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We delve into the critical role of the gut microbiota and its metabolites in the pathogenesis and progression of hepatobiliary and pancreatic (HBP) cancers, illuminating an urgent need for breakthroughs in diagnostic and therapeutic strategies. Given the high mortality rates associated with HBP cancers, which are attributed to aggressive recurrence, metastasis, and poor responses to chemotherapy, exploring microbiome research presents a promising frontier. This research highlights how microbial metabolites, including secondary bile acids, short-chain fatty acids, and lipopolysaccharides, crucially influence cancer cell behaviors such as proliferation, apoptosis, and immune evasion, significantly contributing to the oncogenesis and progression of HBP cancers. By integrating the latest findings, we discuss the association of microbial alterations with HBP cancers, key metabolites, and their implications, and how metabolomics and microbiomics can enhance diagnostic precision. Furthermore, the paper explores strategies for targeted therapies through microbiome metabolomics, including the direct therapeutic effects of microbiome metabolites and potential synergistic effects on conventional therapies. We also recognize that the field of microbial metabolites for the diagnosis and treatment of tumors still has a lot of problems to be solved. The aim of this study is to pioneer microbial metabolite research and provide a reference for HBP cancer diagnosis, treatment, and prognosis.

Abstract Structural annotation of small molecules in tandem mass spectrometry has always been a central challenge in mass spectrometry analysis, especially using a miniaturized mass spectrometer for on-site testing. Here, we propose the Transformer enabled Fragment Tree (TeFT) method, which combines various types of fragmentation tree models and a deep learning Transformer module. It is aimed to generate the specific structure of molecules de novo solely from mass spectrometry spectra. The evaluation results on different open-source databases indicated that the proposed model achieved remarkable results in that the majority of molecular structures of compounds in the test can be successfully recognized. Also, the TeFT has been validated on a miniaturized mass spectrometer with low-resolution spectra for 16 flavonoid alcohols, achieving complete structure prediction for 8 substances. Finally, TeFT confirmed the structure of the compound contained in a Chinese medicine substance called the Anweiyang capsule. These results indicate that the TeFT method is suitable for annotating fragmentation peaks with clear fragmentation rules, particularly when applied to on-site mass spectrometry with lower mass resolution.

Objective: This study aimed to analyse the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and 25-hydroxy-vitamin D (25[OH]D) and early diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) and evaluate the potential roles of these two biomarkers in the clinical diagnosis of DKD. Methods: A total of 422 inpatients with T2DM were retrospectively enrolled between January 2018 and March 2022 at the First Affiliated Hospital of Nanjing Medical University. The baseline clinical parameters of each patient were determined, and their demographic characteristics were extracted from the hospital information system. The patients were separated into groups according to serum Lp-PLA2 and 25(OH)D levels and binary logistic regression analysis was used to determine independent predictors of early DKD incidence. Results: Levels of Lp-PLA2 significantly increased and those of 25(OH)D significantly decreased with DKD progression (both P

Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drugs can alleviate or prevent the effects of CRAB infections, shorten hospital stays, and reduce patient mortality.

Programmed death-1 (PD-1) acts as a T cell checkpoint and is important in controlling T cell exhaustion. Blocking the intercommunication across PD-1 and PD-L1 is promising for advanced lung cancer treatment. However, the response rate requires being strengthened. This study aimed to determine whether the combination treatment of Qingfei mixture (QFM) and PD-1 inhibitor could improve the sensitivity of monoclonal antibody by regulating STAT1/IDO1-mediated tryptophan (Trp)-kynurenine (Kyn) pathway. The in vivo imaging system, immunofluorescence, hematoxylin-eosin staining, TUNEL, flow cytometry, HPLC, and ELISA were used to estimate the anti-tumor effects in LLC-luc tumor-bearing C57BL/6 mice treated with QFM, PD-1 inhibitor, 2-NP (enhancer of STAT1 transcription), and FICZ (AhR agonist) alone or in combination. IFN-γ-mediated A549 and LLC cells were treated with QFM-containing serum and fludarabine (FLU, STAT1 inhibitor), and cell viability, apoptosis, and Kyn content were then evaluated using CCK-8 assays, flow cytometry, and HPLC assays, respectively. Additionally, the expressions of STAT1, IDO1, AhR, NFATc1, TRIP12, PD-1, and PD-L1 were measured in vivo and in vitro. We found QFM increased the anti-cancer actions of PD-1 inhibitors by increasing the CD8+IFNγ+ T cells infiltration and decreasing the ratio of Kyn/Trp. Besides, QFM-containing serum suppressed the proliferation and promoted apoptosis in A549 and LLC cells, meanwhile, FLU boosted the effects of QFM-containing serum. Moreover, the suppression of tumor growth in the combination therapy was attenuated in the mice receiving 2-NP or FICZ. The occurrence of the above results was accompanied by a decrease in STAT1, IDO1, AhR, PD-1, and PD-L1 expressions. Collectively, the findings suggested that QFM may increase the influences of PD-1 inhibitors at least partially by blocking the STAT1/IDO1-mediated tryptophan-kynurenine pathway in lung cancer.

