Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. MATERIALS AND METHODS: UPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. RESULTS: Our analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. CONCLUSION: This study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option.

Molecular Cloning and Functional Analysis of Secretory Phospholipase A2 from Apostichopus japonicus.

Secretory phospholipase A2 (sPLA2) plays important roles in phospholipid metabolism, skin barrier maintenance, immune response and other processes in organisms. sPLA2 of sea cucumber A. japonicus (AjPLA2) has not yet been reported. This study successfully amplified the AjPLA2 sequence. The total cDNA of AjPLA2 is 931 bp, including a 480 bp ORF that encodes 159 amino acids. The AjPLA2 protein includes a 16-aa signal peptide, a 5-aa precursor peptide and a 138-aa mature peptide. Homologous alignment showed that AjPLA2 and the sPLA2s from starfish have the typical domains of the Group IB sPLA2. And additional amino acid sequences were found around the ß-Wing, which is different from the Group IB sPLA2. These results showed that AjPLA2 and sPLA2s from starfish all belong to a new group in the Group I sPLA2 family. AjPLA2 is widely distributed in sea cucumber tissues. The functional analysis also showed that AjPLA2 was upregulated in the intestine by feeding. When the body wall was damaged, it was significantly upregulated around the wound. And the expression levels of AjPLA2 were significantly increased in V. splendens-infected sea cucumbers. The results indicated that AjPLA2 plays roles in the sea cucumber immunologic process. Combined with the upregulation of unsaturated fatty acids (PUFAs) content in A. japonicus, it demonstrated that AjPLA2 could participate in the immune of A. japonicus by hydrolyzing phospholipid and releasing PUFAs. This study had a solid foundation for the further research of AjPLA2 gene function in vivo, development and application of AjPLA2 protein.

Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity. However, the precise mechanisms responsible for the combined impact of corona virus disease 2019 (COVID-19) and diabetes have not yet been elucidated, and effective treatment options for SARS-CoV-2-infected diabetic patients remain limited. To investigate the disease pathogenesis, K18-hACE2 transgenic (hACE2 Tg) mice with a leptin receptor deficiency (hACE2-Lepr -/-) or high-fat diet (hACE2-HFD) background were generated. The two mouse models were intranasally infected with a 5×10 5 median tissue culture infectious dose (TCID 50) of SARS-CoV-2, with serum and lung tissue samples collected at 3 days post-infection. The hACE2-Lepr -/- mice were then administered a combination of low-molecular-weight heparin (LMWH) (1 mg/kg or 5 mg/kg) and insulin via subcutaneous injection prior to intranasal infection with 1×10 4 TCID 50 of SARS-CoV-2. Daily drug administration continued until the euthanasia of the mice. Analyses of viral RNA loads, histopathological changes in lung tissue, and inflammation factors were conducted. Results demonstrated similar SARS-CoV-2 susceptibility in hACE2 Tg mice under both lean (chow diet) and obese (HFD) conditions. However, compared to the hACE2-Lepr +/+ mice, hACE2-Lepr -/- mice exhibited more severe lung injury, enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α, and increased apoptosis. Moreover, combined LMWH and insulin treatment effectively reduced disease progression and severity, attenuated lung pathological changes, and mitigated inflammatory responses. In conclusion, pre-existing diabetes can lead to more severe lung damage upon SARS-CoV-2 infection, and LMWH may be a valuable therapeutic approach for managing COVID-19 patients with diabetes.

Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet-Induced Adiposity.

Recent genetic evidence has linked WNT downstream mutations to fat distribution. However, the roles of WNTs in human obesity remain unclear. Here, the authors screen all Wnt-related paracrine factors in 1994 obese cases and 2161 controls using whole-exome sequencing (WES) and identify that 12 obese patients harbor the same mutations in RSPO1 (p.R219W/Q) predisposing to human obesity. RSPO1 is predominantly expressed in visceral fat, primarily in the fibroblast cluster, and is increased with adiposity. Mice overexpressing human RSPO1 in adipose tissues develop obesity under a high-fat diet (HFD) due to reduced brown/beige fat thermogenesis. In contrast, Rspo1 ablation resists HFD-induced adiposity by increasing thermogenesis. Mechanistically, RSPO1 overexpression or administration significantly inhibits adipocyte mitochondrial respiration and thermogenesis via LGR4-Wnt/ß-catenin signaling pathway. Importantly, humanized knockin mice carrying the hotspot mutation (p.R219W) display suppressed thermogenesis and recapitulate the adiposity feature of obese carriers. The mutation disrupts RSPO1's electrostatic interaction with the extracellular matrix, leading to excessive RSPO1 release that activates LGR4-Wnt/ß-catenin signaling and attenuates thermogenic capacity in differentiated beige adipocytes. Therefore, these findings identify that gain-of-function mutations and excessive expression of RSPO1, acting as a paracrine Wnt activator, suppress fat thermogenesis and contribute to obesity in humans.

