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Major facilitator superfamily (MFS) transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism. Peronophythora litchii causes the most destructive disease on lichi, litchi downy blight. PlM90 was reported as a key oosporogenesis regulator. Here, we identified an MFS transporter gene PlMFS1, which is up-regulated during oospore formation at the late infection stage, while down-regulated in the PlM90 mutant. To investigate PlMFS1 function, we generated PlMFS1 knockout mutants using CRISPR/Cas9-mediated genome editing technology. Compared with the wild-type strain SHS3, PlMFS1 deletion impaired mycelium growth, zoospore release, oospore production and pathogenicity. Furthermore, PlMFS1 deletion significantly affected P. litchii utilization of fructose, lactose and maltose, and may be the PlMFS1 mechanism involved in mycelial growth. PlMFS1 gene deletion also led to deceased laccase activity, laccase-encoding gene downregulation and impaired P. litchii pathogenicity. To our knowledge, this is the first report of an MFS transporter involved in sugar utilization, sexual reproduction, asexual reproduction and pathogenesis in oomycetes.

MIBC is a highly lethal disease, and the patient survival rate has not improved significantly over the last decades. UPPL is a cell line that can be used to recapitulate the luminal-like molecular subtype of bladder cancer and to discover effective treatments to be translated in patients. Here, we investigate the effects of combinational treatments of radiotherapy and immunotherapy in this recently characterized UPPL tumor-bearing mice. We first characterized the baseline tumor microenvironment and the effect of radiation, anti-PD-L1, and combinatorial treatments. Then, the mice were re-challenged with a second tumor (rechallenged tumor) in the contralateral flank of the first tumor to assess the immunological memory. Radiation slowed down the tumor growth. All treatments also decreased the neutrophil population and increased the T cell population. Anti-PD-L1 therapy was not able to synergize with radiation to further delay tumor growth. Furthermore, none of the treatments were able to generate immune memory. The treatments were not sufficient to induce a significant and lasting pool of memory cells. We show here that anti-PD-L1 treatment added to radiotherapy was not enough to achieve T cell-mediated memory in UPPL tumors. Stronger T cell activation signals may be required to enhance radiation efficacy in luminal-like bladder cancer.

A critical event in the pathogenesis of kidney fibrosis is the transition of macrophages into myofibroblasts (MMT). Exosomes play an important role in crosstalk among cells in the kidney and the development of renal fibrosis. However, the role of myofibroblast-derived exosomes in the process of MMT and renal fibrosis progression remains unknown. Here, we examined the role of myofibroblast-derived exosomes in MMT and kidney fibrogenesis. In vitro, transforming growth factor-β1 stimulated the differentiation of kidney fibroblasts into myofibroblasts and promoted exosome release from myofibroblasts. RAW264.7 cells were treated with exosomes derived from myofibroblasts. We found purified exosomes from myofibroblasts trigger the MMT. By contrast, inhibition of exosome production with GW4869 or exosome depletion from the conditioned media abolished the ability of myofibroblasts to induce MMT. Mice treatment with myofibroblast-derived exosomes (Myo-Exo) exhibited severe fibrotic lesion and more abundant MMT cells in kidneys with folic acid (FA) injury, which was negated by TANK-banding kinase-1 inhibitor. Furthermore, suppression of exosome production reduced collagen deposition, extracellular matrix protein accumulation, and MMT in FA nephropathy. Collectively, Myo-Exo enhances the MMT and kidney fibrosis. Blockade of exosomes mediated myofibroblasts–macrophages communication may provide a novel therapeutic target for kidney fibrosis.

This paper investigates the coupling relationship and degree of complex factors corresponding to the metro station construction in the Ningbo region. To this end, the interpretative structural modeling (ISM) method, a structural interpretation model, is utilized to develop the coupling connection network of construction risk factors. Moreover, the cloud model theory and coupling degree model are used to calculate the risk factor coupling degree within and between the construction safety risk subsystems. The analysis indicates that the coupling degree of risk factors within and among subsystems is notably high, falling into categories characterized by high coupling and strong coupling. It is also found that the entire coupling system is in a state of high-strength coupling. Therefore, during the construction process, the coupling impact of risk factors must be avoided, and risk factors must be prevented from further developing into risk events. The quantitative evaluation of the coupling degree between and among risk factor subsystems in this study provides a reference for project risk evaluation and facilitates the development of subsequent construction safety measures.

Abstract Based on the WBS-RBS method, in this study, the risk factors corresponding to the construction risk events of an offshore tunnel foundation pit in Ningbo were identified, and the fuzzy comprehensive evaluation method was used to evaluate the construction safety risk of the project. The system-level risk value was obtained by using the risk event deformation resulting from changes in two factors, namely, “mechanical property of soil” and “stiffness of the envelope structure”, to calculate the new event-level risk value corresponding to the deformation using a finite element numerical model. The findings indicate that the tunnel project has a risk evaluation score of 62.78 and thus falls within the category of high-risk projects. A change in risk factors will alter the likelihood that risk events will occur, which affects the safety risk status of the entire project. When two factors are coupled, a project’s system-level risk can increase dramatically.

