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Abstract Background Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC. Methods We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC. Results In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi. Conclusion For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.

Multi-energy fields provide higher dimensional precision control and desirable performance for microforming processes. The constitutive model under low strain level was established to describe the coupled effect of pulsed current and ultrasonic vibration based on the Kocks-Mecking (K-M) model. Combined with the crystallographic theory, the model introduced acoustic softening effect and electroplastic effect, and described the interaction between pulsed current and ultrasonic vibration under coupled field from the perspective of energy absorption. In the research, the uniaxial tensile test of Inconel 718 sheet with thickness of 0.3 mm was carried out. The ranges of the current density and ultrasonic energy density were 20.9–50.9 A mm−2 and 15.84–57.64 J cm−3, respectively. The results showed that: the facilitation of ultrasonic vibration on dislocation generation was limited with the increase of strain, and the energy generated by ultrasonic vibration was more reflected in the change of Helmholtz free energy; when the energy generated by the current at athermal condition tended to be saturated, the increase of heat became the key to improve the electroplasticity, and the heating model caused by Joule heating effect was established. The constitutive model of coupling electric pulse and ultrasonic treatment was established, combining the characteristics of ultrasonic vibration and pulsed current; the flow stress was described by using the parameters of ultrasonic energy density and current density; The trigonometric function was used to quantitatively describe the competitive relationship between ultrasonic vibration and pulsed current in external work. Two sets of experiments were used to demonstrate the reliability of the model.

It has been known for decades that the formability of metal sheets can be improved effectively by electrically-assisted (EA) forming. However, it remains controversial as to the detailed mechanisms and the manifestation of electrical effects can vary in different materials. In this paper, the EA flow behavior and mechanism of a precipitation hardened AA7075-T6 were studied. The term “electric current density sensitivity” (ECDS) was introduced to describe the athermal effect. The results show that Joule heating is the main influence factor, while the athermal effect varies with the electric–thermal parameters. Here, we report an anomalous negative electric current sensitivity in AA7075-T6, i.e. the flow stress increases with current density under the same temperature and strain rate when the temperature is ≤ 150 °C and strain rate is ≥ 0.005/s. The above phenomena are attributed to the local Joule heating and promoted atom diffusion under the action of the current, leading to the dissolution of GPZ, the formation of fine precipitate and Cr segregation-induced vacancies. Further, an extended dislocation density based constitutive model was proposed to cover the ECDS and softening effect, which could predict the flow behavior of 7075-T6 under EA forming, including the negative electric current sensitivity. The above work provides a viable method to simultaneously control both the shape and performance of the metal part. Meanwhile, the corresponding mechanism shed new light into the understanding of electroplasticity.

Objectively evaluating and defining territorial spatial functions are important prerequisites for optimizing the use of territorial space. However, the results of the evaluation of functions at different levels may differ significantly. How to integrate the evaluation results and guide the spatial utilization at different levels more effectively is worth exploring. This study takes as the research area Yibin City, China, a node city along the Yangtze River in the upper reaches of the Yangtze River. In the study, 185 towns in that city were taken as the primary evaluation units for an indicator system of territorial spatial function constructed on the basis of multivariate data. Research methods such as the entropy method and cluster analysis were adopted to do multilevel evaluations and zoning of territorial spatial functions in Yibin City. The results suggest the following: 1) The distribution of agricultural production, rural living, and ecological regulation functions among the second-level production-living-ecological (PLE) functions of townships were relatively balanced in Yibin City. The production function of industry and mining, urban life function, and ecological product supply function showed spatial directivity. 2) The evaluation results of the first-level PLE functions of townships showed that the areas with substantial PLE functions accounted for approximately 20%, whereas the areas with insignificant functions accounted for approximately 80%, which reflected the “80/20 rule” of spatial functions. 3) In accordance with the cluster analysis of the multilevel evaluation results, the township functions in Yibin were divided into 5 functional areas: urban life-industrial production advantage areas (12%), urban life-rural life advantage areas (8%), rural life-agricultural production-ecological function product supply advantage areas (29%), rural life-agricultural production-ecological service function advantage areas (20%), and ecological service function-agricultural production function advantage areas (31%). 4) In the future, Yibin City should focus on 20% of the significant functional areas and attach importance to the relativity of spatial functions to form a high-quality territorial spatial protection and development pattern. Based on the objectives and requirements of the new territorial spatial planning in China, this study reconstructed the municipal territorial spatial functional areas through a multilevel functional evaluation, which has theoretical and practical significance for forming a new pattern of territorial spatial development and use with joint production, living, and ecological functions.