Purpose: Murine models of pancreatic cancer with damp-heat syndrome were established based on two methods to explore the differences in the composition of intestinal flora and to seek characteristic genera with potential for model evaluation. Methods: In our study, thirty-four C57BL/6J male mice were randomly divided into a control group (Con), a model group (Mod), a classic damp-heat syndrome group (CDHS), and a climate-chamber group (CC). CDHS and CC groups were fed with a high-fat diet and glucose water, while the CDHS group was given 2.4 g/kg alcohol by gavage for 10 days, and the CC group was placed in a climatic chamber with a set temperature of (32 ± 1) °C and humidity of (92 ± 2)% for 10 days. The Mod group, CDHS group, and CC group underwent tumor-building experiments on day 11. Tumorigenicity was then assessed twice a week. After 4 weeks, feces, colon tissue, and tumor tissue were taken from the mice and were tested, and the mice were euthanized afterwards. Results: Mice in the CDHS and CC groups showed symptoms similar to the clinical damp-heat syndrome observed in traditional Chinese medicine (TCM), and exhibited a worse general condition and more rapid tumor growth trend than those in the Mod group. The pathological examination indicated that inflammation was prevalent in the CDHS and CC groups. Both groups had a disrupted intestinal barrier and an overgrowth of pathogenic bacteria such as c_Gammaproteobacteria, o_Enterobacteriales, and g_Bacteroides. Their microbiota composition showed greater diversity. Conclusions: Intestinal flora may have a promising future in the discovery of indicators for evaluating a model of damp-heat syndrome in pancreatic cancer.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Background: Information on the relation of air pollution with non-alcoholic fatty liver disease (NAFLD) is scarce. We thus conducted a large cross-sectional study in Asia to investigate the role of air pollution in NAFLD. Methods: We recruited 329,048 adults (mean age: 41.0 years) without other liver disease (hepatitis and cirrhosis) or excessive alcohol consumption in Taiwan and Hong Kong from 2001 to 2018. The concentrations of nitrogen dioxide (NO2) and ozone (O3) were estimated using a space–time regression model, and the concentrations of fine particulate matter (PM2.5) was evaluated using a satellite-based spatio-temporal model. NAFLD was determined using either the fatty liver index (FLI) or the hepatic steatosis index (HSI). The NAFLD-related advanced fibrosis was defined according to BARD score or the fibrosis-4 (FIB-4). A logistic regression model was adopted to explore the relationships of ambient air pollution with the odds of NAFLD and NAFLD-related advanced fibrosis. Results: We found positive relationships between PM2.5 and the odds of NAFLD and advanced fibrosis, with every standard deviation (SD, 7.5 µg/m3) increases in PM2.5 exposure being associated with a 10% (95% confidence interval [CI]: 9%–11%) increment in the prevalence of NAFLD and an 8% (95% CI: 7%–9%) increment in the prevalence of advanced fibrosis. Similarly, the prevalence of NAFLD and advanced fibrosis increased by 8% (95% CI: 7%–9%) and 7% (95% CI: 6%–8%) with per SD (18.9 µg/m3) increasement in NO2 concentration, respectively. Additionally, for every SD (9.9 µg/m3) increasement in O3 concentration, the prevalence of NAFLD and advanced fibrosis decreased by 12% (95% CI: 11%–13%) and 11% (95% CI: 9%–12%), respectively. Conclusion: Higher ambient PM2.5 and NO2 are linked with higher odds of NAFLD and advanced fibrosis. Our findings indicate that reducing PM2.5 and NO2 concentrations may be an effective way for preventing NAFLD. Further studies on O3 are warranted.

The ocean environment has enormous uncertainty due to the influence of complex waves and undercurrents. The human beings are limited in their abilities to detect and utilize marine resources without powerful tools. Soft robots employ soft materials to simplify the complex mechanical structures in rigid robots and adapt their morphology to the environment, making them suitable for performing some challenging tasks in place of manual labor. Due to superior flexible and deformable bodies, underwater soft robots have played significant roles in numerous applications in recent decades. Meanwhile, various technical challenges still need to be tackled to ensure the reliability and practical performance of underwater soft robots in complicated ocean environment. Nowadays, some researchers have developed underwater soft robotic systems based on biomimetics and other disciplines, aiming at comprehensive exploration of ocean and appropriate utilization of unexploited resources. This review presents the recent advances of underwater soft robots in the aspects of intelligent soft materials, fabrication, actuation, locomotion patterns, power storage, sensing, control, and modeling; additionally, the existing challenges and perspectives are analyzed as well.

In this paper, the video retrieval technique based on model migration makes full use of the migration learning technique to build a text encoder and video encoder to obtain text and video features. The text is preprocessed based on the BERT model, and text features are extracted by combining TF-IDF and mutual information. The logistic regression algorithm is applied to achieve text classification. The text mining techniques above are used to parse YouTube Chinese learning resources to extract their dissemination features. The results show that 5,286 (61.48%) of YouTube Chinese learning resources are from the category of “education,” and 2,294 (26.68%) are from the category of “people and blogs.” The video resources category is the most popular and loved category among learners due to its highest average number of views (1238214.3). The dissemination is significantly impacted by teachers’ performance, vivid language, and interaction during the teaching process. The indirect effect value test between online interaction, technical support, and resource quality, as well as satisfaction and intention to continue using, met the criterion of significance (p

IntroductionPsychological evaluation is required by insurance companies in the United States prior to proceeding with a spinal cord stimulation or a dorsal root ganglion stimulation trial. Since January 2017, we implemented a Multidisciplinary Team Conference for Neuromodulation in our center to facilitate the collaboration between pain physicians and psychologists and to optimize screening of neuromodulation candidates. This study aims to report the impact of this team conference on improvement of neuromodulation outcome in our center.MethodsAppropriateness of neuromodulation were discussed in the team conference after initial visit with the pain specialist and psychological evaluation. For this study, we prospectively and retrospectively collected data on neuromodulation candidates who went through the team conference and those who did not as controls.ResultsWe discussed 461 patients in the team conference sessions from January 2017 to July 2023. Out of these, a spinal cord stimulator or a dorsal root ganglion stimulator trial was performed in 164 patients with 80.5% (132 cases) trial success rate leading to 140 implants. Out of these implants, 26 (18.6%) explanted and 21 (15%) required revision in 41 (29.3%) patients. We performed neuraxial neuromodulation trial for 70 patients without going through the team conference from January 2016 to July 2023 with a trial success rate of 45.7% (32 cases). In this group, 7 (21.9%) and 6 (18.8%) patients underwent explant and revision. The differences between the groups were statistically significant for trial success rate (odds ratio of 4.9 with p-value of