Abstract CO2 electroreduction has garnered significant attention from both the academic and industrial communities. Extracting crucial information related to catalysts from domain literature can help scientists find new and effective electrocatalysts. Herein, we used various advanced machine learning, natural language processing techniques and large language models (LLMs) approaches to extract relevant information about the CO2 electrocatalytic reduction process from scientific literature. By applying the extraction pipeline, we present an open-source corpus for electrocatalytic CO2 reduction. The database contains two types of corpus: (1) the benchmark corpus, which is a collection of 6,985 records extracted from 1,081 publications by catalysis postgraduates; and (2) the extended corpus, which consists of content extracted from 5,941 documents using traditional NLP techniques and LLMs techniques. The Extended Corpus I and II contain 77,016 and 30,283 records, respectively. Furthermore, several domain literature fine-tuned LLMs were developed. Overall, this work will contribute to the exploration of new and effective electrocatalysts by leveraging information from domain literature using cutting-edge computer techniques.

Breast cancer is a common clinical malignant tumor that seriously threatens women’s physical and mental health. Chemotherapy, as the first choice of breast cancer treatment, has limited its application in the clinic due to problems of poor stability, short half-life, and serious toxic side effects. With the emergence of nanotechnology, inorganic materials to prepare mesoporous silica nanoparticles (MSNs) have been widely used in anti-tumor drug carriers. However, their slow degradation rate limits their application in the biomedical field. Therefore, developing low-toxicity MSNs with good biocompatibility, biodegradability, and rapid release at the tumor site is a key scientific issue to be addressed. Here, we prepared DOX-loaded Ca-Mg-doped MSNs by electrostatic adsorption to obtain Ca-Mg@DOX@MSNs with suitable particle sizes and zeta potential, and the incorporation of calcium and magnesium also led to an increase in the degradation rate under acidic conditions and an accelerated release, which reduced the toxicity of DOX and promoted cellular uptake with good anti-tumor effects. This study provides a new idea for the clinical treatment of breast cancer.

Pseudomonas aeruginosa and Mycobacterium abscessus are opportunistic pathogens that cause severe infections in hospitals, and their co-infections are increasingly reported. The interspecies interactions between these two bacterial species and their potential impacts on infections are largely unexplored. In this study, we first demonstrated that P. aeruginosa inhibits the growth of M. abscessus by iron chelating via pqs quorum sensing. Next, through proteomic analysis, we discovered that the PQS molecule significantly changed a large amount of protein expression in M. abscessus, including proteins involved in the type VII secretion system and iron homeostasis. Furthermore, we revealed that PQS significantly enhanced the production of bacterial membrane vesicles (MVs) by M. abscessus. Our study suggests that the P. aeruginosa PQS can serve as an interspecies signaling molecule to communicate with Mycobacterium and affect their physiology and virulence.

The combination of photodynamic therapy (PDT) and pneumatotherapy is emerging as one of the most effective strategies for increasing cancer treatment efficacy while minimizing side effects. Photodynamic forces affect nitric oxide (NO) levels as activated photosensitizers produce NO, and NO levels in the tumor and microenvironment directly impact tumor cell responsiveness to PDT. In this paper, 3-benzenesulfonyl-4-(1-hydroxy ether)-1,2,5-oxadiazole-2-oxide NO donor–silicon phthalocyanine coupling (SiPc–NO) was designed and prepared into self-assembled nanoparticles (SiPc–NO@NPs) by precipitation method. By further introducing arginyl-glycyl-aspartic acid (RGD) on the surface of nanoparticles, NO-photosensitizer delivery systems (SiPc–NO@RGD NPs) with photo-responsive and tumor-targeting properties were finally prepared and preliminarily evaluated in terms of their formulation properties, NO release, and photosensitizing effects. Furthermore, high reactive oxygen species (ROS) generation efficiency and high PDT efficiency in two breast cancer cell lines (human MCF-7 and mouse 4T1) under irradiation were also demonstrated. The novel SiPc–NO@RGD NPs show great potential for application in NO delivery and two-photon bioimaging-guided photodynamic tumor therapy.

