Publications by authors named "Xin Ma"

1,077 Publications

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Cope with the COVID-19 pandemic: Dynamic bed allocation and patient subsidization in a public healthcare system.

Int J Prod Econ 2022 Jan 4;243:108320. Epub 2021 Oct 4.

Department of Management Sciences, City University of Hong Kong, Kowloon, Hong Kong.

In many countries and territories, public hospitals play a major role in coping with the COVID-19 pandemic. For public hospital managers, on the one hand, they must best utilize their hospital beds to serve the COVID-19 patients immediately. On the other hand, they need to consider the need of bed resources from non-COVID-19 patients, including emergency and elective patients. In this work, we consider two control mechanisms for public hospital managers to maximize the overall utility of patients. One is the dynamic allocation of bed resources according to the evolution process of the COVID-19 pandemic. The other is the usage of a subsidy scheme to move elective patients from the public to private hospitals. We develop a dynamic programming model to study the allocation of isolation and ordinary beds and the effect of the subsidy policy in serving three types of patients, COVID-19, emergency, and elective-care. We first show that the dynamic allocation between isolation and ordinary beds can provide a better utilization of bed resources, by cutting down at least 33.5% of the total cost compared with the static policy (i.e., keeping a fixed number of isolation beds) when facing a medium pandemic alert. Our results further show that subsidizing elective patients and referring them to private hospitals is an efficient way to ease the overcrowded situation in public hospitals. Our results demonstrate that, by dynamically conducting bed allocation and subsidy scheme in different phases of the COVID-19 pandemic, patient overall utility can be greatly improved.
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http://dx.doi.org/10.1016/j.ijpe.2021.108320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489298PMC
January 2022

[Analysis of bacterial infection and drug sensitivity in patients with chronic suppurative otitis media].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Oct;35(10):870-874

Department of Otolaryngology,People's Hospital,Peking University,Beijing,100044,China.

To explore the distribution of pathogenic bacteria and drug sensitivity among patients with chronic suppurative otitis media. Patients with chronic suppurative otitis media who were hospitalized in the Department of Otolaryngology, People's Hospital, Peking University for surgery from January 1, 2019 to May 1, 2021 were enrolled as the subjects, then take the deep secretions of the external auditory canal for bacterial culture. Finally, the distribution and drug sensitivity of the pathogenic bacteria are analyzed. A total of 126 patients were enrolled, of which 53 were culture-positive, and 57 strains of bacteria were isolated, including 47 strains of Gram-positive cocci, 10 strains of Gram-negative bacilli. Among Gram-positive cocci, 24 methicillin-sensitive staphylococcus aureus(MSSA) strains, 7 methicillin-resistant staphylococcus aureus(MRSA) strains, 14 coagulase-negative staphylococcus strains, 1 strain enterococcus faecium, and 1 strain otitis Zurich. 4 strains(4/10) of pseudomonas aeruginosa among Gram-negative bacilli. Among them, MSSA has a high resistance rate to levofloxacin, moxifloxacin, clindamycin, and gentamicin, and high sensitivity to oxacillin, vancomycin, linezolid, and rifampin. MRSA is highly resistant to common antibiotics except vancomycin, rifampicin, and linezolid. The Gram-negative bacilli have higher resistance rates to levofloxacin, aztreonam, ciprofloxacin, ceftazidime, and piperacillin/tazobactam, and to meropenem, imipenem, amika star, cefepoxime, cefoperazone/sulbactam, and tobramycin are more sensitive. The results of univariable and multivariable analysis showed that age and bacterial infection were independent factors related to dry ears, and the duration of the disease history was a non-independent factor. The main pathogenic bacteria infections in patients with chronic suppurative otitis media are MSSA, MRSA, and pseudomonas aeruginosa. Whether it is combined with bacterial infection and age are independent factors related to whether patients with chronic suppurative otitis media could have dry ears. Therefore, patients with chronic suppurative otitis media should be treated with specific antibiotics or surgical interventions as soon as possible in combination with drug sensitivity results to avoid prolonging disease course or causing serious infectious complications.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.10.002DOI Listing
October 2021

Spatial light path analysis and calibration of four-mirror-based monocular stereo vision.

Opt Express 2021 Sep;29(20):31249-31269

The feasibility and accuracy of four-mirror-based monocular stereo vision (FMSV) are related to the system layout and calibration accuracy, respectively. In this study, a spatial light path analysis method and a calibration method are proposed for an FMSV system. As two-dimensional light path analysis cannot fully characterize the imaging parameters, a spatial light path model is proposed, which allows refinement of the system design. Then, considering the relationship between the lens distortion and the imaging depth of field (DoF), a DoF-distortion equal-partition-based model is established. In the traditional calibration method, the optical axis must be perpendicular to the chessboard. Here, an accurate and practical FMSV calibration method without this constraint is proposed based on the above model. Using the proposed spatial light path analysis technique, a high-accuracy, high-portability FMSV system is constructed and calibrated, for which the average error of the vision-reconstructed distance is 0.0298 mm. In addition, robot path accuracy is evaluated by the system and compared to laser-tracker measurement results. Hence, high accuracy of 0.031 mm is determined for the proposed vision system.
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http://dx.doi.org/10.1364/OE.435893DOI Listing
September 2021

DNA-Based Artificial Signaling System Mimicking the Dimerization of Receptors for Signal Transduction and Amplification.

Anal Chem 2021 Oct 6. Epub 2021 Oct 6.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, P. R. China.

