Detection of Antibiotic Resistance in Feline-Origin ESBL Escherichia coli from Different Areas of China and the Resistance Elimination of Garlic Oil to Cefquinome on ESBL E. coli.

The development of drug-resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to the share of similar flora between pets and their owners, the detection of pet-origin antibiotic-resistant E. coli is necessary. This study aimed to detect the prevalence of feline-origin ESBL E. coli in China and to explore the resistance elimination effect of garlic oil to cefquinome on ESBL E. coli. Cat fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified by indicator media and polymerase chain reaction (PCR). ESBL genes were detected by PCR and Sanger sequencing. The MICs were determined. The synergistic effect of garlic oil and cefquinome against ESBL E. coli was investigated by checkerboard assays, time-kill and growth curves, drug-resistance curves, PI and NPN staining, and a scanning electronic microscope. A total of 80 E. coli strains were isolated from 101 fecal samples. The rate of ESBL E. coli was 52.5% (42/80). The prevailing ESBL genotypes in China were CTX-M-1, CTX-M-14, and TEM-116. In ESBL E. coli, garlic oil increased the susceptibility to cefquinome with FICIs from 0.2 to 0.7 and enhanced the killing effect of cefquinome with membrane destruction. Resistance to cefquinome decreased with treatment of garlic oil after 15 generations. Our study indicates that ESBL E. coli has been detected in cats kept as pets. The sensitivity of ESBL E. coli to cefquinome was enhanced by garlic oil, indicating that garlic oil may be a potential antibiotic enhancer.

Detection of antibiotic-resistant canine origin Escherichia coli and the synergistic effect of magnolol in reducing the resistance of multidrug-resistant Escherichia coli.

Background: The development of antimicrobial resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to daily close contact, dogs kept as pets share the same E. coli with their owners. Therefore, the detection of antimicrobial resistance in canine E. coli is important, as the results could provide guidance for the future use of antibiotics. This study aimed to detect the prevalence of antibiotic-resistance of canine origin E. coli in Shaanxi province and to explore the inhibition effect of magnolol combined with cefquinome on MDR E. coli, so as to provide evidence for the use of antibiotics. Methods: Canine fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified using various indicator media and polymerase chain reaction (PCR). Drug-resistance genes [aacC2, ant(3')-I, aph(3')-II, aac(6')-Ib-cr, aac(3')-IIe, bla KPC , bla IMP-4 , bla OXA , bla CMY , bla TEM-1 , bla SHV , bla CTX-M-1 , bla CTX-M-9 , Qnra, Qnrb, Qnrs, TetA, TetB, TetM, Ermb] were also detected by PCR. The minimum inhibitory concentration (MIC) was determined for 10 antibiotics using the broth-microdilution method. Synergistic activity of magnolol and cefquinome against multidrug-resistant (MDR) E. coli strains was investigated using checkerboard assays, time-kill curves, and drug-resistance curves. Results: A total of 101 E. coli strains were isolated from 158 fecal samples collected from animal hospitals. MIC determinations showed that 75.25% (76/101) of the E. coli strains were MDR. A total of 22 drug-resistance genes were detected among the 101 strains. The bla TEM-1gene exhibited the highest detection rate (89.77%). The TetA and Sul gene also exhibited high detection rate (66.34 and 53.47%, respectively). Carbapenem-resistant E. coli strains were found in Shangluo and Yan'an. Additionally, in MDR E. coli initially resistant to cefquinome, magnolol increased the susceptibility to cefquinome, with an FICI (Fractional Inhibitory Concentration Index) between 0.125 and 0.5, indicating stable synergy. Furthermore, magnolol enhanced the killing effect of cefquinome against MDR E. coli. Resistance of MDR E. coli to cefquinome decreased markedly after treatment with magnolol for 15 generations. Conclusion: Our study indicates that antibiotic-resistance E. coli has been found in domestic dogs. After treatment with magnolol extracted from the Chinese herb Houpo (Magnolia officinalis), the sensitivity of MDR E. coli to cefquinome was enhanced, indicating that magnolol reverses the resistance of MDR E. coli. The results of this study thus provide reference for the control of E. coli resistance.