Abstract At present, the global energy crisis and environmental pollution coexist, and the demand for sustainable clean energy has been highly concerned. Bioelectrocatalysis that combines the benefits of biocatalysis and electrocatalysis produces high‐value chemicals, clean biofuel, and biodegradable new materials. It has been applied in biosensors, biofuel cells, and bioelectrosynthesis. However, there are certain flaws in the application process of bioelectrocatalysis, such as low accuracy/efficiency, poor stability, and limited experimental conditions. These issues can possibly be solved using machine learning (ML) in recent reports although the combination of them is still not mature. To summarize the progress of ML in bioelectrocatalysis, this paper first introduces the modeling process of ML, then focuses on the reports of ML in bioelectrocatalysis, and ultimately makes a summary and outlook about current issues and future directions. It is believed that there is plenty of scope for this interdisciplinary research direction.

The management of granulocytopenia-associated infections is challenging, and a high mortality rate is associated with traditional supportive therapies. Neutrophils—the primary defenders of the human immune system—have potent bactericidal capabilities. Here, we investigated the dynamic in vivo distribution of neutrophil transfusion and their impact on the treatment outcome of severe granulocytopenic infections. We transfused 89 Zr-labeled neutrophils in the C57BL/6 mice and observed the dynamic neutrophil distribution in mice for 24 h using the micro-positron emission tomography (Micro-PET) technique. The labeled neutrophils were predominantly retained in the lungs and spleen up to 4 h after injection and then redistributed to other organs, such as the spleen, liver, and bone marrow. Neutrophil transfusion did not elicit marked inflammatory responses or organ damage in healthy host mice. Notably, allogeneic neutrophils showed rapid chemotaxis to the infected area of the host within 1 h. Tail vein infusion of approximately 10 7 neutrophils substantially bolstered host immunity, ameliorated the inflammatory state, and increased survival rates in neutrophil-depleted and infected mice. Overall, massive allogeneic neutrophil transfusion had a therapeutic effect in severe infections and can have extensive applications in the future.

BackgroundOnly a few studies that investigated dietary intakes of folate, vitamin B6, and vitamin B12 in relation to cariovascular disease (CVD). This study aimed to assess the association of dietary folate, vitamin B6, and vitamin B12 with CVD in the United States population.MethodsA cross-sectional analysis of 65,322 adults aged ≥ 20 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2018. Before 2003, dietary intake data were assessed using a 24-hour dietary call, and two 24-hour dietary calls were used during 2003 and 2018. Odds ratios and 95% confidence intervals (CIs) for CVD associated with dietary folate, vitamin B6, and vitamin B12 were estimated using multivariate logistic regression models.ResultsDietary vitamin B6 intake were inversely associated with the odds of CVD. In males, the multivariable OR for the highest vs. lowest quartiles of vitamin B6 was 0.77 (95%CI: 0.61–0.97, Ptrend = 0.013) for the odds of CVD. In females, the adjusted OR for the highest quartile of vitamin B6 compared with the lowest quartile was 0.73 (95%CI: 0.56–0.95, Ptrend = 0.038) for the odds of CVD. No significant association was observed between dietary folate and vitamin B12 intakes and the odds of CVD.ConclusionsOur findings indicate that higher intake of dietary vitamin B6 may be associated with lower prevalence of CVD, suggesting that dietary vitamin B6 has major public health implications in the prevention of CVD in the United States population.

Triglyceride and glucose levels are important indicators for determining metabolic syndrome, one of the leading public-health burdens worldwide. Drosophila melanogaster is an ideal model for investigating metabolic diseases because it has 70% homology to human genes and its regulatory mechanism of energy metabolism homeostasis is highly similar to that of mammals. However, traditional analytical methods of triglyceride and glucose are time-consuming, laborious, and costly. In this study, a simple, practical, and reliable near-infrared (NIR) spectroscopic analysis method was developed for the rapid determination of glucose and triglyceride levels in an in vivo model of metabolic disorders using Drosophila induced by high-sugar or high-fat diets. The partial least squares (PLS) model was constructed and optimized using different spectral regions and spectral pretreatment methods. The overall results had satisfactory prediction performance. For Drosophila induced by high-sugar diets, the correlation coefficient (RP) and root mean square error of prediction (RMSEP) were 0.919 and 0.228 mmoL gprot−1 for triglyceride and 0.913 and 0.143 mmoL gprot−1 for glucose respectively; for Drosophila induced by high-fat diets, the RP and RMSEP were 0.871 and 0.097 mmoL gprot−1 for triglyceride and 0.853 and 0.154 mmoL gprot−1 for glucose, respectively. This study demonstrated the potential of using NIR spectroscopy combined with PLS in the determination of triglyceride and glucose levels in Drosophila, providing a rapid and effective method for monitoring metabolite levels during disease development and a possibility for evaluating metabolic diseases in humans in clinical practice.

