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Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China’s primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.

Objective To study the mechanism by which conditioned medium of bone marrow mesenchymal stem cells (BMSCs-CM) facilitates the transition of pro-inflammatory polarized microglia to an anti-inflammatory phenotype. Methods BV2 cells, a mouse microglia cell line, were transformed into a pro-inflammatory phenotype using lipopolysaccharide. The expression of phenotypic genes in BV2 cells was detected using real-time quantitative PCR (RT-qPCR). Enzyme-linked immunosorbent assay was used to measure inflammatory cytokine levels in BV2 cells co-cultured with BMSCs-CM. The expressions of mitophagy-associated proteins were determined using western blot. The mitochondrial membrane potential and ATP levels in BV2 cells were measured using JC-1 staining and an ATP assay kit, respectively. Additionally, we examined the proliferation, apoptosis, and migration of C8-D1A cells, a mouse astrocyte cell line, co-cultured with BV2 cells. Results After co- culture with BMSCs -CM, the mRNA expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase significantly decreased in pro-inflammatory BV2 cells, whereas the expression of CD206 and arginase-1 significantly increased. Moreover, TNF-α and interleukin-6 levels significantly decreased, whereas transforming growth factor-β and interleukin-10 levels significantly increased. Furthermore, co-culture with BMSCs-CM increased mitophagy-associated protein expression, ATP levels, mitochondrial and lysosomal co-localization in these cells and decreased reactive oxygen species levels. Importantly, BMSCs-CM reversed the decrease in the proliferation and migration of C8-D1A cells co-cultured with pro-inflammatory BV2 cells and inhibited the apoptosis of C8-D1A cells. Conclusion BMSCs-CM may promote the transition of polarized microglia from a pro-inflammatory to an anti-inflammatory phenotype by regulating mitophagy and influences the functional state of astrocytes.

Migraine is a prevalent and disabling neurovascular disorder, with women being more susceptible, characterized by unilateral throbbing headache, often accompanied by nausea and vomiting, and often associated with various comorbidities such as brain and cardiovascular diseases, which can have a serious impact on quality of life. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the main first-line medications for the treatment of pain, long-term use often leads to side effects and drug addiction, which emphasizes the need to investigate alternative pain management strategies with fewer adverse effects. Complementary and alternative medicine is a viable pain intervention often used in conjunction with traditional medications, including acupuncture, herbs, moxibustion, transcutaneous electrical stimulation, bio-supplements, and acupressure, which offer non-pharmacological alternatives that are now viable pain management options. This review focuses on the mechanistic doctrine of migraine generation and the role and potential mechanisms of Complementary and Alternative Therapies (CAT) in the treatment of migraine, summarizes the research evidences for CAT as an adjunct or alternative to conventional therapies for migraine, and focuses on the potential of novel migraine therapies (calcitonin gene-related peptide (CGRP) antagonists and pituitary adenylyl cyclase-activating peptide (PACAP) antagonists) with the aim of evaluating CAT therapies as adjunctive or alternative therapies to conventional migraine treatment, thereby providing a broader perspective on migraine management and the design of treatment programs for more effective pain management.

The azimuth axis drive and control of large telescopes based on Segmented Arc Permanent Magnet Synchronous Motor (SAPMSM) is a current research hotspot, and issues such as unknown parameters and external interference are important factors affecting its tracking accuracy. This paper proposes a SAPMSM perturbation suppression strategy for large telescopes based on port-controlled Hamiltonian (PCH) theory. In this study, the Hamiltonian mathematical model of SAPMSM is established and the current controller of the SAPMSM is designed to reduce harmonics by configuring the required interconnection and damping matrix. In order to further improve the accuracy and anti-disturbance performance of speed feedback, a Generalized Proportional Integral Observer (GPIO) is selected for total disturbance observation, estimation and compensation. The experimental results indicated that the algorithm proposed in this paper has lower harmonic content in the phase current of the SAPMSM, which can ensure good position tracking ability and anti-interference performance of large telescopes.

