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Fulltext Does body mass index and height influence the incident risk of ischemic stroke in newly diagnosed type 2 diabetes subjects?

Duan D, Li H, Xu J, Wong L, Xu G, Kong F, et al.

J Diabetes Res, 2019;2019:2591709.
PMID: 30805371 DOI: 10.1155/2019/2591709

Objective: To estimate the incident risk of ischemic stroke (IS) in newly diagnosed type 2 diabetes (T2D) subjects according to different body mass index (BMI) and height categories.

Methods: A total of 25,130 newly diagnosed T2D subjects were included in this study. All T2D subjects were enrolled consecutively from the Chronic Disease Surveillance System (CDSS) of Ningbo. Standardized incidence ratio (SIR) and its 95% confidence interval (95% CI) stratified by BMI categories and height quartiles were used to estimate the incident risk of IS in T2D subjects.

Results: In total, 22,795 subjects completed the follow-up. Among them, 1268 newly diagnosed IS cases were identified, with 149,675 person-years. The SIRs of normal BMI (18.5-24.0 kg/m2), overweight (24.0-28.0 kg/m2), and obese (≥28.0 kg/m2) in overall subjects were 2.56 (95% CI 1.90-3.13), 2.13 (95% CI 1.90-3.13), and 1.87 (95% CI 1.29-2.43), respectively (Ptrend < 0.01), comparing to the general population of Ningbo. For each 1 kg/m2 increment in BMI, the SIR was 0.948 (95% CI 0.903-0.999). For height quartiles, the SIRs of male subjects in quartile 1 (<160 cm), quartile 2 (161-165 cm), quartile 3 (165-170 cm), and quartile 4 (≥171 cm) were 2.27 (95% CI 1.99-2.56), 2.01 (95% CI 1.67-2.45), 1.37 (95% CI 1.05-1.68), and 0.91 (95% CI 0.40-1.32), respectively (Ptrend < 0.01). While for female subjects, the SIRs in quartile 1 (<155 cm), quartile 2 (156-160 cm), quartile 3 (161-165 cm), and quartile 4 (≥166 cm) were 3.57 (95% CI 3.11-3.49), 2.96 (95% CI 2.61-3.31), 1.94 (95% CI 1.51-2.36), and 1.71 (95% CI 0.95-2.47), respectively (Ptrend < 0.01).

Conclusion: Compared to the general population of Ningbo, T2D subjects had a higher incident risk of IS. Furthermore, the IS incident risk was not only higher in newly diagnosed T2D subjects with normal BMI but also lower in taller newly diagnosed T2D subjects.
Does intraoperative fluoroscopy improve acetabular component positioning and limb-length discrepancy during direct anterior total hip arthroplasty? A meta-analysis

Sun C, Lee WG, Ma Q, Zhang X, Zhao Z, Cai X

J Orthop Surg Res, 2023 Aug 08;18(1):586.
PMID: 37553600 DOI: 10.1186/s13018-023-04023-w

BACKGROUND: The positioning of implant components for total hip arthroplasty (THA) is essential for joint stability, polyethylene liner wear, and range of motion. One potential benefit of the direct anterior approach (DAA) for THA is the ability to use intraoperative fluoroscopy for acetabular cup positioning and limb-length evaluation. Previous studies comparing intraoperative fluoroscopy with no fluoroscopy during DAA have reported conflicting results. This meta-analysis aimed to evaluate whether intraoperative fluoroscopy improves component positioning compared to no fluoroscopy during direct anterior total hip arthroplasty.
METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. We searched Web of Science, EMBASE, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in May 2023 to identify studies involving intraoperative fluoroscopy versus no fluoroscopy during direct anterior total hip arthroplasty. Finally, we identified 1262 hips assessed in seven studies.
RESULTS: There were no significant differences in terms of acetabular cup inclination angle (ACIA, P = 0.21), ACIA within safe zone rate (P = 0.97), acetabular cup anteversion angle (ACAA, P = 0.26); ACAA within safe zone rate (P = 0.07), combined safe zone rate (P = 0.33), and limb-length discrepancy (LLD, P = 0.21) between two groups.
CONCLUSION: Even though intraoperative fluoroscopy was not related to an improvement in cup location or LDD. With fewer experienced surgeons, the benefit of intraoperative fluoroscopy might become more evident. More adequately powered and well-designed long-term follow-up studies were required to determine whether the application of the intraoperative fluoroscopy for direct anterior total hip arthroplasty will have clinical benefits and improve the survival of prostheses.
Fulltext Electroactive Biomaterials for Facilitating Bone Defect Repair under Pathological Conditions

Heng BC, Bai Y, Li X, Lim LW, Li W, Ge Z, et al.