Conventional water and fertilizer management practices have led to elevated greenhouse gas emissions from rice fields and decreased the efficiency of water and fertilizer utilization in agricultural land. The implementation of water-saving irrigation and the substitution of chemical fertilizers with organic alternatives can influence CH4 and N2O emissions in rice fields. However, it remains unclear how the simultaneous application of both methods will affect the CH4 and N2O emissions in rice fields. Therefore, two irrigation methods (F: flooded irrigation; C: controlled irrigation) and three fertilization modes (A: full chemical fertilizer; B: bio-organic fertilizer replacing 15% chemical nitrogen fertilizer; C: bio-organic fertilizer replacing 30% chemical nitrogen fertilizer) were set up through field experiments to explore the effect of greenhouse gas emission reduction in rice fields by combining controlled irrigation and bio-organic fertilizers. Substituting some chemical fertilizers with bio-organic fertilizers can lower the peak CH4 and N2O fluxes in rice fields, leading to a decrease in the cumulative CH4 and N2O emissions by 11.9~29.7% and 10.8~57.3%, respectively. The reductions led to a considerable decrease in the global warming potential (GWP) and the greenhouse gas emission intensity (GHGI) by 16.1~48.1% and 16.3~48.1%, respectively. Controlled irrigation significantly reduced CH4 emissions by 55.2~69.4% compared with flooded irrigation in rice fields. However, it also increased N2O emissions by 47.5~207.9%, considerably reducing their GWPs by 11.8~45.5%. Neither bio-organic fertilizer substitution nor controlled irrigation significantly affected rice yield. Replacing 15% of chemical nitrogen fertilizers with bio-organic fertilizers in controlled irrigation rice fields can minimize rice GWP and GHGI. The study’s results are of significant importance for enhancing the regulation of greenhouse gases in farmland and achieving sustainable agriculture through cleaner production.

Inspired by the work Zhong et al. (2018), we study the linear tensor perturbation of both the flat and bent thick branes with inner structure in two-field mimetic gravity. The master equations for the linear tensor perturbations are derived by taking the transverse and traceless gauges. For the Minkowski and Anti-de-Sitter brane, the brane systems are stable against the tensor perturbation. The effective potentials of the tensor perturbations of both the flat and bent thick branes are volcano-like, and this structure may potentially lead to the zero-mode and the resonant modes of the tensor perturbation. We further illustrate the results of massive resonant modes.

Abstract Background Data are limited on whether several easily measured indices are independent predictors of type 2 diabetes mellitus (T2DM) in hypertensive patients. This study aimed to assess the association of hypertriglyceridemic-waist phenotype, triglyceride glucose (TyG) index, lipid accumulation product (LAP), and visceral adiposity index (VAI) with T2DM risk in hypertensive patients. Methods This cross-sectional study included 5321 hypertensive patients from the baseline survey of the Guangzhou Heart Study. Face-to-face questionnaire survey, physical examination, and fasting blood sample collection were completed for all subjects. Odds ratio (OR) with 95% confidence interval (95% CI) were calculated by using the logistic regression model. The potential nonlinear relationship was examined using restricted cubic spline regression. Results The prevalence of T2DM was 19.98% among hypertensive patients. After adjusting for confounders, participants with elevated triglyceride levels and enlarged waist circumference (HTGW) were associated with a 2.57-fold risk of T2DM (OR 2.57, 95% CI 2.05, 3.23). When comparing with subjects within the lowest quartile of the indices, those in the highest quartile of TyG, LAP, and VAI were associated with 5.35-fold (95% CI 4.33, 6.64), 2.65-fold (95% CI 2.11, 3.34), and 2.17-fold (95% CI 1.77, 2.67) risk of T2DM after adjusting for confounders. Every 1-unit increment of TyG, LAP, and VAI was associated with 81%, 38%, and 31% increased risk of T2DM, respectively. The nonlinear association was observed for TyG, LAP, and VAI (all P Non-linear

Despite increasing concerns about the detrimental effects of air pollution on respiratory health, limited evidence is available on these effects in the Hong Kong population, especially in children. In this prospective cohort study between 2012 and 2017, we aimed to investigate the associations between exposure to air pollution (concentrations of fine particulate matter [PM2.5] and nitrogen dioxide [NO2]) and respiratory health (lung function parameters and respiratory diseases and symptoms) in schoolchildren. We recruited 5612 schoolchildren aged 6–16 years in Hong Kong. We estimated the annual average concentrations of ambient PM2.5 and NO2 at each participant’s address using spatiotemporal models. We conducted spirometry tests on all participants to measure their lung function parameters and used a self-administered questionnaire to collect information on their respiratory diseases and symptoms and a wide range of covariates. Linear mixed models were used to investigate the associations between exposure to air pollution and lung function. Mixed-effects logistic regression models with random effects were used to investigate the associations of exposure to air pollution with respiratory diseases and symptoms. In all of the participants, every 5-μg/m3 increase in the ambient PM2.5 concentration was associated with changes of − 13.90 ml (95 % confidence interval [CI]: −23.65 ml, −4.10 ml), − 4.20 ml (−15.60 ml, 7.15 ml), 27.20 ml/s (−3.95 ml/s, 58.35 ml/s), and − 19.80 ml/s (−38.35 ml/s, −1.25 ml/s) in forced expiratory volume in 1 s, forced vital capacity, peak expiratory flow, and maximal mid-expiratory flow, respectively. The corresponding lung function estimates for every 5-μg/m3 increase in the ambient NO2 concentration were − 2.70 ml (−6.05 ml, 0.60 ml), − 1.40 ml (−5.40 ml, 2.60 ml), − 6.60 ml/s (−19.75 ml/s, 6.55 ml/s), and − 3.05 ml/s (−11.10 ml/s, 5.00 ml/s), respectively. We did not observe significant associations between PM2.5/NO2 exposure and most respiratory diseases and symptoms. Stratified analyses by sex and age showed that the associations between exposure to air pollution and lung function parameters were stronger in male participants and older participants (11–14 year old group) than in female participants and younger participants (6–10 year old group), respectively. Our results suggest that chronic exposure to air pollution is detrimental to the respiratory health of schoolchildren, especially that of older boys. Our findings reinforce the importance of air pollution mitigation to protect schoolchildren’s respiratory health.

A through-transmission ultrasonic method is proposed to address limitations in conventional ultrasonic reflection methods for non-destructive testing of ferrite tiles. The method utilizes a dual-probe configuration on both sides of the test piece to measure ultrasonic transmission signals, overcoming issues related to blind zones and orientation limitations in pulse-echo reflection methods. This method demonstrates excellent capabilities for full inspection of internal and external defects in ferrite tiles. Physical field finite element simulations were conducted to analyze detection capabilities and a transmissive testing system is developed based on the simulation results. Experimental validation was performed on artificially manufactured quantified defect samples in aluminum alloy, and the same testing system was applied to evaluate ferrite tile samples. The results confirmed the effectiveness of the system in distinguishing defective (NG) signals from normal defect-free (OK) signals, with a recall rate of at least 95% on samples of various sizes up to 0.1 mm. This research provides insights for quality control and defect detection technology in ferrite tiles.