Resampling combined with stacking learning for prediction of blood-brain barrier permeability of compounds / 生物医学工程学杂志

It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.

Development and global validation of a 1-week-old piglet head finite element model for impact simulations / 中华创伤杂志(英文版)

PURPOSE@#Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research.@*METHODS@#In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model.@*RESULTS@#Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head.@*CONCLUSION@#This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.

Effects of knocking down TSPO on proliferation and autophagy of BV2 cells in OGD/R models / 中国药理学通报

Aim To investigate the effeets of prolifera¬tion and autophagy of BV2 eells in OGD/R models when the 18 ku transloeator protein( TSPO) was inhibi¬ted.Methods BV2 microglia were eultured in vitro and the model established by oxygen-glueose depriva- tion/reperfusion( OGD/R) , the eells were divided into eontrol group and OGD/R group, OGD/R + small hair¬pin RNA negative eontrol group ( OGD/R + NCshR- NA) , OGD/R + TSPO small hairpin RNA group (OGD/R + TSPOshRNA ).The expression of TSPO mRNA and TSPO protein were deteeted by qRT-PCR and Western blot, respectively.In order to study the effeet of TSPO on BV2 microglial eells in OGD/R inju¬ry and autophagy, the cell viability was tested by CCK- 8 assey, the cytotoxicity was deteeted by reactive oxy¬gen speeies ( ROS) , autophagy-related mRNA ( p62 mRNA, LC3B mRNA, Beolin-1 mRNA) expressions were detected by qRT-PCR, and the expression levels of autophagy -related proteins ( p62 , LC3 II /LC3 1 , Beclin-1 ) were detected by Western blot in each group.Result The expression of TSPO mRNA and protein increased significantly in OGD/R group while compared to control group, the cell death and cytotox¬icity increased significantly, the expression levels of LC3B mRNA and Beclin-1 mRNA increased, while the p62 mRNA decreased significantly, the levels of LC3 II/LC3 1 and Beclin-1 protein increased, the expres¬sion of p62 protein decreased significantly in OGD/R group, and the autophagy was activated; compared with OGD/R group, the different levels of cell viabili¬ty, cytotoxicity and autophagy in OGD/R + NCshRNA group were not statistically significant.But the survival rate of cells in OGD/R + TSPOshRNA group signifi¬cantly increased, the levels of cytotoxicity and autoph¬agy were significantly reduced.Conclusions The in¬hibition of TSPO has a significant protective effect on OGD/R injury model in BV2 microglial cells, which may be related to the inhibition of autophagy.

Effects of mangiferin on obesity complicated with type 2 diabetes in MKR mice / 中国药理学通报

Aim To investigate the mechanism of the effect of mangiferin on obesity complicated with type 2 diabetes mellitus in MKR transgenic mice. Methods MKR mice were randomly divided into model group,metformin group(0.11 g·kg-1),mangiferin low-dose group(25 mg·kg-1),mangiferin medium-dose group(50 mg·kg-1),and mangiferin high-dose group(100 mg·kg-1); FVB/N mice of the same age were used as control group. The mice were given intragastric administration for five weeks,the body weight and fasting glucose of mice were measured every week,the oral glucose tolerance(OGTT)was detected on 30th day of administration,and the insulin tolerance(ITT)was detected on 33rd day,and serum metabolic indexes were detected after administration. HE staining,oil-red O staining and Masson staining were used to observe the changes of liver morphology in mice. HE staining was used to observe the changes of fat morphology in mice. Western blot was used to detect the protein expression changes of TNF-α,IL-6,IL-1β in adipose tissues. Results High-dose mangiferin significantly reduced body weight,decreased fasting blood glucose,increased insulin content,and improved OGTT and ITT; it decreased serum triglyceride,alanine aminotransferase and aspartate aminotransferase levels; it also decreased the expression of serum IL-6 and TNF-α; it significantly reduced the expression of inflammatory factors in adipose tissues. Conclusions Mangiferin has therapeutic effects on obese MKR mice with type 2 diabetes,which is related to reducing the inflammatory response in adipose tissues.

