Publications by authors named "Jian Lu"

1,242 Publications

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SARS-CoV-2's origin should be investigated worldwide for pandemic prevention.

Lancet 2021 Sep 17. Epub 2021 Sep 17.

Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China; Chinese Academy of Engineering, Beijing, PR China.

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http://dx.doi.org/10.1016/S0140-6736(21)02020-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448491PMC
September 2021

Construction and characterization of CRISPR/Cas9 knockout rat model of carboxylesterase 2a gene.

Mol Pharmacol 2021 Sep 9. Epub 2021 Sep 9.

East China Normal University, China

Carboxylesterase 2 (CES2), an important metabolic enzyme, plays a critical role in drug biotransformation and lipid metabolism. Although CES2 is very important, few animal models have been generated to study its properties and functions. Rat Ces2 is similar to human CES2A-CES3A-CES4A gene cluster, with highly similar gene structure, function and substrate. In this report, CRISPR/Cas9 technology was firstly used to knock out rat Ces2a, a main subtype of Ces2 mostly distributed in liver and intestine. This model showed the absence of CES2A protein expression in liver. Further pharmacokinetic studies of diltiazem, a typical substrate of CES2A, confirmed the loss of function of CES2A both in vivo and in vitro. At the same time, the expression of CES2C and CES2J protein in liver decreased significantly. The body and liver weight of Ces2a knockout rats also increased, but the food intake did not change. Moreover, the deficiency of Ces2a led to obesity, insulin resistance and liver fat accumulation, which are consistent with the symptoms of nonalcoholic fatty liver disease (NAFLD). Therefore, this rat model is not only a powerful tool to study drug metabolism mediated by CES2, but also a good disease model to study NAFLD. Human CES2 plays a key role in the first-pass hydrolysis metabolism of most oral prodrugs as well as lipid metabolism. In this study, CRISPR/Cas9 technology was used to knock out Ces2a gene in rats for the first time. This model can be used not only in the study of drug metabolism and pharmacokinetics, but also as a disease model of NAFLD and other metabolic disorder.
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http://dx.doi.org/10.1124/molpharm.121.000357DOI Listing
September 2021

Technical note: A fast and accurate analytical dose calculation algorithm for I seed-loaded stent applications.

Med Phys 2021 Sep 4. Epub 2021 Sep 4.

Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.

Purpose: The safety and clinical efficacy of I seed-loaded stent for the treatment of portal vein tumor thrombosis (PVTT) have been shown. Accurate and fast dose calculation of the I seeds with the presence of the stent is necessary for the plan optimization and evaluation. However, the dosimetric characteristics of the seed-loaded stents remain unclear and there is no fast dose calculation technique available. This paper aims to explore a fast and accurate analytical dose calculation method based on Monte Carlo (MC) dose calculation, which takes into account the effect of stent and tissue inhomogeneity.

Methods: A detailed model of the seed-loaded stent was developed using 3D modeling software and subsequently used in MC simulations to calculate the dose distribution around the stent. The dose perturbation caused by the presence of the stent was analyzed, and dose perturbation kernels (DPKs) were derived and stored for future use. Then, the dose calculation method from AAPM TG-43 was adapted by integrating the DPK and appropriate inhomogeneity correction factors (ICF) to calculate dose distributions analytically. To validate the proposed method, several comparisons were performed with other methods in water phantom and voxelized CT phantoms for three patients.

Results: The stent has a considerable dosimetric effect reducing the dose up to 47.2% for single-seed stent and 11.9%-16.1% for 16-seed stent. In a water phantom, dose distributions from MC simulations and TG-43-DP-ICF showed a good agreement with the relative error less than 3.3%. In voxelized CT phantoms, taking MC results as the reference, the relative errors of TG-43 method can be up to 33%, while those of TG-43-DP-ICF method were less than 5%. For a dose matrix with 256 × 256 × 46 grid (corresponding to a phantom of 17.2 × 17.2 × 11.5 cm ) for 16-seed-loaded stent, it only takes 17 s for TG-43-DP-ICF to compute, compared to 25 h for the full MC calculation.

Conclusions: The combination of DPK and inhomogeneity corrections is an effective approach to handle both the presence of stent and tissue heterogeneity. Exhibiting good agreement with MC calculation and computational efficiency, the proposed TG-43-DP-ICF method is adequate for dose evaluation and optimization in seed-loaded stent implantation treatment planning.
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http://dx.doi.org/10.1002/mp.15207DOI Listing
September 2021

Microscopic Volta potential difference on metallic surface promotes the osteogenic differentiation and proliferation of human mesenchymal stem cells.

Mater Sci Eng C Mater Biol Appl 2021 Sep 16;128:112325. Epub 2021 Jul 16.