Adv Sci (Weinh), 2023 Jan;10(2):e2204502.
PMID: 36453574 DOI: 10.1002/advs.202204502

Bone degeneration associated with various diseases is increasing due to rapid aging, sedentary lifestyles, and unhealthy diets. Living bone tissue has bioelectric properties critical to bone remodeling, and bone degeneration under various pathological conditions results in significant changes to these bioelectric properties. There is growing interest in utilizing biomimetic electroactive biomaterials that recapitulate the natural electrophysiological microenvironment of healthy bone tissue to promote bone repair. This review first summarizes the etiology of degenerative bone conditions associated with various diseases such as type II diabetes, osteoporosis, periodontitis, osteoarthritis, rheumatoid arthritis, osteomyelitis, and metastatic osteolysis. Next, the diverse array of natural and synthetic electroactive biomaterials with therapeutic potential are discussed. Putative mechanistic pathways by which electroactive biomaterials can mitigate bone degeneration are critically examined, including the enhancement of osteogenesis and angiogenesis, suppression of inflammation and osteoclastogenesis, as well as their anti-bacterial effects. Finally, the limited research on utilization of electroactive biomaterials in the treatment of bone degeneration associated with the aforementioned diseases are examined. Previous studies have mostly focused on using electroactive biomaterials to treat bone traumatic injuries. It is hoped that this review will encourage more research efforts on the use of electroactive biomaterials for treating degenerative bone conditions.
Fulltext Engineering artificial machines from designable DNA materials for biomedical applications

Qi H, Huang G, Han Y, Zhang X, Li Y, Pingguan-Murphy B, et al.

Tissue Eng Part B Rev, 2015 Jun;21(3):288-97.
PMID: 25547514 DOI: 10.1089/ten.TEB.2014.0494

Deoxyribonucleic acid (DNA) emerges as building bricks for the fabrication of nanostructure with complete artificial architecture and geometry. The amazing ability of DNA in building two- and three-dimensional structures raises the possibility of developing smart nanomachines with versatile controllability for various applications. Here, we overviewed the recent progresses in engineering DNA machines for specific bioengineering and biomedical applications.
Engineering of microscale three-dimensional pancreatic islet models in vitro and their biomedical applications

Gao B, Wang L, Han S, Pingguan-Murphy B, Zhang X, Xu F

Crit Rev Biotechnol, 2016 Aug;36(4):619-29.
PMID: 25669871 DOI: 10.3109/07388551.2014.1002381

Diabetes now is the most common chronic disease in the world inducing heavy burden for the people's health. Based on this, diabetes research such as islet function has become a hot topic in medical institutes of the world. Today, in medical institutes, the conventional experiment platform in vitro is monolayer cell culture. However, with the development of micro- and nano-technologies, several microengineering methods have been developed to fabricate three-dimensional (3D) islet models in vitro which can better mimic the islet of pancreases in vivo. These in vitro islet models have shown better cell function than monolayer cells, indicating their great potential as better experimental platforms to elucidate islet behaviors under both physiological and pathological conditions, such as the molecular mechanisms of diabetes and clinical islet transplantation. In this review, we present the state-of-the-art advances in the microengineering methods for fabricating microscale islet models in vitro. We hope this will help researchers to better understand the progress in the engineering 3D islet models and their biomedical applications such as drug screening and islet transplantation.
Engineering physical microenvironment for stem cell based regenerative medicine

Han YL, Wang S, Zhang X, Li Y, Huang G, Qi H, et al.