The Establishment and Application of Flow Cytometry on the Detection of Jka Antigen in Kidd Blood Group / 中国实验血液学杂志

OBJECTIVE@#To establish a based method flow cytometry to identify the antigen Jka in human red blood cells (RBCs) and verify its accuracy.@*METHODS@#A total of 96 blood samples were enrolled in the study randomly from the voluntary blood donors in Shenzhen Blood Center. The RBCs were incubated with IgG anti-Jka primary antibody, and then labeled with the secondary antibody anti-IgG-Alexa Fluor 647. The fluorescence histograms of each sample were obtained by flow cytometry. Serological agglutination test was used to compare the accuracy of flow cytometry in the detecting of antigen Jka, while PCR-SSP and gene sequencing genotyping were used to verify the accuracy of flow cytometry in the detecting of the antigen in human RBCs.@*RESULTS@#The results of flow cytometry for antigen Jka in human RBCs were consistent with those from serological tests. Samples that demonstrated higher serological agglutination intensity also showed higher fluorescence activity, which indicate more stronger of Jka antigen. The sensitivity of flow cytometry was higher than that of serological test; especially in distinguish Jka weak and negative samples. Flow cytometric results of all samples were consistent with the genotyping results, which confirmed the accuracy of flow cytometry.@*CONCLUSION@#The study established a new flow cytometry-based method successfully for the identification of Jka antigen of Kidd blood group in human RBCs. The Kidd blood group antigen Jka of different intensities can be accurately distinguished by the technique.

Genetic analysis of COL4A4 gene in familial hematuria / 中华肾脏病杂志

Objective:To define more information for familial hematuria by genetic screening in a pedigree with familial hematuria.Methods:This was a 4 generation pedigree included 20 family members. The clinical data and laboratory manifestations of the family members were reviewed and collected from medical records. Meanwhile, the peripheral blood samples of 11 family members of the pedigree were collected, and then DNA samples were extracted by salting out method for genetic analysis. For genetic analysis, firstly, three family members including the proband were selected for whole exome sequencing, and the genetic variations were screened according to the sequence variation interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) for diagnostic sequence interpretation. Then PCR and Sanger sequencing were used to verify the identified pathogenic variants in all family members in the pedigree.Results:In the pedigree, 6 female members had persistent hematuria. Among them, 2 died due to end-stage renal disease, 2 died due to non-renal diseases, and 2 maintained stable renal function. One of the two members with stable renal function was diagnosed as IgA nephropathy by renal biopsy. Moreover, diffuse basement membrane lesions were identified in her renal biopsy sample after the electron microscope examination, which resulted in the suspected diagnosis of Alport syndrome. Genetic testing in this pedigree revealed two novel mutations in COL4A4 gene (NM_000092), c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20. Conclusion:Two novel mutations of COL4A4 gene (c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20) in a hematuria pedigree are related with phenotype of familial hematuria.

MondoA Is Required for Normal Myogenesis and Regulation of the Skeletal Muscle Glycogen Content in Mice

BackgroundSkeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear.MethodsWe generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle.ResultsMAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake.ConclusionMondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study / 生物医学与环境科学（英文）

Objective@#The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.@*Methods@#The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.@*Results@#A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).@*Conclusion@#An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