Transmembrane signal transduction is of profound significance in many biological processes. The dimerization of cell-surface receptors is one prominent mechanism by which signals are transmitted across the membrane and trigger intracellular cascade amplification reactions. Recreating such processes in artificial systems has potential applications in sensing, drug delivery, bioengineering, and providing a new route for a deep understanding of fundamental biological processes. However, it remains a challenge to design artificial signal transduction systems working by the receptor dimerization mechanism in a predictable and smart manner. Here, benefitting from DNA with features of programmability, controllability, and flexible design, we use DNA as a building material to construct an artificial system mimicking dimerization of receptors for signal transduction and cascade amplification. DNA-based membrane-spanning receptor analogues are designed to recognize external signals, which drives two receptors into close spatial proximity to activate DNAzymes inside the cell-mimicking system. The activation of the DNAzyme initiates the catalyzed cleavage of encapsulated substrates and leads to the release of fluorescent second messengers for signal amplification. Such an artificial signal transduction system extends the range of biomimetic DNA-based signaling systems, providing a new avenue to study natural cell signaling processes and artificially regulate biological processes.
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http://dx.doi.org/10.1021/acs.analchem.1c02405DOI Listing
October 2021

Mechanistic insights into trace metal mobilization at the micro-scale in the rhizosphere of Vallisneria spiralis.

Sci Total Environ 2021 Oct 1;806(Pt 3):150735. Epub 2021 Oct 1.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, China.

Mobilization of trace metals in the rhizosphere of macrophytes is controlled by root-driven chemical changes, especially the steep gradients of O and pH from the rhizosphere to bulk sediments. Here, the O and pH dynamics, and the distribution of trace metal, in the rhizosphere of Vallisneria spiralis were obtained using planar optodes and diffusive gradients in thin films, respectively. Radial O loss (ROL) and acidification occurred on all visible roots of V. spiralis and exhibited highly spatiotemporal dynamics depending on the root growth and various environmental conditions. Trace metals showed different mobilization mechanisms in the rhizosphere. ROL and produced Fe(III) (oxyhydr)oxides decreased the mobility of Fe, As, Co, V and W in the rhizosphere. However, Mn, Ni and Cu exhibited greater mobility in the rhizosphere than bulk sediments as a result of the oxidation of metal sulfide and proton-induced dissolution of minerals. In particular, Co and Ni presented increased activity at the interface between rhizosphere and bulk sediment, which was attributed to the redox dissolution processes of Fe and Mn as a result of ROL and rhizosphere acidification. These results provide new insights into the roles of macrophyte root-induced O and pH changes in controlling trace metal mobility in sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150735DOI Listing
October 2021

Robotic versus Laparoscopic Retroperitoneal Lymph node Dissection for Clinical Stage I Non-seminomatous Germ Cell Tumor of Testis: A Comparative Analysis.

Urol J 2021 10 4. Epub 2021 Oct 4.

Department of Urology, the Third Medical Center, Chinese PLA General Hospital, Beijing, China.

Purpose: To compare the treatment outcomes of robotic retroperitoneal lymph node dissection (R-RPLND) versus laparoscopic RPLND (L-RPLND) for clinical stage I non-seminomatous germ cell testicular tumors (NSGCTs).

Materials And Methods: We retrospectively reviewed the data of patients with stage I NSGCTs who underwent robotic or laparoscopic RPLND between 2008 and 2017.  Perioperative data and oncologic outcomes were reviewed and compared between the two groups. Progression-free survival was analyzed using Kaplan-Meier survival curves and compared between two groups.

Results: A total of 31 and 28 patients underwent R-RPLND and L-RPLND respectively. The preoperative characteristics of the patients were comparable in the two groups. Patients in R-RPLND group had significantly shorter median operative time (140 vs. 175 minutes, P < .001), a shorter median duration to surgical drain removal (2 vs. 4 days, P = .002) and a shorter median postoperative hospital stay (5 vs. 6 days, P = .001). There were no statistical differences in intra- and post-operative complication rate between the groups and the oncologic outcomes were similar in the two groups.

Conclusion: In expert hands, R-RPLND and L-RPLND were comparable in oncological parameter and morbidity rate; R-RPLND showed superiority in operation duration, median days to surgical drain removal and postoperative hospital stay for stage I NSGCTs. Multicenter and randomized studies with good power of study and sufficient follow-up duration are required to validate our result.
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http://dx.doi.org/10.22037/uj.v18i.6629DOI Listing
October 2021

Effects of Zinc Sources and Levels on Growth Performance, Zinc Status, Expressions of Zinc Transporters, and Zinc Bioavailability in Weaned Piglets.

Animals (Basel) 2021 Aug 26;11(9). Epub 2021 Aug 26.

Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Science, Zhejiang University, Hangzhou 310058, China.

The present study was conducted to explore the bioavailability of chitosan-zinc chelate (CS-Zn) in weaned piglets, and its characteristics of prepared and oral safety were also involved. A total of 210 crossbred weaned piglets (Duroc × Landrace × Large White) with a mean body weight of 6.30 kg were randomly assigned into seven dietary treatments involving a 2 × 3 factorial arrangement with two Zn sources (CS-Zn and ZnSO) and three levels of added Zn (50, 100, 150 mg Zn/kg) plus a Zn-unsupplemented control diet. The feeding trial lasted 42 days. The AFM image of CS-Zn showed a rougher appearance and smaller size particles. The changes in spectrum peaks evidenced the successful chelating of Zn with chitosan. The XRD patterns revealed the formation of a new crystalline phase. Moreover, the oral acute toxicity test of CS-Zn showed no lethal effects on mice. Weaned piglets fed dietary CS-Zn showed improved weight gain and decreased diarrhea incidence. Additionally, the bioavailability of CS-Zn was higher than that of ZnSO in piglets. Taken together, these results indicate that the prepared CS-Zn chelate, with rough surface and crystalline phase, is non-toxic and show enhanced bioavailability.
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http://dx.doi.org/10.3390/ani11092515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470440PMC
August 2021

Single-cell transcriptome analysis reveals cellular heterogeneity in the ascending aortas of normal and high-fat diet-fed mice.

