Radix Puerariae and Fructus Crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K.

BACKGROUND: Radix puerariae (RP) is a herbal medicines for diabetes, mainly because of anti-oxidative, insulin resistance and hypoglycemic effect. Fructus crataegi (FC) also possesses strong antioxidant activity in vitro. This study focused on the effects of herbal mixture of RP and FC (RPFC) on renal protection through a diabetic rat model. METHODS: Type 2 Diabetic model was established with high fat diet followed by injecting rats a low dose of STZ (25 mg/kg body weight). Rats were randomly divided into five groups: normal, high fat diet, diabetes mellitus, high fat diet plus RPFC prevention, and RPFC prevention before diabetes mellitus. RPFC was given to rats daily by intragastric gavage. The blood bio-chemical index and renal pathological changes were examined. The later includes hematoxylin and eosin staining, periodic acid schiff staining, and Masson trichrome staining. Protein levels of were determined by Western blot and immunohistochemical staining. mRNA levels were detected by RT-PCR. RESULTS: Rats prevented with RPFC resulted in decreasing blood glucose with corresponding vehicle treated rats. Glomerulus mesangial matrix expansion, renal capsule constriction, and renal tubular epithelial cell edema were less severe following RPFC prevention. Moreover, RPFC prevention reduced protein levels of PI3K, AKT, α-SMA and collagen IV in the kidney of diabetic rats. CONCLUSION: Combined prevention with RPFC may inhibit the PI3K/AKT pathway in the kidney, thereby prevent renal injury in diabetic rats.

Cloning, expression and biochemical characterization of recombinant superoxide dismutase from Antarctic psychrophilic bacterium Pseudoalteromonas sp. ANT506.

In this study, a superoxide dismutase gene (PsSOD) from Pseudoalteromonas sp. ANT506 was cloned and over expressed in Escherichia coli. The PsSOD has an open reading frame of 582 bp with a putative product of 193 amino acid residue and an estimated molecular size of 21.4 kDa. His-tagged PsSOD was subsequently purified 12.6-fold by Ni-affinity chromatography and the yield of 22.9%. The characterization of the purified rPsSOD exhibited maximum activity at 30 °C and pH 8.0. The enzyme exhibited 13.9% activity at 0 °C and had high-thermo lability at higher than 50 °C. rPsSOD exhibited well capability to 2.5 M NaCl (62.4%). These results indicated that rPsSOD exhibited special catalytic properties.

Willingness to pay for diabetic retinopathy screening in Qujiang District, rural Guangdong, southern China: a cross-sectional study.

OBJECTIVE: To determine willingness to pay for a diabetic retinopathy screening, and its determinants, among people with diabetes mellitus in Qujiang District of Shaoguan City, rural Guangdong, southern China. DESIGN: This cross-sectional study was conducted through a large-scale screening programme in 2019. We randomly selected 575 (21.5%) among 2677 people over 18 years old with known diabetes who attended the screening. Participants elected to pay nothing or RMB10-RMB120 (US$1.6-US$18.8), in RMB10 intervals, displayed on printed cards. One trained interviewer collected all the data. SETTING: Ten primary health centres in Qujiang District of Shaoguan City, Guangdong. PARTICIPANTS: 545 from the 575 randomly selected people (94.8%) agreed to participate in the study. OUTCOME MEASURES: Proportion of participants willing to pay anything for screening, mean amount they were willing to pay and determinants of these figures. RESULTS: Among 545 participants (mean age 64.6 years (SD±10.4), 40.7% men), 327 (60.0%) were willing to pay something for screening, of whom 273 (83.5%) would pay RMB10-RMB30 (US$1.6-US$4.7). People living in rural areas and those from lower-income families were more likely to be willing to pay anything, while men, urban residents and those covered by employer-linked insurance were willing to pay larger sums (p<0.05 for all). CONCLUSION: Nearly two-thirds of participants were willing to pay for screening in this screening programme organised at the primary care level in rural China. This finding offers the potential that such activities can be sustained and scaled up through user fees.

Six-Year Change in Cataract Surgical Coverage and Postoperative Visual Outcomes in Rural Southern China: The Yangxi Eye Study.