The relationship between heart rate variability and urine albumin/creatinine ratio in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To explore the relationship between heart rate variability (HRV) and urine albumin/creatinine ratio (ACR) in patients with type 2 diabetes.Methods:A total of 1 543 patients with type 2 diabetes were selected from the Department of Endocrinology of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and all the participants received 24-hour Holter monitoring and ACR measurement. HRV parameters include the standard deviation of all normal to normal intervals (SDNN), root mean square differences of successive RR intervals (rMSSD), the percent of adjacent RR intervals with a difference greater than 50 ms (PNN50), low frequency (LF), high frequency (HF), the ratio of LF to HF (LF/HF). Multivariate linear regression was used to analyze the relationship between HRV and ACR. Logistic regression was performed to further analyze the relationship between HRV and albuminuria while HRV parameter was divided into ≤25% (Q1) and ≥25% (Q2-Q4).Results:Multivariate linear regression results showed that the decrease of HRV parameters [ln(SDNN), ln(PNN50), ln(LF), ln(HF), ln(LF/HF)] was closely related to the increase of ln(ACR) (all P<0.05). Logistic regression analysis results showed that SDNN( OR=1.669, 95% CI 1.290-2.159), PNN50( OR=1.372, 95% CI 1.063-1.770), LF( OR=1.918, 95% CI 1.441-2.551), and LF/HF ( OR=1.623, 95% CI 1.220-2.183) were independent risk factors for albuminuria (all P<0.05); Furthermore, logistic regression analysis stratified by the median duration of diabetes (10 years) and cardiovascular disease found that in patients with diabetes≤10 years or without cardiovascular disease, the risk of albuminuria in the SDNN and LF Q1 group were higher than that in the Q2-Q4 group; while in patients with diabetes>10 years or with cardiovascular disease, the risk of albuminuria in the SDNN, PNN50, LF, and LF/HF Q1 group were higher than that in the Q2-Q4 group. Conclusion:The reduction of HRV parameters in patients with type 2 diabetes is closely related to the increase of ACR. With the progress of diabetes, more HRV parameters demonstrated predictive effect for risk of albuminuria.

Factors Related to Rehabilitation Outcome of Dysphagia for Patients with Cricopharyngeal Dysfunction / 中国康复理论与实践

Objective:To analyze the factors related to rehabilitation outcome of dysphagia for patients with cricopharyngeal dysfunction. Methods:From October, 2017 to December, 2020, 16 inpatients with cricopharyngeal dysfunction in Beijing Bo'ai Hospital accepted swallowing training and balloon dilatation. They also finished Shaker exercise out of treatment rooms, and the compliance was recorded. They were assessed with Ichiro Fujishima's Ingestion-Swallowing Function Rating Scale, and divided into effective and ineffective groups according to the result of assessment. The factors such as ages, education levels, courses of disease, time of treatment, compliance, balloon dilation modes, balloon dilation times and maximum water capacity of the balloon were recorded. Results:The score of swallowing improved after treatment (Z = -3.550, P < 0.001). There were significant differences between groups in age (Z = 0.833, P = 0.031) and compliance (P = 0.003). Age negatively correlated with effect (r = -0.533, P = 0.033), and compliance positively correlated (r = 0.856, P < 0.001). Conclusion:Age and compliance to rehabilitation relate to the outcome of dysphagia for patients with cricopharyngeal dysfunction. It is more effective in patients with good compliance and younger age.

MondoA Is Required for Normal Myogenesis and Regulation of the Skeletal Muscle Glycogen Content in Mice

BackgroundSkeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear.MethodsWe generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle.ResultsMAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake.ConclusionMondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.