State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address:

Endogenous microscopic electric cues play an essential role in bone's remodeling and self-repair. Modulating the extracellular electrical environment, by means of external electric stimulation or changing surface potential of implants, was manifested to facilitate the osteointegration. The microscopic potential difference, originating from heterogeneous microstructures of materials, may mimic the endogenous electric signals to stimulate surrounding cells. In this study, the spark-plasma sintered Ti/Ta hybrid metal was fabricated and utilized to realize a surface microscopic potential difference at the same magnitude as endogenous potentials. Activated by the electric stimulation, the mesenchymal stem cells exhibited the anisotropic and polygonal cellular morphology on the Ti/Ta hybrid metal. The microscopic electric potential difference coordinated the cells proliferation on the subsequent days. Moreover, the results showed that the osteo-lineage differentiation on Ti/Ta hybrid metal were in vitro boosted over the control groups. Tailoring microstructures of material to obtain a reasonable electric microenvironment may be a necessary principle to achieve more favorable cell responses to implants, suggesting an extra degree of freedom in bone-repairing material design.
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http://dx.doi.org/10.1016/j.msec.2021.112325DOI Listing
September 2021

[Construction of squalene producing cell factories and screening, cloning and expression of key genes].

Sheng Wu Gong Cheng Xue Bao 2021 Aug;37(8):2813-2824

Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Squalene is widely used in pharmaceutical, nutraceutical, cosmetics and other fields because of its strong antioxidative, antibacterial and anti-tumor activities. In order to produce squalene, a gene ispA encoding farnesyl pyrophosphate synthase was overexpressed in a previously engineered Escherichia coli strain capable of efficiently producing terpenoids, resulting in a chassis strain that efficiently synthesizes triterpenoids. Through phylogenetic analysis, screening, cloning and expression of squalene synthase derived from different prokaryotes, engineered E. coli strains capable of efficiently producing squalene were obtained. Among them, squalene produced by strains harboring squalene synthase derived from Thermosynechococcus elongatus and Synechococcus lividus reached (16.5±1.4) mg/g DCW ((167.1±14.3) mg/L broth) and (12.0±1.9) mg/g DCW ((121.8±19.5) mg/L broth), respectively. Compared with the first-generation strains harboring the human-derived squalene synthase, the squalene synthase derived from T. elongatus and S. lividus remarkably increased the squalene production by 3.3 times and 2.4 times, respectively, making progress toward the cost-effective heterologous production of squalene.
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http://dx.doi.org/10.13345/j.cjb.200677DOI Listing
August 2021

Predicting the different progressions of early pressure injury by ultraviolet photography in rat models.

Int Wound J 2021 Sep 1. Epub 2021 Sep 1.

Device Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.

Early pressure injury (PI) can result in either spontaneous healing (SH) or deterioration into ulcer (DU). However, determining whether PI will progress into SH or DU on the basis of non-blanchable erythema only is difficult. In this study, we constructed two animal PI models to mimic SH and DU injuries and observed haemorrhage by using ultraviolet (UV) photography to develop potential clinical indicators for predicting the progression of early PI. Macroscopy, UV photography, and skin temperature observations were obtained. In the SH group, macroscopic observation showed the erythema was obvious at 0.5 hours after decompression and faded gradually had almost disappeared at 72 hours. In the DU group, the erythema persisted, and an erosion appeared at 24 hours after decompression and expanded at 36 hours. The erythema developed into an obvious ulcer at 48 hours and enlarged at 72 hours. The obvious ulcer found at 48 hours through macroscopic observation was clearly visible at 36 hours with UV photography, and a significant difference in grey values between the two groups was found at as early as 18 hours (P < .05). This study provided evidence showing that UV photography can predict the different progression stages of early PI. Additionally, when combined with the transparent disc method, UV photography also can be used to identify the circulatory disorders of early PI, such as haemorrhage or hyperaemia and even congestion.
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http://dx.doi.org/10.1111/iwj.13681DOI Listing
September 2021

CYP3A deficiency alters bile acid homeostasis and leads to changes in hepatic susceptibility in rats.

Toxicol Appl Pharmacol 2021 Oct 28;429:115703. Epub 2021 Aug 28.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address:

Cytochrome P450 3A (CYP3A) as an important enzyme metabolizes many drugs and a variety of endogenous substances. Bile acids (BA) regulate physiological function by activating BA receptors. In this study, CYP3A1/2 gene knockout (KO) and wild-type (WT) rats were used to investigate the regulatory effects of CYP3A on BA homeostasis and liver function. Compared with WT rats, BA concentrations in serum, liver and small intestine of CYP3A1/2 KO rats increased significantly, which was due to the decrease of catabolism and the increase of synthesis. In particular, the composition of serum BA (overall hydrophobicity) presented an age- and CYP3A-dependent manner. With the aging of WT rats, the serum BA became more hydrophobic, while this trend was delayed in CYP3A1/2 KO rats. Moreover, the level of serum total cholesterol, the precursor of BA synthesis, decreased by about 20% in CYP3A1/2 KO rats, which is due to the low synthesis but high biotransformation rate. The increase of BA pool further led to the change of transcription level of BA receptor in liver (pregnane X receptor) and small intestine (Takeda G-protein receptor 5), and affected the function and morphology of CYP3A1/2 KO rat liver. In conclusion, CYP3A is a key regulator of BA homeostasis in rats, especially in regulating BA pool size, composition and balance of anabolism, and prevents susceptibility to hepatotoxicity under BA overload.
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http://dx.doi.org/10.1016/j.taap.2021.115703DOI Listing
October 2021

Effects of Energy-Restricted Feeding during Rearing on the Performance, Uniformity, and Development of Rugao Layer Breeders at the Initiation of the Laying Period.