Exp Mol Med 2021 Sep 21;53(9):1379-1389. Epub 2021 Sep 21.

Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.

The aorta contains numerous cell types that contribute to vascular inflammation and thus the progression of aortic diseases. However, the heterogeneity and cellular composition of the ascending aorta in the setting of a high-fat diet (HFD) have not been fully assessed. We performed single-cell RNA sequencing on ascending aortas from mice fed a normal diet and mice fed a HFD. Unsupervised cluster analysis of the transcriptional profiles from 24,001 aortic cells identified 27 clusters representing 10 cell types: endothelial cells (ECs), fibroblasts, vascular smooth muscle cells (SMCs), immune cells (B cells, T cells, macrophages, and dendritic cells), mesothelial cells, pericytes, and neural cells. After HFD intake, subpopulations of endothelial cells with lipid transport and angiogenesis capacity and extensive expression of contractile genes were defined. In the HFD group, three major SMC subpopulations showed increased expression of extracellular matrix-degradation genes, and a synthetic SMC subcluster was proportionally increased. This increase was accompanied by upregulation of proinflammatory genes. Under HFD conditions, aortic-resident macrophage numbers were increased, and blood-derived macrophages showed the strongest expression of proinflammatory cytokines. Our study elucidates the nature and range of the cellular composition of the ascending aorta and increases understanding of the development and progression of aortic inflammatory disease.
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http://dx.doi.org/10.1038/s12276-021-00671-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492660PMC
September 2021

Effects of two inhibitors of metabolic glutamate receptor 5 on expression of endogenous homer scaffold protein 1 in the auditory cortex of mice with tinnitus.

Bioengineered 2021 12;12(1):7156-7164

Department of Otorhinolaryngology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China.

Tinnitus is deemed as the result of abnormal neural activities in the brain, and Homer proteins are expressed in the brain that convey nociception. The expression of Homer in tinnitus has not been studied. We hypothesized that expression of Homer in the auditory cortex was altered after tinnitus treatment. Mice were injected with sodium salicylate to induce tinnitus. Expression of Homer was detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry assays. We found that Homer1 expression was upregulated in the auditory cortex of mice with tinnitus, while expression of Homer2 or Homer3 exhibited no significant alteration. Effects of two inhibitors of metabolic glutamate receptor 5 (mGluR5), noncompetitive 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) and competitive α-methyl-4-carboxyphenylglycine (MCPG), on the tinnitus scores of the mice and on Homer1 expression were detected. MPEP significantly reduced tinnitus scores and suppressed Homer1 expression in a concentration dependent manner. MCPG had no significant effects on tinnitus scores or Homer1 expression. In conclusion, Homer1 expression was upregulated in the auditory cortex of mice after tinnitus, and was suppressed by noncompetitive mGluR5 inhibitor MPEP, but not competitive mGluR5 inhibitor MCPG.
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http://dx.doi.org/10.1080/21655979.2021.1979354DOI Listing
December 2021

The semaphorin 4A-neuropilin 1 axis alleviates kidney ischemia reperfusion injury by promoting the stability and function of regulatory T cells.

Kidney Int 2021 Sep 14. Epub 2021 Sep 14.

Department of Urology, The 3(rd) Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Urology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Previous studies have suggested the role of CD4Foxp3 regulatory T cells (Tregs) in protection against kidney ischemia reperfusion injury via their immunosuppressive properties. Unfortunately, the associated mechanisms of Tregs in kidney ischemia reperfusion injury have not been fully elucidated. Semaphorin 4A (Sema4A) is essential for maintaining the immunosuppressive capacity of Tregs in tumors. However, whether Sema4A can alleviate kidney ischemia reperfusion injury through Tregs has not yet been demonstrated. Here, we investigated the effect and mechanism of Sema4A on the development of kidney ischemia reperfusion injury. Administration of recombinant human Sema4A-Fc chimera protein prior to ischemia reperfusion injury promoted the expansion and function of Tregs and decreased the accumulation of neutrophils and proinflammatory macrophages thereby attenuating functional and histological injury of the injured kidneys. Depletion of Tregs abrogated the protective effect of Sema4A on kidney ischemia reperfusion injury, suggesting Tregs as the main target cell type for Sema4A in the development of this injury. Mechanistically, Sema4A bound to neuropilin 1 (Nrp1), a cell surface receptor for Sema4A and other ligands and a key regulator of Tregs, which then promoted recruitment of phosphatase and tensin homologue and suppressed the Akt-mTOR pathway in Foxp3 mice but not in Nrp1Foxp3 mice. Consistently, Treg-specific deletion of Nrp1 blocked the effect of Sema4A on the expansion and function of Treg cells. Thus, our results demonstrate that the Sema4A-Nrp1 axis alleviates the development of ischemia reperfusion injury by promoting the stability and function of Tregs in mouse kidneys.
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http://dx.doi.org/10.1016/j.kint.2021.08.023DOI Listing
September 2021

Effects of Injection of Polysaccharide on the Intestinal Development and Mucosal Immunity in Broiler Chickens.

