Publications by authors named "Lei Ma"

620 Publications

Clinical and Prognostic Significance of CD117 in Non-Small Cell Lung Cancer: A Systemic Meta-Analysis.

Authors:
Ying Su Ru Chen Zhongcheng Han Rong Xu Lili Ma Reyina Wufuli Hongbo Liu Fang Wang Lei Ma Rui Chen Jiang Liu

Pathobiology 2021 Jun 9:1-10. Epub 2021 Jun 9.

Department of Oncology, People's Hospital of Xinjiang Uygur, Urumqi, China.

The aim of this study was to assess the relationship of cluster of differentiation 117 (CD117) expression with the clinicopathological characteristics and the prognosis in patients with non-small cell lung cancer (NSCLC). No meta-analysis concerning the correlation of CD117 expression with clinical and prognostic values of the patients with NSCLC is reported. A systematic literature search was conducted to achieve eligible studies. The combined odds ratios (ORs) or hazard ratios (HRs: multivariate Cox analysis) with their 95% confidence intervals (CIs) were calculated in this analysis. Final 17 eligible studies with 4,893 NSCLC patients using immunohistochemical detection were included in this meta-analysis. CD117 expression was not correlated with gender (male vs. female), clinical stage (stages 3-4 vs. stages 1-2), tumor grade (grade 3 vs. grades 1-2), T-stage (T-stages 3-4 vs. T-stages 0-2), distal metastasis, and disease-free survival (DFS) of NSCLC (all p values >0.05). CD117 expression was associated with lymph node metastasis (positive vs. negative: OR = 0.74, 95% CI = 0.56-0.97, p = 0.03), histological type (adenocarcinoma (AC) versus squamous cell carcinoma (SCC): OR = 1.74, 95% CI = 1.26-2.39, p = 0.001), and a worse overall survival (OS) (HR = 1.89, 95% CI = 1.22-2.92, p = 0.004). The expression of CD117 was significantly higher in AC than in SCC. CD117 may be an independent prognostic indicator for worse OS in NSCLC.
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http://dx.doi.org/10.1159/000514386DOI Listing
June 2021

High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion.

Authors:
Haining Zhong Cesar C Ceballos Crystian I Massengill Michael A Muniak Lei Ma Maozhen Qin Stefanie Kaech Petrie Tianyi Mao

Elife 2021 Jun 8;10. Epub 2021 Jun 8.

Vollum Institute, Oregon Health and Science University, Portland, United States.

Precise and efficient insertion of large DNA fragments into somatic cells using gene editing technologies to label or modify endogenous proteins remains challenging. Non-specific insertions/deletions (INDELs) resulting from the non-homologous end joining pathway make the process error-prone. Further, the insert is not readily removable. Here, we describe a method called R-mediated nsertion of xon (CRISPIE) that can precisely and reversibly label endogenous proteins using CRISPR/Cas9-based editing. CRISPIE inserts a designer donor module, which consists of an exon encoding the protein sequence flanked by intron sequences, into an intronic location in the target gene. INDELs at the insertion junction will be spliced out, leaving mRNAs nearly error-free. We used CRISPIE to fluorescently label endogenous proteins in mammalian neurons with previously unachieved efficiency. We demonstrate that this method is broadly applicable, and that the insert can be readily removed later. CRISPIE permits protein sequence insertion with high fidelity, efficiency, and flexibility.
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http://dx.doi.org/10.7554/eLife.64911DOI Listing
June 2021

High miR-3650 expression in nasopharyngeal carcinoma and its clinical prognostic values.

Authors:
Qiang Ruan Xian-Zi Yang Lin Zhu Qing-Jun He Si-Yu Zhu Yue-Feng Wen Lei Ma

Pathol Res Pract 2021 May 30;224:153506. Epub 2021 May 30.

Department of Medical Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China. Electronic address:

Background: A recent study has reported that miR-3650 expression was significant reduced in hepatocellular carcinoma and predicted poor prognosis. However, the role of miR-3650 in nasopharyngeal carcinoma (NPC) remains indefinite.

Methods: Total 140 cases of NPCs were included in this study. The expression of miR-3650 was determined in NPC tissues and adjacent nontumor tissues using qRT-PCR. Then the relationship between miR-3650 expression and clinicopathological features as well as survival were analyzed.

Results: The expression of miR-3650 was significant higher in NPC tissues than that in adjacent nontumor tissues (P <  0.001). High expression of miR-3650 was significant correlated with tumor progression and distant metastasis of NPC patients. And patients with high miR-3650 expression have much worse 5-year overall survival (OS) and 5-year progression-free survival (PFS) than those with low expression (all P <  0.0001). Furthermore, Cox regression analysis showed that miR-3650 was an independent risk predictor for OS and PFS in NPC patients (all P =  0.000).

Conclusion: Our results demonstrated for the first time that miR-3650 was markedly upregulated in NPC tissues and positively associated with tumor progression and poor survival, suggesting that miR-3650 may be a potential novel prognostic biomarker and therapeutic target for NPC patients.
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http://dx.doi.org/10.1016/j.prp.2021.153506DOI Listing
May 2021

The optimum dietary methionine requirement of juvenile humpback grouper (Cromileptes altivelis): effects on growth, micromorphology, protein and lipid metabolism.

Authors:
Misbah Irm Wei Mu Wu Xiaoyi Lina Geng Xiao Wang Bo Ye Lei Ma Zhiyu Zhou

Amino Acids 2021 Jun 3. Epub 2021 Jun 3.

State Key Laboratory of Marine Resource Utilization in South China Sea, Haikou, Hainan, 570228, PR China.

An 8-week feeding trial was conducted to evaluate optimum dietary methionine (Met) requirement of juvenile humpback grouper (Cromileptes altivelis) and the influence of dietary methionine (Met) supplementations on growth, gut micromorphology, protein and lipid metabolism. Seven isoproteic (48.91%) and isolipidic diets (10%) were made to contain 0.70, 0.88, 1.04, 1.27 1.46, 1.61 and 1.76% of dry matter Met levels. Results showed that lower survival, weight gain (WG%), protein efficiency ratio (PER), protein productive value (PPV) but higher daily feed intake (DFI) and feed conversion ratio (FCR) were observed in the Met deficient groups (0.70 and 0.88%). Optimum dietary Met requirement for humpback grouper was found to be 1.07% through the straight-broken line analysis of WG% against Met. Fish fed Met deficient diets (0.70, 0.88%) exhibited lower mRNA levels of growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor-I (IGF-1), target of rapamycin (TOR) as well as S6 kinase 1 (S6K1) than other dietary groups. Whereas, expression of genes related to general control nonderepressible (GCN2) kinase i.e., GCN2 and C/EBPβ enhancer-binding protein β was upregulated in fish fed low Met diets (P < 0.05). The mRNA expression of hepatic fatty acid synthase (FAS) and sterol regulatory element-binding protein-1 (SREBP-1) were higher in fish fed 0.70 and 0.88% dietary Met group and the lipolytic genes, hepatic peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyl transferase-1 (CPT-1) showed an opposite variation tendency as FAS or SREBP1. Generally, the optimum Met requirement for humpback grouper was predicted to be 1.07% of dry matter.
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http://dx.doi.org/10.1007/s00726-021-03014-7DOI Listing
June 2021

Synthesis and Stability of Hydrogen Storage Material Aluminum Hydride.