PURPOSE: The purpose of this study was to investigate a 6-year change in cataract surgical coverage (CSC), effective cataract surgical coverage (eCSC), and visual outcomes in an elderly population in rural southern China. DESIGN: This is a prospective population-based study with a 6-year follow-up. METHODS: The study included rural residents aged 50 years and above in southern China with comprehensive eye examinations at baseline and follow-up in 2014 and 2020, respectively. RESULTS: Five thousand six hundred thirty-eight participants underwent baseline examinations (mean age 66.1±10.2 y, 50.8% women); and 3141 (64.9%) of 4841 eligible survivors attended the 6-year follow-up. Cataract surgical coverage was 41.7% and 40.6% at baseline and follow-up, respectively, while eCSC were 32.6% and 26.6%. In multivariate models, the 6-year likelihood of cataract surgery decreased with older age [odds ratio (OR)=0.97 per year, 95% confidence interval (CI): 0.94, 0.99, P =0.012] and worse baseline presenting uncorrected visual acuity (PVA) in the worse-seeing eye (OR=0.35 per unit logarithm of the minimum angle of resolution (logMAR), 95% CI: 0.25, 0.48, P <0.001), and increased with prior cataract surgical history at baseline (OR=3.88, 95% CI: 1.91, 7.09, P <0.001). The likelihood of receiving effective cataract surgery decreased with worse baseline PVA in the worse eye (OR=0.49 per unit logMAR, 95% CI: 0.24, 0.97, P =0.042) and better-seeing eye (OR=0.68 per unit logMAR, 95% CI: 0.48, 0.95, P =0.026). Posterior capsular opacification was the main reason for PVA <6/18, reporting it in logMAR (0.5) in operated eyes (38.4% at baseline; 28.1% at follow-up). CONCLUSIONS: World Health Organization has established a global target of increasing eCSC by 30% before 2030, but no increase was found in rural southern China between 2014 and 2020, let alone reaching the World Health Organization target of 56.3%. Strategies to improve surgery incidence should focus on older persons and those with worse preoperative PVA.

Outreach screening to address demographic and economic barriers to diabetic retinopathy care in rural China.

IMPORTANCE: Poor access to existing care for diabetic retinopathy (DR) limits effectiveness of proven treatments. OBJECTIVES: We examined whether outreach screening in rural China improves equity of access. DESIGN, SETTING AND PARTICIPANTS: We compared prevalence of female sex, age > = 65 years, primary education or below, and requiring referral care for DR between three cohorts with diabetes examined for DR in neighboring areas of Guangdong, China: passive case detection at secondary-level hospitals (n = 193); persons screened during primary-level DR outreach (n = 182); and individuals with newly- or previously-diagnosed diabetes in a population survey (n = 579). The latter reflected the "ideal" reach of a screening program. RESULTS: Compared to the population cohort, passive case detection reached fewer women (50·8% vs. 62·3%, p = 0·006), older adults (37·8% vs. 51·3%, p < 0·001), and less-educated persons (39·9% vs. 89·6%, p < 0·001). Outreach screening, compared to passive case detection, improved representation of the elderly (49·5% vs. 37·8%, p = 0·03) and less-educated (70·3% vs. 39·9%, p<0·001). The proportion of women (59.8% vs 62.3%, P>0.300) and persons aged > = 65 years (49.5% vs 51.3%, p = 0.723) in the outreach screening and population cohorts did not differ significantly. Prevalence of requiring referral care for DR was significantly higher in the outreach screening cohort (28·0%) than the population (14·0%) and passive case detection cohorts (7·3%, p<0·001 for both). CONCLUSIONS AND RELEVANCE: Primary-level outreach screening improves access for the poorly-educated and elderly, and removes gender inequity in access to DR care in this setting, while also identifying more severely-affected patients than case finding in hospital.

Bacteriophage Cocktails Protect Dairy Cows Against Mastitis Caused By Drug Resistant Escherichia coli Infection.