Front Vet Sci 2021 30;8:738816. Epub 2021 Aug 30.

Basic Medical College, Jilin Medical University, Jilin, China.

The purpose of this study was to examine the effects of injection of polysaccharide (APS) on hatchability, body weight (BW), intestinal histomorphology, the number of IgA cells and sIgA content in intestine, and the expression of intestinal immune-related genes in broiler chickens. On day 18 of the incubation, a total of 960 live embryo eggs were weighed and randomly divided into 4 treatment groups: a control group and three APS groups. The eggs in the control group were injected with 0.5 mL physiological saline. The eggs in the APS groups were injected with 3 different amounts of APS in 0.5 mL physiological saline: 1 mg (APS), 2 mg (APS) and 4 mg (APS). The solution was injected into the amnion of each egg. The results showed that injection of APS did not affect the hatchability but increased the body weight of the 14 d and 21 d chickens, with a significant increase observed in the APS group ( < 0.05). At most time points, the villus height (VH) was increased ( < 0.05) and the crypt depth (CD) was decreased ( < 0.05) in the small intestine of the broilers, with higher VH/CD ratios in the APS and APS groups compared with the control group. The number of IgA cells in the mucosa and the secretory immunoglobulin A (sIgA) levels in the intestinal washings were higher in the APS and APS groups than in the APS and control groups. The gene expression levels of interleukin (IL)-2, interleukin (IL)-4, interferon gamma (IFN-γ), and Toll-like receptor (TLR)-4 were significantly enhanced by APS stimulation at most time points ( < 0.05). These results indicated that injection of APS has the potential of promoting intestinal development and enhancing intestinal mucosal immunity of broiler chickens in the early stage after hatching.
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http://dx.doi.org/10.3389/fvets.2021.738816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435677PMC
August 2021

Biomechanical assessment of two types and two different locations of subtalar arthroereisis implants for flexible flatfoot: A cadaveric study.

Clin Biomech (Bristol, Avon) 2021 Aug 30;89:105475. Epub 2021 Aug 30.

Department of Orthopedics, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China. Electronic address:

Background: Subtalar arthroereisis refers to the implantation of a sinus tarsi implant for the treatment of flexible flatfoot. The purpose of this study was to compare the ability to correct the flatfoot deformity and contact pressure of the posterior subtalar joint between two types of self-locking wedge implants and between two different positions for the same device in a cadaveric flatfoot model.

Methods: The flatfoot model was created in ten cadaver feet through ligament sectioning and cyclic loading. Three kinds of arthroereisis procedures were evaluated: Talar-Fit (type I self-locking wedge implant) anchored in the sinus portion of the tarsal sinus (T-sinus group), Talar-Fit in the canalis portion (T-canalis group), and HyProCure (type II) in the canalis portion (H group). Corrective ability in the sagittal and transverse planes were measured with clinometers. Contact pressure was measured with pressure-sensitive films.

Findings: T-canalis group provided more sagittal (mean difference for size 10 mm: 1.9°, P = 0.014; mean difference for size 11 mm: 3.1°, P = 0.037) and transverse (mean difference for size 8 mm: 1.8°, P = 0.049; mean difference for size 11 mm: 2.2°, P = 0.049) corrections than T-sinus group. The flattening process shifted the peak pressure of the posterior subtalar joint to the posteromedial side (P < 0.05) and arthroereisis helped the distribution of contact pressure restore uniformity (all P > 0.05).

Interpretation: A self-locking wedge implant inserted in the canalis portion of the tarsal sinus achieved better correction than an implant inserted in the sinus portion.
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http://dx.doi.org/10.1016/j.clinbiomech.2021.105475DOI Listing
August 2021

Predictive performance of eLIFT for liver inflammation and fibrosis in chronic liver diseases.

Int J Med Sci 2021 27;18(15):3599-3608. Epub 2021 Aug 27.

Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

The easy liver fibrosis test (eLIFT) is a novel predictor of liver fibrosis in chronic liver disease (CLD). This study aimed to evaluate the predictive value of the eLIFT for liver inflammation and fibrosis in CLD patients. We enrolled 1125 patients with CLD who underwent liver biopsy. The predictive accuracy for liver inflammation and fibrosis of the eLIFT was assessed and compared to that of the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 score (FIB-4), and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) by ROC (Receiver Operating Characteristic) analysis and decision curve analysis (DCA). The areas under the ROC curves (AUROCs) of the eLIFT for assessing liver inflammation G ≥ 2 and G ≥ 3 were 0.77 (0.75-0.80) and 0.81 (0.79-0.84), with cut-offs of 8.0 and 11.0, respectively. The AUROCs of the eLIFT for predicting fibrosis stages S ≥ 2 and S4 were 0.72 (0.70-0.76) and 0.76 (0.72-0.80), with cut-offs of 9.0 and 10.0, respectively. In discriminating G≥2 inflammation, the AUROC of the eLIFT was better than that of the FIB-4, with no difference compared with the GPR, but lower than that of the APRI. When discriminating G≥3 inflammation, the AUROC of the eLIFT was comparable to that of the APRI and GPR but superior to that of the FIB-4. There were no significant differences between the four indexes for predicting S≥2 and S4. The eLIFT is a potentially useful noninvasive predictor of liver inflammation and fibrosis in patients with CLD.
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http://dx.doi.org/10.7150/ijms.62386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436088PMC
August 2021

LAMP assay for distinguishing and in lotus () rhizomes.