Authors:
Wenda Su Fangfang Zhao Lei Ma Ruixian Tang Yanru Dong Guolong Kong Yu Zhang Sulin Niu Gen Tang Yue Wang Aimin Pang Wei Li Liangming Wei

Materials (Basel) 2021 May 28;14(11). Epub 2021 May 28.

Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Microelectronics and Nanoscience, School of Electronics Information and Electrical Engineering, Shanghai Jiao Tong University, Dong Chuan Road No. 800, Shanghai 200240, China.

Aluminum hydride (AlH) is a binary metal hydride with a mass hydrogen density of more than 10% and bulk hydrogen density of 148 kg H2/m3. Pure aluminum hydride can easily release hydrogen when heated. Due to the high hydrogen density and low decomposition temperature, aluminum hydride has become one of the most promising hydrogen storage media for wide applications, including fuel cell, reducing agents, and rocket fuel additive. Compared with aluminum powder, AlH has a higher energy density, which can significantly reduce the ignition temperature and produce H fuel in the combustion process, thus reducing the relative mass of combustion products. In this paper, the research progress about the structure, synthesis, and stability of aluminum hydride in recent decades is reviewed. We also put forward the challenges for application of AlH and outlook the possible opportunity for AlH in the future.
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http://dx.doi.org/10.3390/ma14112898DOI Listing
May 2021

Sparse PLS-Based Method for Overlapping Metabolite Set Enrichment Analysis.

Authors:
Lingli Deng Lei Ma Kian-Kai Cheng Xiangnan Xu Daniel Raftery Jiyang Dong

J Proteome Res 2021 06 18;20(6):3204-3213. Epub 2021 May 18.

Department of Electronic Science, National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen 361005, China.

Metabolite set enrichment analysis (MSEA) has gained increasing research interest for identification of perturbed metabolic pathways in metabolomics. The method incorporates predefined metabolic pathways information in the analysis where metabolite sets are typically assumed to be mutually exclusive to each other. However, metabolic pathways are known to contain common metabolites and intermediates. This situation, along with limitations in metabolite detection or coverage leads to overlapping, incomplete metabolite sets in pathway analysis. For overlapping metabolite sets, MSEA tends to result in high false positives due to improper weights allocated to the overlapping metabolites. Here, we proposed an extended partial least squares (PLS) model with a new sparse scheme for overlapping metabolite set enrichment analysis, named overlapping group PLS (ogPLS) analysis. The weight vector of the ogPLS model was decomposed into pathway-specific subvectors, and then a group lasso penalty was imposed on these subvectors to achieve a proper weight allocation for the overlapping metabolites. Two strategies were adopted in the proposed ogPLS model to identify the perturbed metabolic pathways. The first strategy involves debiasing regularization, which was used to reduce inequalities amongst the predefined metabolic pathways. The second strategy is stable selection, which was used to rank pathways while avoiding the nuisance problems of model parameter optimization. Both simulated and real-world metabolomic datasets were used to evaluate the proposed method and compare with two other MSEA methods including Global-test and the multiblock PLS (MB-PLS)-based pathway importance in projection (PIP) methods. Using a simulated dataset with known perturbed pathways, the average true discovery rate for the ogPLS method was found to be higher than the Global-test and the MB-PLS-based PIP methods. Analysis with a real-world metabolomics dataset also indicated that the developed method was less prone to select pathways with highly overlapped detected metabolite sets. Compared with the two other methods, the proposed method features higher accuracy, lower false-positive rate, and is more robust when applied to overlapping metabolite set analysis. The developed ogPLS method may serve as an alternative MSEA method to facilitate biological interpretation of metabolomics data for overlapping metabolite sets.
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http://dx.doi.org/10.1021/acs.jproteome.1c00064DOI Listing
June 2021

Potential role of chimeric genes in pathway-related gene co-expression modules.

Authors:
Piaopiao Li Yingxia Li Lei Ma

World J Surg Oncol 2021 May 12;19(1):149. Epub 2021 May 12.

College of Life Science, Shihezi University, Shihezi, Xinjiang, 832000, China.

Background: Gene fusion has epigenetic modification functions. The novel proteins encoded by gene fusion products play a role in cancer development. Therefore, a better understanding of the novel protein products may provide insights into the pathogenesis of tumors. However, the characteristics of chimeric genes are rarely studied. Here, we used weighted co-expression network analysis to investigate the biological roles and underlying mechanisms of chimeric genes.

Methods: Download the pig transcriptome data, we screened chimeric genes and parental genes from 688 sequences and 153 samples, predict their domains, and analyze their associations. We constructed a co-expression network of chimeric genes in pigs and conducted Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis on the generated modules using DAVID to identify key networks and modules related to chimeric genes.

Results: Our findings showed that most of the protein domains of chimeric genes were derived from fused pre-genes. Chimeric genes were enriched in modules involved in the negative regulation of cell proliferation and protein localization to centrosomes. In addition, the chimeric genes were related to the growth factor-β superfamily, which regulates cell growth and differentiation. Furthermore, in helper T cells, chimeric genes regulate the specific recognition of T cell receptors, implying that chimeric genes play a key role in the regulation pathway of T cells. Chimeric genes can produce new domains, and some chimeric genes are a key role involved in pathway-related function.

Conclusions: Most chimeric genes show binding activity. Domains of chimeric genes are derived from several combinations of parent genes. Chimeric genes play a key role in the regulation of several cellular pathways. Our findings may provide new directions to explore the roles of chimeric genes in tumors.
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http://dx.doi.org/10.1186/s12957-021-02248-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117532PMC
May 2021

Altered Behavioral Performance in the Neuron-Specific HIF-1- and HIF-2-Deficient Mice Following Chronic Hypoxic Exposure.

Authors:
Lei Ma J Sebastian Garcia-Medina Geisa Ortet Joseph C LaManna Kui Xu

Adv Exp Med Biol 2021 ;1269:271-276

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.