Abstract Limited data exists on the association between Direct bilirubin (DBIL) and Indirect bilirubin (IBIL) with the risk of chronic kidney disease (CKD) among patients with hypertension. This study aimed to assess the relationship between DBIL and IBIL with the risk of CKD in a cohort of Chinese adults diagnosed with hypertension. This study included 14 182 Chinese patients with hypertension between the ages of 27 and 96. CKD, the outcome variable, was defined by an estimated glomerular filtration rate (eGFR)

The dynamic mechanical behavior and cushioning performance of honeycomb sandwich panels, which are extensively employed in product cushioning packaging due to their exceptional energy absorption capabilities, were examined using a combination of experimental and numerical methods. Several factors, such as maximum acceleration–static stress, cushioning coefficient–static stress, and other curves, were analyzed under various impact conditions. The simulated stress–strain, deformation modes, cushioning coefficients, and other parameters demonstrate consistency with the experimental results. The acceleration, maximum compression, and cushioning coefficient obtained from the experiment and simulation calculation were 30.68 g, 15.44 mm, and 2.65, and 31.96 g, 14.91 mm, and 2.79, respectively. The results indicate that all error values were less than 5%, confirming the precision and reliability of the model. Furthermore, the model was utilized to simulate and predict the cushioning performance of honeycomb sandwich panels with different cell structures and paper thicknesses. These results provide a solid basis for enhancing the design of subsequent honeycomb element structures.

In China, cadmium (Cd) stress has a significant role in limiting the development and productivity of purple flowering stalks (Brassica campestris var. purpuraria). Exogenous selenium supplementation has been demonstrated in earlier research to mitigate the effects of Cd stress in a range of plant species; nevertheless, the physiological and molecular processes by which exogenous selenium increases vegetable shoots’ resistance to Cd stress remain unclear. Purple flowering stalks (Brassica campestris var. purpuraria) were chosen as the study subject to examine the effects of treatment with sodium selenite (Na2SeO3) on the physiology and transcriptome alterations of cadmium stress. Purple flowering stalk leaves treated with exogenous selenium had higher glutathione content, photosynthetic capacity, and antioxidant enzyme activities compared to the leaves treated with Cd stress alone. Conversely, the contents of proline, soluble proteins, soluble sugars, malondialdehyde, and intercellular CO2 concentration tended to decrease. Transcriptome analysis revealed that 2643 differentially expressed genes (DEGs) were implicated in the response of exogenous selenium treatment to Cd stress. The metabolic pathways associated with flavonoid production, carotenoid synthesis, glutathione metabolism, and glucosinolate biosynthesis were among those enriched in these differentially expressed genes. Furthermore, we discovered DEGs connected to the production route of glucosinolates. This work sheds fresh light on how purple flowering stalks’ tolerance to cadmium stress is improved by exogenous selenium.

Objectives: To study the value of standardized volume and intravoxel incoherent motion (IVIM) parameters of the spleen based on tumor burden for predicting treatment response in newly diagnosed acute leukemia (AL). Methods: Patients with newly diagnosed AL were recruited and underwent abdominal IVIM diffusion-weighted imaging within one week before the first induction chemotherapy. Quantitative parameters of magnetic resonance imaging (MRI) included the standardized volume (representing volumetric tumor burden) and IVIM parameters (standard apparent diffusion coefficient [sADC]; pure diffusion coefficient [D]; pseudo-diffusion coefficient [D∗]; and pseudo-perfusion fraction [f], representing functional tumor burden) of the spleen. Clinical biomarkers of tumor burden were collected. Patients were divided into complete remission (CR) and non-CR groups according to the treatment response after the first standardized induction chemotherapy, and the MRI and clinical parameters were compared between the two groups. The correlations of MRI parameters with clinical biomarkers were analyzed. Multivariate logistic regression was performed to determine the independent predictors for treatment response. Receiver operating characteristic curves were used to analyze the predicted performance. Results: 76 AL patients (CR: n = 43; non-CR: n = 33) were evaluated. Standardized spleen volume, sADC, D, f, white blood cell counts, and lactate dehydrogenase were significantly different between CR and non-CR groups (all p