Animals (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou 225125, China.

The aim of this study was to assess the effects of energy-restricted feeding during rearing on the performance, uniformity, and development of layer breeders at the initiation of the laying period. A total of 2400 8-week-old Rugao layer breeders were randomly assigned to one of five groups (480 pullets per group) with eight replicates and were fed one of five diets that were nutritionally equal with the exception of apparent metabolizable energy corrected for nitrogen (AME) content (2850, 2750, 2650, 2550, and 2450 kcal AME/kg) from 8 to 18 weeks of age. The daily amount of feed was restricted to the absolute quantity of the diet consumed by laying hens fed 2850 kcal AME per kg diet ad libitum (control). From 18 to 21 weeks of age, all hens were fed a basal diet ad libitum. The body weight (BW) of the laying pullets decreased linearly with increasing energy restriction ( < 0.001) but recovered within 3 weeks of ad libitum feeding ( = 0.290). A gradual increase in the degree of energy restriction resulted in a gradual decrease in average daily weight gain (ADG) and a gradual increase in the feed conversion ratio (FCR) and energy conversion ratio (ECR) from 8 to 18 weeks of age ( < 0.001, < 0.001, = 0.008). In contrast, the ADG and ADFI ( < 0.001, < 0.001) gradually increased, while the FCR and ECR ( < 0.001, < 0.001) gradually improved from 18 to 21 weeks of age. From 8 to 21 weeks of age, ECR improved ( = 0.005) with an increasing degree of energy restriction. The energy-restricted feeding for 6 weeks to the end of the trial improved BW uniformity ( < 0.05). The relative length and circumference of tarsus ( < 0.001, < 0.001), and the relative weights and lengths of the small intestine, duodenum, jejunum, ileum, and caeca increased linearly ( < 0.001, = 0.012, < 0.007, = 0.012, = 0.040; < 0.001, = 0.003, = 0.032, = 0.029, = 0.040) with increasing energy restriction at 18 weeks of age. After switching to feeding for 3 weeks, the relative weights and lengths of the small intestine, duodenum, and jejunum of laying pullets increased linearly with increasing energy restriction ( < 0.001, = 0.016, = 0.011; = 0.009, = 0.028, = 0.032). In conclusion, moderate energy restriction (85.97%, 2450 vs. 2850 kcal AME/kg) from 8 to 18 weeks of age and switching to ad libitum feeding from 18 to 21 weeks of age can be used to improve BW uniformity and stimulate the development of the duodenum and jejunum of native layer breeders at the initiation of the laying period without compromising BW.
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http://dx.doi.org/10.3390/ani11082222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388481PMC
July 2021

Key Compounds and Metabolic Pathway Responsible for the Browning in Dangshan Pear ( spp.) Wine.

J Agric Food Chem 2021 Sep 25;69(35):10311-10320. Epub 2021 Aug 25.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, P. R. China.

Based on hydrophilic interaction liquid chromatography (HILIC) liquid chromatography-mass spectrometry (LC-MS), untargeted differential metabolomics analysis was performed on the pear wine samples before and after browning to determine the key compounds that affect the browning of Dangshan pear wine. A total of 196 significantly differential metabolites were found, 22 of which might be related to the browning of Dangshan pear wine. d-(+)-glucose, l-phenylalanine, l-norleucine, methionine, d-(+)-proline, aloin, and rutin were the key differential metabolites in pear wine before and after browning. The Maillard reaction of d-(+)-glucose, l-norleucine, methionine, and the oxidation of aloin played critical roles in the browning of Dangshan pear wine. The reaction of aloin and glucose to form 5-hydroxyaloin A, 7-hydroxyaloin B, and elgonica-dimer A was one of the important metabolic pathways in which the phenolic compounds formed anthraquinone during the browning process of Dangshan pear wine.
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http://dx.doi.org/10.1021/acs.jafc.1c03966DOI Listing
September 2021

Soft, Bistable Actuators for Reconfigurable 3D Electronics.

ACS Appl Mater Interfaces 2021 Sep 24;13(35):41968-41977. Epub 2021 Aug 24.

Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen 518000, China.

Existing strategies for reconfigurable three-dimensional (3D) electronics are greatly constrained by either the complicated driven mechanisms or harsh demands for conductive materials. Developing a simple and robust strategy for 3D electronics reconstruction and function extension remains a challenge. Here, we propose a solvent-driven bistable actuator, which acts as a substrate to reconstruct the combined 3D electronic device. Extraction of silicon oil from a hybrid poly(dimethylsiloxane) (PDMS) circle sheet buckles the dish to a bistable structure. The ultraviolet (UV)/ozone treatment on one surface of the PDMS structure introduces an oxidized layer, yielding a bilayered, solvent-driven bistable smart actuator. The snap-back stimulus to the oxidized layer differs from the snap-through stimulus. Experimental and numerical studies reveal the fundamental regulations for buckling configurations and the bistable behavior of the actuator. The prepared bistable actuator drives the bonded kirigami polyimide (PI) sheets to diverse 3D structures from the original bending configuration, reversibly. A frequency-reconfigurable electrically small monopole antenna is presented as a demonstration, which paves a way for the applications of this actuator in the field of reconfigurable 3D electronics.
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http://dx.doi.org/10.1021/acsami.1c08722DOI Listing
September 2021

Rare variant alleles increase human susceptibility to zoonotic H7N9 influenza virus.