Hypoxia-inducible factors (HIFs) are transcriptional regulators that mediate in mice for HIF-1 and HIF-2. The objective of this study was to investigate the effect of neuronal deletion of HIF-1 and HIF-2 in hypoxic adaptation by using the neuron-specific knockout (KO) mice. The floxed control and KO mice were used. Hypoxic mice were kept in a hypobaric chamber at a pressure of 300 torr (0.4 ATM, which was equivalent to 8% oxygen under normobaric condition) for 3 weeks. The littermate, normoxic control mice were housed in the same room next to the chamber to match ambient conditions. Body weights were monitored throughout the 3-week course. Cognitive function was measured using a Y-maze test; motor functions were measured using the rotarod test and the grip strength test. The hematocrit increased significantly at the end of 3-week hypoxic exposure in both control and KO mice. In the Y-maze test, the alternation rate (indicative of sustained cognition) trended lower in the KO mice compared to the controls following hypoxia (%, 51.3 ± 13.1, n = 6 vs. 63.2 ± 12.0, n = 8). In the rotarod test, the latency (seconds) in the KO mice was significantly lower compared to the controls (50.4 ± 5.7 vs. 77.1 ± 5.0, n = 3 each before hypoxia and 66.4 ± 3.4, n = 6 vs. 98.1 ± 15.4 after hypoxia, n = 3). The grip strength in the KO mice was similar compared to the control mice before hypoxia, but the strength of KO mice trended higher after hypoxic exposure. Our data suggest that deficiency of neuronal HIF-1 and HIF-2 may result in changes in behavioral performance and other adaptative responses to hypoxia.
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http://dx.doi.org/10.1007/978-3-030-48238-1_43DOI Listing
May 2021

Design and synthesis of novel diosgenin-triazole hybrids targeting inflammation as potential neuroprotective agents.

Authors:
Yi Huang Weiwei Huang Guixiang Yang Rui Wang Lei Ma

Bioorg Med Chem Lett 2021 Jul 6;43:128092. Epub 2021 May 6.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China. Electronic address:

Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is expected to increase as the global population ages. Recent studies provide increasing evidence that inflammation plays a key role in the pathogenesis and progression of AD. Diosgenin, an active ingredient in Dioscorea nipponica Makino, is a promising bioactive lead compound in the treatment of Alzheimer's disease, which exhibited anti-inflammatory activity. To search for more efficient anti-Alzheimer agents, a series of novel diosgenin-triazolyl hybrids were designed, synthesized, and their neuroprotective effects against oxygen-glucose deprivation-induced neurotoxicity and LPS-induced NO production were evaluated. Most of these new hybrids displayed better activities than DIO. In particular, the promising compound L6 not only demonstrated an excellent neuroprotective effect but also showed the best anti-inflammatory activity. The structure-activity relationship study illustrated that the introduction of benzyl or phenyl triazole did improve the activity, and the introduction of benzyl triazole was better than that of phenyl triazole. The results we obtained showed that the diosgenin skeleton could be a promising structural template for the development of new anti-Alzheimer drug candidates, and compound L6 has the potential to be an important lead compound for further research.
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http://dx.doi.org/10.1016/j.bmcl.2021.128092DOI Listing
July 2021

Facile preparation of solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone and photopolymerization.

Authors:
Rongzhen Fang Yan Liu Lei Ma Xiang Yu Yiguang Jin

Mater Sci Eng C Mater Biol Appl 2021 May 26;124:112063. Epub 2021 Mar 26.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China; Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Drug solid dispersions improve the dissolution of drugs in aqueous media for enhancement of oral bioavailability. The current preparation methods of drug solid dispersions mainly involve the evaporation of solvents or the melting of drugs and matrix. Here, we create a new and simple method for the preparation of drug solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone (NVP) and then NVP photopolymerization. A variety of drugs were explored to find whether they were suitable for this method and only some of them were soluble in NVP and formed transparent and hard solid dispersions, including fluconazole, ketoconazole, bifonazole, miconazole nitrate, sulfamethoxazole, aspirin, ibuprofen and artesunate. The formation of photocuring solid dispersions was highly related to the free radical scavenging function of drugs. Those drugs with strong free radical scavenging capability, including curcumin, resveratrol, quercetin, genistein, puerarin, nicergoline, olanzapine, indomethacin, did not form solid dispersions. They scavenged 2,2-diphenyl-1-picrylhydrazyl free radicals, which was demonstrated by ultraviolet spectrometry and electron spin resonance. The scavenging of free radicals stopped the chain polymerization of NVP. The Fourier transform infrared spectra, X-ray diffraction and differential scanning calorimetry of ibuprofen solid dispersions and artesunate solid dispersions showed the molecularly miscible state of the drugs and the hydrogen bonding between the drugs and polyvinyl pyrrolidone. The NVP-based solid dispersions of the two drugs had faster and more complete dissolution than their traditional solid dispersions. The NVP photopolymerization-based solid dispersion method provides a new choice for the production of solid dispersions in the research and industrial fields.
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http://dx.doi.org/10.1016/j.msec.2021.112063DOI Listing
May 2021

Physiological characterization of chitin synthase A responsible for the biosynthesis of cuticle chitin in Culex pipiens pallens (Diptera: Culicidae).

Authors:
Xiaoshan Yang Yang Xu Qi Yin Hongbo Zhang Haitao Yin Yan Sun Lei Ma Dan Zhou Bo Shen

Parasit Vectors 2021 May 1;14(1):234. Epub 2021 May 1.

Department of Pathogen Biology, Nanjing Medical University, Nanjing, China.

Background: The pathogens transmitted by mosquitoes to humans and animals cause several emerging and resurgent infectious diseases. Increasing insecticide resistance requires rational action to control the target vector population. Chitin is indispensable for insect growth and development and absent from vertebrates and higher plants. Chitin synthase A (CHSA) is a crucial enzyme in chitin synthesis; therefore, identifying and characterizing how CHSA determines chitin content may contribute to the development of novel vector control strategies.

Results: The injection of small interfering RNA targeting CHSA (siCHSA) to knockdown CHSA transcripts in larval, pupal and adult stages of Culex pipiens pallens resulted in the appearance of different lethal phenotypes. When larval and pupal stages were injected with siCHSA, CHSA knockdown prevented larval molting, pupation and adult eclosion, and affected the production of chitin and chitin degradation, which resulted in an ecdysis defect phenotype of mosquitoes. When siCHSA was injected into mosquitoes in the adult stage, CHSA knockdown also affected the laminar organization of the mesoderm and the formation of pseudo-orthogonal patterns of the large fibers of the endoderm.

Conclusion: We provide a systematic and comprehensive description of the effects of CHSA on morphogenesis and metamorphosis. The results show that CHSA not only affects chitin synthesis during molting, but also might be involved in chitin degradation. Our results further show that CHSA is important for the structural integrity of the adult mosquito cuticle.
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http://dx.doi.org/10.1186/s13071-021-04741-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088658PMC
May 2021

Multicolorimetric ELISA biosensors on a paper/polymer hybrid analytical device for visual point-of-care detection of infection diseases.

Authors:
Lei Ma Yousef Abugalyon XiuJun Li

Anal Bioanal Chem 2021 Apr 26. Epub 2021 Apr 26.