BackgroundUncertainty still remained about the relationship between visceral adiposity index (VAI) and hyperuricemia. The aim of this study was to investigate whether VAI was an independent risk factor for hyperuricemia in hypertensive Chinese patients.MethodsA cross-sectional study including 13176 hypertensive participants (6478 males) recruited from Wuyuan County, Jiangxi province, was conducted. All patients received anthropometric measurements, completed questionnaires and provided blood samples for biochemical testing. VAI was calculated by waist circumference, BMI, triglyceride and high-density lipoprotein cholesterol. Hyperuricemia was defined as serum uric acid ≥ 7 mg/dL in men and ≥ 6 mg/dL in women.ResultsOverall, the average level of uric acid was 7.8 ± 2.0 mg/dL in males and 6.34 ± 1.78 in females and prevalence of hyperuricemia was 61.4% and 51.30%, respectively. In multivariate logistic regression analysis, the risk of hyperuricemia increased 1.77 times and 1.88 times with the increase of ln VAI in males (OR:1.77, 95% CI: 1.62, 1.94) and females (OR:1.88, 95% CI: 1.73, 2.04). For males, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.34 (95% CI: 1.14, 1.57),1.82(95% CI: 1.54, 2.14) and 2.97 (95% CI: 2.48, 3.57). For females, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.48 (95% CI: 1.28, 1.72), 1.99 (95% CI: 1.71, 2.32) and 2.92 (95% CI: 2.50, 3.42).ConclusionsThis study found that VAI was an independent risk factor for hyperuricemia among hypertensive patients, which may provide some strategies for reducing the level of uric acid.

BackgroundEpithelial ovarian tumors (EOTs) are a group of heterogeneous neoplasms. It is importance to preoperatively differentiate the histologic subtypes of EOTs. Our study aims to investigate the potential of radiomics signatures based on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps for categorizing EOTs.MethodsThis retrospectively enrolled 146 EOTs patients [34 with borderline EOT(BEOT), 30 with type I and 82 with type II epithelial ovarian cancer (EOC)]. A total of 390 radiomics features were extracted from DWI and ADC maps. Subsequently, the LASSO algorithm was used to reduce the feature dimensions. A radiomics signature was established using multivariable logistic regression method with 3-fold cross-validation and repeated 50 times. Patients with bilateral lesions were included in the validation cohort and a heuristic selection method was established to select the tumor with maximum probability for final consideration. A nomogram incorporating the radiomics signature and clinical characteristics was also developed. Receiver operator characteristic, decision curve analysis (DCA), and net reclassification index (NRI) were applied to compare the diagnostic performance and clinical net benefit of predictive model.ResultsFor distinguishing BEOT from EOC, the radiomics signature and nomogram showed more favorable discrimination than the clinical model (0.915 vs. 0.852 and 0.954 vs. 0.852, respectively) in the training cohort. In classifying early-stage type I and type II EOC, the radiomics signature exhibited superior diagnostic performance over the clinical model (AUC 0.905 vs. 0.735). The diagnostic efficacy of the nomogram was the same as that of the radiomics model with NRI value of -0.1591 (P = 0.7268). DCA also showed that the radiomics model and combined model had higher net benefits than the clinical model.ConclusionRadiomics analysis based on DWI, and ADC maps serve as an effective quantitative approach to categorize EOTs.

Abstract Three‐dimensional porous graphene (3D‐PG) has attracted much attention due to its excellent electrochemical performance. Chemical reduction is one of common methods for preparing porous graphene. In order to develop a green and facile method for preparing three‐dimensional porous graphene, in this paper, 3D‐PG was fabricated by reduction of graphene oxide (GO) with ascorbic acid (AA) as reductant in hydrothermal condition based on non‐toxic, non‐flammable and mild reducing performance of ascorbic acid. It was found that the size and distribution of pores could be controlled by the reduction time and the concentration of AA in the solution. The pore sizes in R0, R1 and R2 were in the range of 0.5–1 μm, 1–1.5 μm, and 1.5–3 μm, respectively. It was found that the average pore size and volume increased along with the amount of reductants. Under optimal conditions – a reaction time of 20 h and a ratio of GO to AA=1 : 1 – the CV area of the so‐obtained sample R1‐20 at 100 mV was 0.06 and the specific capacitance of the 3D‐PG electrode reaches 153.5 F ⋅ g−1, which is suitable for use in supercapacitors.