Abstract Background This study aimed to assess the reproducibility and validity of a food frequency questionnaire (FFQ) developed for diet-related studies in a rural population. Methods One hundred fifty-four healthy residents were interviewed with a 76-item FFQ at baseline (FFQ1) and 1 month later (FFQ2) to assess reproducibility, and required to complete two three-day dietary recalls (DRs) between two FFQs to determine the validity by comparing DRs with FFQ1. Results Crude Spearman correlation coefficients between FFQ1 and FFQ2 ranged from 0.58 to 0.92 and energy-adjusted coefficients ranged from 0.62 to 0.92; weighted kappa statistic covered a spectrum from 0.45 to 0.81, depicting moderate to good agreements. For validity, there were moderate to strong associations (0.40–0.68) in most nutrients and food between FFQ1 and DRs; weighted kappa statistic demonstrated fair to moderate agreements for nutrients and food (0.21–0.49). Conclusions The results suggest that the FFQ has reasonably reproducibility and validity in measuring most nutrients and food intake, and it can be used to explore the dietary habits in studying the diet-disease relationship in Chinese rural populations.

Abstract Background Taiwan has gone through rapid industrialization, urbanization and economic growth in the 20th and early 21st centuries. Therefore, the population has experienced significant changes in the physical and social environment during the life course, which may affect the overall adiposity. Our aim was to examine the age trajectories of height, weight and body mass index (BMI) in the Taiwanese population and to explore the influences of sex, birth cohort and education. Methods The sample comprised 572,358 residents between 20 and 94 years of age in Taiwan who attended at least one health examination during 1996 to 2017 in a cohort study. Repeated measures of body weight and height were collected using an auto-anthropometer. We conducted a series of linear mixed-effects growth curve models to examine the trajectory of height, weight, and BMI across the life course with stratification by sex. Results Age-related trajectories of BMI differed between men and women and stronger cohort effects were observed among men, with younger cohorts having higher BMI. After holding cohort and age variables constant, men with junior high or lower education were shorter, thinner and had higher BMI than men with university or higher education (effect sizes: − 3.138 cm, p

ABSTRACT With the globally prevailing carbapenemase-producing (CP) Citrobacter spp., polymyxin antibiotics have been reconsidered as one of the last-resort treatment options. Our study was conducted to investigate the prevalence of mcr-9 in Citrobacter species. From October to November 2021, 650 fecal samples and 215 Citrobacter isolates were collected from healthy individuals and infected patients, respectively. Isolates were screened for the presence of the mcr-9 gene by the PCR method. mcr-9-carrying strains were identified by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Due to the susceptibility to colistin, Citrobacter spp. isolates were first induced to increase the expression of mcr-9 on China blue agar plates containing colistin and were then subjected to conjugation experiments. Whole-genome sequencing was performed on the Illumina NovaSeq PE150 system. The prevalence of mcr-9 in the Citrobacter genus from healthy guts and infected patients was 0.62% and 1.86%, respectively. In all mcr-9-positive strains, MICs of polymyxin B were observed at ≤2 μg/mL, displaying a nonresistant phenotype. As for conjugation experiments, only one isolate successfully transferred the mcr-9 gene to Escherichia coli C600. Whole-genome sequencing showed that eight mcr-9-positive Citrobacter isolates carried mcr-9 and genes encoding resistance to beta-lactam antibiotics, including blaCMY, blaDHA, blaSHV, blaTEM, and blaCTX-M. We also discovered that mcr-9 could be located on the pKPC-CAV1321 plasmid. Our study investigated the prevalence of mcr-9 in Citrobacter spp. in both healthy individuals and infected patients and described the carriage of mcr-9 on the pKPC-CAV1321 plasmid for the first time. IMPORTANCE The emergence of mcr homologues posed a serious threat to the therapeutic efficiency of polymyxin antibiotics. Citrobacter freundii is generally regarded as an opportunistic pathogen associated with a variety of nosocomial infections. In this study, we investigated the prevalence of mcr-9 in Citrobacter spp. isolates from healthy individuals and infected patients and highlighted the importance of the rational use of antibiotics. In addition, this epidemiological investigation is the first to describe the carriage of mcr-9 on plasmid pKPC-CAV1321 and confirms the horizontal transfer of this plasmid. Our research may shed new light on further studies of mcr-9 dissemination in humans.

Purpose: To examine the differences in gene expression between ruptured and non-ruptured nucleus pulposus tissues of the intervertebral discs using gene chip technology.Methods: A total of 8 patients with nucleus pulposus from a lumbar disc herniation (LDH) undergoing discectomy in our hospital were selected, including 4 ruptured and 4 non-ruptured herniated nucleus pulposus cases. Total RNA was extracted from cells by using TRIzol reagent. Nucleus pulposus cDNA probes of the two groups were obtained by the single marker method and hybridized with a human gene expression profiling chip (Agilent). The fluorescence signal images were scanned by a laser, and the obtained genes were analyzed by bioinformatics.Results: There were 75 differentially expressed genes with more than 2-fold-changes, of which 56 were up-regulated and 19 were down-regulated. The differential expression of THSD7A, which was up-regulated 18 times, was the most significant, followed by CCL5, AQP3 and SDC4.Conclusion: THSD7A can be used as a characteristic differentially expressed gene in human ruptured nucleus pulposus. Moreover, CCL5, AQP3 and SDC4 may improve the chemotaxis of stem cell migration for self-healing of damaged disc tissue, increase water uptake by nucleus accumbens cells, and inhibit the inflammatory response, thus delaying the process of intervertebral disc degeneration.

Abstract Background Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non‐small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation. Methods We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography–mass spectrometry (LC–MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC–MS‐based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice. Results Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all‐trans‐retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL‐8 and NF‐κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri‐colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all‐trans‐retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri‐treated Lewis lung cancer (LLC). Conclusions Overall, these results pointed out that P. copri‐nervonic acid/all‐trans‐retinoic acid axis may contribute to the pathogenesis of NSCLC.