Deparment of Chemistry and Biochemistry, The University of Texas at El Paso, 500 West University Ave, El Paso, TX, 79968, USA.

Enzyme-linked immunosorbent assay (ELISA) is widely used for the detection of disease biomarkers. However, it utilizes time-consuming procedures and expensive instruments, making it infeasible for point-of-care (POC) analysis especially in resource-limited settings. In this work, a multicolorimetric ELISA biosensor integrated on a paper/polymer hybrid microfluidic device was developed for rapid visual detection of disease biomarkers at point of care, without using costly equipment. This multicolormetric ELISA platform was built on multiple distinct color variants resulted from the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and the etching of gold nanorods (AuNRs). The vivid color changes could be easily distinguished by the naked eye, and their red mean values allowed quantitative biomarker detection, without using any sophisticated instruments. When this multicolorimetric ELISA was integrated on a paper/polymer hybrid analytical device, it not only provided integrated processing and high portability but also enabled fast assays in about 50 min due to the unique advantages of paper/polymer hybrid devices. The limit of detection of 9.1 ng/μL of the hepatitis C virus core antigen, a biomarker for hepatitis C, was achieved using this multicolorimetric ELISA platform. This multicolor ELISA analytical device provides a new versatile, user-friendly, affordable, and portable immunosensing platform with high potential for on-site detections of various viruses, proteins, and biomarkers for low-resource settings such as at home, public venues, rural areas, and developing nations.
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http://dx.doi.org/10.1007/s00216-021-03359-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075012PMC
April 2021

Breaking Neural Reasoning Architectures With Metamorphic Relation-Based Adversarial Examples.

Authors:
Alvin Chan Lei Ma Felix Juefei-Xu Yew-Soon Ong Xiaofei Xie Minhui Xue Yang Liu

IEEE Trans Neural Netw Learn Syst 2021 Apr 22;PP. Epub 2021 Apr 22.

The ability to read, reason, and infer lies at the heart of neural reasoning architectures. After all, the ability to perform logical reasoning over language remains a coveted goal of Artificial Intelligence. To this end, models such as the Turing-complete differentiable neural computer (DNC) boast of real logical reasoning capabilities, along with the ability to reason beyond simple surface-level matching. In this brief, we propose the first probe into DNC's logical reasoning capabilities with a focus on text-based question answering (QA). More concretely, we propose a conceptually simple but effective adversarial attack based on metamorphic relations. Our proposed adversarial attack reduces DNCs' state-of-the-art accuracy from 100% to 1.5% in the worst case, exposing weaknesses and susceptibilities in modern neural reasoning architectures. We further empirically explore possibilities to defend against such attacks and demonstrate the utility of our adversarial framework as a simple scalable method to improve model adversarial robustness.
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http://dx.doi.org/10.1109/TNNLS.2021.3072166DOI Listing
April 2021

Salivary Microbiome Variation in Early Childhood Caries of Children 3-6 Years of Age and Its Association With Iron Deficiency Anemia and Extrinsic Black Stain.

Authors:
Rui Han Jin Yue Haozhi Lin Nan Du Jinfeng Wang Shuting Wang Fanzhi Kong Jiaying Wang Wei Gao Lei Ma Shoushan Bu

Front Cell Infect Microbiol 2021 23;11:628327. Epub 2021 Mar 23.

Department of Stomatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ECC is a common clinical manifestation of the oral cavity in childhood and Iron deficiency-anemia (IDA) is a high-risk factor but extrinsic black stain on the tooth surface is a protective factor for caries. There is limited information about oral microecological change in early children who suffer from ECC with IDA and extrinsic black stain (BS). This study enrolled 136 children aged 3-6 years. Dental caries and teeth BS were examined. Saliva was collected for 16S rRNA gene and fingertip blood were for Hemoglobin test. There are 93 ECC including 13 with IDA (IDA ECC) and 80 without IDA (NIDA ECC) and 43 caries free (CF) including 17 with BS (BSCF) and 26 without BS (NBS CF). Statistical analysis of microbiota data showed differences of the oral flora in different groups. The oral flora of the IDA ECC group had a high diversity, while the BSCF group had a low diversity. The bacterial genera Bacillus, Moraxella, and Rhodococcus were enriched in the IDA ECC while Neisseria was enriched in the NIDA ECC. Neisseria only exhibited high abundance in the BSCF, and the remaining genera exhibited high abundance in the NBSCF. Interestingly, the BSCF had the same trend as the NIDA ECC, and the opposite trend was observed with IDA ECC. We established random forest classifier using these biomarkers to predict disease outcomes. The random forest classifier achieved the best accuracy in predicting the outcome of caries, anemia and black stain using seven, one and eight biomarkers, respectively; and the accuracies of the classifiers were 93.35%, 94.62% and 95.23%, respectively. Our selected biomarkers can achieve good prediction, suggesting their potential clinical implications.
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http://dx.doi.org/10.3389/fcimb.2021.628327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044945PMC
March 2021

Design, synthesis, and biological evaluation of diosgenin-indole derivatives as dual-functional agents for the treatment of Alzheimer's disease.

Authors:
Li-Cheng Zhou Ying-Fan Liang Yi Huang Gui-Xiang Yang Lu-Lu Zheng Jia-Min Sun Yang Li Fu-Li Zhu He-Wen Qian Rui Wang Lei Ma

Eur J Med Chem 2021 Jul 3;219:113426. Epub 2021 Apr 3.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. Electronic address:

The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against HO (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aβ (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by HO (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aβ (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aβ was -40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aβ. The predicted values of brain/blood partition coefficient (-0.733) and polar surface area (85.118 Å) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by HO. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aβ-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.
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http://dx.doi.org/10.1016/j.ejmech.2021.113426DOI Listing
July 2021

Milk Beta-Hydroxybutyrate and Fat to Protein Ratio Patterns during the First Five Months of Lactation in Holstein Dairy Cows Presenting Treated Left Displaced Abomasum and Other Post-Partum Diseases.

Authors:
Mariana Alves Caipira Lei João Simões

Animals (Basel) 2021 Mar 14;11(3). Epub 2021 Mar 14.

Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal.