Science 2021 08;373(6557):918-922

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China.

Zoonotic avian influenza A virus (IAV) infections are rare. Sustained transmission of these IAVs between humans has not been observed, suggesting a role for host genes. We used whole-genome sequencing to compare avian IAV H7N9 patients with healthy controls and observed a strong association between H7N9 infection and rare, heterozygous single-nucleotide variants in the gene. codes for myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase known to control IAV infections in transgenic mice. Most of the MxA variants identified lost the ability to inhibit avian IAVs, including H7N9, in transfected human cell lines. Nearly all of the inactive MxA variants exerted a dominant-negative effect on the antiviral function of wild-type MxA, suggesting an MxA null phenotype in heterozygous carriers. Our study provides genetic evidence for a crucial role of the -based antiviral defense in controlling zoonotic IAV infections in humans.
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http://dx.doi.org/10.1126/science.abg5953DOI Listing
August 2021

Prenatal genetic diagnosis of omphalocele by karyotyping, chromosomal microarray analysis and exome sequencing.

Ann Med 2021 12;53(1):1285-1291

Gentic Medical Center, Guangdong Women and Children Hospital, Guangzhou, PR China.

Objectives: The aim of this study is to share our experience in the prenatal diagnosis of omphalocele by karyotyping, chromosomal microarray analysis (CMA) and whole exome sequencing (WES).

Methods: In this retrospective study, 81 cases of omphalocele were identified from 2015 to 2020. Associated anomalies and prenatal diagnosis based on karyotyping, CMA and WES were analysed.

Results: Fifty-eight (71.6%) of the 81 foetuses had other ultrasound anomalies. Giant omphalocele was present in 11 cases (13.6%) and small omphalocele was present in 70 cases (86.4%). Chromosomal abnormalities were found in 24 foetuses (29.6%, 24/81), the most common of which were trisomy 18 (58.8%, 11/24) and trisomy 13 (29.2%, 7/24). Compared to isolated omphalocele, non-isolated omphalocele was accompanied by an increased prevalence of chromosomal abnormalities (4.3% (1/23) 39.7% (23/58),  = 8.226,  = .004). All chromosomal abnormalities were found in small omphalocele. Aside from aneuploidy, CMA showed one pathogenic copy number variants (CNVs) for a detection rate of 1.2%, one variants of unknown significance (VOUS) and one instance of loss of heterozygosity (LOH). WES was performed on 3 non-isolated cases, and one was found to have pathogenic variants.

Conclusions: The most common genetic cause of omphalocele is aneuploidy and the prevalence of chromosomal abnormalities is increased with non-isolated and small omphalocele. CMA and WES can be useful for providing further genetic information to assist in prenatal counselling and pregnancy management.
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http://dx.doi.org/10.1080/07853890.2021.1962966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366676PMC
December 2021

[Preimplantation Genetic Diagnosis of α/β Complex Thalassemia by Next Generation Sequencing].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Aug;29(4):1275-1279

Medical Genetics Center, Key Laboratory of Metabolic and Genetic Disease in Women and Children, Guangdong Women and Children Hospital, Guangzhou 511442, Guangdong Province, China E-mail:

Objective: To explore the application value of next generation sequencing (NGS) in preimplantation genetic diagnosis of α/β complex thalassemia couple.

Methods: The coding regions of α-globin genes (HBA1, HBA2) and β-globin gene (HBB) were selected as the target regions. The high-density and closely linked single nucleotide polymorphism (SNP) sites were selected as the genetic linkage markers in the upstream and downstream 2M regions of the gene. After NGS, the effective SNP sites were selected to construct the haplotype of the couple, and the risk chromosome of the mutation carried by the couple was determined. The NGS technology was used to sequence the variations of HBA1, HBA2 and HBB directly and construct haplotype linkage analysis for preimplantation genetic diagnosis.

Results: Direct sequencing and haplotype linkage analysis of HBA1, HBA2 and HBB showed that two of the six blastocysts were α/β complex thalassemia, one was β-thalassemia heterozygote, two were α-thalassemias heterozygotes, and one was intermediate α-thalassemia. A well-developed embryo underwent preimplantation genetic diagnosis was implanted into the mother's uterus, and a healthy infant was born at term.

Conclusion: Preimplantation genetic diagnosis can be carried out by NGS technology in α/β complex thalassemia couples, and abortion caused by aneuploid embryo selection can be avoided.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.04.041DOI Listing
August 2021

Pyraclostrobin induced AMPK/mTOR pathways mediated autophagy in RAW264.7 macrophages.