Drug Discov Today, 2014 Jun;19(6):763-73.
PMID: 24508818 DOI: 10.1016/j.drudis.2014.01.015

Regenerative medicine has rapidly evolved over the past decade owing to its potential applications to improve human health. Targeted differentiations of stem cells promise to regenerate a variety of tissues and/or organs despite significant challenges. Recent studies have demonstrated the vital role of the physical microenvironment in regulating stem cell fate and improving differentiation efficiency. In this review, we summarize the main physical cues that are crucial for controlling stem cell differentiation. Recent advances in the technologies for the construction of physical microenvironment and their implications in controlling stem cell fate are also highlighted.
Enhanced hydrophobic interaction between fish (Cyprinus carpio L.) scale gelatin and curcumin: Mechanism study

Li H, Wan Mustapha WA, Tian G, Dong N, Zhao F, Zhang X, et al.

Food Chem, 2024 Jan 15;431:137102.
PMID: 37579608 DOI: 10.1016/j.foodchem.2023.137102

To enhance the solubility of hydrophobic nutrients, the hydrophobicity of fish scale gelatin hydrolysate (FSGH) was increased with moderate acid or alkali hydrolysis. Acid-induced FSG hydrolysate (AcFSGH) at 3 h showed a superior curcumin loading efficiency (18.30 ± 0.38 μg/mL) among all FSGHs. Compared with FSG, the proportion of hydrophobic amino acids (from 41.1% to 46.4%) and the hydrophobic interaction (from 12.72 to 20.10 mg/mL) was significantly increased in the AcFSGH. Meanwhile, the transformation of the α-helix (from 12.8% to 4.9%) to the β-sheet (from 29.0% to 42.8%) was also observed in the AcFSGH. Based on the observation in the molecular weight and morphological analysis, AcFSGH acquired the best hydrophobic interaction with curcumin, presumably due to the formation of the flexible structure of the linear hydrolyzates. The above results call for an investigation of the role of FSG hydrolysate in the synthesis of nanoparticles loaded with bioactive lipophilic compounds.
Enhancing electronic metal support interaction (EMSI) over Pt/TiO2 for efficient catalytic wet air oxidation of phenol in wastewater

Fu J, Zhang X, Li H, Chen B, Ye S, Zhang N, et al.

J Hazard Mater, 2022 Mar 15;426:128088.
PMID: 34959211 DOI: 10.1016/j.jhazmat.2021.128088

Phenol is one of the major hazardous organic compounds in industrial wastewater. In this work, a highly active Pt/TiO2 catalyst for catalytic wet air oxidation (CWAO) of phenol was obtained by supporting pre-synthesized Pt on TiO2. During the followed hydrogen reduction, strong hydrogen spillover occurred without the migration of TiO2 onto Pt. The reduced support then enhanced the electron transfer from TiO2 to Pt, increasing the percentage of partially negative Pt (Ptδ-), which has been confirmed by XPS. The strong EMSI made the obtained catalyst far more active than Pt/TiO2 prepared by impregnation method. The electron-enriched Pt/TiO2 achieved total organic carbon (TOC) conversion of 88.8% and TOF 149 h-1 at 100 °C and 2 MPa O2, while conventional Pt/TiO2 gave TOC conversion of 39.5% and TOF 41 h-1 for CWAO of phenol. Our work indicates that the enhancement of EMSI between metal and support can be an effective approach to develop highly active catalysts for phenol treatment.
Epidemiology and characteristics of the dengue outbreak in Guangdong, Southern China, in 2014

Huang L, Luo X, Shao J, Yan H, Qiu Y, Ke P, et al.

Eur J Clin Microbiol Infect Dis, 2016 Feb;35(2):269-77.
PMID: 26700953 DOI: 10.1007/s10096-015-2540-5