The main objective of the present study was to evaluate the beta-hydroxybutyrate (BHB) and fat to protein content (F:P) ratio patterns in the milk of Holstein cows with postpartum diseases throughout the first five months of lactation. This prospective study was performed at Vestjyske Dyrlaeger ApS (Nørre Nebel, Denmark). The milk fat, protein, and BHB were evaluated in the Danish Eurofins laboratory according to the monthly averaged days in milk (DIM1 to 5). According to clinical records, five groups were formed: A (control group; cows without diseases; = 32), B (cows with left displaced abomasum -LDA- and concomitant diseases; = 25); C (cows with other diseases up to DIM3; = 13); D (cows with foot disorders up to DIM3; = 26); and E (cows with disease manifestations in DIM4 and DIM5; = 26). All the sick cows were treated after diagnosis, and laparoscopy was performed on cows with LDA. In group B, a higher concentration of BHB (0.18 ± 0.02 mmol/L; < 0.001) was observed than in the control group (0.07 ± 0.02 mmol/L; < 0.001) in DIM1, presenting an odds ratio (OR) = 8.9. In all groups, BHB decreased to 0.03-0.05 mmol/L ( < 0.05) since DIM3. The F:P ratio was higher in group B (1.77 ± 0.07) than in group A (1.32 ± 0.06; < 0.05) in DIM1. A similar profile is observed in DIM2. It was observed that animals in group B were four to six times more likely to have a F:P ratio ≥1.29 during DIM1 (OR = 4.0; 95% CI:1.3-14.4; = 0.01) and DIM2 (OR = 5.9; 95% CI %:1.9-21.9; < 0.01), than cows in group A. There were also moderate and high correlations between the F:P ratio and the BHB for DIM1 (r = 0.57; r = 0.33; RSD = 0.09; < 0.001) and DIM2 (r = 0.78; r = 0.60; RSD = 0.07; < 0.001), respectively. We concluded that animals affected by LDA in the postpartum period have a higher concentration of BHB in milk in DIM1 and all treated animals quickly recover BHB levels up to DIM3. The F:P ratio is a viable and economic indicator, mainly in DIM1 and DIM2, to estimate BHB concentration and energy balance in cows with LDA and other postpartum diseases.
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http://dx.doi.org/10.3390/ani11030816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999714PMC
March 2021

Loss of BRMS2 induces cell growth inhibition and translation capacity reduction in colorectal cancer cells.

Authors:
Yaofu Liu Weimin Xu Xin Xu Zhengzhi Tan Jing Xu Lei Ma Peng Du Yili Yang

Am J Cancer Res 2021 1;11(3):930-944. Epub 2021 Mar 1.

Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College Suzhou, China.

A variety of chemotherapeutic drugs targeting ribosome processing have been developed and applied to cancer treatment mainly based on the impaired ribosome biogenesis checkpoint (IRBC). The IMP U3 small nucleolar ribonucleoprotein 3 (IMP3, BRMS2) has been identified as a participant in pre-rRNA processing for nearly twenty years. However, the roles of BRMS2 in cancers still unknown. In this research, a tissue microarray (TMA) with 151 paired tissues showed the aberrant overexpression of BRMS2 in CRC tissues which was associated with the worse prognosis. To clarify the function of BRMS2 in CRC cells, an inducible knockdown system was introduced and and the cell growth was drastically suppressed. Mechanistically, we found depletion of BRMS2 markedly decreased the protein translation rates which can limit cell growth. Furthermore, to confirm whether the IRBC played a role, multiple approaches including detection of the p53 pathway, depletion of BRMS2 in p53-mutated SW620 cells, and co-depletion of RPL11 were taken. To our surprise, IRBC was not activated. That indicated BRMS2 may play a unique role in ribosome biosynthesis and IRBC. Taken together, our results demonstrated the oncogenic function of BRMS2 in CRC cells and supported its potential as a therapeutic target.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994161PMC
March 2021

Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia.

Authors:
Gui-Xiang Yang Jia-Min Sun Lu-Lu Zheng Li Zhang Jie Li Hai-Xian Gan Yan Huang Jin Huang Xing-Xing Diao Yun Tang Rui Wang Lei Ma

Bioorg Med Chem 2021 May 19;37:116109. Epub 2021 Mar 19.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China. Electronic address:

A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
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http://dx.doi.org/10.1016/j.bmc.2021.116109DOI Listing
May 2021

MiR-4448 is involved in deltamethrin resistance by targeting CYP4H31 in Culex pipiens pallens.

Authors:
Xixi Li Shengli Hu Haitao Yin Hongbo Zhang Dan Zhou Yan Sun Lei Ma Bo Shen Changliang Zhu

Parasit Vectors 2021 Mar 16;14(1):159. Epub 2021 Mar 16.

Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People's Republic of China.

Background: Culex pipiens (Cx. pipiens) complex, which acts as a vector of viruses and is widespread and abundant worldwide, including West Nile virus, Japanese encephalitis virus, and Sindbis virus, can cause serious vector-borne diseases affecting human health. Unfortunately, mosquitoes have developed deltamethrin resistance because of its long-term overuse, representing a major challenge to mosquito control. Understanding the molecular regulatory mechanisms of resistance is vital to control mosquitoes. MicroRNAs (miRNAs) are short non-coding RNAs that have been demonstrated to be important regulators of gene expression across a wide variety of organisms, which might function in mosquito deltamethrin resistance. In the present study, we aimed to investigate the regulatory functions of miR-4448 and CYP4H31 in the formation of insecticidal resistance in mosquito Culex pipiens pallens.

Methods: We used quantitative real-time reverse transcription PCR to measure miR-4448 and CYP4H31 (encoding a cytochrome P450) expression levels. The regulatory functions of miR-4448 and CYP4H31 were assessed using dual-luciferase reporter assays. Then, oral feeding, RNA interference, and the American Centers for Disease Control and Prevention bottle bioassay were used to determine miR-4448's association with deltamethrin resistance by targeting CYP4H31 in vivo. Cell Counting Kit-8 (CCK-8) was also used to detect the viability of pIB/V5-His-CYP4H31-transfected C6/36 cells after deltamethrin treatment in vitro.

Results: MiR-4448 was downregulated in the deltamethrin-resistant strain (DR strain), whereas CYP4H31 was downregulated in deltamethrin-susceptible strain. CYP4H31 expression was downregulated by miR-4448 recognizing and binding to its 3' untranslated region. Functional verification experiments showed that miR-4448 overexpression resulted in lower expression of CYP4H31. The mortality of miR-4448 mimic-injected DR strain mosquitoes was higher than that of the controls. CCK-8 assays showed that CYP4H31 decreased cellular resistance to deltamethrin in vitro and the mortality of the DR strain increased when CYP4H31 was knocked down in vivo.

Conclusions: In mosquitoes, miR-4448 participates in deltamethrin resistance by targeting CYP4H31. The results of the present study increase our understanding of deltamethrin resistance mechanisms.
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http://dx.doi.org/10.1186/s13071-021-04665-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962327PMC
March 2021

Strong interaction between Au nanoparticles and porous polyurethane sponge enables efficient environmental catalysis with high reusability.

Authors:
Qijie Jin Lei Ma Wan Zhou Cindy Himmelhaver Ramana Chintalapalle Yuesong Shen XiuJun Li

Catal Today 2020 Dec 20;358:246-253. Epub 2020 Jan 20.

Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, USA.