Context Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) is a compound preparation commonly used for treating cerebral ischaemia/reperfusion injury in ischaemic stroke in China. However, its potential mechanisms on ischaemic stroke remain unknown. Objective This study explores the potential mechanisms of Xingxiong injection in vivo or in vitro. Materials and methods Sprague-Dawley (SD) rats were randomly assigned to five groups: the sham (normal saline), the model (normal saline) and the Xingxiong injection groups (12.5, 25 or 50 mL/kg). The rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 14 d. Xingxiong injection was administered via intraperitoneal (i.p.) injection immediately after ischaemia induction for 14 d. Afterwards, rats were sacrificed at 14 d induced by administration of Xingxiong injection. Results Xingxiong injection significantly reduces infarct volume (23%) and neurological deficit scores (93%) compared with the MCAO/R group. Additionally, Xingxiong injection inhibits the loss in mitochondrial membrane potential (43%) and reduces caspase-3 level (44%), decreases NOX (41%), protein carbonyl (29%), 4-HNE (40%) and 8-OhdG (41%) levels, inhibits the expression of inflammatory factors, such as TNF-α (26%), IL-1β (34%), IL-6 (39%), MCP-1 (36%), CD11a (41%) and ICAM-1 (43%). Moreover, Xingxiong injection can increase p-Akt/Akt (35%) and Nrf2 (47%) protein expression and inhibit NLRP3 (42%) protein expression. Conclusions Xingxiong injection prevents cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome. These findings provide experimental evidence for clinical use of drugs in the treatment of ischaemic stroke.

ABSTRACT Klebsiella pneumoniae, a pathogen of critical clinical concern, urgently demands effective therapeutic options owing to its drug resistance. Polymyxins are increasingly regarded as a last-line therapeutic option for the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, polymyxin resistance in K. pneumoniae is an emerging issue. Here, we report that gallium nitrate (GaNt), an antimicrobial candidate, exhibits a potentiating effect on colistin against MDR K. pneumoniae clinical isolates. To further confirm this, we investigated the efficacy of combined GaNt and colistin in vitro using spot dilution and rapid time-kill assays and growth curve inhibition tests and in vivo using a murine lung infection model. The results showed that GaNt significantly increased the antimicrobial activity of colistin, especially in the iron-limiting media. Mechanistic studies demonstrated that bacterial antioxidant activity was repressed by GaNt, as revealed by RNA sequencing (RNA-seq), leading to intracellular accumulation of reactive oxygen species (ROS) in K. pneumoniae, which was enhanced in the presence of colistin. Therefore, oxidative stress induced by GaNt and colistin augments the colistin-mediated killing of wild-type cells, which can be abolished by dimethyl sulfoxide (DMSO), an effective ROS scavenger. Collectively, our study indicates that GaNt has a notable impact on the antimicrobial activity of colistin against K. pneumoniae, revealing the potential of GaNt as a novel colistin adjuvant to improve the treatment outcomes of bacterial infections. IMPORTANCE This study aimed to determine the antimicrobial activity of GaNt combined with colistin against Klebsiella pneumoniae in vitro and in vivo. Our results suggest that by combining GaNt with colistin, antioxidant activity was suppressed and reactive oxygen species accumulation was induced in bacterial cells, enhancing antimicrobial activity against K. pneumoniae. We found that GaNt functioned as an antibiotic adjuvant when combined with colistin by inhibiting the growth of multidrug-resistant K. pneumoniae. Our study provides insight into the use of an adjuvant to boost the antibiotic potential of colistin for treating infections caused by multidrug-resistant K. pneumoniae.

Background: RAR-related orphan receptor C (RORC) plays an important role in autoimmune responses and inflammation. However, its function in cancer immunity is still unclear. Its potential value in cancer immunotherapy (CIT) needs to be further studied.Methods: Expression and clinical data for 33 cancers were obtained from UCSC-Xena. The correlation between RORC expression and clinical parameters was analyzed using the limma software package to assess the prognostic value of RORC. Timer2.0 and DriverDBv3 were used to analyze the RORC mutation and methylation profiles. RORC-associated signaling pathways were identified by GSEA. The correlations of RORC expression with tumor microenvironment factors were further assessed, including immune cell infiltration (obtained by CIBERSORT) and immunomodulators (in pancancer datasets from the Tumor-Immune System Interactions and Drug Bank [TISIDB] database). In addition, the correlations of RORC with four CIT biomarkers (tumor mutational burden, microsatellite instability, programmed death ligand-1, and mismatch repair) were explored. Furthermore, three CIT cohorts (GSE67501, GSE168204, and IMvigor210) from the Gene Expression Omnibus database and a previously published study were used to determine the association between RORC expression and CIT response.Results: RORC was differentially expressed in many tumor tissues relative to normal tissues (20/33). In a small number of cancers, RORC expression was correlated with age (7/33), sex (4/33), and tumor stage (9/33). Furthermore, RORC expression showed prognostic value in many cancers, especially in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and mesothelioma (MESO). The mutation rate of RORC in most cancer types was low, while RORC was hypermethylated or hypomethylated in multiple cancers. RORC was associated with a variety of biological processes and signal transduction pathways in various cancers. Furthermore, RORC was strongly correlated with immune cell infiltration, immunomodulators, and CIT biomarkers. However, no significant association was found between RORC and CIT response in the three CIT cohorts.Conclusion Our findings revealed the potential immunotherapeutic value of RORC for various cancers and provides preliminary evidence for the application of RORC in CIT.