Bone marrow is one of the most important organs in the human body. The evaluation of bone marrow microstructure and gender-related cellular and capillary networks in healthy young adults can help to better understand the process of bone metabolism. Intravoxel incoherent motion (IVIM) provides both diffusion and perfusion quantifications without requiring intravenous contrast agent injection. In this prospective study, 60 healthy young age-matched volunteers (30 men and 30 women) underwent MRI scans at 1.5 T using multi–b-value diffusion-weighted imaging on sagittal planes covering the lumbar bone marrow. The apparent diffusion coefficient (ADC), true ADC (D), pseudo-ADC (D*), and perfusion fraction (f) were calculated from the diffusion-weighted images using the mono- and bi-exponential models. Lumbar cancellous bone (L2–L4) was selected as the region of interest. An independent t-test was used to detect significant differences in ADC values and IVIM parameters between men and women. The differences in IVIM parameters among the L2, L3, and L4 groups were compared with analysis of variance. The D and f values in women were significantly higher than that in men (p = 0.001, 0.026). However, D* was significantly lower in women than that in men (p = 0.001). Furthermore, there was no significant gender difference for the conventional ADC value (p = 0.186). Moreover, there were no significant differences in the D, f, and D* values among the L2, L3, and L4 vertebras of women or men. IVIM parameters can show differences in bone marrow between young women and men. As a non-invasive method, it can assess bone marrow microstructure, such as cellularity and perfusion.

Background and aimsThe relationship between the new obesity index weight-adjusted-waist index (WWI) and hyperuricemia is unclear. We aimed to explore the association of the WWI and hyperuricemia among the hypertensive population.MethodsA total of 14,078 hypertension participants with complete data were included in our study. WWI was calculated by waist circumference divided by the square root of weight. Specifically, men with 420 μmol/L and women with 360 μmol/L were considered to have hyperuricemia.ResultsThe prevalence of hyperuricemia was 61.1% in men and 51.4% in women. On the whole, multivariate logistic regression analyses found that there was a linear positive correlation of WWI with hyperuricemia in both men (OR: 1.37; 95%CI: 1.25, 1.49) and women (OR: 1.35; 95%CI: 1.26, 1.45). Subgroup analysis found that the relationship between WWI and hyperuricemia was stable in stratified subgroups (all P-interactions >.05).ConclusionWWI showed a positive association with hyperuricemia among hypertension patients.

In a previous study, we developed a dihydropteroate synthase (DHPS)-based biosensor for multi-sulfonamides (SAs), which could detect 29 SAs with IC50 values below 100 ng mL−1. The purpose of the present study was to apply the DHPS-based biosensor to different food matrices and evaluate the influence of matrix effects on the performance of the biosensor by using sulfamethazine (SMZ) as a reference analyte. The results show that different sample pretreatment procedures were required for each food sample to ensure the accuracy and precision of the biosensor. The limit of detection (LOD) for SMZ in chicken, pork, egg and honey was 17.82, 20.55, 23.22, and 5.57 μg kg−1, respectively. The recovery values ranged from 47.6% to 135.1%, and the coefficients of variation (CV) were less than 25.6%. Taken together, our findings show that the DHPS-DHPPP biosensor is a suitable screening method for the screening of multi-SAs in different food matrices.