Mastitis caused by Escherichia coli (E. coli) remains a threat to dairy animals and impacts animal welfare and causes great economic loss. Furthermore, antibiotic resistance and the lagged development of novel antibacterial drugs greatly challenge the livestock industry. Phage therapy has regained attention. In this study, three lytic phages, termed vB_EcoM_SYGD1 (SYGD1), vB_EcoP_SYGE1 (SYGE1), and vB_EcoM_SYGMH1 (SYGMH1), were isolated from sewage of dairy farm. The three phages showed a broad host range and high bacteriolytic efficiency against E. coli from different sources. Genome sequence and transmission electron microscope analysis revealed that SYGD1 and SYGMH1 belong to the Myoviridae, and SYGE1 belong to the Autographiviridae of the order Caudovirales. All three phages remained stable under a wide range of temperatures or pH and were almost unaffected in chloroform. Specially, a mastitis infected cow model, which challenged by a drug resistant E. coli, was used to evaluate the efficacy of phages. The results showed that the cocktails consists of three phages significantly reduced the number of bacteria, somatic cells, and inflammatory factors, alleviated the symptoms of mastitis in cattle, and achieved the same effect as antibiotic treatment. Overall, our study demonstrated that phage cocktail may be a promising alternative therapy against mastitis caused by drug resistant E. coli.

Phage vB_PaeS-PAJD-1 Rescues Murine Mastitis Infected With Multidrug-Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a Gram-negative pathogen that causes a variety of infections in humans and animals. Due to the inappropriate use of antibiotics, multi-drug resistant (MDR) P. aeruginosa strains have emerged and are prevailing. In recent years, cow mastitis caused by MDR P. aeruginosa has attracted attention. In this study, a microbial community analysis revealed that P. aeruginosa could be a cause of pathogen-induced cow mastitis. Five MDR P. aeruginosa strains were isolated from milk diagnosed as mastitis positive. To seek an alternative antibacterial agent against MDR, P. aeruginosa, a lytic phage, designated vB_PaeS_PAJD-1 (PAJD-1), was isolated from dairy farm sewage. PAJD-1 was morphologically classified as Siphoviridae and was estimated to be about 57.9 kb. Phage PAJD-1 showed broad host ranges and a strong lytic ability. A one-step growth curve analysis showed a relatively short latency period (20 min) and a relatively high burst size (223 PFU per infected cell). Phage PAJD-1 remained stable over wide temperature and pH ranges. Intramammary-administered PAJD-1 reduced bacterial concentrations and repaired mammary glands in mice with mastitis induced by MDR P. aeruginosa. Furthermore, the cell wall hydrolase (termed endolysin) from phage PAJD-1 exhibited a strong bacteriolytic and a wide antibacterial spectrum against MDR P. aeruginosa. These findings present phage PAJD-1 as a candidate for phagotherapy against MDR P. aeruginosa infection.

Activation of mTORC1 by LSECtin in macrophages directs intestinal repair in inflammatory bowel disease.

Damage to intestinal epithelial cells and the induction of cellular apoptosis are characteristics of inflammatory bowel disease. The C-type lectin receptor family member LSECtin promotes apoptotic cell clearance by macrophages and induces the production of anti-inflammatory/tissue growth factors, which direct intestinal repair in experimental colitis. However, the mechanisms by which the phagocytosis of apoptotic cells triggers the pro-repair function of macrophages remain largely undefined. Here, using immunoprecipitation in combination with mass spectrometry to identify LSECtin-interacting proteins, we found that LSECtin interacted with mTOR, exhibiting a role in activating mTORC1. Mechanistically, apoptotic cells enhance the interaction between LSECtin and mTOR, and increase the activation of mTORC1 induced by LSECtin in macrophages. Elevated mTORC1 signaling triggers macrophages to produce anti-inflammatory/tissue growth factors that contribute to the proliferation of epithelial cells and promote the reestablishment of tissue homeostasis. Collectively, our findings suggest that LSECtin-dependent apoptotic cell clearance by macrophages activates mTORC1, and thus contributes to intestinal regeneration and the remission of colitis.

Porcine Epidemic Diarrhoea Virus Induces Cell-cycle Arrest through the DNA Damage-signalling Pathway.