Background: The incidence of cancer is higher among patients with end-stage renal disease but it remains uncertain whether a mild decrease in renal function affects cancer. Objective: To measure the effect of impaired renal function, represented by the estimated glomerular filtration rate (eGFR), personal health behaviors, and long-term exposure to fine particulate matter (PM2.5) on the risk of urothelial carcinoma (UC) incidence. Design, setting, and participants: We performed a population-based cohort study of 372 008 participants aged ≥30 yr with no prior cancer history using the MJ health examination database (2000–2015) and UC diagnosis data from the Taiwan Cancer Registry database. Outcome measurements and statistical analysis: Cox proportional hazards models were used to quantify the association between eGFR and UC incidence. Results and limitations: We detected 383 UC cases during a median follow-up of 10.3 yr. Low eGFR was significantly associated with UC (p value for trend

Background: To evaluate and compare the effectiveness of four types of non-pharmaceutical interventions (NPIs) to contain the time-varying effective reproduction number (Rt) of coronavirus disease-2019 (COVID-19). Methods: This study included 1,908,197 confirmed COVID-19 cases from 190 countries between 23 January and 13 April 2020. The implemented NPIs were categorised into four types: mandatory face mask in public, isolation or quarantine, social distancing and traffic restriction (referred to as mandatory mask, quarantine, distancing and traffic hereafter, respectively). Results: The implementations of mandatory mask, quarantine, distancing and traffic were associated with changes (95% confidence interval, CI) of −15.14% (from −21.79% to −7.93%), −11.40% (from −13.66% to −9.07%), −42.94% (from −44.24% to −41.60%) and −9.26% (from −11.46% to −7.01%) in the Rt of COVID-19 when compared with those without the implementation of the corresponding measures. Distancing and the simultaneous implementation of two or more types of NPIs seemed to be associated with a greater decrease in the Rt of COVID-19. Conclusion: Our study indicates that NPIs can significantly contain the COVID-19 pandemic. Distancing and the simultaneous implementation of two or more NPIs should be the strategic priorities for containing COVID-19.

Abstract Hierarchical magnetic-dielectric composites are promising functional materials with prospective applications in microwave absorption (MA) field. Herein, a three-dimension hierarchical “nanotubes on microrods,” core–shell magnetic metal–carbon composite is rationally constructed for the first time via a fast metal–organic frameworks-based ligand exchange strategy followed by a carbonization treatment with melamine. Abundant magnetic CoFe nanoparticles are embedded within one-dimensional graphitized carbon/carbon nanotubes supported on micro-scale Mo2N rod (Mo2N@CoFe@C/CNT), constructing a special multi-dimension hierarchical MA material. Ligand exchange reaction is found to determine the formation of hierarchical magnetic-dielectric composite, which is assembled by dielectric Mo2N as core and spatially dispersed CoFe nanoparticles within C/CNTs as shell. Mo2N@CoFe@C/CNT composites exhibit superior MA performance with maximum reflection loss of − 53.5 dB at 2 mm thickness and show a broad effective absorption bandwidth of 5.0 GHz. The Mo2N@CoFe@C/CNT composites hold the following advantages: (1) hierarchical core–shell structure offers plentiful of heterojunction interfaces and triggers interfacial polarization, (2) unique electronic migration/hop paths in the graphitized C/CNTs and Mo2N rod facilitate conductive loss, (3) highly dispersed magnetic CoFe nanoparticles within “tubes on rods” matrix build multi-scale magnetic coupling network and reinforce magnetic response capability, confirmed by the off-axis electron holography.

Abstract Background Physical activity (PA) increases a person’s inhalation of air pollutants due to greater ventilation, possibly leading to larger adverse health effects. This study aims to investigate the combined effects of long-term exposure to fine particulate matter (PM2.5) and habitual PA on lung function in adults. Methods This was a longitudinal cohort study that included 278,065 Taiwan residents with an age of 20 years old or above who joined a standard medical screening programme between 2001 and 2014. Each participant received at least one medical examination (including spirometric, blood, and urinary tests and a standard self-administered questionnaire survey) during the study period. We estimated the 2-year average PM2.5 concentrations at each participant’s address using a new physical model based on observational data. Information on the participants’ PA was collected using the standard self-administrated questionnaire. Generalised linear mixed models were used to investigate the combined effects of PM2.5 and PA on pulmonary function. We also performed stratified analyses by different levels of PM2.5 exposure and habitual PA. Results Each 10 MET-h increase in PA was associated with a higher level of 0.20%, 0.16%, and 0.19% in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and maximum mid-expiratory flow (MMEF), respectively, after adjusting for PM2.5 exposure and a wide range of covariates including age, sex education, body mass index, lifestyles, and health conditions. Each 10 μg/m3 increase in PM2.5 was associated with a lower FVC, FEV1, and MMEF (2.43%, 2.78% and 3.10%, respectively). Negative interactions were observed, and PM2.5 exposure was associated with a greater reduction in lung function among the participants with higher PA levels. Conclusions We found significant negative interaction effects between long-term exposure to PM2.5 and habitual PA, suggesting that the increased intake of PM2.5 due to PA may attenuate the benefits of habitual PA on lung function. However, the PA benefits generally remained stable at different stratum of PM2.5 in the stratified analyses, and habitual PA may still be recommended to people residing in relatively polluted regions.

Abstract Background The effects of dietary factors on prognosis of esophageal cancer remain unclear. This systematic review and meta-analysis aimed to assess the association between dietary intake and the risk of mortality among patients with esophageal cancer. Methods Six electronic databases (PubMed, Web of Science, OVID, ProQuest, CNKI and Wanfang) were searched for studies published up to Oct. 2019 that examined the association between dietary intake and all-cause mortality, esophageal cancer-specific mortality and esophageal cancer recurrence. The pooled hazard ratio (HR) with 95% confidence interval (CI) were derived by comparing the highest with the lowest categories of each dietary item and by using random effect models. Results A total of 15 cohort studies were included in this study and all reported pre-diagnosis dietary exposure; two focused on dietary folate, 12 on alcohol consumption and three on other dietary components (sugary beverages, phytochemicals and preserved vegetables). When comparing the highest with the lowest categories, dietary folate intake was associated with a reduced risk of esophageal cancer-specific mortality in patients with esophageal squamous cell carcinoma (HR: 0.41, 95% CI: 0.25–0.69), with low heterogeneity (I 2 = 0%, P = 0.788). When comparing the highest with the lowest categories of alcohol consumption, alcohol consumption was associated with an increased risk of all-cause mortality in patients with esophageal squamous cell carcinoma (HR: 1.29, 95% CI: 1.07–1.55; heterogeneity: I 2 = 53%, P = 0.030), but this increased risk was not significant in patients with esophageal adenocarcinoma (HR = 1.05, 95% CI: 0.84–1.32). Conclusions This review with pre-diagnostic dietary exposure showed that dietary folate intake was associated with a reduced risk of mortality of esophageal squamous cell carcinoma, whereas alcohol consumption was associated with an increased risk. More studies are needed to investigate effect of dietary factors, especially post-diagnosis dietary consumption, on esophageal cancer prognosis.