Abstract Background Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expression, influencing the development of diseases. Results To investigate the alterations of microRNA profiling in negative lens-induced myopia (NLIM) guinea pigs and to explore the regulatory role of microRNAs in the occurrence and the development of myopia, we first established the NLIM guinea pig model after induction for 2 weeks. Further, we isolated sclera to purify total messenger RNA (mRNA) in both NLIM and NLIM fellow sclera. Using next generation sequencing technique and bioinformatics analysis, we identified the differentially expressed microRNAs in NLIM guinea pigs, performed the bioinformatics annotation for the differentially expressed microRNAs, and validated the expression of differentially expressed microRNAs. As a result, we successfully established an NLIM model in guinea pigs, identified 27 differentially expressed microRNAs in NLIM guinea pig sclera, including 10 upregulated and 17 downregulated microRNAs. The KEGG annotation showed the main signaling pathways were closely associated with PPAR signaling, pyruvate and propanoate metabolisms, and TGF-beta signaling pathways. Conclusions Our findings indicate that the development of myopia is mainly involved in the disorder of metabolic processes in NLIM guinea pigs. The PPAR signaling, pyruvate and propanoate metabolism pathways may play roles in the development of myopia.

Order financing, as an innovative business in the financial supply chain model of banks and other financial institutions, has served more and more small and medium-sized enterprises in recent years, and has also brought new profit points to the financial and logistics industries. Businesses urgently need to carry out relevant risk evaluation research on the risks brought by banks and other financial institutions. Based on this background, this article has carried out relevant research on the construction and evaluation method of the risk evaluation index system of order financing business. Through project research and literature review, the research on the risk evaluation theory and method of order financing carried out by banks and other financial institutions is not perfect. The role-played in order financing and the key risk variables faced by financial institutions, and innovatively proposed an evaluation method based on the logistics model. Based on the analysis of order financing risk factors, and through literature review and expert interviews, an evaluation index system initially constructed from five aspects: financing companies, downstream core companies, logistics companies, supply chain operations and external environment. Through questionnaire surveys and statistical analysis of the survey results, a complete, qualitied the risk evaluation index system for order financing business was finally determined. Taking the order-financing project jointly carried out by commercial banks and logistics companies as an example.

BackgroundBlood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup.MethodsWe conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters.ResultsOf 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090–0.507; HR: 1.066, 95% CI 1.030–1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128–0.612) and 4.458 (1.817–10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity.ConclusionLower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.

Background: Chronic kidney disease (CKD) has been a globally public health problem over the past decades. The maintenance of physical and mental health is of importance for patients nowadays. Notably, depression is prevalent and associated with various adverse events in CKD patients without dialysis. Prior studies have reported that pain, negative illness perception, pain, and low self-esteem are potential risk factors of depression, while few studies have comprehensively investigated the mechanisms among these factors and depression among this population.Purpose: This study aims to investigate the prevalence of depression and further explore the factors associated with depression among CKD patients without dialysis in China.Design and Methods: We conducted a cross-sectional study in patients with diagnosed CKD to investigate the prevalence of depression was by the Beck Depression Inventory-II (BDI-II). The data on pain interference, illness perception, and self-esteem were also collected via self-administered questionnaires. A structural equation model (SEM) was used to examine the factors associated with depression.Main Findings: From June to October 2019, we successfully interviewed 334 CKD patients at the outpatient clinics. Their mean age was 45.6 years (ranging from 19 to 74 years), and 48.5% were male. Most respondents were at early CKD stages (77.5% stage 1–3) and the prevalence of depression was 22.2%. We found a moderate association between illness perception and depression, which was modified by self-esteem. Similar but weaker association was found between pain interference and depression.Conclusion and Recommendations: Negative illness perception, low self-esteem and severe pain interference were associated with depression among Chinese CKD patients without dialysis. Future studies are warranted to investigate the underlying mechanism and formulate the intervention strategies for this high-risk population.