Plant Dis 2021 Sep 8. Epub 2021 Sep 8.

Jiangsu Academy of Agricultural Sciences, 117941, zhonglingjie 50,Nanjing, China, Nanjing, China, 210014;

The yields of edible rhizome from the cultivation of the perennial hydrophyte lotus () can be severely reduced by rhizome rot disease caused by species. There is a lack of rapid field-applicable methods for detection of these pathogens on lotus plants displaying symptoms of rhizome-rot. (91%) and (9%) were identified at different frequencies from lotus samples showing symptoms of rhizome-rot. As these two species can cause different severity of disease and their morphology is very similar, molecular-diagnostic based methods to detect these two species were developed. Based on the comparison of the mitochondrial genome of the two species, three specific DNA loci targets were found. The designed primer sets for conventional PCR, qPCR and loop-mediated isothermal amplification (LAMP) precisely distinguished the above two species when isolated from lotus and other plants. The LAMP detection limits were 10 pg/μl and 1 pg/μl of total DNA for and , respectively. We also carried out field-mimicked experiments on lotus seedlings and rhizomes (including inoculated samples and field diseased samples), and the results indicated that the LAMP primer sets and the supporting portable methods are suitable for the rapid diagnosis of the lotus disease in the field. The LAMP-based detection method will aid in the rapid identification of whether or are infecting lotus plants with symptoms of rhizome-rot, and can facilitate efficient pesticide use and prevent the disease spread through vegetative propagation of Fusarium-infected lotus rhizomes.
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http://dx.doi.org/10.1094/PDIS-06-21-1223-REDOI Listing
September 2021

[Metabolic engineering of L-cysteine supply modules for enhanced production of bacitracin in Bacillus licheniformis].

Sheng Wu Gong Cheng Xue Bao 2021 Aug;37(8):2803-2812

Environmental Microbial Technology Center of Hubei Province, State Key Laboratory of Biocatalysis and Enzyme Engineering, College of Life Sciences, Hubei University, Wuhan 430062, Hubei, China.

Bacitracin is a broad-spectrum antibiotics mainly produced by Bacillus, and is used as veterinary medicine in the fields of livestock and poultry breeding. Insufficient supply of precursor amino acids might be an important factor that hinders high-level microbial production of bacitracin. We investigated the effect of strengthening L-cysteine supply on bacitracin production by an industrial bacitracin producer, Bacillus licheniformis DW2. Overexpression of cysK encoding L-cysteine synthase led to a 9.17% increase of the bacitracin titer. Moreover, overexpression of cysE encoding L-serine acetyltransferase and cysP encoding thiosulfate/sulfate intracellular transporter increased the bacitracin titers by 7.23% and 8.52%, respectively. Moreover, overexpression of a putative cystine importer TcyP led to a 29.19% increase of intracellular L-cysteine, and bacitracin titer was increased by 7.79%. Subsequently, the strong promoter PbacA was used to replace the promoters of genes cysP, cysE and tcyP in strain DW2::ysK, respectively. The resulted strain CYS4 (DW2::cysK-PbacA-(cysP)-PbacA(cysE)- PbacA(tcyP) produced 910.02 U/mL bacitracin, which was 21.10% higher than that of the original strain DW2 (747.71 U/mL). Together with the experiments in 3 L fermenters, this research demonstrated that enhancing intracellular L-cysteine supply is an effective strategy to increase bacitracin production of B. licheniformis.
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http://dx.doi.org/10.13345/j.cjb.200623DOI Listing
August 2021

Fast Determination of the Lignin Monomer Compositions of Genetic Variants of Poplar Fast Pyrolysis/Atmospheric Pressure Chemical Ionization Mass Spectrometry.

J Am Soc Mass Spectrom 2021 Oct 31;32(10):2546-2551. Epub 2021 Aug 31.

Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States.

The proportional content of the phenylpropanoid monomeric units (4-hydroxyphenyl (H), guaiacyl (G), and syringyl (S)) in lignin is of paramount importance in germ plasm screening and for evaluating the results of plant breeding and genetic engineering. This content is usually determined using a tedious and slow (2 days/sample) method involving derivatization followed by reductive cleavage (DFRC) combined with GC/MS or NMR analysis. We report here a fast mass spectrometric method for the determination of the monomer content. This method is based on the fast pyrolysis of a lignin sample inside the ion source area of a linear quadrupole ion trap mass spectrometer. The evaporated pyrolysis products are promptly deprotonated negative-ion mode atmospheric pressure chemical ionization ((-)APCI) and analyzed by the mass spectrometer to determine the monomer content. The results obtained for the wild-type and six genetic variants of poplar were consistent with those obtained by the DFRC method. However, the mass spectrometry method requires only a small amount of sample (50 μg) and the use of only small amounts of three benign chemicals, methanol, water, and ammonium hydroxide, as opposed to DFRC that requires substantially larger amounts of sample (10 mg or more) and large amounts of several hazardous chemicals. Furthermore, the mass spectrometry method is substantially faster (3 min/sample), more precise, and the data interpretation is more straightforward as only nine ions measured by the mass spectrometer are considered.
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http://dx.doi.org/10.1021/jasms.1c00186DOI Listing
October 2021

Identification of Four Enhancer-Associated Genes as Risk Signature for Diffuse Glioma Patients.

J Mol Neurosci 2021 Aug 31. Epub 2021 Aug 31.

Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

The abnormal expressions of enhancer-associated genes have been reported to be correlated with poor prognosis of tumors, including glioblastoma (GBM). The objective of the current study is to predict prognosis by identifying enhancer-associated genes (EAGs). The profiles of genome-wide expressions of low-grade glioma (LGG) and GBM tissues in The Cancer Genome Atlas (TCGA) dataset were obtained to explore the expression patterns of EAGs in diffuse glioma. The capacity of prognosis prediction was validated by Rembrandt and GSE16011. Moreover, qPCR was utilized to confirm the effect of JQ1 and THZ1 on the EAGs. We detected 35 differentially expressed EAGs, which were predictive of overall survival. These candidate EAGs were then subjected to the multivariate cox regression analysis and were further scoped down to four signature genes, including TRAM2, SMAGP, KDELC2, and C7ORF25. A total of 662 patients were then stratified according to the expression levels of these four signature genes. The high-risk group accounted for poorer prognosis based on the Rembrandt and GSE16011 databases. The results of qPCR also demonstrated that the expression of the four EAGs could be abolished by JQ1 (bromodomain inhibitor) and THZ1 (CDK7 inhibitor) treatment. Our study not only highlights the potential role of EAGs, which can be used to improve clinical prognosis prediction in patients with diffuse glioma, but also sheds light on the specific biomarkers and therapeutic targets for diffuse glioma patients.
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http://dx.doi.org/10.1007/s12031-021-01861-3DOI Listing
August 2021

Recent development of near-infrared photoacoustic probes based on small-molecule organic dye.

RSC Chem Biol 2021 Jun 24;2(3):743-758. Epub 2021 Mar 24.

Key Laboratory of Pesticides and Chemical Biology, Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, Center of Chemical Biology, College of Chemistry, Central China Normal University Wuhan 430079 China

Photoacoustic imaging (PAI), which integrates the higher spatial resolution of optical imaging and the deeper penetration depth of ultrasound imaging, has attracted great attention. Various photoacoustic probes including inorganic and organic agents have been well fabricated in last decades. Among them, small-molecule based agents are most promising candidates for preclinical/clinical applications due to their favorite features and facile functionalization. In recent years, PAI, in the near-infrared region (NIR, 700-1700 nm) has developed rapidly and has made remarkable achievements in the biomedical field. Compared with the visible light region (400-700 nm), it can significantly reduce light scattering and meanwhile provide deeper tissue penetration. In this review, we discuss the recent developments of near-infrared photoacoustic probes based on small molecule dyes, which focus on their "always on" and "activatable" form in biomedicine. Further, we also suggest current challenges and perspectives.
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http://dx.doi.org/10.1039/d0cb00225aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341990PMC
June 2021

Construction and Characterization of a Gradient Strength Promoter Library for Fine-Tuned Gene Expression in .

ACS Synth Biol 2021 09 27;10(9):2331-2339. Epub 2021 Aug 27.

State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan, 430062, People's Republic of China.

DW2 is an important industrial strain for bacitracin production, and it is also used for biochemical production, however, the lack of effective toolkit for precise regulation of gene expression hindered its application seriously. Here, a gradient strength promoter library was constructed based on bacitracin synthetase gene cluster promoter P. First, different P promoter variants were constructed via coupling P with various 5'-UTRs, and expression ranges of 32.6-741.8% were attained among these promoters. Then, three promoters, P (strong), P (middle), and P (weakest), were applied for red fluorescent protein (RFP) and keratinase expression assays, and these promoters were proven to have good universality for different proteins. Second, the promoter of bacitracin synthetase gene cluster was replaced by these three promoters, and bacitraicn titer was enhanced by 14.62% when P was applied, which was decreased by 98.05% under the mediation of P compared with that of the original strain DW2. Third, promoters P, P, and P were selected to regulate the expression levels of critical genes that are responsible for pucheriminic acid synthesis, and pucheriminic acid yield was increased by 194.1% via manipulating synthetic and competitive pathways. Finally, promoters P, P, and P were applied for green fluorescent protein (GFP) and RFP expression in , and consistent effects were attained based on our results. Taken together, a gradient strength promoter library was constructed in this research, which provided an effective toolkit for fine-tuning gene expression and reprogramming metabolite metabolic flux in .
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http://dx.doi.org/10.1021/acssynbio.1c00242DOI Listing
September 2021

Analysis of the evolution of potential and free furfural compounds in the production chain of infant formula and risk assessment.

Food Chem 2021 Aug 9;368:130814. Epub 2021 Aug 9.

College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China. Electronic address:

Furfural compounds are produced during infant formula production when heat treatment is involved. In this study, a robust method was established for determining potential and free furfural compounds (furfural, 5-methyl-2-furfural, 2-acetylfuran and 5-hydroxymethyl-2-furfural) using a modified QuEChERS technique coupled with GC-MS/MS. Further, 36 samples of two batches, covering the whole infant formula production chain were analyzed by the method to investigate how furfurals evolved during process. Then risk assessment was conducted using the Toxtree and T.E.S.T. software and evaluated by hazard quotient. Results showed the contents of bound and free 5-hydroxymethyl-2-furfural demonstrated largest increase during spray-drying (6-11 times) and homogenization stages (12-33 times), respectively. As the sum up of bound and free 5-hydroxymethyl-2-furfural, potential 5-hydroxymethyl-2-furfural was found can cause safety risks in the production chain due to the high hazard quotient value (3.11), indicating it should be controlled in homogenization and spray-drying stages.
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http://dx.doi.org/10.1016/j.foodchem.2021.130814DOI Listing
August 2021

Brigatinib vs Alectinib in Crizotinib-Resistant Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer (ALTA-3).

