and examining pathological changes in liver tissues. Subsequently, serum levels of liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total cholesterol [TC], and triglycerides [TG]), inflammatory markers (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, and IL-1ß), and mitochondrial dysfunction indicators (fission 1 protein [Fis1], dynamin-related protein 1 [Drp1], mitofusin 2 [Mfn2], SID1 transmembrane family member 2 [SIDT2], and mitochondrial membrane potential [MMP]) in the liver and cells were evaluated. The N6-methyladenosine (m6A) modification level of primary microRNA (pri-miRNA) and m6A enrichment on pri-miR-34a were quantified. Co-immunoprecipitation and dual-luciferase reporter gene assays were utilized to validate gene interactions. Our findings revealed highly elevated METTL14 expression in NAFLD mouse and cell models. Silencing METTL14 reduced weight gain and mitigated adverse liver function indices, inflammation, hepatic steatosis, and structural damage in NAFLD mice. It also led to a decrease in Fis1/Drp1 levels and an increase in MMP/Mfn2 in the liver and cells. Moreover, METTL14 increased the m6A level, promoting the binding of DiGeorge syndrome critical region 8 (DGCR8) to pri-miR-34a, which enhanced miR-34a-5p expression. Databases and dual-luciferase reporter gene assays indicated that miR-34a-5p could suppress SIDT2 expression. The overexpression of miR-34a-5p or inhibition of SIDT2 expression negated the alleviative effects of METTL14 silencing on mitochondrial homeostasis imbalance. In conclusion, METTL14, through m6A modification, modulates the miR-34a-5p/SIDT2 axis, impairing mitochondrial homeostasis in NAFLD.

Microfluidic one-step synthesis of a metal-organic framework for osteoarthritis therapeutic microRNAs delivery.

As a class of short non-coding ribonucleic acids (RNAs), microRNAs (miRNA) regulate gene expression in human cells and are expected to be nucleic acid drugs to regulate and treat a variety of biological processes and diseases. However, the issues with potential materials toxicity, quantity production, poor cellular uptake, and endosomal entrapment limit their further applications in clinical practice. Herein, ZIF-8, a metal-organic framework with noncytotoxic zinc (II) as the metal coordination center, was selected as miRNA delivery vector was used to prepare miR-200c-3p@ZIF-8 in one step by Y-shape microfluidic chip to achieve intracellular release with low toxicity, batch size, and efficient cellular uptake. The obtained miR-200c-3p@ZIF-8 was identified by TEM, particle size analysis, XRD, XPS, and zeta potential. Compared with the traditional hydrothermal method, the encapsulation efficiency of miR-200c-3p@ZIF-8 prepared by the microfluidic method is higher, and the particle size is more uniform and controllable. The experimental results in cellular level verified that the ZIF-8 vectors with low cytotoxicity and high miRNAs loading efficiency could significantly improve cellular uptake and endosomal escape of miRNAs, providing a robust and general strategy for nucleic acid drug delivery. As a model, the prepared miR-200c-3p@ZIF-8 is confirmed to be effective in osteoarthritis treatment.

A torus source and its application for non-primary radiation evaluation.

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.

Nanoemulsion of the Essential Oil from Blumea balsamifera (L.) DC. and Its Effect on Trauma Repair.

The essential oil, extracted from the Hmong medicine Blumea balsamifera (L.) DC. (BBO), is a purely natural wound repair agent. Its application has, however, been restricted due to its low solubility and high volatility properties. In this study, we have developed a nanoemulsion formulation to improve the characteristics of BBO. The particle size of the nanoemulsion was normally distributed, and 71% of its range was concentrated between 10-100 nm, with an average particle size of 62.8 nm and an encapsulation rate of 98%. After 7 days of application, the wound healing rate of the BBO nanoemulsion (BBO-NE) group was 1.5 times higher than that of the normal BBO group. Along with histological observations, nanoemulsion formulation has been demonstrated to significantly improve the efficacy of BBO for wound repair. In addition, inflammation-related TLR4, CD14 and IRAK-1 gene transcript levels were significantly reduced after the administration of BBO-NE compared to the BBO group, with downregulation of 47.8%, 35.7% and 57.8%, respectively, while the secretion of pro-inflammatory factors IL-6 and TNF-α was also significantly reduced by 83.8% and 32.7%, respectively, in the nanoformulation administration (BBO-NE) group compared to the BBO group. In contrast, the anti-inflammatory factor IL-10 was significantly increased by 4.2-fold. It was further found that the drug penetration per unit area increased significantly 6.30% to 19.5% at different time points after the application of the BBO-NE compared to the BBO. In conclusion, nano-formulation enhanced the drug penetration of the BBO, reduced inflammatory factors, increased the level of anti-inflammatory factors, and promoted collagen deposition, thereby accelerating wound repair.

Virus impacted community adaptation in oligotrophic groundwater environment revealed by Hi-C coupled metagenomic and viromic study.