INTRODUCTION: Porcine epidemic diarrhoea virus (PEDV) infection causes watery diarrhoea, vomiting, anorexia, and weight loss, especially among neonatal piglets, inflicting on them morbidity and mortality potentially reaching 90%-100%. Despite it being known that certain mammalian cell phases are arrested by PEDV, the mechanisms have not been elucidated, and PEDV pathogenesis is poorly understood. This study determined the effect of an epidemic PEDV strain on cell cycle progression. MATERIAL AND METHODS: We observed the effect of the PEDV SHpd/2012 strain on an infected Vero cell cycle through flow cytometry and Western blot, investigating the interrelationships of cell-cycle arrest, the DNA damage-signalling pathway caused by PEDV and the phosphorylation levels of the key molecules Chk.2 and H2A.X involved upstream and downstream in this pathway. RESULTS: PEDV induced Vero cell-cycle arrest at the G1/G0 phase. The phosphorylation levels of Chk.2 and H2A.X increased with the prolongation of PEDV infection, and no significant cell-cycle arrest was observed after treatment with ATM or Chk.2 inhibitors. The proliferation of PEDV was also inhibited by treatment with ATM or Chk.2 inhibitors. CONCLUSION: PEDV-induced cell-cycle arrest is associated with activation of DNA damage-signalling pathways. Our findings elucidate the molecular basis of PEDV replication and provide evidence to support further evaluation of PEDV pathogenesis.

Pulse wave velocity as a marker of arteriosclerosis and its comorbidities in Chinese patients.

To obtain reliable data on the epidemiology of arteriosclerosis and the comorbidities in patients with hypertension (HP), coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) and stroke, we evaluated the clinical significance of pulse wave velocity (PWV) as an indicator of arteriosclerosis and its comorbidities in Chinese patients. A total of 910 subjects, including 748 Chinese patients with one or more cardiovascular risk factors (80.2% male, mean age 73.69+/-5.03 years) and 162 healthy volunteers (78.4% male, mean age 73.60+/-5.32 years) were recruited into the study. PWV was measured in 910 subjects, and large artery arteriosclerosis was defined as PWV >or=12 m/s. Multivariable logistic regression analyses were performed to identify risk factors associated with arteriosclerosis. The prevalence of large artery arteriosclerosis in the patients overall was 67.4%, and the prevalence was higher in patients with than in those without HP (63.3% vs. 34.0%; odds ratio [OR]: 3.451), T2DM (24.8% vs. 11.1%; OR: 2.854), CHD (56.1% vs. 45.1%; OR: 1.246) and stroke (26.6% vs. 19.2%; OR: 1.236), but the OR values of CHD and stroke did not differ significantly (p>0.05). After multiple logistic regression analysis, female sex, older age, HP and T2DM were risk factors for large artery arteriosclerosis. In conclusion, PWV can be used as a routine measurement to scan arteriosclerosis in patients with HP or T2DM.

Correlation between brachial-ankle pulse wave velocity and arterial compliance and cardiovascular risk factors in elderly patients with arteriosclerosis.

The objective of this study was to investigate an association between major cardiovascular risk factors and each of brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI), capacitive arterial compliance (C1), and oscillatory arterial compliance (C2) in elderly patients with arteriosclerosis. We analyzed 160 elderly patients with arteriosclerosis. Vessel wall properties were assessed by baPWV and ABI using a VP-1000 Automatic Arteriosclerosis Measurement System, and C1 and C2 were measured using a DO-2020 Cardiovascular Profiling Instrument. In multiple regression analysis, baPWV was significantly correlated with systolic blood pressure (SBP), mean artery pressure, pulse pressure, diastolic blood pressure (DBP), age, and heart rate (r = 0.670, 0.627, 0.580, 0.523, 0.490, 0.200; p < 0.05), ABI was significantly correlated with pulse pressure, SBP and age (r = -0.250, -0.206, -0.168; p < 0.05), C1 was significantly correlated with pulse pressure, SBP, mean artery pressure, age, DBP and heart rate (r = -0.481, -0.469, -0.363, -0.356, -0.239, -0.188; p < 0.05), and C2 was significantly correlated with age, SBP, pulse pressure, DBP, fasting blood glucose, mean artery pressure and heart rate (r = -0.411, -0.395, -0.383, -0.277, -0.213, -0.183, -0.173; p < 0.05). There were no close correlations between baPWV, ABI, or C1 and fasting blood glucose, total cholesterol, triglycerides, or body mass index. Moreover, there were significant correlations between baPWV and C1 (r = -0.444, p < 0.001), and between baPWV and C2 (r = -0.257, p < 0.01). In conclusion, these findings underscore the efficacy of baPWV and ABI in identifying the vascular damage of the aged.