Future Oncol 2021 Aug 23. Epub 2021 Aug 23.

Department of Medical Oncology, National Taiwan University Cancer Center, No. 57, Ln. 155, Sec. 3, Keelung Road, Da'an District, Taipei City, Taiwan.

Crizotinib is highly efficacious and more tolerable than chemotherapy for ALK non-small-cell lung cancer (NSCLC), but its progression-free survival benefit and intracranial efficacy have limitations. Head-to-head comparisons of next-generation ALK inhibitors in patients with ALK NSCLC progressing on crizotinib will contribute toward optimizing survival. This international, Phase III, randomized, open-label study (ALTA-3) will therefore assign patients with locally advanced or metastatic ALK NSCLC progressing on crizotinib to receive either brigatinib 180 mg qd (7-day lead-in at 90 mg qd) or alectinib 600 mg twice daily. The primary end point is progression-free survival as assessed by a blinded Independent Review Committee; the key secondary end point is overall survival. Trial registration number: NCT03596866 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2021-0608DOI Listing
August 2021

Captopril alleviates lung inflammation in SARS-CoV-2-infected hypertensive mice.

Zool Res 2021 Sep;42(5):633-636

School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression. In the present study, we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-CoV-2. Results revealed that SARS-CoV-2 replication was delayed in hypertensive mouse lungs. In contrast, SARS-CoV-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-CoV-2-infected normotensive mice. Furthermore, antihypertensive treatment alleviated lung inflammation induced by SARS-CoV-2 replication (interleukin (IL)-1β up-regulation and increased immune cell infiltration). No differences in lung inflammation were observed between the SARS-CoV-2-infected normotensive mice and hypertensive mice. Our findings suggest that captopril treatment may alleviate COVID-19 progression but not affect viral replication.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455464PMC
September 2021

Migraine and Cochlear Symptoms.

Curr Med Sci 2021 Aug 17;41(4):649-653. Epub 2021 Aug 17.

Department of Otorhinolaryngology, Peking University People's Hospital, Beijing, 100044, China.

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.
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http://dx.doi.org/10.1007/s11596-021-2410-6DOI Listing
August 2021

Treatment of postoperative delirium with continuous theta burst stimulation: study protocol for a randomised controlled trial.

BMJ Open 2021 08 16;11(8):e048093. Epub 2021 Aug 16.

Department of Psychiatry, Shanghai Tenth People's Hospital, Shanghai, China

Introduction: Postoperative delirium is one of the most common postoperative complications among elderly patients (65 years old or older). However, there are no effective treatments for this condition. Recent research suggests that continuous theta burst stimulation (cTBS), a non-invasive brain stimulation, can reduce pain level, improve cognitive function and affective symptoms in multiple diseases or dysfunctions, including anxiety disorders, major depressive disorder, sleep disorders and pain. But the potential benefits of cTBS in reducing postoperative delirium have not been investigated. Therefore, we propose determining whether cTBS can prevent and/or treat postoperative delirium in senior patients.

Methods And Analysis: The study will be a double-blind, randomised controlled trial. Participants (65 years old or older) undergoing scheduled orthopaedic surgery (≥2 hours, general anaesthesia) will be randomised to receive either cTBS or sham stimulation with a focal figure-of-eight coil over the right dorsolateral prefrontal cortex at 80% of the resting motor threshold. Every patient will receive 2-3 sets of stimulations during postoperative days (40 s per session, 3 sessions per set, 1 set per day). Participants will be assessed twice daily by a research assistant blinded to allocation. The primary outcome will be the incidence of postoperative delirium measured by the Confusion Assessment Method on postoperative days 1, 2 and 3. The secondary outcomes will be the severity and duration of postoperative delirium, cognitive function, pain, sleep quality, activities of daily living, length of hospital stay, discharge-to-facility or home, and rate of complication and mortality during the hospital stay.

Ethics And Dissemination: Ethical approval has been obtained from the ethics committee of Shanghai 10th People's Hospital. The principal investigator will submit a research progress report to the ethics committee regularly. All participants will provide written informed consent. Study results will be published in a peer-reviewed journal.

Trial Registration Number: NCT04661904.
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http://dx.doi.org/10.1136/bmjopen-2020-048093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370542PMC
August 2021

Improved soil-crop system management aids in NH emission mitigation in China.

Environ Pollut 2021 Nov 26;289:117844. Epub 2021 Jul 26.

Rothamsted Research, North Wyke, Devon, EX20 2SB, UK.

High ammonia (NH) emissions from fertilized soil in China have led to various concerns regarding environmental safety and public health. In response to China's blue skies protection campaign, effective NH reduction measures need to consider both mitigation efficiency and food security. In this context, we conducted a meta-analysis (including 2980 observations from 447 studies) to select effective measures based on absolute (AV) and yield-scaled (YSAV) NH volatilization reduction potential, with the aim of establishing a comprehensive NH mitigation framework covering various crop production sectors, and offering a range of potential solutions. The results showed that manipulating crop density, using an intermittent irrigation regime for paddy field rice, applying N as split applications or partially substituting inorganic fertilizer N with organic N sources could achieve reductions in AV and YSAV reduction of 10-20 %; adopting drip irrigation regimes, adding water surface barrier films to paddy fields, or using double inhibitor (urease and nitrification), slow-release or biofertilizers could achieve 20-40 % mitigation; plastic film mulching, applying fertilizer by irrigation or using controlled-release fertilizers could yield 40-60 % reduction; use of a urease inhibitor, fully substituting fertilizer N with organic N, or applying fertilizer by deep placement could decrease AV and YSAV by over 60 %. In addition, use of soil amendments, applying suitable inorganic N sources, or adopting crop rotation, intercropping or a rice-fish production model all had significant benefits to control AV. The adoption of any particular strategy should consider local accessibility and affordability, direct intervention by local/government authorities and demonstration to encourage the uptake of technologies and practices, particularly in NH pollution hotspot areas. Together, this could ensure food security and environmental sustainability.
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http://dx.doi.org/10.1016/j.envpol.2021.117844DOI Listing
November 2021

Research on insulator defect detection algorithm of transmission line based on CenterNet.