Emerging studies have revealed that N6-methyladenosine modification is involved in the development of various cancers. However, the m6A modification pattern of endometrioid ovarian cancer (EOC) has not been demonstrated. In the present study, high-throughput sequencing combined with methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing were used to obtain the transcriptome-wide m6A modifications of endometrioid ovarian cancer for the first time. The roles of methyltransferase-like 3 (METTL3) in EOC cell line COV362 were explored. In total, 39,237 m6A-modified peaks related to 17,082 genes were identified in the EOC group, and 52,848 m6A peaks representing 19,349 genes were detected in endometriosis group. Functional enrichment analysis revealed that m6A enriched genes were associated with tight junctions, cell adhesion molecules, platinum drug resistance, adherens junction, and more. METTL3 knockdown in the COV362 cells significantly decreased cell proliferation, promoted cell apoptosis, and induced cell cycle arrest at the G0/G1 phase. Our study presented the transcriptome-wide m6A modifications of endometrioid ovarian cancer for the first time and revealed various differentially expressed genes with methylated m6A modifications. This study may provide new directions for in-depth research of the underlying molecular mechanisms and signaling pathways of EOC development and progression.

The utilizations of microfluidic chips for single RBC (red blood cell) studies have attracted great interests in recent years to filter, trap, analyze, and release single erythrocytes for various applications. Researchers in this field have highlighted the vast potential in developing micro devices for industrial and academia usages, including lab-on-a-chip and organ-on-a-chip systems. This article critically reviews the current state-of-the-art and recent advances of microfluidics for single RBC analyses, including integrated sensors and microfluidic platforms for microscopic/tomographic/spectroscopic single RBC analyses, trapping arrays (including bifurcating channels), dielectrophoretic and agglutination/aggregation studies, as well as clinical implications covering cancer, sepsis, prenatal, and Sickle Cell diseases. Microfluidics based RBC microarrays, sorting/counting and trapping techniques (including acoustic, dielectrophoretic, hydrodynamic, magnetic, and optical techniques) are also reviewed. Lastly, organs on chips, multi-organ chips, and drug discovery involving single RBC are described. The limitations and drawbacks of each technology are addressed and future prospects are discussed.

Background: Several studies reported that long-term exposure to fine particulate matter (PM2.5) was associated with an increased risk of chronic obstructive pulmonary disease (COPD). It remains unclear whether reduced PM2.5 can decrease the risk of COPD development. Objective: To investigate the associations of dynamic changes (including deterioration and improvement) in long-term exposure to ambient PM2.5 with changes in lung function and the incidence of COPD. Methods: A total of 133,119 adults (aged 18 years or older) were recruited in Taiwan between 2001 and 2014. All participants underwent at least two standard medical examinations including spirometry test. We estimated PM2.5 concentrations using a high-resolution (1 km2) satellite-based spatio-temporal model. The change in PM2.5 (ΔPM2.5) was defined as the difference in concentration of PM2.5 between the respective visit and the previous visit. We used a multivariable mixed linear model and time-varying Cox model to investigate the associations of change in PM2.5 with annual change of lung function and the incidence of COPD, respectively. Result: The PM2.5 concentration in Taiwan increased during 2002–2004 and began to decrease around 2005. Every 5-µg/m3/year decrease in the annual change of PM2.5 (i.e., ΔPM2.5/year of 5 µg/m3/year) was associated with an average increase of 19.93 mL/year (95 %CI: 17.42,22.43) in forced expiratory volume in 1 s (FEV1), 12.76 mL/year (95 %CI: 9.84,15.66) in forced vital capacity (FVC), 70.22 mL/s/year (95 %CI: 64.69,76.16) in midexpiratory flow between 25 and 75% of the forced vital capacity (MEF25-75), 0.27%/year (95 %CI: 0.21%, 0.32%) in FEV1/FVC/year. Every 5 µg/m3 decrease in PM2.5 (i.e., ΔPM2.5 of 5 µg/m3) was associated with a 12% (95 %CI: 7%, 17%) reduced risk of COPD development. The stratified and sensitivity analyses generally yielded similar results. Conclusion: An improvement in PM2.5 pollution exposure was associated with an attenuated decline in lung function parameters of FEV1, FVC, MEF25-75, and FEV1/FVC, and a decreased risk of COPD development. Our findings suggest that strategies aimed at reducing air pollution may effectively combat the risk of COPD development.

Electroencephalography (EEG) was widely investigated in brain status detection and disease diagnosis, in which the fractal analysis played an important role. In this paper, the roughness scaling extraction (RSE) algorithm proposed in our previous study on surface morphologies was applied to calculate the fractal dimensions (FDs) of artificial profiles and EEG signals. Fractal profiles with ideal FDs ranging from 1.01 to 1.99 were generated through the Weierstrass-Mandelbrot function. The RSE algorithm and the traditional algorithms, including the Higuchi algorithm, the Katz algorithm, and the box counting algorithm, were compared by analyzing the artificial profiles. Based on the mean relative errors and mean square errors, it was found that the RSE algorithm was more accurate than the traditional algorithms. To investigate the influence of noise on FD calculation, noise with different levels was added to the fractal profiles. The RSE and Higuchi algorithms were found reliable at signal-to-noise ratios of 50 and 40 dB, while the accuracy of RSE was also superior to that of the Higuchi. The RSE, Higuchi, and Katz algorithms were utilized to analyze the EEG signals of epilepsy events. The significant FD increasing, which corresponded to the seizure onset, could be detected, and the overlapping between the seizure and non-seizure statuses was small by using the RSE algorithm, indicating its feasibility for the EEG fractal analysis.