Measurement(s) brain measurement (resting/task) • mouse trajectory; binary decision-making Technology Type(s) high-density EEG • Experiment

Abstract Background In clinical practice, sufentanil has a stronger sedative effect on patients than fentanyl at equivalent doses. This study hypothesized that, at equivalent doses, patients undergoing gynaecologic laparoscopic surgery (GLS) receiving fentanyl would have an earlier emergence from anaesthesia (EA), a shorter time to extubation (TE), and a better degree of wakefulness. Therefore, this study evaluated the effects of equipotent doses of fentanyl and sufentanil on the quality of emergence in patients undergoing GLS. Methods One hundred seven patients scheduled for GLS under general anaesthesia were randomly divided into two groups and were induced with 0.35 µg/kg sufentanil (Group S; n = 55) or 3.5 µg/kg fentanyl (Group F; n = 52). When the GLS was almost over, the patient's abdominal cavity was flushed with warm saline, and 5 µg of sufentanil or 50 µg of fentanyl in a double-blind manner was intravenously injected into the patients. The primary outcomes of the study included EA, TE, the rate of leaving the surgical bed voluntarily and the incidence of endotracheal tube tolerance. The Ramsay Sedation Scale (RSS), and Verbal Rating Scale (VRS) scores at 15 and 30 min in the postanaesthesia care unit (PACU), as well as other adverse events, including nausea and vomiting, itching, delirium, dizziness, chills, and respiratory depression (SpO2

Abstract Low-density neutrophils (LDNs) have been described in tumors and various autoimmune diseases, where they exhibit immune dysfunction and alter disease progression. Nevertheless, LDNs have been rarely reported in sepsis. We studied sepsis patients admitted to the intensive care unit. Wright-Giemsa stain assay and Transmission electron microscopy were performed to detect the morphology of neutrophils. Flow cytometry was used to analyze the number and function of LDNs. Concentration of cytokines was measured using ELISA. Neutrophil chemotaxis was examined using an under-agarose chemotaxis model. We found that LDNs were significantly elevated in patients with sepsis. Phenotypes and morphological characteristics suggest that LDNs may be formed by mixtures of neutrophils at various maturation stages. In vitro experiments showed that LDN formation was closely associated with neutrophil degranulation. We preliminarily discussed changes in immune function in LDNs. Compared with high-density neutrophils, expression levels of CXC chemokine receptor 4 on LDN surfaces were increased, phagocytotic capacity was decreased, and life span was prolonged. The chemotactic ability of LDNs was significantly reduced, possibly related to the increased expression of P2X1. These data suggest that LDNs are essential components of neutrophils in sepsis. To clarify the source and dysfunction mechanism of LDN in sepsis may be helpful for the diagnosis and treatment of sepsis in the future.

The catalytic production of higher alcohols (HAs) is a promising path for converting CO2 into value-added chemical products. The application is still limited by the low selectivity of HAs (less than 10%) on most catalysts. Here, we report a tandem catalyst consisting of Mn-Cu-K modified iron carbide and CuZnAlZr catalyst. The modification of iron carbide with Mn, Cu and K promoters improves the formation of HAs (13.5% Sel.), and the construction of tandem catalysts with CuZnAlZr can further enhance the catalytic performance. By examining different catalyst filling methods and the filling ratio of the tandem catalyst, it was found that the powder mixing resulted in a higher selectivity of HAs with a mass ratio of the two components of 1:1, and a synergistic effect leads to a higher selectivity of HAs (15.5%) with about 40% of propanol and butanol among HAs.

The challenging nature of nearshore tunnel construction environments introduces a multitude of potential hazards, consequently escalating the likelihood of incidents such as water influx. Existing construction safety risk management methodologies often depend on subjective experiences, leading to inconsistent reliability in assessment outcomes. The multifaceted nature of construction safety risk factors, their sources, and structures complicate the validation of these assessments, thus compromising their precision. Moreover, risk assessments generally occur pre-construction, leaving on-site personnel incapable of recommending pragmatic mitigation strategies based on real-time safety issues. To address these concerns, this paper introduces a construction safety risk assessment approach for nearshore tunnels based on multi-data fusion. In addressing the issue of temporal effectiveness when the conflict factor K in traditional Dempster–Shafer (DS) evidence theory nears infinity, the confidence Hellinger distance is incorporated for improvement. This is designed to accurately demonstrate the degree of conflict between two evidence chains. Subsequently, an integrated evaluation of construction safety risks for a specific nearshore tunnel in Ningbo is conducted through the calculation of similarity, support degree, and weight factors. Simultaneously, the Revit secondary development technology is utilized to visualize risk monitoring point warnings. The evaluation concludes that monitoring point K7+860 exhibits a level II risk, whereas other monitoring points maintain a normal status.