Viruses play a crucial role in microbial mortality, diversity and biogeochemical cycles. Groundwater is the largest global freshwater and one of the most oligotrophic aquatic systems on Earth, but how microbial and viral communities are shaped in this special habitat is largely unexplored. In this study, we collected groundwater samples from 23 to 60 m aquifers at Yinchuan Plain, China. In total, 1920 non-reductant viral contigs were retrieved from metagenomes and viromes constructed by Illumina and Nanopore hybrid sequencing. Only 3% of them could be clustered with known viruses, most of which were Caudoviricetes. Coupling 1.2 Tb Hi-C sequencing with CRISPR matching and homology search, we connected 469 viruses with their hosts while some viral clusters presented a broad-host-range trait. Meanwhile, a large proportion of biosynthesis related auxiliary metabolism genes were identified. Those characteristics might benefit viruses for a better survival in this special oligotrophic environment. Additionally, the groundwater virome showed genomic features distinct from those of the open ocean and wastewater treatment facilities in GC distribution and unannotated gene compositions. This paper expands the current knowledge of the global viromic records and serves as a foundation for a more thorough understanding of viruses in groundwater.

Endophytic fungus Biscogniauxia petrensis produces antibacterial substances.

Widespread drug resistance and limited antibiotics challenge the treatment of pathogenic bacteria, which leads to a focus on searching for new antimicrobial lead compounds. We found the endophytic fungus Biscogniauxia petrensis MFLUCC14-0151 from the medicinal plant Dendrobium harveyanum had antibacterial activity for the first time. This work aimed to reveal the capacity of Biscogniauxia petrensis MFLUCC14-0151 against foodborne pathogenic bacteria and identify its bioactive substances. Bioassay-guided isolation led to the discovery of six infrequent active monomers, including (10R)-Xylariterpenoid B (1), Xylariterpenoid C (2), Tricycloalternarene 1b (3), Tricycloalternarene 3b (4), Funicin (5) and Vinetorin (6) from MFLUCC14-0151 for the first time. The results of antibacterial tests showed that (10R)-Xylariterpenoid B and Xylariterpenoid C exhibited inhibitory activities against Streptococcus agalactiae with MIC values ranging from 99.21 to 100.00 µM, and against Streptococcus aureus with MIC values ranging from 49.60 to 50.00 µM. Tricycloalternarene 1b and Tricycloalternarene 3b showed inhibitory effects on Streptococcus agalactiae with MIC values ranging from 36.13 to 75.76 µM. Unexpectedly, Funicin and Vinetorin exhibited remarkable antagonistic activities against Streptococcus agalactiae with MIC values of 10.35 and 10.21 µM, respectively, and against Streptococcus aureus with MIC values of 5.17 and 20.42 µM, respectively. In conclusion, we suggest that the isolated compounds Funicin and Vinetorin may be promising lead compounds for natural antibacterial agents.

New Spirostane from a Fungus Neohelicomyces hyalosporus and Its Bioactivity.

A new spirostane, namely neohelicomyine B (1), together with six known steroids (2-7) were isolated from the fermentation of fungus Neohelicomyces hyalosporus. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The bioactivities of compounds 1-7 were evaluated using cellular assays. Compound 1 displayed moderate cytotoxicity against HepG2 cells (hepatoma cells) with IC50 value of 8.4±2.1 µM. Compound 7 also exhibited cytotoxic activity against HepG2 cells with the IC50 value of 3.0±0.2 µM.

Comparative effectiveness of different probiotics supplements for triple helicobacter pylori eradication: a network meta-analysis.

Background: Probiotics has been reported as an effective supplement for Helicobacter pylori eradication. However, knowledge of their comparative efficacy is still lacking. Aim: In this study, we used network meta-analysis of current probiotics supplement used in standard triple therapy to assess and rank their comparative effectiveness. Methods: All randomized controlled trials from three main databases (PubMed, Embase and Cochrane Library) up to April 2022 were collected and filtered to meet our criterion. We used Bayesian network meta-analysis to evaluate the eligible randomized controlled trials and gave a rank for the efficiency and incidence of side effects of each probiotics supplement. The ranking probability for each therapy was assessed by means of surfaces under cumulative ranking values. Subgroup analysis was conducted to evaluate other possible influencing factors. Results: 34 eligible randomized controlled trials entered the following meta-analysis, including 9,004 patients randomized to 10 kinds of therapies. Result showed that most probiotics added therapies had better outcomes than triple therapy, among which Bifidobacterium-Lactobacillus and Bifidobacterium-Lactobacillus-Saccharomyces adjuvant therapy could obtain comprehensive benefit with high eradication rate (78.3% and 88.2% respectively), and cause few side effects. Combination of different probiotics, adding probiotics before or after triple therapy and longer duration of probiotics can improve therapeutic effect in H.pylori infected individuals. Conclusion: For triple therapy of H.pylori infection, adding probiotics can increase eradication rate and bring protective effect. Considering the overall influence, Bifidobacterium-Lactobacillus or Bifidobacterium-Lactobacillus-Saccharomyces therapy can be a better choice in improving H.pylori eradication process.