A novel and recoverable platform of polyurethane (PU) sponge-supported Au nanoparticle catalyst was obtained by a water-based in-situ preparation process. The structure, chemical, and morphology properties of this platform were characterized by XRD, TGA, SEM, FT-IR, and XPS. The Au/PU sponge platform exhibited excellent catalytic performances in catalytic reductions of -nitrophenol and -nitroaniline at room temperature, and both catalytic reactions could be completed within 4.5 and 1.5 min, respectively. Furthermore, the strong interaction between Au nanoparticles and the PU sponge enabled the catalyst system to maintain a high catalytic efficiency after 5 recycling times, since the PU sponge reduced the trend of leaching and aggregation of Au nanoparticles. The unique nature of Au nanoparticles and the porous PU sponge along with their strong interaction resulted in a highly efficient, recoverable, and cost-effective multifunctional catalyst. The AuNP/Sponge nanocatalyst platform has great potential for wide environmental and other catalytic applications.
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http://dx.doi.org/10.1016/j.cattod.2020.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944585PMC
December 2020

The IGF-1/GH-GLUTs-plasma glucose regulating axis in hybrid grouper (Epinephelus fuscoguttatus♀ × epinephelus lanceolatus♂) fed a high-carbohydrate diet.

Authors:
Lina Geng Xiao Wang Xiaoyi Wu Zhiyu Zhou Wei Mu Bo Ye Lei Ma

Gen Comp Endocrinol 2021 Jun 9;307:113744. Epub 2021 Mar 9.

Hainan Provincial Key Laboratory for Tropical Hydrobiology and Biotechnology, Department of Aquaculture, Hainan University, Haikou, Hainan 570228, China.

The carnivorous teleost fish is often intolerant to high levels of postprandial plasma glucose. This study aimed to evaluate the effects of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) administrations on plasma glucose levels and expression of glucose transporters (GLUTs) in various tissues of hybrid grouper, and hence to further clarify the hormone-GLUTs-plasma glucose regulating axis. Twenty-four experimental fish (average body weight: 77.5 ± 5.4 g) were selected and injected with recombinant human IGF-1 (0.2 μg/g body weight) and PBS (0.01 mol/L) in enterocoelia, respectively, and in the GH injected experiment, the same quantity of fish (average body weight: 103.8 ± 5.8 g) were administrated with GH at a dose of 0.5 μg/g body weight or with PBS at a dose of 0.01 mol/L. Results showed that plasma glucose level was significantly (P < 0.05) declined by the IGF-1 administration but elevated by the GH administration. Plasma IGF-1 concentration was significantly (P < 0.01) elevated by the IGF-1 administration, while GH concentration did not significantly (P ≥ 0.05) respond to the GH administration. The relative mRNA levels of insulin-like growth factor-1 receptor a (IGF-Ra) in liver and muscle were decreased significantly with the IGF-1 administration, and a similar variation tendency was also found in insulin-like growth factor-1 receptor b (IGF-Rb) in liver, muscle and adipose tissues. Besides, the relative mRNA level of insulin receptor (IRS) in liver was significantly increased in the IGF-1 administrated group. After the GH administration, the mRNA levels of hepatic growth factor receptor 2 (GHR2) and IGF-1 were significantly elevated. As for GLUTs, the relative mRNA levels of GLUT1 and GLUT2 in liver were obviously elevated by the IGF-1 administration, while the mRNA level of GLUT4 in muscle was reduced. In liver, the protein levels of GLUT1, 2 and 4 were significantly elevated by the IGF-1 administration, and in adipose, only GLUT1 was observed to have a significantly increased protein level. The mRNA expression of GLUTs was less affected by the GH administration. The protein level of GLUT1 in liver was significantly reduced by the GH administration, while in adipose, it was significantly increased. The protein level of GLUT2 in liver or adipose showed an opposite variation as that of GLUT1. Overall, IGF-1 had a hypoglycemic effect on hybrid grouper, and this probably was through up-regulating the protein levels of hepatic GLUT1, 2 and 4 and adipose GLUT1. GH showed an opposite role in regulating plasma glucose level as IGF-1.
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http://dx.doi.org/10.1016/j.ygcen.2021.113744DOI Listing
June 2021

Extracts from Chinese herbs with anti-amyloid and neuroprotective activities.

Authors:
Zuzana Bednarikova Miroslav Gancar Rui Wang Lulu Zheng Yun Tang Yating Luo Yan Huang Barbora Spodniakova Lei Ma Zuzana Gazova

Int J Biol Macromol 2021 May 3;179:475-484. Epub 2021 Mar 3.

Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Košice, Slovakia. Electronic address:

Many Chinese herbs are well known for their neuroprotective and anti-oxidant properties. Extracts of Salvia miltiorrhiza and Anemarrhenae asphodeloides, tanshinone IIA (tanIIA), salvianolic acid B (Sal B) and sarsasapogenin (ML-1), were selected to study their dissociation potential towards Aβ peptide fibrils and neuroprotective effect on cells. Moreover, derivatives of sarsasapogenin (ML-2, ML-3 and ML-4) have been prepared by the addition of modified carbamate moiety. TanIIA and Sal B have shown to possess a strong ability to dissociate Aβ fibrils. The dissociation potential of ML-1 increased upon the introduction of carbamate moiety with N-heterocycles. In silico data revealed that derivatives ML-4 and Sal B interact with Aβ regions responsible for fibril stabilization through hydrogen bonds. Contrary, tanIIA binds close to a central hydrophobic region, which may lead to destabilization of fibrils. Sarsasapogenin derivative ML-2 decreased nitride oxide production, and derivative ML-4 enhanced the growth of neurites. The reported data highlight the possibility of using active compounds to design novel treatment agents for Alzheimer's disease.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.013DOI Listing
May 2021

A simple Field Programmable Gate Array (FPGA) based high precision low-jitter delay generator.

Authors:
Zeyang Chen Xiaohan Wang Ziwen Zhou Ramiro Moro Lei Ma

Rev Sci Instrum 2021 Feb;92(2):024701

Tianjin International Center for Nanoparticles and Nanosystems, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China.

Pulse delay generators are ubiquitous in laboratories to coordinate and control the timing between different devices in applications that include lasers, mass spectrometers, and other scientific instruments. The most important required characteristics are precision, to control time exactly, and low-jitter, to minimize uncertainty in experiments. Here, we introduce a new design of a high precision and low-jitter digital delay generator based on a Field Programmable Gate Array (FPGA). The final delay is composed of steps of 4.2 ns (coarse delay) with fine steps of 16 ps (fine delay). The coarse delay is generated by a 240 MHz pulse sequence from the FPGA with a 50 MHz clock. An embedded time-to-digital conversion unit is used to measure the interval between the external trigger and the clock signal, which, together with an integrated delay generator, is used to realize the fine delay. Jitter compensation is achieved through a measurement-and-feedback module. A computer interface is designed to control the system through a Nios II processor. Measurements confirm a time resolution of 16 ± 2 ps with jitter below 450 ± 20 ps (at 24 °C) with a maximum delay of 1 s. The whole system is simple in structure and low in cost.
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http://dx.doi.org/10.1063/5.0030341DOI Listing
February 2021

Functional characterization of a novel copper-dependent lytic polysaccharide monooxygenase TgAA11 from Trichoderma guizhouense NJAU 4742 in the oxidative degradation of chitin.