The function and heterogeneity of neutrophils in neonatal umbilical cord blood (UCB) have not been characterized. In this study, we analyzed the neutrophils in UCB and healthy adults using single-cell RNA sequencing analysis for the first time. We found that neutrophils divided into six subpopulations (G2, G3, G4, G5a, G5b, and G5c) with different marker genes and different functions under homeostasis. Compared with healthy adults, neutrophils of UCB were more naïve and have more obvious degranulation and activation functions. Moreover, we found significant differences in the amount and function of G5b cells between healthy adults and UCB. The amount of G5b group in UCB was lower, but it has more degranulation, secretion and activation functions. In addition, we noted a new subset of G5c labeled by CD52, which almost did not exist in UCB. Besides, its differential genes were enriched in terms such as protein synthesis and mRNA transcription. Furthermore, uncharacteristic transcription factors ZNF-276, ZNF-319 and ZNF-354A were identified in our study. In summary, we first examined the heterogeneity and functional diversity of neutrophils in UCB, and these data provided new insights into the mechanism of neutrophil-mediated diseases of neonates and the wider use of neutrophils in UCB.

Fungal cellulases usually contain a family 1 carbohydrate-binding module (CBM1), and its role was considered to recognize the substrate specifically. This study testified that the CBM1s derived from cellobiohydrolase I of Trichoderma reesei, Penicillium oxalicum, and Penicillium funiculosum could be used as an effective accessory protein in cellulase cocktails to enhance the saccharification of lignocellulose, and its enhancement effect was significantly superior to some reported accessory proteins, such as bovine serum albumin (BSA). The promoting effects of the CBM1s were related to not only the CBM1 sources and protein dosages, but also the substrate characteristics and solid consistency during enzymatic hydrolysis. The adsorption capacity of the CBM1s, the adsorption kinetic of TrCBM from T. reesei and cellobiohydrolase, endoglucanase, and β-glucosidase from P. oxalicum, and the effect of adding TrCBM on enzyme activities of free cellulases in the hydrolysis system were investigated, and the binding conformations and affinities of CBM1s to cellulose and lignin were predicted by molecular docking. It was speculated that the higher affinity of the CBM1s to lignin than cellulases could potentially enable the CBM1s to displace cellulase adsorbed on lignin or to preferentially adsorb onto lignin to avoid ineffective adsorption of cellulase onto lignin, which enhanced cellulase system efficiency during enzymatic hydrolysis of lignocellulose.

Abstract Background Although the immune function of neutrophils in sepsis has been well described, the heterogeneity of neutrophils remains unclear during the process of sepsis. Methods In this study, we used a mouse CLP model to simulate the clinical scenario of patients with sepsis, neutrophil infiltration, abnormal distribution and dysfunction was analyzed. LPS was used to stimulate neutrophils in vitro to simulate sepsis; single-cell gene sequencing technology was used to explore the immunological typing. To explore the immunological function of immunosuppressive neutrophils, PD-L1 knockout neutrophils were cocultured with lymphocytes from wild-type mice. Results We found that neutrophils presented variant dysfunction at the late stage of sepsis, including inhibition of apoptosis, seriously damaged chemotaxis and extensive infiltration into the tissues. Single-cell RNA sequencing revealed that multiple subclusters of neutrophils were differentiated after LPS stimulation. The two-dimensional spatial distribution analysis showed that Foxp3+ T cells were much closer to Ly-6G than the CD4+ and CD8+ cells, indicating that infiltrated neutrophils may play immunomodulatory effect on surrounding T-regs. Further observations showed that LPS mediates PD-L1 over expression through p38α-MSK1/-MK2 pathway in neutrophils. The subsets of highly expressed PD-L1 exert immunosuppressive effect under direct contact mode, including inhibition of T cell activation and induction of T cell apoptosis and trans-differentiation. Conclusions Taken together, our data identify a previously unknown immunosuppressive subset of neutrophils as inhibitory neutrophil in order to more accurately describe the phenotype and characteristics of these cells in sepsis.

Corn fiber, a by-product from the corn-processing industry, is an attractive feedstock for cellulosic ethanol because of its rich carbohydrate content (mainly residual starch, cellulose, and hemicellulose), abundant reserves, easy collection, and almost no transportation cost. However, the complex structure and components of corn fiber, especially hemicellulose, make it difficult to be effectively hydrolyzed into fermentable sugars through enzymatic hydrolysis. This study developed a simple and easy industrialized process without detoxification treatment for high-yield ethanol produced from corn fiber. Corn fiber was pretreated by dilute acid under the conditions optimized by Box-Behnken design (0.5% H2SO4 at 105°C for 43 min), and 81.8% of total sugars, including glucose, xylose, and arabinose, could be recovered, then the mixture (solid and hydrolysates) was directly used for semi-simultaneous saccharification and fermentation without detoxification, and ethanol yield reached about 81% of the theoretical yield.