J Environ Sci Health B 2021 Aug 4:1-8. Epub 2021 Aug 4.

Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Pyraclostrobin(PCT) is a highly effective and broad-spectrum strobilurin fungicide. The mode action of PCT is inhibiting mitochondrial respiration. With the widespread use of PCT in preventing and controlling crop diseases, its potential safety risks to mammals have gradually attracted attention. This paper focuses on the cytotoxicity of PCT and its molecular mechanism, RAW264.7 macrophages were selected as a research model and conducted systematic toxicology studies in vitro, including MTT assay, colony formation assay, alkaline comet assay, fluorescent staining, ATP assay and Western blotting. The results revealed that PCT decreased viability and inhibited the proliferation of RAW264.7 cells in a concentration- dependent manner. Interestingly, PCT induced DNA damage, the resulting autophagosome, the accumulation of Beclin-1, the reduction of p62, the translocation and the formation of LC3-II. Furthermore, the results showed that PCT-induced the production of excessive ROS, leading to mitochondrial permeability transition pore (mPTP) opening, ATP depletion, and the elimination of mitochondria by autophagy. Furthermore, PCT treatment group significantly enhanced the phosphorylation level of AMPK, decreased the mTOR and p70s6k phosphorylation levels and activated the AMPK/mTOR signaling pathway in RAW264.7 cells. In conclusion, these results showed that PCT induced autophagy in the RAW264.7 cells might potentially have risks to mammal safety.
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http://dx.doi.org/10.1080/03601234.2021.1956248DOI Listing
August 2021

Risky Driver Recognition with Class Imbalance Data and Automated Machine Learning Framework.

Int J Environ Res Public Health 2021 07 15;18(14). Epub 2021 Jul 15.

Key Laboratory of Road and Traffic Engineering of the State Ministry of Education, College of Transportation Engineering, Tongji University, Shanghai 201804, China.

Identifying high-risk drivers before an accident happens is necessary for traffic accident control and prevention. Due to the class-imbalance nature of driving data, high-risk samples as the minority class are usually ill-treated by standard classification algorithms. Instead of applying preset sampling or cost-sensitive learning, this paper proposes a novel automated machine learning framework that simultaneously and automatically searches for the optimal sampling, cost-sensitive loss function, and probability calibration to handle class-imbalance problem in recognition of risky drivers. The hyperparameters that control sampling ratio and class weight, along with other hyperparameters, are optimized by Bayesian optimization. To demonstrate the performance of the proposed automated learning framework, we establish a risky driver recognition model as a case study, using video-extracted vehicle trajectory data of 2427 private cars on a German highway. Based on rear-end collision risk evaluation, only 4.29% of all drivers are labeled as risky drivers. The inputs of the recognition model are the discrete Fourier transform coefficients of target vehicle's longitudinal speed, lateral speed, and the gap between the target vehicle and its preceding vehicle. Among 12 sampling methods, 2 cost-sensitive loss functions, and 2 probability calibration methods, the result of automated machine learning is consistent with manual searching but much more computation-efficient. We find that the combination of Support Vector Machine-based Synthetic Minority Oversampling TEchnique (SVMSMOTE) sampling, cost-sensitive cross-entropy loss function, and isotonic regression can significantly improve the recognition ability and reduce the error of predicted probability.
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http://dx.doi.org/10.3390/ijerph18147534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305749PMC
July 2021

Ultrasound-mediated microbubbles cavitation enhanced chemotherapy of advanced prostate cancer by increasing the permeability of blood-prostate barrier.

Transl Oncol 2021 Oct 13;14(10):101177. Epub 2021 Jul 13.

Department of Urology, Peking University Third Hospital, Beijing 100191, China. Electronic address:

Although chemotherapy is an important treatment for advanced prostate cancer, its efficacy is relatively limited. Ultrasound-induced cavitation plays an important role in drug delivery and gene transfection. However, whether cavitation can improve the efficacy of chemotherapy for prostate cancer remains unclear. In this study, we treated RM-1 mouse prostate carcinoma cells with a combination of ultrasound-mediated microbubble cavitation and paclitaxel. Our results showed that combination therapy led to a more pronounced inhibition of cell viability and increased cell apoptosis. The enhanced efficacy of chemotherapy was attributed to the increased cell permeability induced by cavitation. Importantly, compared with chemotherapy alone (nab-paclitaxel), chemotherapy combined with ultrasound-mediated microbubble cavitation significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice in an orthotopic mouse model of RM-1 prostate carcinoma, indicating the synergistic effects of combined therapy on tumor reduction. Furthermore, we analyzed tumor-infiltrating lymphocytes and found that during chemotherapy, the proportions of CTLA4 cells and PD-1/CTLA4 cells in CD8 T cells slightly increased after cavitation treatment.
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http://dx.doi.org/10.1016/j.tranon.2021.101177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287239PMC
October 2021

On the origin of SARS-CoV-2-The blind watchmaker argument.