Potential anti-gout properties of Wuwei Shexiang pills based on network pharmacology and pharmacological verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuwei Shexiang Pills (WWSX), a classic Tibetan medicine, consists of Chebulae Fructus (removed pit), Aucklandiae Radix, Moschus, Aconiti Fiavi Radix, and Acori Calami Rhizoma. It is used clinically in China to treat joint pain, swelling and other symptoms, and has the function of dispelling wind and relieving pain. However, to date, the mechanism of how it works against gout is still unclear. AIMS OF THE STUDY: Using network pharmacology, molecular docking and pharmacological verification to explore the potential anti-gout properties of WWSX. MATERIALS AND METHODS: With the use of UPLC-Q/TOF-MS, the main components of WWSX were obtained and screened for potential anti-inflammatory components by network pharmacology and molecular docking. The anti-inflammatory activity of the components screened from WWSX was also tested by in vitro assays. The anti-gout mechanism of WWSX was predicted by network pharmacology, and the pharmacological validation experiments using gouty arthritis model and mouse air pouch model were used to explore the multifaceted mechanism of WWSX to modify gout. RESULT: Thirty-eight active ingredients were obtained from the UPLC-Q/TOF-MS detection. The network pharmacology and molecular docking analysis showed that 104 co-targets were participated in the treatment of gout, and the main signaling pathways involved were NOD-like receptor pathway, NF-κB pathway and MAPK pathway. Pharmacological evaluation showed that WWSX could significantly improve gout in gouty arthritis models and mouse air pouch models by modulating the above pathways. CONCLUSION: This work has predicted and validated the anti-inflammatory material basis and predicted the anti-gout mechanism of WWSX which was verified by network pharmacology, molecular docking and in vitro cellular studies. The results reveal the mechanism of WWSX in the treatment of gout and provide a theoretical basis for its clinical application.

Chemotherapy-induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin.

BACKGROUND AND PURPOSE: Intravenous infusion of chemotherapy drugs can cause severe chemotherapy-induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear. EXPERIMENTAL APPROACH: RNA-sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein-5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone-marrow-derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN-induced CIP in vivo. The anti-CIP effect of aescin was evaluated, both in vivo and in vivo. KEY RESULTS: Here, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN-induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL-1ß. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis. CONCLUSION AND IMPLICATIONS: These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP.

Integrating network pharmacology and pharmacological validation to explore the effect of Shi Wei Ru Xiang powder on suppressing hyperuricemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Shi Wei Ru Xiang powder (SWR) is a traditional Tibetan medicinal formula with the effect of dispelling dampness and dispersing cold. In clinical practice, SWR is generally used for the treatment of hyperuricemia (HUA). However, its exact pharmacological mechanism remains unclear. AIMS OF THE STUDY: To preliminarily elucidate the regulatory effects and possible mechanisms of SWR on hyperuricemia using network pharmacology and experimental validation. MATERIALS AND METHODS: A mouse model of hyperuricemia was used to evaluate the alleviating effect of SWR on hyperuricemia. The major components of SWR were acquired by UPLC-Q/TOF-MS. The potential molecular targets and associated signaling pathways were predicted through network pharmacology. The mechanism of action of SWR in ameliorating hyperuricemia was further investigated by pharmacological evaluation. RESULTS: Mice with hyperuricemia and renal dysfunction were ameliorated by SWR. The 36 components of SWR included phenolic acids, terpenoids, alkaloids and flavonoids were identified. Network pharmacological analysis showed the involvement of the above compounds, and 115 targets were involved to treat hyperuricemia, involving multiple biological processes and different signaling pathways. Pharmacological experiments validated that SWR ameliorated hyperuricemic nephropathy in mice by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, nuclear factor kappaB (NF-κB) signaling pathway and NOD-like receptor signaling pathway. CONCLUSION: MAPK signaling pathway, NF-κB signaling pathway and NOD-like receptor signaling pathway play important roles in the therapeutic effects of SWR on hyperuricemia.