The pathophysiological mechanisms, especially the roles of immune cells, underlying early stages of severe burn injury have not yet been fully clarified. Here, we analyzed circulating neutrophils (PMNs) in healthy donors and early burned patients by single-cell RNA sequencing to provide a comprehensive transcriptional landscape of PMNs in heterogeneity and functional multiplicity. Circulating PMNs in the healthy donors and burned groups were divided into five subgroups (G3, G4, G5a, G5b, G5c) with different functions. The dominant subsets of PMNs in homeostasis and burn injury significantly differed between groups. In addition, cells in the same subpopulation had the same core identity markers but performed different functions in healthy and burned states. Under burned conditions, PMN activation was very evident and accompanied by clear degranulation and metabolic abnormalities. Interestingly, was found that PMN activation, degranulation, chemotaxis, phagocytosis and reactive oxygen species (ROS) production in burned patients significantly differed between day 1 and days 2 or 3, thus providing a theoretical basis for PMN interventions in early burn stages. Significantly, previously undescribed transcription factors were also identified, including ZNF-787, ZNF-467, ZNF-189, ZNF-770, ZNF-262. In conclusion, this study conducted for the first time a detailed analysis of the heterogeneity and functional multiplicity of PMNs in early stages of severe burn injuries. Our findings attempted to clarify the influence of PMN heterogeneity on the pathophysiology and related mechanisms of burn injuries, which can provide new ideas for further research in burn intervention.

Enrofloxacin (ENR) is one of the most common drugs used in poultry production to treat bacterial diseases, and there is a high risk of drug interactions (DDIs) between polyether anticoccidial drugs added to poultry feed over time. This may affect the efficacy of antibiotics or lead to toxicity, posing a potential risk to the environment and food safety. This study aimed to investigate the DDI of ENR and salinomycin (SAL) in broilers and the mechanism of their DDI. We found that SAL increased the area under the curve and elimination half-life of ENR and ciprofloxacin (CIP) by 1.3 and 2.4 times, 1.2 and 2.5 times, respectively. Cytochrome 3A4 (CYP3A4), p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) were important factors for the DDI between ENR and SAL in broilers. ENR and SAL are substrates of CYP3A4, P-gp and BCRP in broilers; ENR and SAL inhibited the expression of CYP3A4 activity in a time- and concentration-dependent. Meanwhile, ENR downregulated the expression of P-gp and BCRP in a time- and concentration-dependent manner. A single oral administration of SAL inhibited CYP3A4, P-gp, and BCRP, but long-term mixed feeding upregulated the expression of CYP3A4, P-gp, and BCRP. Molecular docking revealed that ENR and SAL compete with each other for CYP3A4 to affect hepatic metabolism, and compete with ATP for P-gp and BCRP binding sites to inhibit efflux. ENR and SAL in broilers can lead to severe DDI. Drug residues and resistance following co-administration of ENR and SAL and other SAL-based drug-feed interactions warrant further study.

Objective: Rapid eye movement (REM) sleep behavior disorder (RBD) is a disease characterized by dream enacting behavior and is now commonly believed to be a harbinger to alpha-synucleinopathy diseases such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. The aim of this study was to explore the quasi-stable topological structure of the brain in RBD by analyzing resting-state electroencephalography (EEG) microstates.Methods: We enrolled 22 participants with RBD and 46 healthy controls (HCs) with age and gender-matched. After the resting-state EEG recordings were acquired, EEG microstate features were analyzed to assess the functional networks of all participants.Results: Significant differences in the brain topological structure and temporal characteristics of sub-second brain activity were identified between the RBD and HCs. The RBD group had a shorter average duration of microstate A and microstate D when compared with HCs, and microstate B contributed more, while microstate D contributed significantly less to the RBD group. Furthermore, the average duration and proportion of microstate D were negatively correlated with the RBD questionnaire Hong Kong (RBDQ-HK) score.Conclusion: The result of this study indicates that the microstate dynamics is disturbed in RBD, which might jeopardize the flexibility and adaptability of the brain. Microstates are potential biomarkers to explore the early electrophysiological abnormality of alpha-synucleinopathy diseases.