Cloning, expression, purification, and characterization of glutaredoxin from Antarctic sea-ice bacterium Pseudoalteromonas sp. AN178.

Glutaredoxins (Grxs) are small ubiquitous redox enzymes that catalyze glutathione-dependent reactions to reduce protein disulfide. In this study, a full-length Grx gene (PsGrx) with 270 nucleotides was isolated from Antarctic sea-ice bacterium Pseudoalteromonas sp. AN178. It encoded deduced 89 amino acid residues with the molecular weight 9.8 kDa. Sequence analysis of the amino acid sequence revealed the catalytic motif CPYC. Recombinant PsGrx (rPsGrx) stably expressed in E. coli BL21 was purified to apparent homogeneity by Ni-affinity chromatography. rPsGrx exhibited optimal activity at 30°C and pH 8.0 and showed 25.5% of the activity at 0°C. It retained 65.0% of activity after incubation at 40°C for 20 min and still exhibited 37.0% activity in 1.0 M NaCl. These results indicated that rPsGrx was a typical cold active protein with low thermostability.

Power enhancement of piezoelectric transformers by adding heat transfer equipment.

It is known that piezoelectric transformers have several inherent advantages compared with conventional electromagnetic transformers. However, the maximum power capacity of piezoelectric transformers is not as large as electromagnetic transformers in practice, especially in the case of high output current. The theoretical power density of piezoelectric transformers calculated by stress boundary can reach 330 W/cm(3), but no piezoelectric transformer has ever reached such a high power density in practice. The power density of piezoelectric transformers is limited to 33 W/cm(3) in practical applications. The underlying reason is that the maximum passing current of the piezoelectric material (mechanical current) is limited by the temperature rise caused by heat generation. To increase this current and the power capacity, we proposed to add a thermal pad to the piezoelectric transformer to dissipate heat. The experimental results showed that the proposed techniques can increase by 3 times the output current of the piezoelectric transformer. A theoretical-phenomenological model which explains the relationship between vibration velocity and generated heat is also established to verify the experimental results.

Analyses of the heat dissipated by losses in a piezoelectric transformer.

In this paper, a new approach to the thermal management of piezoelectric transformers is proposed. Starting from the electromechanical equations, including mechanical and dielectrical losses, and knowing the piezoelectric material characteristics, an analytical model was developed and the theoretical profile of the heat sources was deduced. To check these theoretical points of view, a thermal characterization of a Rosen-type piezoelectric transformer was done. The temperature field on the surface of the PT was measured in thermal transient steps. Knowing the specific temperature, the experimental heat sources were obtained. As expected, they are related to the square modulus of the strain or stress profiles on the one hand and to mechanical losses on the other, which confirms the theoretical results. Experimental data and calculation results are matched for several resistance loads and frequencies tested.

[Determination of the aortic pulse wave velocity in 545 healthy subjects].

OBJECTIVE: To understand the aortic pulse wave velocity (PWV) in mid-aged and elderly populations and to study the correlation between gender and PWV and the tendency of PWV on different age groups. METHODS: According to the clinical trial guideline, we selected 545 healthy subjects (age, 31-85 years, 395 men and 150 women), and measured carotid-femoral PWV, using Complior. RESULTS: The average value of PWV in Chinese healthy subjects was 11.62 +/- 2.97 m/s. There was no significant difference in the PWV values between males and females who were older than 40 years, but the values of PWV were lower in females than in males in the 30-39 year-old group. PWV was positively correlated with age. In the present study, the reference values of PWV were established in the different age groups, based on the regression equations between PWV and age. CONCLUSION: Aortic pulse wave velocity seemed to be influenced by age but hardly influenced by gender in healthy subjects, so that the reference value of PWV should be established according to the different age groups. When aorta got stiffer, the value PWV got larger accordingly when age was increasing.