Background: Diabetes correlates with poor prognosis in patients with COVID-19, but very few studies have evaluated whether impaired fasting glucose (IFG) is also a risk factor for the poor outcomes of patients with COVID-19. Here we aimed to examine the associations between IFG and diabetes at admission with risks of complications and mortality among patients with COVID-19.Methods: In this multicenter retrospective cohort study, we enrolled 312 hospitalized patients with COVID-19 from 5 hospitals in Wuhan from Jan 1 to Mar 17, 2020. Clinical information, laboratory findings, complications, treatment regimens, and mortality status were collected. The associations between hyperglycemia and diabetes status at admission with primary composite end-point events (including mechanical ventilation, admission to intensive care unit, or death) were analyzed by Cox proportional hazards regression models.Results: The median age of the patients was 57 years (interquartile range 38–66), and 172 (55%) were women. At the time of hospital admission, 84 (27%) had diabetes (and 36 were new-diagnosed), 62 (20%) had IFG, and 166 (53%) had normal fasting glucose (NFG) levels. Compared to patients with NFG, patients with IFG and diabetes developed more primary composite end-point events (9 [5%], 11 [18%], 26 [31%]), including receiving mechanical ventilation (5 [3%], 6 [10%], 21 [25%]), and death (4 [2%], 9 [15%], 20 [24%]). Multivariable Cox regression analyses showed diabetes was associated increased risks of primary composite end-point events (hazard ratio 3.53; 95% confidence interval 1.48–8.40) and mortality (6.25; 1.91–20.45), and IFG was associated with an increased risk of mortality (4.11; 1.15–14.74), after adjusting for age, sex, hospitals and comorbidities.Conclusion: IFG and diabetes at admission were associated with higher risks of adverse outcomes among patients with COVID-19.

Context: Bergenin, isolated from the herb of Bergenia purpurascens (Hook. f. et Thoms.) Engl., has anti-inflammatory, antitussive, and wound healing activities. However, whether bergenin affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods: In this study, the inhibitory effects of bergenin (100 μM) on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated, enzyme kinetics and time-dependent inhibition studies were also performed in vitro using human liver microsomes (HLMs). Results: The results showed that bergenin inhibited the activity of CYP3A4, 2E1 and 2C9, with IC50 values of 14.39, 22.83 and 15.11 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that bergenin was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1 and 2C9, with Ki values of 7.71, 11.39 and 8.89 μM, respectively. In addition, bergenin is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.025/3.50 μM−1 min−1. Discussion and conclusions: The in vitro studies of bergenin with CYP isoforms indicate that bergenin has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, 2E1 and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.

Abstract Rewetting after precipitation events plays an important role in regulating soil carbon (C) and nitrogen (N) turnover processes in arid and semiarid ecosystems. Here, we conducted a 48-h rewetting simulation experiment with measurements of soil C and N mineralization rates (R C and R N, respectively) and microbial biomass N (MBN) at high temporal resolution to explore the pulse responses of R C and R N. R C and R N responded strongly and rapidly to rewetting over the short term. The maximum R C value (because of pulse effects) ranged from 16.53 to 19.33 µg C gsoil −1 h−1, observed 10 min after rewetting. The maximum R N varied from 22.86 to 40.87 µg N gsoil −1 h−1, appearing 5–6 h after rewetting. The responses of soil microbial growth to rewetting were rapid, and the maximum MBN was observed 2–3 h after rewetting. Unexpectedly, there was no correlation between R C, R N, and MBN during the process of rewetting, and R C and R N were uncoupled. In sum, the pulse responses of R C, R N, and microbial growth to simulated rewetting were rapid, strong, and asynchronous, which offers insights into the different responses of microbes to rewetting and mechanisms behind microbes.

Acrylic impact modifiers (ACRs) with different soft/hard monomer ratios (mass ratios) were prepared by semi-continuous seed emulsion copolymerization using the soft monomer butyl acrylate and the hard monomer methyl methacrylate, which were used to toughen polylactide (PLA). The effect of soft/hard ACR monomer ratio on the mechanical properties of PLA/ACR blends was investigated. The results showed that the impact strength and the elongation at break of PLA/ACR blends increased with increasing soft/hard ACR monomer ratio, while the tensile and flexural strengths of PLA had little change. The impact strength of PLA/ACR blends could be increased about 4 times more than that of pure PLA when the soft/hard monomer ratio of ACR was 90/10, which was the optimal ratio for good mechanical properties of PLA. Additionally, the possible mechanism of ACR toughening in PLA was discussed through impact fracture phase morphology analysis.