Abstract Background Harpins are proteins secreted by the type III secretion system of Gram-negative bacteria during pathogen–plant interactions that can act as elicitors, stimulating defense and plant growth in many types of non-host plants. Harpin-treated plants have higher resistance, quality and yields and, therefore, harpin proteins may potentially have many valuable agricultural applications. Harpins are characterized by high thermal stability at 100 °C. However, it is unknown whether harpins are still active at temperatures above 100 °C or whether different temperatures affect the activity of the harpin protein in different ways. The mechanism responsible for the heat stability of harpins is also unknown. Results We identified a novel harpin, HpaXpm, from the cassava blight bacteria Xanthomonas phaseoli pv. manihotis HNHK. The predicted secondary structure and 3-D structure indicated that the HpaXpm protein has two β-strand domains and two major α-helical domains located at the N- and C-terminal regions, respectively. A phylogenetic tree generated using the maximum likelihood method grouped HpaXpm in clade I of the Hpa1 group along with harpins produced by other Xanthomonas spp. (i.e., HpaG-Xag, HpaG-Xcm, Hpa1-Xac, and Hpa1Xm). Phenotypic assays showed that HpaXpm induced the hypersensitive response (HR), defense responses, and growth promotion in non-host plants more effectively than Hp1Xoo (X. oryzae pv. oryzae). Quantitative real-time PCR analysis indicated that HpaXpm proteins subjected to heat treatments at 100 °C, 150 °C, or 200 °C were still able to stimulate the expression of function-related genes (i.e., the HR marker genes Hin1 and Hsr203J, the defense-related gene NPR1, and the plant growth enhancement-related gene NtEXP6); however, the ability of heat-treated HpaXpm to induce HR was different at different temperatures. Conclusions These findings add a new member to the harpin family. HpaXpm is heat-stable up to 200 °C and is able to stimulate powerful beneficial biological functions that could potentially be more valuable for agricultural applications than those stimulated by Hpa1Xoo. We hypothesize that the extreme heat resistance of HpaXpm is because the structure of harpin is very stable and, therefore, the HpaXpm structure is less affected by temperature.

Zero-valent iron permeable reactive barrier (ZVI-PRB) has attracted great attention for its high efficiency and low cost in the in-site remediation process. However, passivating oxide layers are usually yielded and covered on the surface of ZVI, which shorten the service life of PRB. In this study, Morganella morganii subsp was used to hydrolyse the passivating oxide layers on ZVI. The hydrolysing condition was optimized. The highest Cr(VI) removal efficiency was achieved with glucose of 4 g/L, yeast powder of 6 g/L and pH = 7. With Morganella morganii subsp, the maximum removal quality of ZVI was increased from 19.96 mg/g to 24.35 mg/g, indicating Morganella morganii subsp could improve the reduction ability of ZVI. SEM-EDS analysis also showed that M. morganii subsp could promote the surface corrosion of ZVI and adsorb Cr simultaneously.

Microbial transformation is an environment-friendly approach to produce diosgenin from natural plant tubers. However, improving the bioconversion efficiency of this process remains a challenge. Saponin hydrolase plays a major role during the transformation. a-rhamnase, b-glycosidase and C3 b-glycosidase have been identified as three key enzymes in the stepwise conversion of saponins to diosgenin. The three enzymes have not been molecularly characterized. Here, a-rhamnase, b-glycosidase and C3 b-glycosidase were purified from Trichoderma reesei, Trichoderma viride and Aspergillus fumigatus, respectively. SDS-polyacrylamide gel electrophoresis showed that the molecular masses of the three enzymes were approximately 60, 36 and 56 kDa, respectively. a-rhamnase could efficiently hydrolyse the terminal rhamnoside on the C3 site in saponins. b-glycosidase could cleave the terminal b-glycoside at the C3 position, while C3 b-glycosidase demonstrated significant affinity to the b-glycoside at the C3 position. The amino acid sequences of the three saponin hydrolases were determined. Reverse transcription-PCR was used to clone the three plasmids with lengths of approximately 1035, 1416 and 1752 bp from the strains and expressed in Escherichia coli. The recombinant saponin hydrolases from the recombinant strains also demonstrated the hydrolysing of rhamnoside and glycosides of saponins similar to those of the wild-type hydrolases from T. reesei, T. viride, and A. fumigatus. The findings could facilitate the construction of recombinant cells by gene fusion to produce diosgenin from plant tubers.

Background: The mental health status of older men is affected by several factors. Perceived social support, rumination, sleep quality, and physical activity are key factors that affect the mental health status of men over 60 years old. The mechanisms of their interactions have not been fully elucidated. The purpose of this research was to explore the relationship and interaction mechanisms among perceived social support, rumination, physical activity and sleep quality. The differences in physical activity levels of individuals in different characteristics groups were also investigated. Methods: A total of 296 valid questionnaires were collected and the participants had a mean age of 69.94 ± 7.97. The Perceived Social Support (PSS), Ruminative Responses Scale (RRS), Pittsburgh Sleep Quality Index (PSQI), and the International Physical Activity Questionnaire (IPAQ) were administered to older men in Guangdong Province over 60 years old to collect data on perceived social support, rumination, physical activity and sleep quality. The established hypotheses were tested using mediation model and moderation model. The mediating effect of rumination between perceived social support and sleep quality and the moderating effect of physical activity between perceived social support and sleep quality were examined. Results: (1) The findings showed that the levels of physical activity varied significantly based on characteristics variables such as age, perceived age, residence, and amount of housework undertaken. (2) Perceived social support was negatively correlated with rumination and poor sleep quality, and rumination was positively correlated with poor sleep quality. (3) Rumination partially mediated the relationship between perceived social support and sleep quality, with a mediating effect of 36.9%. (4) Physical activity moderated the relationship between perceived social support and sleep quality, with a significant moderating effect observed for moderate-high intensity physical activity compared with low intensity physical activity. Conclusions: Older men who perceived social support reduced rumination level and improved sleep quality. Moderate-high physical activity positively modulated the relationship between perceived social support and sleep quality more effectively than low physical activity level. The present findings can be used to establish recommendations and measures to improve the mental health of older men.