Surface charge changes in spike RBD mutations of SARS-CoV-2 and its variant strains alter the virus evasiveness via HSPGs: A review and mechanistic hypothesis.

With the COVID-19 pandemic continuing, more contagious SARS-CoV-2 variants, including Omicron, have been emerging. The mutations, especially those that occurred on the spike (S) protein receptor-binding domain (RBD), are of significant concern due to their potential capacity to increase viral infectivity, virulence, and breakthrough antibodies' protection. However, the molecular mechanism involved in the pathophysiological change of SARS-CoV-2 mutations remains poorly understood. Here, we summarized 21 RBD mutations and their human angiotensin-converting enzyme 2 (hACE2) and/or neutralizing antibodies' binding characteristics. We found that most RBD mutations, which could increase surface positive charge or polarity, enhanced their hACE2 binding affinity and immune evasion. Based on the dependence of electrostatic interaction of the epitope residue of virus and docking protein (like virus receptors or antibodies) for its invasion, we postulated that the charge and/or polarity changes of novel mutations on the RBD domain of S protein could affect its affinity for the hACE2 and antibodies. Thus, we modeled mutant S trimers and RBD-hACE2 complexes and calculated their electrotactic distribution to study surface charge changes. Meanwhile, we emphasized that heparan sulfate proteoglycans (HSPGs) might play an important role in the hACE2-mediated entry of SARS-CoV-2 into cells. Those hypotheses provide some hints on how SARS-CoV-2 mutations enhance viral fitness and immune evasion, which may indicate potential ways for drug design, next-generation vaccine development, and antibody therapies.

Dynamics, gene transfer, and ecological function of intracellular and extracellular DNA in environmental microbiome.

Extracellular DNA (eDNA) and intracellular DNA (iDNA) extensively exist in both terrestrial and aquatic environment systems and have been found to play a significant role in the nutrient cycling and genetic information transmission between the environment and microorganisms. As inert DNA sequences, eDNA is able to present stability in the environment from the ribosome enzyme lysis, therein acting as the historical genetic information archive of the microbiome. As a consequence, both eDNA and iDNA can shed light on the functional gene variety and the corresponding microbial activity. In addition, eDNA is a ubiquitous composition of the cell membrane, which exerts a great impact on the resistance of outer stress from environmental pollutants, such as heavy metals, antibiotics, pesticides, and so on. This study focuses on the environmental dynamics and the ecological functions of the eDNA and iDNA from the perspectives of environmental behavior, genetic information transmission, resistance to the environmental contaminants, and so on. By reviewing the status quo and the future vista of the e/iDNAs research, this article sheds light on exploring the ecological functioning of the e/iDNAs in the environmental microbiome.

Metagenomics reveals functional profiling of microbial communities in OCP contaminated sites with rapeseed oil and tartaric acid biostimulation.

Organochlorine pesticides (OCPs) contaminated sites pose great threats to both human health and environmental safety. Targeted bioremediation in these regions largely depends on microbial diversity and activity. This study applied metagenomics to characterize the microbial communities and functional groups composition features during independent or simultaneous rapeseed oil and tartaric acid applications, as well as the degradation kinetics of OCPs. Results showed that: the degradation rates of α-chlordane, ß-chlordane and mirex were better when (0.50% w/w) rapeseed oil and (0.05 mol L-1) tartaric acid were applied simultaneously than singular use, yielding removal rates of 56.4%, 53.9%, and 49.4%, respectively. Meanwhile, bio-stimulation facilitated microbial enzyme (catalase/superoxide dismutase/peroxidase) activity in soils significantly, promoting the growth of dominant bacterial communities. Classification at phylum level showed that the relative abundance of Proteobacteria was significantly increased (p < 0.05). Network analysis showed that bio-stimulation substantially increased the dominant bacterial community's proportion, especially Proteobacteria. The functional gene results illustrated that bio-stimulation facilitated total relative abundance of degradation genes, phosphorus, carbon, nitrogen, sulfur metabolic genes, and iron transporting genes (p < 0.05). In metabolic pathways, functional genes related to methanogenesis and ammonia generation were markedly upregulated, indicating that bio-stimulation promoted the transformation of metabolic genes, such as carbon and nitrogen. This research is conducive to exploring the microbiological response mechanisms of bio-stimulation in indigenous flora, which may provide technical support for assessing the microbial ecological remediation outcomes of bio-stimulation in OCP contaminated sites.

Risk factors for massive hemorrhage during the treatment of cesarean scar pregnancy: a systematic review and meta-analysis.