Sci China Life Sci 2021 09 16;64(9):1560-1563. Epub 2021 Jul 16.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

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http://dx.doi.org/10.1007/s11427-021-1972-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284035PMC
September 2021

Ultrawide photonic band gaps with the limit of gap-midgap ratio of 200% produced from complete-connected networks.

Opt Express 2021 Jul;29(14):21576-21585

A kind of one-dimensional (1D) complete-connected network (CCN) is designed and its extraordinary optical property for producing an ultrawide photonic band gap (PBG) is investigated. The gap-midgap ratio formulaes of the largest PBGs created by CCNs are analytically derived, and the results indicate that with the increment of the node number in a unit cell, the number of the loops that can produce antiresonances increases fleetly, and consequently the gap-midgap ratio of the PBG produced by CCNs enlarges rapidly and tends rapidly to the limit at 200%. Moreover, the general transmission formula for 1D CCNs is analytically determined. Due to the periodicity, two types of transmission resonance peaks are generated, and the condition is analytically obtained from the transmission formula. This kind of CCN may have wide applications to design superwide band optical filters, optical devices with large PBGs and strong photonic attenuations, and other related optical communication and optical increment processing devices.
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http://dx.doi.org/10.1364/OE.422985DOI Listing
July 2021

Study on relationship between bacterial diversity and quality of Huangjiu (Chinese Rice Wine) fermentation.

Food Sci Nutr 2021 Jul 4;9(7):3885-3892. Epub 2021 Jun 4.

Shaoxing Jianhu Brewing Co., Ltd Shaoxing China.

Huangjiu (Chinese rice wine) is brewed in an open environment, where bacteria play an important role during the fermentation process. In this study, bacterial community structure and composition changes in the fermented mash liquid of mechanized Huangjiu, well-fermented manual Huangjiu (wines of good qualities), and poorly fermented manual Huangjiu (wines of poor qualities: spoilage, high acidity, low alcohol content) in different fermentation stages from Guyuelongshan Shaoxing Huangjiu company were analyzed via metagenomic sequencing. And bacterial metabolic difference was analyzed via gene prediction of metabolic pathway enzymes. The results showed that the bacterial diversity degree was abundant, and the number of bacterial species in every sample was approximately 200-400. Lactic acid bacteria (LAB) dominated the bacterial community of Huangjiu fermentation, and was predominant species in well-fermented Huangjiu while had an absolute dominance in spoilage Huangjiu. Further, gene prediction revealed that transformation of malate to pyruvate and lactate anabolism was more active in mash liquid of well-fermented manual Huangjiu, while acetate accumulation was stronger in mash liquid of poorly fermented manual Huangjiu, which explained acidity excess reason in poorly fermented Huangjiu at gene level.
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http://dx.doi.org/10.1002/fsn3.2369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269602PMC
July 2021

[Analysis of clinical feature and genetic basis of a rare case with Olmsted syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jul;38(7):674-677

Medical Genetic Center of Guangdong Women and Children Hospital, Key Laboratory of Maternal and Children's Metabolic-Genetic Diseases of Guangdong Province, Guangzhou, Guangdong 511442, China.

Objective: To analyze the clinical and genetic characteristics of a patient featuring autosomal dominant Olmsted syndrome.

Methods: Clinical features of the patient was reviewed. High-throughput sequencing was carried out to detect potential genetic variants.

Results: The proband, a 12-year-old girl, featured excessive keratinization on hands and feet, contracture of finger joints, and abnormal position and residual contraction of the fifth toes. Skin biopsy showed significant hyperkeratosis, epidermal hyperplasia, and mild interepidermal cell edema. A de novo heterozygous missense variant c.2016G>T(p.Met672Ile) was identified in the TRPV3 gene by high-throughout sequencing. The result was verified by Sanger sequencing.

Conclusion: The destructive palmoplantar keratosis in the child may be attributed to the c.2016G>T(p.Met672Ile) variant of the TRPV3 gene. Aboving finding has provided new evidence for the correlation of genetic variants with clinical phenotypes of Olmsted syndrome.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200811-00597DOI Listing
July 2021

[Consensus on technological standards for non-invasive prenatal screening of pathogenic copy number variations by high-throughput sequencing of maternal plasma cell-free DNA].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jul;38(7):613-619

The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, China.

Genomic disorders caused by pathogenic copy number variation (pCNV) have proven to underlie a significant proportion of birth defects. With technological advance, improvement of bioinformatics analysis procedure, and accumulation of clinical data, non-invasive prenatal screening of pCNV (NIPS-pCNV) by high-throughput sequencing of maternal plasma cell-free DNA has been put to use in clinical settings. Specialized standards for clinical application of NIPS-pCNV are required. Based on the discussion, 10 pCNV-associated diseases with well-defined conditions and 5 common chromosomal aneuploidy syndromes are recommended as the target of screening in this consensus. Meanwhile, a standardized procedure for NIPS-pCNV is also provided, which may facilitate propagation of this technique in clinical settings.
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http://dx.doi.org/10.3760/cma.j.cn511374-20201208-00855DOI Listing
July 2021

MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice.

Cell Death Discov 2021 Jun 17;7(1):165. Epub 2021 Jun 17.