Dengue is a rapidly spreading mosquito-borne disease caused by the dengue virus (DENV) and has emerged as a severe public health problem around the world. Guangdong, one of the southern Chinese provinces, experienced a serious outbreak of dengue in 2014, which was believed to be the worst dengue epidemic in China over the last 20 years. To better understand the epidemic, we collected the epidemiological data of the outbreak and analyzed 14,594 clinically suspected dengue patients from 25 hospitals in Guangdong. Dengue cases were then laboratory-confirmed by the detection of DENV non-structural protein 1 (NS1) antigen and/or DENV RNA. Afterwards, clinical manifestations of dengue patients were analyzed and 93 laboratory-positive serum specimens were chosen for the DENV serotyping and molecular analysis. Our data showed that the 2014 dengue outbreak in Guangdong had spread to 20 cities and more than 45 thousand people suffered from dengue fever. Of 14,594 participants, 11,387 were definitively diagnosed. Most manifested with a typical non-severe clinical course, and 1.96 % developed to severe dengue. The strains isolated successfully from the serum samples were identified as DENV-1. Genetic analyses revealed that the strains were classified into genotypes I and V of DENV-1, and the dengue epidemic of Guangdong in 2014 was caused by indigenous cases and imported cases from the neighboring Southeast Asian countries of Malaysia and Singapore. Overall, our study is informative and significant to the 2014 dengue outbreak in Guangdong and will provide crucial implications for dengue prevention and control in China and elsewhere.
Ethnic disparity in central arterial stiffness and its determinants among Asians with type 2 diabetes

Zhang X, Liu JJ, Sum CF, Ying YL, Tavintharan S, Ng XW, et al.

Atherosclerosis, 2015 Sep;242(1):22-8.
PMID: 26162317 DOI: 10.1016/j.atherosclerosis.2015.06.019

OBJECTIVE: We previously reported ethnic disparity in adverse outcomes among Asians with type 2 diabetes (T2DM) in Singapore. Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to study ethnic disparity in central arterial stiffness and its determinants in a multi-ethnic T2DM Asian cohort.
METHODS: Arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV) and augmentation index (AI) using applanation tonometry method in Chinese (N = 1045), Malays (N = 458) and Indians (N = 468). Linear regression model was used to evaluate predictors of PWV and AI.
RESULTS: PWV was higher in Malays (10.1 ± 3.0 m/s) than Chinese (9.7 ± 2.8 m/s) and Indians (9.6 ± 3.1 m/s) (P = 0.018). AI was higher in Indians (28.1 ± 10.8%) than Malays (25.9 ± 10.1%) and Chinese (26.1 ± 10.7%) (P < 0.001). Malays remain associated with higher PWV (β = 0.299, P = 0.048) post-adjustment for age, gender, duration of diabetes, hemoglobin A1c, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), soluble receptor for advanced glycation end-products, urinary albumin-to-creatinine ratio, and insulin usage, which were all independent predictors of PWV. Indians remain associated with higher AI (β = 2.776, P < 0.001) post-adjustment for age, gender, BMI, SBP, DBP, and height, which were independent predictors of AI. These variables explained 27.7% and 33.4% of the variance in PWV and AI respectively.
CONCLUSIONS: Malays and Indians with T2DM have higher central arterial stiffness, which may explain their higher risk for adverse outcomes. Modifying traditional major vascular risk factors may partially alleviate their excess cardiovascular risk through modulating arterial stiffness.
KEYWORDS: Arterial stiffness; Augmentation index; Pulse wave velocity; Type 2 diabetes
Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.

Phys Rev Lett, 2024 Jan 12;132(2):021803.
PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
Fulltext Exploring the transformative power of blended learning for Business English majors in China (2012-2022) - A bibliometric voyage

Asmawi A, Dong H, Zhang X, Sun L

Heliyon, 2024 Jan 30;10(2):e24276.
PMID: 38293544 DOI: 10.1016/j.heliyon.2024.e24276

This paper thoroughly examines the time distribution, author collaboration, research institutions, research hotspots, theme clustering, and research changes and trends based on 345 CNKI literatures in the field of blended learning for Business English majors in China from 2012 to 2022. It reveals that: Research on blended learning for Business English majors in China from 2012 to 2022 can be divided into Steady Start Stage (2012-2017), Rapid Growth Stage (2018-2020) and Stable Development Stage (2021-2022). High-frequency keywords such as blended teaching mode, MOOC, flipped classroom, SPOC, etc. are hotspots of current scholars' attention. The themes of research on blended learning of business English majors in China mainly include Teaching Reform of Business English Majors, Exploration of Blended Teaching Mode and Design, and Application of Internet Teaching Platform. "Teaching Reform", "Online and Offline", "Application of Smart Platform" are the current research frontier issues in the development of blended learning for Business English majors in China. In general, China's research on blended learning for business English majors has achieved fruitful results under China's policies. Future research should concentrate on the construction of a technology environment for blended learning between learners, a variety of intelligent learning tools and mobile devices, and should be steadily bolstered in the field of blended learning for business English majors, particularly in practical application, effectiveness analysis, distance education, training and continuing education, innovation education, etc.
Extended-Range Prediction Model Using NSGA-III Optimized RNN-GRU-LSTM for Driver Stress and Drowsiness