Authors:
Lei Ma Zhiying Liu Zhijian Kong Mengmeng Wang Tuo Li Han Zhu Qun Wan Dongyang Liu Qirong Shen

Carbohydr Polym 2021 Apr 30;258:117708. Epub 2021 Jan 30.

·Jiangsu Provincial Key Lab of Solid Organic Waste Utilization, Jiangsu Collaborative Innovation Center of Solid Organic Wastes, Educational Ministry Engineering Center of Resource-saving Fertilizers, Nanjing Agricultural University, Nanjing 210095, Jiangsu, People's Republic of China; Nanjing Agricultural University, Nanjing 210095, People's Republic of China.

Lytic polysaccharide monooxygenases (LPMOs) are attracting much attention for their potential application in biodegradation. However, there are limited studies on the characterization of the AA11 family. Here, a novel AA11 family protein, TgAA11, from Trichoderma guizhouense NJAU 4742 was characterized, and the isothermal titration calorimetry (ITC) analysis results showed that it exhibited tight binding capacity for copper ions with a K value of 4.83 ± 0.79 μM. The MALDI-TOF-MS analysis results indicated that TgAA11 could act on β-chitin to form C1 oxidation products, and some deacetylated chitooligosaccharides. In addition, the degradation of α-chitin and β-chitin by a chitinolytic enzyme Sg-chi was substantially increased in the presence of TgAA11 by 39.9 % and 288.2 %, respectively. Furthermore, the active site residues predicted showed that His61 and Tyr142 might be critical for the active site residues of the TgAA11 protein. This study will contribute to the understanding of the function of AA11 LPMOs in the degradation of chitin.
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http://dx.doi.org/10.1016/j.carbpol.2021.117708DOI Listing
April 2021

Functional expression and purification of recombinant full-length human ATG7 protein with HIV-1 Tat peptide in Escherichia coli.

Authors:
Guofu Dong Xi Zhao Junwang Guo Lei Ma Hongmei Zhou Qi Liu Xuelong Zhao Changzhen Wang Ke Wu

Protein Expr Purif 2021 Jun 13;182:105844. Epub 2021 Feb 13.

Beijing Key Laboratory of Radiation Biology (No. BZ0325) and Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. Electronic address:

The human autophagy-related protein ATG7 (hATG7), an E1-like ubiquitin enzyme, activates two ubiquitin-like proteins, LC3 (Atg8) and Atg12, and promotes autophagosome formation. While hATG7 plays an essential role for the autophagy conjugation system, the production of full-length functional hATG7 in bacterial systems remains challenging. Previous studies have demonstrated that the HIV-1 virus-encoded Tat peptide ('GRKKRRQRRR') can increase the yield and solubility of heterologous proteins. Here, functional full-length hATG7 was expressed using the pET28b-Tat expression vector in the Escherichia coli BL21 (DE3) strain. Recombinant hATG7 protein aggregated as inclusion bodies while expressed with widely used prokaryotic expression plasmids. In contrast, the solubility of Tat-tagged hATG7 increased significantly with prolonged time compared to Tat-free hATG7. The recombinant proteins were purified to >90% homogeneity under native conditions with a single step of affinity chromatography purification. The results of in vitro pull-down and LC3B-I lipidation assays showed that Tat-tagged hATG7 directly interacted with LC3B-I and promoted LC3B-I lipidation, suggesting that Tat-tagged hATG7 has significant catalytic activity. Overall, this study provides a novel method for improving the functional expression of full-length hATG7 in bacterial systems by fusion with the Tat peptide, a process which may be applied in future studies of hATG7 structure and function.
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http://dx.doi.org/10.1016/j.pep.2021.105844DOI Listing
June 2021

ReMOT Control Delivery of CRISPR-Cas9 Ribonucleoprotein Complex to Induce Germline Mutagenesis in the Disease Vector Mosquitoes Culex pipiens pallens (Diptera: Culicidae).

Authors:
Xixi Li Yang Xu Hongbo Zhang Haitao Yin Dan Zhou Yan Sun Lei Ma Bo Shen Changliang Zhu

J Med Entomol 2021 May;58(3):1202-1209

Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.

The wide distribution of Culex (Cx.) pipiens complex mosquitoes makes it difficult to prevent the transmission of mosquito-borne diseases in humans. Gene editing using CRISPR/Cas9 is an effective technique with the potential to solve the growing problem of mosquito-borne diseases. This study uses the ReMOT Control technique in Culex pipiens pallens (L.) to produce genetically modified mosquitoes. A microinjection system was established by injecting 60 adult female mosquitoes-14 µl injection mixture was required, and no precipitation occurred with ≤1 µl of endosomal release reagents (chloroquine or saponin). The efficiency of delivery of the P2C-enhanced green fluorescent protein-Cas9 (P2C-EGFP-Cas9) ribonucleoprotein complex into the ovary was 100% when injected at 24 h post-bloodmeal (the peak of vitellogenesis). Using this method for KMO knockout, we found that gene editing in the ovary could also occur when P2C-Cas9 RNP complex was injected into the hemolymph of adult Cx. pipiens pallens by ReMOT Control. In the chloroquine group, of the 2,251 G0 progeny screened, 9 individuals showed with white and mosaic eye phenotypes. In the saponin group, of the 2,462 G0 progeny screened, 8 mutant individuals were observed. Sequencing results showed 13 bp deletions, further confirming the fact that gene editing occurred. In conclusion, the successful application of ReMOT Control in Cx. pipiens pallens not only provides the basic parameters (injection parameters and injection time) for this method but also facilitates the study of mosquito biology and control.
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http://dx.doi.org/10.1093/jme/tjab016DOI Listing
May 2021

Piperazine-Derived α Antagonist 1- Benzyl-N- (3-(4- (2-Methoxyphenyl) Piperazine-1-yl) Propyl) -1H- Indole-2- Carboxamide Induces Apoptosis in Benign Prostatic Hyperplasia Independently of α1-Adrenoceptor Blocking.

Authors:
Qing Xiao Qi-Meng Liu Ru-Chao Jiang Kai-Feng Chen Xiang Zhu Lei Ma Wei-Xi Li Fei He Jun-Jun Huang

Front Pharmacol 2020 27;11:594038. Epub 2021 Jan 27.

The Fifth Affiliated Hospital, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China.