Residues Tyr59, Gly78, Ser79, Met103, Gln107, Ile136 and Glu137 in human arsenic (+3 oxidation state) methyltransferase (hAS3MT) were deduced to form a potential hydrogen bond network around S-adenosylmethionine (SAM) from the sequence alignment between Cyanidioschyzon merolae arsenite S-adenosylmethyltransferase (CmArsM) and hAS3MT. Herein, seven mutants Y59A, G78A, S79A, M103A, Q107A, I136A and E137A were obtained. Their catalytic activities and conformations were characterized and models were built. Y59A and G78A were completely inactive. Only 7.0%, 10.6% and 13.8% inorganic arsenic (iAs) was transformed to monomethylated arsenicals (MMA) when M103A, Q107A and I136A were used as the enzyme. The Vmax (the maximal velocity of the reaction) values of M103A, Q107A, I136A and E137A were decreased to 8%, 22%, 15% and 50% of that of WT-hAS3MT, respectively. The KM(SAM) (the Michaelis constant for SAM) values of mutants M103A, I136A and E137A were 15.7, 8.9 and 5.1 fold higher than that of WT-hAS3MT, respectively, indicating that their affinities for SAM were weakened. The altered microenvironment of SAM and the reduced capacity of binding arsenic deduced from KM(As) (the Michaelis constant for iAs) value probably synergetically reduced the catalytic activity of Q107A. The catalytic activity of S79A was higher than that of WT despite of the higher KM(SAM) , suggesting that Ser79 did not impact the catalytic activity of hAS3MT. In short, residues Tyr59 and Gly78 significantly influenced the catalytic activity of hAS3MT as well as Met103, Ile136 and Glu137 because they were closely associated with SAM-binding, while residue Gln107 did not affect SAM-binding regardless of affecting the catalytic activity of hAS3MT. Modeling and our experimental results suggest that the adenine ring of SAM is sandwiched between Ile136 and Met103, the amide group of SAM is hydrogen bonded to Gly78 in hAS3MT and SAM is bonded to Tyr59 with van der Waals, cation-π and hydrogen bonding contacts.

Arsenic (III) methyltransferase (AS3MT) catalyzes the process of arsenic methylation. Each arsenite (iAs(3+)) binds to three cysteine residues, methylarsenite (MMA(3+)) binds to two, and dimethylarsenite (DMA(3+)) binds to one. However, only two As-binding sites (Cys156 and Cys206) have been confirmed on human AS3MT (hAS3MT). The third As-binding site is still undefined. Residue Cys72 in Cyanidioschyzon merolae arsenite S-adenosylmethyltransferase (CmArsM) may be the third As-binding site. The corresponding residue in hAS3MT is Cys61. Functions of Cys32, Cys61, and Cys85 in hAS3MT are unclear though Cys32, Cys61, and Cys85 in rat AS3MT have no effect on the enzyme activity. This is why the functions of Cys32, Cys61, and Cys85 in hAS3MT merit investigation. Here, three mutants were designed, C32S, C61S, and C85S. Their catalytic activities and conformations were determined, and the catalytic capacities of C156S and C206S were studied. Unlike C85S, mutants C32S and C61S were completely inactive in the methylation of iAs(3+) and active in the methylation of MMA(3+). The catalytic activity of C85S was also less pronounced than that of WT-hAS3MT. All these findings suggest that Cys32 and Cys61 markedly influence the catalytic activity of hAS3MT. Cys32 and Cys61 are necessary to the first step of methylation but not to the second. Cys156 and Cys206 are required for both the first and second steps of methylation. The S(C32) is located far from arsenic in the WT-hAS3MT-SAM-As model. The distances between S(C61) and arsenic in WT-hAS3MT-As and WT-hAS3MT-SAM-As models are 7.5 Å and 4.1 Å, respectively. This indicates that SAM-binding to hAS3MT shortens the distance between S(C61) and arsenic and promotes As-binding to hAS3MT. This is consistent with the fact that SAM is the first substrate to bind to hAS3MT and iAs is the second. Model of WT-hAS3MT-SAM-As and the experimental results indicate that Cys61 is the third As-binding site.