Chui KT, Gupta BB, Liu RW, Zhang X, Vasant P, Thomas JJ

Sensors (Basel), 2021 Sep 25;21(19).
PMID: 34640732 DOI: 10.3390/s21196412

Road traffic accidents have been listed in the top 10 global causes of death for many decades. Traditional measures such as education and legislation have contributed to limited improvements in terms of reducing accidents due to people driving in undesirable statuses, such as when suffering from stress or drowsiness. Attention is drawn to predicting drivers' future status so that precautions can be taken in advance as effective preventative measures. Common prediction algorithms include recurrent neural networks (RNNs), gated recurrent units (GRUs), and long short-term memory (LSTM) networks. To benefit from the advantages of each algorithm, nondominated sorting genetic algorithm-III (NSGA-III) can be applied to merge the three algorithms. This is named NSGA-III-optimized RNN-GRU-LSTM. An analysis can be made to compare the proposed prediction algorithm with the individual RNN, GRU, and LSTM algorithms. Our proposed model improves the overall accuracy by 11.2-13.6% and 10.2-12.2% in driver stress prediction and driver drowsiness prediction, respectively. Likewise, it improves the overall accuracy by 6.9-12.7% and 6.9-8.9%, respectively, compared with boosting learning with multiple RNNs, multiple GRUs, and multiple LSTMs algorithms. Compared with existing works, this proposal offers to enhance performance by taking some key factors into account-namely, using a real-world driving dataset, a greater sample size, hybrid algorithms, and cross-validation. Future research directions have been suggested for further exploration and performance enhancement.
Fulltext Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci

Kachuri L, Amos CI, McKay JD, Johansson M, Vineis P, Bueno-de-Mesquita HB, et al.

Carcinogenesis, 2016 Jan;37(1):96-105.
PMID: 26590902 DOI: 10.1093/carcin/bgv165

Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
Fulltext Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study

Miller V, Mente A, Dehghan M, Rangarajan S, Zhang X, Swaminathan S, et al.

Lancet, 2017 Nov 04;390(10107):2037-2049.
PMID: 28864331 DOI: 10.1016/S0140-6736(17)32253-5

BACKGROUND: The association between intake of fruits, vegetables, and legumes with cardiovascular disease and deaths has been investigated extensively in Europe, the USA, Japan, and China, but little or no data are available from the Middle East, South America, Africa, or south Asia.
METHODS: We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality.
FINDINGS: Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3·91 (SD 2·77) servings per day. During a median 7·4 years (5·5-9·3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0·90, 95% CI 0·74-1·10, ptrend=0·1301), myocardial infarction (0·99, 0·74-1·31; ptrend=0·2033), stroke (0·92, 0·67-1·25; ptrend=0·7092), cardiovascular mortality (0·73, 0·53-1·02; ptrend=0·0568), non-cardiovascular mortality (0·84, 0·68-1·04; ptrend =0·0038), and total mortality (0·81, 0·68-0·96; ptrend<0·0001). The HR for total mortality was lowest for three to four servings per day (0·78, 95% CI 0·69-0·88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality.
INTERPRETATION: Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day).
FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).
Functional analysis of Trichinella spiralis serine protease 1.2 by siRNA mediated RNA interference

Yang F, Guo KX, Yang DQ, Liu RD, Long SR, Zhang X, et al.