Department of General Surgery, Tianjin Medical University General Hospital, Anshan Road, Tianjin, 300052, China.

Regulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4 and CD8 T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.
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http://dx.doi.org/10.1038/s41420-021-00534-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257678PMC
June 2021

The lncRNA PVT1 regulates autophagy in regulatory T cells to suppress heart transplant rejection in mice by targeting miR-146a.

Cell Immunol 2021 Sep 26;367:104400. Epub 2021 Jun 26.

Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China. Electronic address:

Regulatory T cells (Tregs) are indispensable for the maintenance of immune tolerance. The purpose of this study was to investigate the effect of the interaction of the lncRNA PVT1 and miR-146a on Treg autophagy and reveal the mechanism to alleviate transplant rejection. PVT1 and miR-146a expression levels were analyzed by qRT-PCR. Bioinformatic analysis and methylation profiling were used to determine the relationship between PVT1 and miR-146a. Altered autophagic status in Tregs was detected by western blotting. The effect of autophagy on Treg function was assessed in cell coculture in vitro and in animal models. Our results showed that PVT1 expression was reduced in Tregs during rejection and negatively correlated with miR-146a expression. Higher PVT1 expression was associated with higher autophagy in Tregs. Further, highly autophagic Tregs had stronger inhibitory effects on CD4 T cells in vitro, prolonged allograft survival and alleviated rejection in vivo. Mechanistic studies showed that overexpression of PVT1 enhanced TNF receptor-associated factor (TRAF) 6 expression by directly targeting miR-146a. MiR-146a overexpression reversed PVT1-induced Treg autophagy and inhibited PVT1-induced TRAF6 expression. The present study shows a novel regulatory pathway of the autophagy program that comprises PVT1, miR-146a, and TRAF6. Our findings may provide potential targets and new therapeutic strategies for transplant rejection.
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http://dx.doi.org/10.1016/j.cellimm.2021.104400DOI Listing
September 2021

[Corrigendum] Lentivirus‑mediated RNA interference of clusterin enhances the chemosensitivity of EJ bladder cancer cells to epirubicin .

Mol Med Rep 2021 Sep 2;24(3). Epub 2021 Jul 2.

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510080, P.R. China.

Subsequently to the publication of the above paper, the authors have realized that Fig. 2A in this paper contained an error. The image selected to represent the experiment showing the invasion ability of EJ cells in the epirubicine/LV‑NC group of Fig. 2A was chosen mistakenly during the figure compilation process. A corrected version of Fig. 2 is shown on the next page. Note that this error did not affect either the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in 6: 1133‑1139, 2012; DOI: 10.3892/mmr.2012.1017].
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http://dx.doi.org/10.3892/mmr.2021.12267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281266PMC
September 2021

Deep Learning with Quantitative Features of Magnetic Resonance Images to Predict Biochemical Recurrence of Radical Prostatectomy: A Multi-Center Study.

Cancers (Basel) 2021 Jun 21;13(12). Epub 2021 Jun 21.

Department of Urology, Peking University Third Hospital, Peking University, Beijing 100191, China.

Biochemical recurrence (BCR) occurs in up to 27% of patients after radical prostatectomy (RP) and often compromises oncologic survival. To determine whether imaging signatures on clinical prostate magnetic resonance imaging (MRI) could noninvasively characterize biochemical recurrence and optimize treatment. We retrospectively enrolled 485 patients underwent RP from 2010 to 2017 in three institutions. Quantitative and interpretable features were extracted from T2 delineated tumors. Deep learning-based survival analysis was then applied to develop the deep-radiomic signature (DRS-BCR). The model's performance was further evaluated, in comparison with conventional clinical models. The model achieved C-index of 0.802 in both primary and validating cohorts, outweighed the CAPRA-S score (0.677), NCCN model (0.586) and Gleason grade group systems (0.583). With application analysis, DRS-BCR model can significantly reduce false-positive predictions, so that nearly one-third of patients could benefit from the model by avoiding overtreatments. The deep learning-based survival analysis assisted quantitative image features from MRI performed well in prediction for BCR and has significant potential in optimizing systemic neoadjuvant or adjuvant therapies for prostate cancer patients.
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http://dx.doi.org/10.3390/cancers13123098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234539PMC
June 2021

Microstructure Evolution and Mechanical Properties of Austenite Stainless Steel with Gradient Twinned Structure by Surface Mechanical Attrition Treatment.

Nanomaterials (Basel) 2021 Jun 21;11(6). Epub 2021 Jun 21.

Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong 999077, China.

Gradient structures in engineering materials produce an impressive synergy of strength and plasticity, thereafter, have recently attracted extensive attention in the material families. Gradient structured stainless steels (SS) were prepared by surface mechanical attrition treatment (SMAT) with different impacting velocities. The microstructures of the treated samples are characterized by gradient twin fraction and phase constituents. Quantitative relations of gradient microstructure with impacting time and mechanical properties are analyzed according to the observations of SEM, TEM, XRD, and tests of mechanical property. The processed SSs exhibited to be simultaneously stiff, strong, and ductile, which can be attributed to the co-operation of the different spatial distributions of multi-scaled structures. The formation of gradient twinned structure is resolved and the strengthening by gradient structure is explored.
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http://dx.doi.org/10.3390/nano11061624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234077PMC
June 2021

A Regression Model to Predict Augmented Renal Clearance in Critically Ill Obstetric Patients and Effects on Vancomycin Treatment.