Changing transmission dynamics of COVID-19 in China: a nationwide population-based piecewise mathematical modelling study

BackgroundThe first case of COVID-19 atypical pneumonia was reported in Wuhan, China on December 1, 2019. Since then, at least 33 other countries have been affected and there is a possibility of a global outbreak. A tremendous amount of effort has been made to understand its transmission dynamics; however, the temporal and spatial transmission heterogeneity and changing epidemiology have been mostly ignored. The epidemic mechanism of COVID-19 remains largely unclear. MethodsEpidemiological data on COVID-19 in China and daily population movement data from Wuhan to other cities were obtained and analyzed. To describe the transmission dynamics of COVID-19 at different spatio-temporal scales, we used a three-stage continuous-time Susceptible-Exposed-Infectious-Recovered (SEIR) meta-population model based on the characteristics and transmission dynamics of each stage: 1) local epidemic from December 1, 2019 to January 9, 2020; 2) long-distance spread due to the Spring Festival travel rush from January 10 to 22, 2020; and 3) intra-provincial transmission from January 23, 2020 when travel restrictions were imposed. Together with the basic reproduction number (R0) for mathematical modelling, we also considered the variation in infectivity and introduced the controlled reproduction number (Rc) by assuming that exposed individuals to be infectious; we then simulated the future spread of COVID across Wuhan and all the provinces in mainland China. In addition, we built a novel source tracing algorithm to infer the initial exposed number of individuals in Wuhan on January 10, 2020, to estimate the number of infections early during this epidemic. FindingsThe spatial patterns of disease spread were heterogeneous. The estimated controlled reproduction number (Rc) in the neighboring provinces of Hubei province were relatively large, and the nationwide reproduction number - except for Hubei - ranged from 0.98 to 2.74 with an average of 1.79 (95% CI 1.77-1.80). Infectivity was significantly greater for exposed than infectious individuals, and exposed individuals were predicted to have become the major source of infection after January 23. For the epidemic process, most provinces reached their epidemic peak before February 10, 2020. It is expected that the maximum number of infections will be approached by the end of March. The final infectious size is estimated to be about 58,000 for Wuhan, 20,800 for the rest of Hubei province, and 17,000 for the other provinces in mainland China. Moreover, the estimated number of the exposed individuals is much greater than the officially reported number of infectious individuals in Wuhan on January 10, 2020. InterpretationThe transmission dynamics of COVID-19 have been changing over time and were heterogeneous across regions. There was a substantial underestimation of the number of exposed individuals in Wuhan early in the epidemic, and the Spring Festival travel rush played an important role in enhancing and accelerating the spread of COVID-19. However, Chinas unprecedented large-scale travel restrictions quickly reduced Rc. The next challenge for the control of COVID-19 will be the second great population movement brought by removing these travel restrictions.

COVID-19 transmission in Mainland China is associated with temperature and humidity: a time-series analysis

COVID-19 has become a pandemic. The influence of meteorological factors on the transmission and spread of COVID-19 if of interest. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces (in Hubei from December 1, 2019 to February 11, 2020 and in other provinces from January 20, 2020 to Februarys 11, 2020). A Generalized Additive Model (GAM) was fitted to quantify the province-specific associations between meteorological variables and the daily cases of COVID-19 during the study periods. In the model, the 14-day exponential moving averages (EMAs) of AT and ARH, and their interaction were included with time trend and health-seeking behavior adjusted. Their spatial distributions were visualized. AT and ARH showed significantly negative associations with COVID-19 with a significant interaction between them (0.04, 95% confidence interval: 0.004-0.07) in Hubei. Every 1{degrees}C increase in the AT led to a decrease in the daily confirmed cases by 36% to 57% when ARH was in the range from 67% to 85.5%. Every 1% increase in ARH led to a decrease in the daily confirmed cases by 11% to 22% when AT was in the range from 5.04{degrees}C to 8.2{degrees}C. However, these associations were not consistent throughout Mainland China.

Target Discovery in Ralstonia solanacearum through an Activity-Based Protein Profiling Technique Based on Bioactive Oxadiazole Sulfones.