Trop Biomed, 2020 Jun 01;37(2):458-470.
PMID: 33612815

A T. spiralis serine protease 1.2 (TsSP1.2) was identified in the muscle larvae (ML) and intestinal larvae surface/excretory-secretory (ES) proteins by immunoproteomics. The aim of this study was to determine the TsSP1.2 function in the process of T. spiralis intrusion, growth and reproduction by using RNA interference (RNAi). RNAi was used to silence the expression of TsSP1.2 mRNA and protein in the nematode. On 2 days after the ML were electroporated with 2 µM of TsSP1.2-specific siRNA 534, TsSP1.2 mRNA and protein expression declined in 56.44 and 84.48%, respectively, compared with untreated ML. Although TsSP1.2 silencing did not impair worm viability, larval intrusion of intestinal epithelium cells (IEC) was suppressed by 57.18% (P < 0.01) and the suppression was siRNA-dose dependent (r = 0.976). Infection of mice with siRNA 534 transfected ML produced a 57.16% reduction of enteral adult burden and 71.46% reduction of muscle larva burden (P < 0.05). Moreover, silencing of TsSP1.2 gene in ML resulted in worm development impediment and reduction of female fertility. The results showed that silencing of TsSP1.2 by RNAi inhibited larval intrusion and development, and reduced female fecundity. TsSP1.2 plays a crucial role for worm invasion and development in T. spiralis life cycle, and is a potential vaccine/drug target against Trichinella infection.
Functional transcriptome reveals hepatopancreatic lipid metabolism during the molting cycle of the Chinese mitten crab Eriocheir sinensis

Li Z, Zhang G, Pan K, Niu X, Shu-Chien AC, Chen T, et al.

Comp Biochem Physiol A Mol Integr Physiol, 2023 Oct;284:111474.
PMID: 37406959 DOI: 10.1016/j.cbpa.2023.111474

Crustacean molting is highly related to energy and lipid metabolism. This study was conducted to detect the changes of total lipids (TL), triacylglyceride (TAG), phospholipid (PL) and lipid droplets in hepatopancreas, and then to investigate the gene expression patterns related to hepatopancreatic lipid metabolism during the molting cycle of Chinese mitten crab Eriocheir sinensis. Hepatopancreatic TL and TAG increased significantly from post-molt stage to pre-molt stage, then decreased significantly from pre-molt stage to ecdysis stage, which is consistent to the changes of neutral lipid-rich adipocytes in hepatopancreas. By transcriptomic analysis, 65,325 transcripts were sequenced and assembled, and 28,033 transcripts were annotated. Most genes were related to energy metabolism, and the enriched genes were involved in carbohydrate and lipid metabolism and biosynthesis, especially in de novo synthesis of fatty acids and TAG, and ketone body production. Compared to the inter-molt stages, acetyl-CoA carboxylase, fatty acid synthase and other genes related to the synthesis of fatty acids were upregulated in the pre-molt stage. TAG synthesis related genes, including Glycerol-3-phosphate acyltransferase and 1-acylglycerol-3-phosphate acyltransferases, were upregulated in the post-molt stage compared to the inter-molt stage. The expression of ketone body-related genes had no significant changes during the molting cycle. Compared to the TAG synthetic pathway, ketone body biosynthesis may contribute less/secondarily to fatty acid metabolic processes, which could be involved in the other physiological processes or metabolism. In conclusion, these results showed that TAG is the major lipid deposition during inter- and pre-molt stages, and the most genes are related to the fatty acids and TAG metabolism in the hepatopancreas during the molting cycle of E. sinensis.
Fulltext Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin

Cheah PS, Prabhakar S, Yellen D, Beauchamp RL, Zhang X, Kasamatsu S, et al.

Sci Adv, 2021 Jan;7(2).
PMID: 33523984 DOI: 10.1126/sciadv.abb1703

Tuberous sclerosis complex (TSC) results from loss of a tumor suppressor gene - TSC1 or TSC2, encoding hamartin and tuberin, respectively. These proteins formed a complex to inhibit mTORC1-mediated cell growth and proliferation. Loss of either protein leads to overgrowth lesions in many vital organs. Gene therapy was evaluated in a mouse model of TSC2 using an adeno-associated virus (AAV) vector carrying the complementary for a "condensed" form of human tuberin (cTuberin). Functionality of cTuberin was verified in culture. A mouse model of TSC2 was generated by AAV-Cre recombinase disruption of Tsc2-floxed alleles at birth, leading to a shortened lifespan (mean 58 days) and brain pathology consistent with TSC. When these mice were injected intravenously on day 21 with AAV9-cTuberin, the mean survival was extended to 462 days with reduction in brain pathology. This demonstrates the potential of treating life-threatening TSC2 lesions with a single intravenous injection of AAV9-cTuberin.
Fulltext Genetic and Biological Effects of ICAM-1 E469K Polymorphism in Diabetic Kidney Disease