Stroke has been the leading cause of disability due to the induced spasticity in the upper extremity. The constant flexion of spastic fingers following stroke has not been well described. Accurate measurements for joint stiffness help clinicians have a better access to the level of impairment after stroke. Previously, we conducted a method for quantifying the passive finger joint stiffness based on the pressure-angle relationship between the spastic fingers and the soft-elastic composite actuator (SECA). However, it lacks a ground-truth to demonstrate the compatibility between the SECA-facilitated stiffness estimation and standard joint stiffness quantification procedure. In this study, we compare the passive metacarpophalangeal (MCP) joint stiffness measured using the SECA with the results from our designed standalone mechatronics device, which measures the passive metacarpophalangeal joint torque and angle during passive finger rotation. Results obtained from the fitting model that concludes the stiffness characteristic are further compared with the results obtained from SECA-Finger model, as well as the clinical score of Modified Ashworth Scale (MAS) for grading spasticity. These findings suggest the possibility of passive MCP joint stiffness quantification using the soft robotic actuator during the performance of different tasks in hand rehabilitation.

Exosomes (30–100 nm in diameter) are a group of cell-derived membrane vesicles, packaged as valuable cargo with lipid, proteins, and genetic materials from their parent cells. With the increasing interest in exosomes for diagnostic and therapeutic applications, the rapid isolation of pure exosome populations has become a hot topic. In this paper, we propose modified microchannels with aptamer in a microfluidics system for rapid and efficient isolation of exosomes by targeting exosome-carrying CD63 and PTK 7. The capture efficiency in surface-modified channels reaches around 107–108 particles/mL in 20 min, and purified exosomes with reliable size can be achieved.

Background and AimsPancreatic ductal adenocarcinoma (PDAC) is one of refractory malignancies without efficient therapeutics. Babao Dan (BBD) was partially effective to suppress tumor growth of PDAC in clinical practice. However, the molecular mechanisms were unclear.MethodsWe established PDAC mice models and treated them with BBD through intragastric administration. Treatment and control groups were then subjected to high-throughput RNA sequencing. We presented the transcriptional changes upon BBD treatment by using computational analysis comparing BBD treatment and control groups. Functional enrichment analysis was employed to investigate the biological processes or pathways that BBD modulates.ResultsBBD treatment showed strong suppression on tumor growth of PDAC, even stronger than Gemcitabine. Through differential analysis comparing BBD treatment and control groups, we identified 638 up-regulated and 259 down-regulated genes in the BBD treatment group. BBD was found to activate tumor suppressor genes, such as MTUS1, PDGFB, SOD3, and UCHL1. Furthermore, we revealed that BBD treatment inhibited cancer-related pathways and elevated activities of metabolism-related processes. The BBD-modulated metabolic genes were further showed to be associated with patient survival in an independent cohort with pancreatic cancer.ConclusionBBD repressed the tumor growth of PDAC. BBD treatment modulated expression of cancer-related genes in PDAC. BBD suppressed cancer-related pathways and activated metabolic processes in PDAC. Our study suggests BBD treatment as potential effective therapeutics for patients with pancreatic cancer.

Background: Information on the association between long-term exposure to PM2.5 and gastrointestinal cancer mortality is scarce. Objectives: This study investigated the association between long-term exposure to PM2.5 and deaths from gastrointestinal cancer and its subtypes in adults in Taiwan. Methods: A total of 385,650 Taiwanese adults (≥18 years old) jointed a standard medical examination program between 2001 and 2014 and were followed up until 2016. Their vital data were obtained from the National Death Registry maintained by the Ministry of Health and Welfare in Taiwan. We estimated the ambient PM2.5 concentration at individual’s address utilising a satellite-based spatiotemporal model at a resolution of 1 km2. Cox proportional hazard regression model was used to investigate the associations between ambient PM2.5 and deaths from gastrointestinal, stomach, colorectal and liver cancers. Results: We found that each 10 µg/m3 increase in PM2.5 was associated with an increased hazard risk (HR) of 1.09 (95% confidence interval (CI): 1.03–1.16) and 1.13 (95%CI: 1.02–1.24) in deaths from gastrointestinal and liver cancers, respectively. The association between PM2.5 and death from colorectal cancer was marginally statistically significant [HR: 1.13 (95%CI: 1.00–1.26)]. We did not find significant associations between PM2.5 and mortality from stomach cancer. Conclusions: Long-term exposure to ambient PM2.5 was associated with an increased risk of deaths from gastrointestinal cancers, liver cancer and also potentially colorectal cancer. Air pollution control strategies are necessary to reduce the burden of gastrointestinal cancer. Keywords: Long-term exposure, PM2.5 air pollution, Gastrointestinal cancer mortality, Live cancer mortality, Taiwan

Strokes cause severe impairment of hand function because of the spasticity in the affected upper extremities. Proper spasticity evaluation is critical to facilitate neural plasticity for rehabilitation after stroke. However, existing methods for measuring spasticity, e.g. Modified Ashworth Scale (MAS), highly depends on clinicians’ experiences, which are subjective and lacks quantitative details. Here, we introduce the first rehabilitation actuator that objectively reflects the condition of post-stroke finger spasticity. The actuator is 3D printed with soft materials. By considering the finger and the actuator together, the spasticity, i.e. stiffness, in finger is obtained from the pressure–angle relationship. The method is validated by simulations using finite element analysis (FEA) and experiments on mannequin fingers. Furthermore, it is examined on four stroke subjects and four healthy subjects. Results show the finger stiffness increases significantly from healthy subjects to stroke subjects, particularly those with high MAS score. For patients with the same MAS score, stiffness variation can be a few times. With this soft actuator, a hand rehabilitation robot that may tell the therapeutic progress during the rehabilitation training is readily available.