Front Pharmacol 2021 11;12:622948. Epub 2021 Jun 11.

Good Clinical Practice Office, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China.

Augmented renal clearance (ARC) risk factors and effects on vancomycin (VCM) of obstetric patients were possibly different from other populations based on pathophysiological characteristics. Our study was to establish a regression model for prediction of ARC and analyze the effects of ARC on VCM treatment in critically ill obstetric patients. We retrospectively included 427 patients, grouped into ARC and non-ARC patients. Logistic regression analysis was used to analyze the factors related to ARC. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model for ARC. Patients who received VCM therapy were collected. The published VCM population pharmacokinetic (PPK) model was used to calculate pharmacokinetic parameters. A linear regression analysis was made between the predicted and measured concentrations. Of the 427 patients, ARC was present in 201 patients (47.1%). The independent risk factors of ARC were heavier, greater gestational age, higher albumin level, fewer caesarean section, severe preeclampsia and vasoactive drug; more infection, hypertriglyceridemia and acute pancreatitis. We established the above nine-variable prediction regression model and calculated the predicted probability. ROC curve showed that the predicted probability of combined weight, albumin and gestational age had better sensitivity (70.0%) and specificity (89.8%) as well as the maximal area under the curve (AUC, AUC = 0.863). 41 cases received VCM; 21 cases (51.2%) had ARC. The initial trough concentration in ARC patients was lower than in non-ARC patients (7.9 ± 3.2 mg/L vs 9.5 ± 3.3 mg/L; = 0.033). Comparing the predicted trough concentration of two published VCM PPK models with the measured trough concentration, correlation coefficients () were all more than 0.8 in the ARC group and non-ARC group. AUC was significantly decreased in the ARC group ( = 0.003; = 0.013), and clearance (CL) increased in the ARC group ( < 0.001; = 0.008) when compared with the non-ARC group. ARC is a common state in critically ill obstetric patients. The regression model of nine variables had high predictive value for predicting ARC. The published VCM PPK models had good predictive performance for predicting trough concentrations of obstetric patients. Pharmacokinetic parameters of VCM are different in ARC obstetric patients, which results in enhanced VCM clearance and decreased trough concentration.
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http://dx.doi.org/10.3389/fphar.2021.622948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226118PMC
June 2021

Real-time tracking of organ-shape and vessel-locations for surgical navigation using MEMS tri-axis magnetic sensors.

Med Eng Phys 2021 Jul 28;93:42-48. Epub 2021 May 28.

Device Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Namiki 1-2-1, Tsukuba, Ibaraki 305-8564, Japan.

Laparoscopic surgery is less invasive to patients; however, fatal bleeding occurs when a surgeon misinterprets the anatomical location of the blood vessels. Therefore, we have proposed a location tracking system by generating an artificial magnetic field around a patient and attaching MEMS magnetic sensor nodes to certain locations of the patient's organs for real-time tracking of the organ shape and vessel locations. This paper presents the detailed system design and configuration. The results suggest that a high spatial resolution of 1-2 mm may be achieved by static and ultralow-frequency magnetic fields for rotation recognition of each sensor node and noise cancelation of the entire system. The algorithm for creating the navigation 'map' has been investigated from both efficiency and accuracy perspectives, which is essential for practical applications of the above system in surgical navigation.
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http://dx.doi.org/10.1016/j.medengphy.2021.05.020DOI Listing
July 2021

Effects of different parameters on the removal of atrazine in a water environment by biosorption.

J Pestic Sci 2021 May;46(2):214-221

Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

Atrazine is the most extensively used herbicide in the agricultural and forestry sectors. Nevertheless, along with the increasing usage amount of Atrazine, its harm exposed gradually, the main problem is its residues in the environment. Microbial adsorption may effectively reduce the pollution caused by atrazine residue in the environment. In this study, a strain of fungi with the function of adsorbing atrazine was selected using microbial screening technology. According to its phenotypic characteristics and 18S rDNA gene sequencing, this strain was of the species genus and was named ECUST-TXZC2018. By studying the dynamic adsorption effect of this strain on atrazine, we found that this strain adsorbed atrazine after 36 hr at pH=5-7, and 20-30°C with more than 70% adsorption. These results demonstrated that ECUST-TXZC2018 had potential application ability to control atrazine residue pollution through the biosorption function.
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http://dx.doi.org/10.1584/jpestics.D20-043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175221PMC
May 2021

A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy.

Chin Med J (Engl) 2021 Jun 16;134(13):1576-1583. Epub 2021 Jun 16.

Department of Urology, Peking University Third Hospital, Beijing 100191, China.

Background: Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS).

Methods: A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score.

Results: A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram.

Conclusions: PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.
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http://dx.doi.org/10.1097/CM9.0000000000001607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280057PMC
June 2021
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