PLoS One 2021 29;16(7):e0255135. Epub 2021 Jul 29.

Department of Electrical Engineering, Northeast Electric Power University, Jilin, China.

The reliability of the insulator has directly affected the stable operation of electric power system. The detection of defective insulators has always been an important issue in smart grid systems. However, the traditional transmission line detection method has low accuracy and poor real-time performance. We present an insulator defect detection method based on CenterNet. In order to improve detection efficiency, we simplified the backbone network. In addition, an attention mechanism is utilized to suppress useless information and improve the accuracy of network detection. In image preprocessing, the blurring of some detected images results in the samples being discarded, so we use super-resolution reconstruction algorithm to reconstruct the blurred images to enhance the dataset. The results show that the AP of the proposed method reaches 96.16% and the reasoning speed reaches 30FPS under the test condition of NVIDIA GTX 1080 test conditions. Compared with Faster R-CNN, YOLOV3, RetinaNet and FSAF, the detection accuracy of proposed method is greatly improved, which fully proves the effectiveness of the proposed method.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255135PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320933PMC
July 2021

Research on insulator defect detection algorithm of transmission line based on CenterNet.

PLoS One 2021 29;16(7):e0255135. Epub 2021 Jul 29.

Department of Electrical Engineering, Northeast Electric Power University, Jilin, China.

The reliability of the insulator has directly affected the stable operation of electric power system. The detection of defective insulators has always been an important issue in smart grid systems. However, the traditional transmission line detection method has low accuracy and poor real-time performance. We present an insulator defect detection method based on CenterNet. In order to improve detection efficiency, we simplified the backbone network. In addition, an attention mechanism is utilized to suppress useless information and improve the accuracy of network detection. In image preprocessing, the blurring of some detected images results in the samples being discarded, so we use super-resolution reconstruction algorithm to reconstruct the blurred images to enhance the dataset. The results show that the AP of the proposed method reaches 96.16% and the reasoning speed reaches 30FPS under the test condition of NVIDIA GTX 1080 test conditions. Compared with Faster R-CNN, YOLOV3, RetinaNet and FSAF, the detection accuracy of proposed method is greatly improved, which fully proves the effectiveness of the proposed method.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255135PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320933PMC
July 2021

The construction of recombinant Lactobacillus casei expressing hemagglutinin-neuraminidase protein and its immune response in chickens.

Microb Pathog 2021 Sep 16;158:105091. Epub 2021 Jul 16.

College of Animal Science and Technology, Jilin Agricultural University, Jilin, 130118, China; Center for Reproductive Medicine, Jilin Medical University, Jilin, 132013, China. Electronic address:

Newcastle disease virus (NDV) is one of the most important diseases in poultry. The present study generated recombinant surface-displayed Lactobacillus casei (L. casei) expressing the hemagglutinin-neuraminidase (HN) of NDV (Lc-pPG-HN) and a live pPG vector (Lc-pPG) and evaluated their immunogenicity. A 1670 bp HN gene fragment was successfully amplified and cloned into a prokaryotic protein expression system. Protein expression in the resulting recombinant Lc-pPG-HN (surface displayed) strain was verified using Western blotting and indirect immunofluorescence. A single band was observed on the Western blots, and the molecular weight of the corresponding protein was 63 kDa. A fluorescent signal for Lc-pPG-HN was observed using fluorescence microscopy. A total of 270 healthy chicks were divided into three treatment groups. Five replicates were used for each treatment, while six chicks were used per replicate. The following three treatment groups were used: physiological saline group (Control), Lc-pPG group and recombinant vaccine group (Lc-pPG-HN). The primary immunization and booster immunization of the chicks were performed via oral administration on 1 and 10 days old. Tissue and blood samples were collected from chickens that received oral recombinant L. casei strains on 1, 7, 14 and 21 days post-immunization for immune-related index analyses. Chickens orally immunized with Lc-pPG-HN showed significantly increased body weights and immune organ indices. Oral immunization with Lc-pPG-HN also enhanced the concentrations of serum interleukin-2 (IL-2), interferon-γ (IFN-γ), intestinal lavage fluid secretory immunoglobulin A (SIgA) and histomorphological development of the small intestine. Our results also indicated that recombinant L. casei significantly increased Lactobacillus and Bifidobacterium colonization and decreased the relative abundance of Escherichia coli (E. coli) in the chicken caecum. Similar enhancement effects from hemagglutination inhibition were also observed in the antibody titers. Oral administration of Lc-pPG-HN effectively protected against NDV and alleviated the symptoms of the NDV challenge. In summary, recombinant L. casei had positive impacts on the performance, immunological function, gut development, and microbiota of growing chicks and may be a potential therapeutic candidate against NDV.
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http://dx.doi.org/10.1016/j.micpath.2021.105091DOI Listing
September 2021
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