Ralstonia solanacearum is an extremely destructive and rebellious phytopathogen that can cause bacterial wilt diseases in more than 200 plant species. To explore and discover the potential targets in R. solanacearum for the purpose of developing new agrochemicals targeting this infection, here, we exploited a typical activity-based protein profiling technique for target discovery in R. solanacearum based on an activity-based probe 1 derived from bioactive oxadiazole sulfones. A total of 65 specific targets were identified with high confidence through a quantitative chemical proteomic approach. Three representative proteins (glycine cleavage system H protein, thiol peroxidase, and dihydrolipoamide S-succinyltransferase) were validated as the targets by using the immunoblotting analysis with their respective antibodies. Additionally, the in vitro interaction between the recombinant thiol peroxidase and probe 1 further confirmed that this protein was a target of oxadiazole sulfones. We anticipated that these discovered protein targets in R. solanacearum can stimulate the discovery and development of novel agrochemicals targeting bacterial infections caused by R. solanacearum.

Investigation on the mechanisms of effects of high fat and high fructose diet on rat aging / 中华内分泌代谢杂志

Objective:To investigate the mechanisms of effects of high fat and high fructose diet on rat aging.Methods:Adult male SD rats were divided into normal diet(ND) group and high fat and high fructose diet(HFHFD) group. After treatment for 48 weeks, these rats were sacrificed and the blood, liver, and brain tissues were collected. Serum triglyceride(TG), total cholesterol(TC), low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C) levels were determined by automatic biochemical analyzer. The serum levels of interluekin-2(IL-2), IL-6, and advanced glycation end products(AGEs) were measured using enzyme linked immunosorbent assay. The expressions of p16, p21, and p53 genes in the liver and brain tissues were detected by real-time quantitative PCR and western blot.Results:After 48 weeks treatment, there were significant differences in body weight and fasting plasma glucose between two groups. Serum TG, TC, and LDL-C in HFHFD group were significantly higher than those in the ND group( P<0.05), with an increase trend in HDL-C but without statistical difference. Compared with ND group, the level of IL-2 in HFHFD group was significantly decreased while the levels of IL-6 and AGEs were significantly increased(all P<0.05). The levels of p16 and p21 mRNA expressions as well as p53 and p21 protein expressions in liver and brain in HFHFD group were markedly increased compared with ND group(all P<0.05). Conclusion:Long-term high fat and high fructose diets accelerate the aging process of rats, which may be related to the damage of the immune system and the changes of cell senescence related gene expressions in liver and brain tissues.

Correlation between serum dipeptidyl peptidase 4 activity and abnormal lipid metabolism / 中华内分泌代谢杂志

Objective:Dipeptidyl peptidase 4 (DPP4) is an incretin lyase, while DPP4 inhibitors have been used clinically as hypoglycemic drugs. Serum DPP4 is related to metabolic diseases such as cardiovascular disease and obesity, and lipid metabolic disorder is an important part of metabolic syndrome. This study was designed to explore the relationship between DPP4 and lipid metabolic disorder.Methods:There were 3644 participants from Chengqiao Town, Chongming District, Shanghai. All of the subjects recruited were residents between 40-70 years old, who have not diagnosed as diabetes mellitus (DM) and who have never used any lipid-lowering drugs. Glucose, insulin, lipid level, DPP4 activity and liver enzymes in serum of all participants were tested. In addition, height, weight and blood pressure were also recorded.Results:Participants were divided into four groups (Q1-Q4) according to the quartile value of serum DPP4 activities. Along with the increase of serum DPP4 activity, triglyceride, total cholesterol, and blood glucose levels increased, and triglyceride increased from (1.23 ± 0.70) mmol/L to (2.31 ± 1.89) mmol/L. Compared with cholesterol levels, the triglyceride was more closely related to DPP4 activity [the correlation coefficients of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were 0.424, 0.281, 0.142, and 0.027, respectively]. After adjusting for confounding factors (age, gender, BMI), the result was similar. With the increase of DPP4 enzyme activity, the Q4 group had a higher risk of developing hyperglyceridemia ( OR=5.25) than the Q1 group, and the result was almost unchanged after adjusting for confounding factors and blood glucose levels ( OR=4.90). Conclusion:Serum DPP4 activity is independently related to blood lipid levels, and is particularly closely related to blood TG levels.