PURPOSE: Cesarean scar pregnancy (CSP) is one of the serious complications associated with cesarean delivery (CD). This meta-analysis aims to identify risk factors associated with massive hemorrhage during the CSP treatment. METHODS: Eight electronic databases were searched for case-control studies published before December 31th, 2018, which compared the possible factors causing massive bleeding during the CSP treatment. Quantitative synthesis was performed by RevMan 5.3. Sensitivity analysis and publication bias were performed by Stata 12.0. RESULTS: Total 20 case - control studies including 3101 CSP patients with previous CD met the inclusion criteria. Bleeding group had 573 patients and the control group had 2528 patients. The risk factors for massive bleeding during CSP treatment included multiple gravidities (MD = 0.15, 95% CI 0.03-0.28, P = 0.73), big maximum diameter of gestation sac (MD = 18.49 mm, 95%CI 15.34-21.65, P < 0.01), high gestational days (MD = 8.98 days, 95% CI 4.12-13.84, P < 0.01), high ß-HCG level (MD = 21.39 IU/ml, 95% CI 7.36-35.41, P = 0.03; MD = 3.02 U/ml, 95% CI 0.21-5.84, P < 0.01) and rich blood flow around the lesion (OR = 6.73, 95% CI 3.93-11.51, P = 0.59). While, thick myometrium (MD = - 4.94 mm, 95% CI - 6.12 to - 3.75, P < 0.01) may be protective factor. CONCLUSIONS: Multiple gravidities, big gestation sac, large gestational days, high serum ß-HCG level, abundant blood supply to pregnancy sac and thin myometrium maybe the risk factors for massive bleeding during the CSP treatment.

Characterization and ecological function of bacterial communities in seabed sediments of the southwestern Yellow Sea and northwestern East China Sea, Western Pacific.

The marine ecosystems of the marginal seas of the Western Pacific region are frequently disturbed by terrigenous materials. It is of great significance to investigate the ecological functioning of these marine areas, which can be well understood by exploring the microbial communities of sediments. However, the geographical distribution, composition, and genetic functions of sedimentary bacterial communities of the Yellow Sea and East China Sea (YEC Seas) are poorly understood. In this work, sediment samples were collected from YEC Sea areas to investigate bacterial communities by high-throughput sequencing. A total of 1960 genera were determined, with Proteobacteria being the dominant phylum (45.03%), followed by Planctomycetes, Bacteroidetes, Acidobacteria, and Chloroflexi. Correlation analysis indicates that the bacterial composition is influenced by environmental factors, including pressure, depth, seawater density, salinity, organic matter content, nutrient, and heavy metal. Approximately 178 metabolism pathways annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were detected in the bacterial communities, including ones for nutrient metabolism (C, 3.04%; S, 0.70%; N, 0.52%; and P, 0.22%) and exogenous pollutant metabolism (e.g., polycyclic aromatic hydrocarbons (PAHs), chlorobenzene, and benzoate; up to 4.97%). The results demonstrate that the abundant bacterial communities in the sediments of the YEC Seas are important for maintaining marine ecological functioning, especially for elemental biogeochemical cycling and exogenous pollutant transformation.

Osteobiography of a seventh-century potter at the Oupan kiln, China by osteological and multi-isotope approach.

In recent years, the reconstruction of individual life history by the multi-isotope analysis of different skeletal elements has become an active topic in bioarchaeological field. However, most studies focus on the persons with high social status and none cares for craftsmen with low social status. In this study, we undertook a comprehensive analysis on a human skeleton buried in the Oupan kiln, Anhui, China to recover his osteobiography. The archaeological context and dating result (534-644 cal. AD) indicate that he might be a potter at the kiln during the Sui and early Tang Dynasty, characteristic of low social hierarchy. The osteological investigation suggests that he had abnormal vertebrae related to long-term physical labor. In general, the isotopic data demonstrate that he mainly consumed C3(wheat, beans)/C4(millets)-based terrestrial foods. The isotopic (C, N) profiles of dentin sections and isotopic data (C, O) of bone apatite and teeth enamel indicate that he had experienced dramatic dietary changes and/or several migrations throughout the childhood and adulthood. His turbulent life trajectory was highly relevant to his identity and low social status. Our study provides a pilot insight into the life history of craftsmen who was generally overlooked in archaeological, historic and anthropological research.

A review of bacteriophage therapy for pathogenic bacteria inactivation in the soil environment.