Zhang X, Seman NA, Falhammar H, Brismar K, Gu HF

J Diabetes Res, 2020;2020:8305460.
PMID: 32626783 DOI: 10.1155/2020/8305460

Diabetic kidney disease (DKD) is a complex disease, in which local inflammatory stress results from both metabolic and hemodynamic derangements. Intercellular adhesion molecule 1 (ICAM-1) is an acute-phase protein marker of inflammation. In the recent years, clinical observations have reported that increased serum/plasma ICAM-1 levels are positively correlated with albuminuria in the patients with type 1 (T1D) and type 2 diabetes (T2D). Genetic association studies have demonstrated that genetic polymorphisms, including SNP rs5498 (E469K, G/A), in the ICAM1 gene is associated with DKD. rs5498 is a nonsynonymous SNP and caused by substitution between E (Glu) and K (Lys) for ICAM-1 protein. In this review, we first summarized the genetic effects of ICAM1 E469K polymorphism in DKD and then demonstrated the possible changes of ICAM-1 protein crystal structures according to the genotypes of this polymorphism. Finally, we discussed the genetic effects of the ICAM1 E469K polymorphism and the biological role of increased circulating ICAM-1 protein and its formation changes in DKD.
Fulltext Genetic diversity and transmission patterns of Burkholderia pseudomallei on Hainan island, China, revealed by a population genomics analysis

Zheng H, Qin J, Chen H, Hu H, Zhang X, Yang C, et al.

Microb Genom, 2021 11;7(11).
PMID: 34762026 DOI: 10.1099/mgen.0.000659

Burkholderia pseudomallei is a Gram-negative soil-dwelling bacillus that causes melioidosis, a frequently fatal infectious disease, in tropical and subtropical regions. Previous studies have identified the overall genetic and evolutionary characteristics of B. pseudomallei on a global scale, including its origin and transmission routes. However, beyond its known hyperendemicity foci in northern Australia and Southeast Asia, the distribution and genetic characteristics of B. pseudomallei in most tropical regions remain poorly understood, including in southern China. Here, we sequenced the genomes of 122 B. pseudomallei strains collected from Hainan, an island in southern China, in 2002-2018, to investigate the population structure, relationships with global strains, local epidemiology, and virulence and antimicrobial-resistance factors. A phylogenetic analysis and hierarchical clustering divided the Hainan strains into nine phylogenic groups (PGs), 80 % of which were concentrated within five major groups (group 1: corresponding to minor sequence types [STs], 12.3 %; group 3: ST46 and ST50, 31.1 %; group 9: ST58, 13.1 %; group 11: ST55, 8.2 %; group 15: mainly ST658, 15.6%). A phylogenetic analysis that included global strains suggested that B. pseudomallei in Hainan originated from Southeast Asian countries, transmitted in multiple historical importation events. We also identified several mutual transmission events between Hainan and Southeast Asian countries in recent years, including three importation events from Thailand and Singapore to Hainan and three exportation events from Hainan to Singapore, Malaysia, and Taiwan island. A statistical analysis of the temporal distribution showed that the Hainan strains of groups 3, 9, and 15 have dominated the disease epidemic locally in the last 5 years. The spatial distribution of the Hainan strains demonstrated that some PGs are distributed in different cities on Hainan island, and by combining phylogenic and geographic distribution information, we detected 21 between-city transmission events, indicating its frequent local transmission. The detection of virulence factor genes showed that 56 % of the Hainan strains in group 1 encode a B. pseudomallei-specific adherence factor, boaB, confirming the specific pathogenic characteristics of the Hainan strains in group 1. An analysis of the antimicrobial-resistance potential of B. pseudomallei showed that various kinds of alterations were identified in clinically relevant antibiotic resistance factors, such as AmrR, PenA and PBP3, etc. Our results clarify the population structure, local epidemiology, and pathogenic characteristics of B. pseudomallei in Hainan, providing further insight into its regional and global transmission networks and improving our knowledge of its global phylogeography.

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