Effects of resistant dextrin on liver fat deposition and the AMPK signaling pathway in high-fat diet-fed mice / 中华内分泌代谢杂志

Objective:To study the effects of resistant dextrin (RD) on liver fat deposition in high-fat diet-fed (HFD) mice, and to further explore whether it can regulate the AMPK signaling pathway.Methods:Thirty-six 4-week-old male C57BL/6 mice were randomly divided into three groups: normal control group (chow), high-fat diet group (HFD), and high-fat diet+ resistant dextrin group (HFD+ RD, 10 g·kg -1·d -1). After 12 weeks of intervention, the liver tissues and serum samples were collected. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), aspartate aminotransferase (AST), alanine transaminase (ALT) levels and liver TG were measured. Liver tissue HE and oil red O staining were performed to observe hepatocyte steatosis and liver fat deposition. Quantitative real-time PCR was performed to detect the relative expression of fatty acid synthesis related genes SREBP1, ACC, SCD1 in the liver tissue, and Western blot was performed to detect relative protein levels of pAMPK, SREBP1, Fasn, and ACC in the liver. Results:Compared with chow group, the body weight gain, fasting blood glucose (FBG), serum TC, LDL-C, HDL-C, and ALT levels were increased in HFD group ( P<0.01), and serum AST level was also increased ( P<0.05). Moreover, liver oil red O staining revealed that liver fat deposition was much more obvious in HFD group than that in chow group, and liver TG was also increased in HFD group ( P<0.01). The mRNA levels of SREBP1 and ACC were increased in HFD group compared with that in chow group, and the protein level of pAMPK was reduced in HFD group ( P<0.05). As compared with HFD group, the body weight gain, serum TG, TC, LDL-C, HDL-C and ALT levels were significantly reduced in RD group ( P<0.01), and FBG level was also reduced ( P<0.05). Moreover, RD treatment alleviated liver fat deposition and TG accumulation ( P<0.01). The mRNA levels of SREBP1, ACC, and SCD1 were all reduced in RD group compared with HFD group. The protein level of pAMPK was increased, and the expression of Fasn was reduced with RD treatment ( P<0.01). Conclusion:Resistant dextrin improves liver fat deposition and activates the AMPK signaling pathway in HFD-fed mice.

Allele Frequency and Distribution of Single Nucleotide Polymorphisms in Promoter Region of Gene Encoding the Kidd Blood Group Antigens / 中国实验血液学杂志

OBJECTIVE@#To study the single nucleotide polymorphisms (SNPs) in promoter region of the Jk gene and its allele frequency as well as distribution characteristics in the Chinese Han nationality population.@*METHODS@#127 blood samples containing 8 Jk(a-b-) and 119 samples (as control) taken randomly from voluntary blood donors of Chinese Han nationality persons in Shenzhen Blood Center were collected. The Kidd phenotypes were identified by using the serologic test and urea hemolysis test; the Jk promoter, exon 1-11 region and respective flanking area were amplified and sequenced, then the sequence information was analyzed.@*RESULTS@#8 Jk(a-b-) samples all carried JkB/JkB allele which belongs to 2 kind of Jk genotypes commonly observed in Chinese Han nationality population. 6 IVS5-1g>a and 2 896G>A were found in 8 Jk(a-b-) samples. Besides, all Jk(a-b-) samples were homozygous for JkB/JkB allele. Three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene were found and sequenceds calculation of allele and genotype frequencies showed that the result accorded with Hardy-Weinberg equilibrium, indicating that the population in this study possesses representative characteristics of the Chinese Han nationality population.@*CONCLUSION@#The polymorphism of the Jk gene occurs in promoter region. This study calculates the allele frequencies of three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene, and shows their distribution characteristics in distinct Kidd phenotypes. These findings provide the basic foundation for further population genetics research.