The emerging contamination of pathogenic bacteria in the soil has caused a serious threat to public health and environmental security. Therefore, effective methods to inactivate pathogenic bacteria and decrease the environmental risks are urgently required. As a century-old technique, bacteriophage (phage) therapy has a high efficiency in targeting and inactivating pathogenic bacteria in different environmental systems. This review provides an update on the status of bacteriophage therapy for the inactivation of pathogenic bacteria in the soil environment. Specifically, the applications of phage therapy in soil-plant and soil-groundwater systems are summarized. In addition, the impact of phage therapy on soil functioning is described, including soil function gene transmission, soil microbial community stability, and soil nutrient cycling. Soil factors, such as soil temperature, pH, clay mineral, water content, and nutrient components, influence the survival and activity of phages in the soil. Finally, the future research prospects of phage therapy in soil environments are described.

Metaphire guillelmi gut as hospitable micro-environment for the potential transmission of antibiotic resistance genes.

Earthworm gut played an important role in the transformation of various contaminants in the soil environments. With the increasing application of organic fertilizer recently, the ingestion of antibiotics, antibiotic resistance bacteria (ARB), and antibiotic resistance genes (ARGs) made the earthworm gut a potential favorable micro-environment for the transmission of ARGs in the soil. In this work, the conventional plate incubation and high-throughput sequencing methods were both employed to investigate the composition of the cultivable and overall ARB/ARGs in the Metaphire guillelmi earthworm gut. A total of 87 cultivable isolates that resisted tetracycline (TC) and/or sulfadiazine (SD) were obtained, most of which belonged to phylum Firmicutes, genus Bacillus. Meanwhile, the counts of isolates with TC-SD dual resistance were higher than those with sole SD or TC resistance. Moreover, higher ARB counts and diversity were detected in the earthworm gut by high-throughput sequencing technique than those by the classical plate cultivation. Overall, the combination of conventional cultivable bacteria isolation and high-throughput sequencing methods provided a comprehensive understanding of the ARB composition in the earthworm gut. The results demonstrate that the earthworm gut is a hospitable micro-environment for ARB colonization. The potential role of earthworm intestinal ARB and ARGs proliferation in soil environments warrants further research.

Comparing polyvalent bacteriophage and bacteriophage cocktails for controlling antibiotic-resistant bacteria in soil-plant system.

Antibiotic resistant pathogenic bacteria (ARPB) residual in soil-plant system has caused serious threat against public health and environmental safety. Being capable of targeted lysing host bacteria, phage therapy has been proposed as promising method to control the ARPB contamination in environments. In this study, microcosm trials were performed to investigate the impact of various phage treatments on the dissipation of tetracycline resistant Escherichia coli K-12 and chloramphenicol resistant Pseudomonas aeruginosa PAO1 in soil-carrot system. After 70 days of incubation, all the four phage treatments significantly decreased the abundance of the pathogenic bacteria and the corresponding antibiotic resistance genes (tetW and cmlA) in the soil-carrot system (p < 0.05), following the order of the cocktail phage treatment (phages ΦYSZ1 + ΦYSZ2) > the polyvalent phage (ΦYSZ3 phage with broad host range) treatment > host-specific phage (ΦYSZ2 and ΦYSZ1) treatments > the control. In addition, the polyvalent phage treatment also exerted positive impact on the diversity and stability of the bacterial community in the system, suggesting that this is an environmentally friendly technique with broad applications in the biocontrol of ARPB/ARGs in soil-plant system.

Biochar combined with polyvalent phage therapy to mitigate antibiotic resistance pathogenic bacteria vertical transfer risk in an undisturbed soil column system.

The vertical migration of antibiotic resistance pathogenic bacteria (ARPB) and antibiotic resistance genes (ARGs) in the surface soil-vadose soil system has become a new threat to ecological safety and public health; there is an imperative need to develop an efficient technique for targeted control and inactivation of ARPB in these systems. In this work, undisturbed soil columns (0 ∼ -5 m) were constructed to investigate the impact of biochar amendment or/and polyvalent bacteriophage (ΦYSZ-KK) therapy on the vertical control and inactivation of tetracycline-resistant Escherichia coli K-12 and chloramphenicol-resistant Klebsiella pneumonia K-6. The simultaneous application of polyvalent phage and biochar impeded the vertical migration of ARPB from the top soil to lower soil layers and stimulated the ARPB dissipation in the soil column. After 60-day incubation, levels of ARPB and ARGs decreased significantly in the soil column by magnitudes of 2-6. Additionally, high throughput sequencing indicated that the simultaneous application of biochar and phage clearly maintained the structure and diversity of the soil microbial communities (p < 0.05). This work therefore demonstrates that the application of a biochar/phage combination is an environmentally friendly, efficacious measure for the control and inactivation of ARPB/ARGs in vertical soil column systems.