Based on hybrid wavelength pumping and tapered Yb-doped fibers (T-YDFs), a 650 W all-fiber single-frequency polarization-maintaining fiber amplifier was demonstrated experimentally at 1030 nm. Different pump power ratios in the T-YDF-based power-amplifier stage were proposed to investigate their influence on the transverse mode instability (TMI) effect. The highest TMI threshold was obtained when the pump power ratio of 940 nm to 976 nm was 1:4.4. A measured M2 factor of 1.7 and a polarization extinction ratio of 14 dB at the maximum output power were obtained. To the best of our knowledge, these results exhibit the highest output power of any all-fiber single-frequency polarization-maintaining fiber amplifiers created up to now.

A 1560 nm high-power linearly-polarized all-fiber single-frequency narrow-linewidth laser with near diffraction-limited beam quality is demonstrated. The Yb–Er energy transfer efficiency and the ability of the signal laser to capture pump light have been improved by specifically choosing the pumping wavelength and the input signal power in the final power amplifier stage of this laser system. Under the off-peak absorption pumping wavelength of 940 nm, along with the maximum input signal power of 6 W, a maximum output power of 102 W with a slope efficiency of 40.5% is acquired. At the highest output power status, a polarization extinction ratio (PER) of 15.5 dB, a linewidth of 3.05 kHz, and a beam quality of Mx2 = 1.14, My2 = 1.06 are obtained, respectively. This advanced single-frequency fiber laser has great potential for the long-range coherent Doppler lidar and the next generation of gravitational wave detection.

Abstract Objectives To evaluate the value of chemotactic function of neutrophils in patients with severe infections. Methods A computer vision‐based cellular chemotaxis analysis platform was established for the dynamic assessment of neutrophil chemotaxis. Fifty‐three patients in the intensive care unit were eligible for the study. In parallel, 142 healthy volunteers were recruited to detect and establish the normal values for chemotactic function. Four chemotactic function indicators were determined–chemotaxis distance (CD), chemotaxis cell ratio (CCR), chemotaxis index (CI) and maximum speed of chemotaxis (Vmax). The chemotaxis function scores (CFS) were calculated for further correlation analysis with clinical data. Results The normal ranges of indicators were established as CD ≥ 1755.85 µm, CCR ≥ 3.34%, CI ≥ 39.63, Vmax ≥ 14.63 µm min−1 and CFS ≥ 15. We found that the chemotactic function of neutrophils in patients suffering from infections was significantly impaired. The mean values of CD, CCR, CI, Vmax and CFS were 1452.8 µm (P

ABSTRACT Chromoblastomycosis is a chronic fungal infection. Itraconazole and terbinafine are the most recommended antifungal drugs for chromoblastomycosis, while amphotericin B is not usually recommended. A patient with chromoblastomycosis in our hospital showed poor clinical responses to itraconazole and terbinafine. The fungus isolated from the lesions of this patient was identified as Fonsecaea nubica and numbered zssy0803. In vitro antifungal susceptibilities of F. nubica zssy0803 to terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin were evaluated, as well as the combinations of terbinafine with the other four antifungals. The combined effect of terbinafine and amphotericin B on other 20 clinical F. nubica strains was also evaluated. The minimal inhibitory concentrations of terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin on F. nubica zssy0803 were 0.25 μg/mL, 2 μg/mL, 1 μg/mL, 4 μg/mL and 8 μg/mL, respectively. The combination of terbinafine and amphotericin B showed the lowest fractional inhibitory concentration index of 0.28 to F. nubica zssy0803 in comparison with combinations of terbinafine and the other four antifungal drugs. The combination of terbinafine and amphotericin B was also synergistic for all the other 20 F. nubica strains. Then, the combination of oral terbinafine (500 mg/day) and intralesional injections of amphotericin B (1 mg/mL) was used to treat this patient. After this combined therapy for 25 weeks and terbinafine monotherapy for additional 12 weeks, the patient was cured. These findings indicate for the first time that terbinafine and amphotericin B are synergistic in killing F. nubica both in vitro and in vivo.