Previous studies have indicated that α antagonist naftopidil (NAF) suppresses prostate growth by decreasing cell proliferation without affecting apoptosis and prostate volume in benign prostatic hyperplasia (BPH). A NAF-derived α1D/1A antagonist 1- benzyl-N-(3-(4-(2-methoxyphenyl) piperazine-1-yl) propyl)-1H-indole-2- carboxamide (HJZ-12) has been reported from our laboratory, which exhibits high subtype-selectivity to both α- and α- AR (47.9- and 19.1- fold, respectively) with respect to a1B-AR . However, no further study was conducted. In the present study, a pharmacological evaluation of HJZ-12 in BPH was performed on an estrogen/androgen-induced rat BPH model and human BPH-1 cell line. , HJZ-12 exhibited better performance than NAF in preventing the progression of rat prostatic hyperplasia by not only decreasing prostate weight and proliferation (similar to NAF) but also, shrinking prostate volume and inducing prostate apoptosis (different from NAF). , HJZ-12 exhibited significant cell viability inhibition and apoptotic induction in BPH-1 cell line, without presenting cell anti-proliferation properties. Intriguingly, the role of HJZ-12 on cell viability and apoptosis was an α1-independent action. Furthermore, RNA-Seq analysis was applied to screen out six anti-apoptotic genes (Bcl-3, B-lymphoma Mo-MLV insertion region 1 [Bmi-1], ITGA2, FGFR3, RRS1, and SGK1). Amongst them, Bmi-1 was involved in the apoptotic induction of HJZ-12 in BPH-1. Overall, HJZ-12 played a remarkable role in preventing the progression of prostatic hyperplasia through α1-independent apoptotic induction, indicating that it will be a multi-target effective candidate for BPH treatment.
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http://dx.doi.org/10.3389/fphar.2020.594038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873900PMC
January 2021

Surgical site infection after posterior lumbar interbody fusion and instrumentation in patients with lumbar degenerative disease.

Authors:
Honglei Pei Haiying Wang Meiyun Chen Lei Ma Guobin Liu Wenyuan Ding

Int Wound J 2021 Feb 12. Epub 2021 Feb 12.

Department of Spinal Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China.

We designed this retrospective study with aims to investigate the incidence and risk factors associated with surgical site infection (SSI) following posterior lumbar interbody fusion (PLIF) and instrumentation in patients with lumbar degenerative disease. Eligible patients treated between January 2016 and June 2019 were included. Electronic medical records were inquired for data extraction and collection. Patients with SSI and without SSI were compared using the univariate analyses, and the association between variables and risk of SSI was investigated using multivariate logistics regression analyses. Among 1269 patients, 43 were found to have SSI, indicating a rate of 3.4%. Microbiological culture tests showed 88.4% patients had a positive result. Four SSIs were caused by mixed bacterial, and the remaining 34 by single bacteria. Multiple drug-resistant strains were detected in 25 (65.8%) SSIs, with meticillin-resistant coagulase-negative staphylococcus (MRCNS) predominating (12, 48.0%). ASA III and above (odd ratio (OR), 1.67; 95% confidence interval (CI), 1.11 to 3.07), preoperative stay (OR, 1.13; 95% CI, 1.04 to 1.23), heart disease (OR, 2.88; 95% CI, 1.24 to 6.71), diabetes mellitus (OR, 3.28; 95% CI, 1.66 to 6.47) and renal insufficiency (OR, 4.23; 95% CI, 1.26 to 10.21), prolonged prophylactic antibiotics use (OR, 4.43; 95% CI, 2.30 to 8.54), and the reduced lymphocyte count (OR, 2.11; 95% CI, 1.03 to 4.33) were identified as independent risk factors associated with SSI. These factors, although most not modifiable, should be kept in mind, optimised for surgical conditions, or readily adjusted in the future postoperative management of antibiotics, to reduce postoperative SSIs.
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http://dx.doi.org/10.1111/iwj.13562DOI Listing
February 2021

The design of X-band EPR cavity with narrow detection aperture for in vivo fingernail dosimetry after accidental exposure to ionizing radiation.

Authors:
Junwang Guo Xiaoxiao Luan Ye Tian Lei Ma Xiaoguang Bi Jierui Zou Guofu Dong Ye Liu Yonggang Li Jing Ning Ke Wu

Sci Rep 2021 Feb 8;11(1):2883. Epub 2021 Feb 8.

Beijing Institute of Radiation Medicine, Beijing Key Laboratory of Radiation Biology (No. BZ0325), Beijing, 100850, China.

For the purpose of assessing the radiation dose of the victims involved in the nuclear emergency or radiation accident, a new type of X-band EPR resonant cavity for in vivo fingernail EPR dosimetry was designed and a homemade EPR spectrometer for in vivo fingernail detection was constructed. The microwave resonant mode of the cavity was rectangular TE101, and there was a narrow aperture for fingernail detection opened on the cavity's wall at the position of high detection sensitivity. The DPPH dot sample and the fingernail samples were measured based on the in vivo fingernail EPR spectrometer. The measurements of the DPPH dot sample verified the preliminary functional applicable of the EPR spectrometer and illustrated the microwave power and modulation response features. The fingernails after irradiation by gamma-ray were measured and the radiation-induced signal was acquired. The results indicated that the cavity and the in vivo EPR dosimeter instrument was able to detect the radiation-induced signal in irradiated fingernail, and preliminarily verified the basic function of the instrument and its potential for emergency dose estimate after a radiation accident.
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http://dx.doi.org/10.1038/s41598-021-82462-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870891PMC
February 2021

Estimating Reference Bony Shape Models for Orthognathic Surgical Planning Using 3D Point-Cloud Deep Learning.

Authors:
Deqiang Xiao Chunfeng Lian Han Deng Tianshu Kuang Qin Liu Lei Ma Daeseung Kim Yankun Lang Xu Chen Jaime Gateno Steve Shen James Jiong Xia Pew-Thian Yap

IEEE J Biomed Health Inform 2021 Jan 26;PP. Epub 2021 Jan 26.

Orthognathic surgical outcomes rely heavily on the quality of surgical planning. Automatic estimation of a reference facial bone shape significantly reduces experience-dependent variability and improves planning accuracy and efficiency. We propose an end-to-end deep learning framework to estimate patient-specific reference bony shape models for patients with orthognathic deformities. Specifically, we apply a point-cloud network to learn a vertex-wise deformation field from a patients deformed bony shape, represented as a point cloud. The estimated deformation field is then used to correct the deformed bony shape to output a patient-specific reference bony surface model. To train our network effectively, we introduce a simulation strategy to synthesize deformed bones from any given normal bone, producing a relatively large and diverse dataset of shapes for training. Our method was evaluated using both synthetic and real patient data. Experimental results show that our framework estimates realistic reference bony shape models for patients with varying deformities. The performance of our method is consistently better than an existing method and several deep point-cloud networks. Our end-to-end estimation framework based on geometric deep learning shows great potential for improving clinical workflows.
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http://dx.doi.org/10.1109/JBHI.2021.3054494DOI Listing
January 2021