Targeted inactivation of antibiotic-resistant Escherichia coli and Pseudomonas aeruginosa in a soil-lettuce system by combined polyvalent bacteriophage and biochar treatment.

High abundances of antibiotic-resistant pathogenic bacteria (ARPB) and antibiotic resistance genes (ARGs) in agricultural soil-plant systems have become serious threats to human health and environmental safety. Therefore, it is crucial to develop targeted technology to control existing antibiotic resistance (AR) contamination and potential dissemination in soil-plant systems. In this work, polyvalent bacteriophage (phage) therapy and biochar amendment were applied separately and in combination to stimulate ARPB/ARG dissipation in a soil-lettuce system. With combined application of biochar and polyvalent phage, the abundance of Escherichia coli K-12 (tetR) and Pseudomonas aeruginosa PAO1 (ampR + fosR) and their corresponding ARGs (tetM, tetQ, tetW, ampC, and fosA) significantly decreased in the soil after 63 days' incubation (p < 0.05). Similar results for endophytic K-12 and PAO1, and ARGs, were also obtained in lettuce tissues following combined treatment. Additionally, high throughput sequencing revealed that biochar and polyvalent phage synergetically improved the structural diversity and functional stability of the indigenous bacterial communities in soil and the endophytic ones in lettuce. Hence, this work proposes a novel biotechnology that combines biochar amendment and polyvalent phage therapy to achieve targeted inactivation of ARPB, which stimulates ARG dissipation in soil-lettuce systems.

'Agricultural Waste to Treasure' - Biochar and eggshell to impede soil antibiotics/antibiotic resistant bacteria (genes) from accumulating in Solanum tuberosum L.

Soil contamination with antibiotics and antibiotic resistant bacteria/genes (ARB/ARGs) has becoming an emerging environmental problem. Moreover, the mixed pollutants' transfer and accumulation from soil to tuberous vegetables has posed a great threat against food security and human health. In this work, the application of two absorbing materials (maize biochar and sulfate modified eggshell) was able to reduce the poisonous effect of soil antibiotics on potato root system by stimulate the dissipation of water-soluble antibiotics in soil; and also improve food quality by increasing potato starch, protein, fat, and vitamins. Meanwhile, both amendments could effectively decrease the classes and the accumulative abundance of ARB and ARGs (sulI, sulII, catI, catII, ermA, ermB) in the edible parts of potato. The lowest abundance of ARGs was detected in the biochar application treatment, with the accumulative ARG level of 8.9 × 102 and 7.2 × 102 copies mL-1 in potato peel (sull + catI + ermA) and tuberous root (sulI), respectively. It is the first study to demonstrate the feasibility of biochar and eggshell derived from agricultural wastes as green absorbing materials to reduce soil antibiotic, ARB, and ARGs accumulation risk in tuberous vegetable.

Treatment of Ureteral Fibroepithelial Polyp by Ureteroscopy Combined with Holmium Laser or Thulium Laser: A Retrospective Study.

BACKGROUND AND OBJECTIVE: Ureteral fibroepithelial polyps (UFPs) are rare benign tumors and ureteroscopy has been used for treatment. We compared the effect of UFP by ureteroscopy combined with holmium laser or thulium laser. METHODS: Twenty-five patients with UFPs were treated in our hospital between May 2003 and April 2013. All patients received ultrasound check and intravenous urography (IVU). We performed ureteroscopy operation and found ureteral polyps, so we resected the polyps with holmium laser (12 cases) or thulium laser (13 cases). During the 3-year follow-up, all patients received IVU 2 or 3 months after the double-J stent was removed, and ultrasonic checks every 3-6 months after that. RESULTS: All patients had UFPs resected. Three patients in the holmium laser group had ureteral perforation during operation, and four patients in the holmium laser group developed ureterostenosis. No patients in thulium laser group experienced any severe complications during the procedure. Further, during follow-up, there was no indication of an increase of hydronephrosis in any patients. These findings lead to conclude there were no developments of ureterostenosis nor an experience of any reoccurrence in thulium laser group. CONCLUSIONS: Ureteroscopy operations, combined with holmium or thulium laser resection, are effective methods for treating UFP, but thulium laser does better in reducing the incidence of ureterostenosis.