The study aimed to clarify the potential immune-related targets and mechanisms of Qingyihuaji Formula (QYHJ) against pancreatic cancer (PC) through network pharmacology and weighted gene co-expression network analysis (WGCNA). Active ingredients of herbs in QYHJ were identified by the TCMSP database. Then, the putative targets of active ingredients were predicted with SwissTargetPrediction and the STITCH databases. The expression profiles of GSE32676 were downloaded from the GEO database. WGCNA was used to identify the co-expression modules. Besides, the putative targets, immune-related targets, and the critical module genes were mapped with the specific disease to select the overlapped genes (OGEs). Functional enrichment analysis of putative targets and OGEs was conducted. The overall survival (OS) analysis of OGEs was investigated using the Kaplan-Meier plotter. The relative expression and methylation levels of OGEs were detected in UALCAN, human protein atlas (HPA), Oncomine, DiseaseMeth version 2.0 and, MEXPRESS database, respectively. Gene set enrichment analysis (GSEA) was conducted to elucidate the key pathways of highly-expressed OGEs further. OS analyses found that 12 up-regulated OGEs, including CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 that could be utilized as potential diagnostic indicators for PC. Further, methylation analyses suggested that the abnormal up-regulation of these OGEs probably resulted from hypomethylation, and GSEA revealed the genes markedly related to cell cycle and proliferation of PC. This study identified CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 might be used as reliable immune-related biomarkers for prognosis of PC, which may be essential immunotherapies targets of QYHJ.

Recently, intestinal flora plays a vital role in the occurrence and development of tumors and there is link between cancer immunotherapy and Akkermansia muciniphila (Akk). However, the therapeutic efficacy of Akk in lung cancer remained unclear. Hence, our study is aimed at investigating the antitumor effects of cisplatin (CDDP) combined with Akk on lung cancer. Using the murine lung cancer model by subcutaneously inoculating Lewis lung cancer model, 50 mice were divided into five groups: normal, model, CDDP, CDDP+Akk, and CDDP+antibiotics. After treatment within 5 weeks, compared with the model group, the administered group improved the changes of tumor pathomorphology. Compared with the CDDP group, CDDP combining with Akk slowed down the growth of tumor volume, downregulated the levels of ki-67, p53, and factor-associated suicide (Fas) ligand proteins and upregulated Fas proteins, increased the levels of interferon-γ, interleukin-6, and tumor necrosis factor-α, and suppressed the expression of CD4+CD25+Foxp3+ Treg in mouse peripheral blood and spleen. In addition, transcriptome analysis indicated that Akk combining with CDDP increased obviously the levels of IFI27l2 and IGFBP7 and was related to those pathways including the cytokine-cytokine receptor interaction, Th17 cell differentiation, FOXO, JAK-STAT, and PI3K-Akt signaling pathways. These results suggested that the therapeutic efficacy of the combined treatment of Akk and CDDP was superior to the only CDDP treatment, which could enhance immune regulation and would be a promising strategy for the treatment of lung cancer.

This paper describes a generative design methodology for a micro hydrodynamic single-RBC (red blood cell) trap for applications in microfluidics-based single-cell analysis. One key challenge in single-cell microfluidic traps is to achieve desired through-slit flowrates to trap cells under implicit constraints. In this work, the cell-trapping design with validation from experimental data has been developed by the generative design methodology with an evolutionary algorithm. L-shaped trapping slits have been generated iteratively for the optimal geometries to trap living-cells suspended in flow channels. Without using the generative design, the slits have low flow velocities incapable of trapping single cells. After a search with 30,000 solutions, the optimized geometry was found to increase the through-slit velocities by 49%. Fabricated and experimentally tested prototypes have achieved 4 out of 4 trapping efficiency of RBCs. This evolutionary algorithm and trapping design can be applied to cells of various sizes.

The properties of cathode materials play an important role in the development and application for lithium ion batteries. However, their phase transition, low conductivity and side reaction with electrolyte restrict the further improvement of battery performance. Coating is one of the effective techniques to overcome these problems. This paper focuses on the influence of surface coating on the properties of cathode materials for lithium ion batteries. The research progress of various coating materials was summarized. The modification mechanism of coating materials was also elaborated. And the future development trend of coating materials was proposed, for example, exploring continuously new coating materials with excellent performance, investigating in depth coating mechanism, and optimizing further coating technologies.

[Objectives] How to maintain propulsion capability in a CODOG propulsion system damage situation has important significance. [Methods] A ‘Hull-Engine-CPP-Rudder’ simulation model of a CODOG marine power plant is established on Simulink using the modularized method, and a dissymmetrical main engine urgent working mode is proposed and simulated. [Results] The results show that in the dissymmetrical working mode, two different engines cannot work simultaneously at designed capacity. However, by adjusting the pitch of the CPP, one engine can work at designed capacity and the other can work at partial load capacity; under this working mode, if high speed is demanded, the gas turbine should work at designed capacity. The CPP pitch driven by diesel should be maintained at a high value near the maximum. The maximum speed of this working mode is 84.4% of the designed speed, which is higher than the speed of the single shaft working mode driven by a gas turbine. [Conclusions] The research results of this paper can provide useful references for the design of ship propulsion systems.

Background: Shaoyao Ruangan mixture (SRM) has been applied clinically for more than 20 years in Zhejiang Cancer Hospital to treat patients with primary liver cancer (PLC). Intestinal microecology plays an important role in the emergence of liver diseases. This study aimed to reveal connections among SRM, intestinal microbiota and PLC, and the potential targets of SRM for liver cancer. Methods: We established a control group, a PLC model group, and a treatment group of mice to analyze the inhibitory effect of SRM on PLC and its intestinal flora target. We also evaluated drug efficacy of SRM and analyzed specific changes in intestinal flora by 16S rDNA sequencing of stools. As the serum interleukin (IL)-10 level could be an independent prognostic factor for unresectable liver cancer, we detected IL-10 levels and analyzed their association with the abundance of specific bacteria. Results: Liver tumors in the treatment group were smaller and fewer than those in the model group ( P = .046). The abundance of Bacteroides was significantly higher in the model group than that in the control group, while SRM significantly reduced the increasing abundance of Bacteroides in mice with PLC. We found that the IL-10 level was positively correlated with the abundance of Bacteroides . Conclusion: SRM can effectively inhibit the progression of PLC and increase Bacteroides abundance. In view of the association between Bacteroides and liver cancer and the significant positive correlation between Bacteroides and IL-10 levels, Bacteroides may be the target intestinal flora of SRM to inhibit PLC.