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ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

《农业科学与工程前沿（英文）》 2022年 第9卷 第1期 doi: 10.15302/J-FASE- 2021390

摘要：

It has previously been shown that tryptophan, the biosynthesis precursor of Peganum harmala alkaloids, and its derivatives have anti-TMV activity both in vitro and in vivo. Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of l-tryptophan with triphosgene to produce l-tryptophan-N-carboxylic anhydride, which then reacts with n-octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a>40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.

 

关键词： antiviral plant protectant / antiviral in the greenhouse / field evaluation / l-trp-NCA / synthesis optimization / toxicity tests    

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ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

Wentao XU, Hao TIAN, Hongjian SONG, Yuxiu LIU, Yongqiang LI, Qingmin WANG

《农业科学与工程前沿（英文）》   页码 110-119 doi: 10.15302/J-FASE-2021390

摘要： It has previously been shown that tryptophan, the biosynthesis precursor of alkaloids, and its derivatives have anti-TMV activity both and . Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of L-tryptophan with triphosgene to produce L-tryptophan- -carboxylic anhydride, which then reacts with -octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a > 40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.

关键词： antiviral plant protectant     antiviral in the greenhouse     field evaluation     L-trp-NCA     synthesis optimization     toxicity tests    

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Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

《化学科学与工程前沿（英文）》 2009年 第3卷 第3期   页码 305-309 doi: 10.1007/s11705-009-0021-z

摘要： A series of new benzimidazole derivatives were designed and synthesized. Their chemical structures were testified by H NMR, infrared spectroscopy (IR), mass spectrography (MS), and elemental analysis. Their potent antiviral properties indicated the prospect of new drugs. Compound , , , , , , and were identified as novel antivirus with much better selective activity and inhibitory activity than the comparable ribavirin against Coxsackie virus B in VERO cells.

关键词： benzimidazole     coxsackie virus B3     antiviral properties    

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Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

《医学前沿（英文）》 2019年 第13卷 第6期   页码 658-666 doi: 10.1007/s11684-019-0707-7

摘要： Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12–213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (>5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP>5.5 was associated with the presence of cirrhosis ( =0.001), co-existing non-alcoholic steatohepatitis (NASH) ( = 0.035), and GT 1 ( = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis ( = 0.003), Child–Pugh score<6 ( = 0.015), and baseline AFP<10 ( = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child–Pugh score<6, and baseline AFP<10.

关键词： chronic hepatitis C     α fetoprotein     direct acting antiviral treatment     cirrhosis    

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Field scale measurement of greenhouse gas emissions from land applied swine manure

Devin L. Maurer, Jacek A. Koziel, Kelsey Bruning

《环境科学与工程前沿（英文）》 2017年 第11卷 第3期 doi: 10.1007/s11783-017-0915-9

摘要： Greenhouse gas emissions (GHGs) from swine production systems are relatively well researched with the exception of emissions from land application of manure. GHGs inventories are needed for process-based modeling and science-based regulations. Thus, the objective of this observational study was to measure GHG fluxes from land application of swine manure on a typical corn field. Assessment of GHG emissions from deep injected land-applied swine manure, fall and reapplication in the spring, on a typical US Midwestern corn-on-corn farm was completed. Static chambers were used for flux measurement along with gas analysis on a GC-FID-ECD. Measured gas concentrations were used to estimate GHGs flux using four different models: linear regression, nonlinear regression, first order linear regression and the revised Hutchinson and Mosier (HMR) model, respectively for comparisons. Cumulative flux estimates after manure application of 5.85 × 10 g·ha (1 ha= 0.01 km ) of CO , 6.60 × 10 g·ha of CH , and 3.48 × 10 g·ha N O for the fall trial and 3.11 × 10 g·ha of CO , 2.95 × 10 g·ha of CH , and 1.47 × 10 g·ha N O after the spring reapplication trial were observed. The N O net cumulative flux represents 0.595% of nitrogen applied in swine manure for the fall trial.

关键词： Climate change     Emissions     Greenhouse gases     Land application     Swine manure    

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 260-267 doi: 10.15302/J-FASE-2016116

摘要： The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词： antiviral     blood brain barrier     chemokines and cytokines     innate immunity     rabies virus    

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ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

《农业科学与工程前沿（英文）》 2021年 第8卷 第4期   页码 603-622 doi: 10.15302/J-FASE -2021397

摘要：

The COVID-19 infections caused by SARS-CoV-2 have resulted in millions of people being infected and thousands of deaths globally since November 2019. To date, no unique therapeutic agent has been developed to slow the progression of this pandemic. Despite possessing antiviral traits the potential of bacteriocins to combat SARS-CoV-2 infection has not been fully investigated. This review summarizes the mechanisms by which bacteriocins can be manipulated and implemented as effective virus entry blockers with infection suppression potential properties to highly transmissible viruses through comprehensive immune modulations that are potentially effective against COVID-19. These antimicrobial peptides have been suggested as effective antiviral therapeutics and therapeutic supplements to prevent rapid virus transmission. This review also provides a new insight into the cellular and molecular alterations which have made SARS-CoV-2 self-modified with diversified infection patterns. In addition, the possible applications of antimicrobial peptides through both natural and induced mechanisms in infection prevention perspectives on changeable virulence cases are comprehensively analyzed. Specific attention is given to the antiviral mechanisms of the molecules along with their integrative use with synthetic biology and nanosensor technology for rapid detection. Novel bacteriocin based therapeutics with cutting-edge technologies might be potential substitutes for existing time-consuming and expensive approaches to fight this newly emerged global threat.

 

关键词： antimicrobial proteins / antiviral profiling of bacteriocins / antiviral therapeutics / immunomodulation / nanosensor technology / mutated SARS-CoV-2    

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Enhanced Fenton-like process over Cu/L(+)-ascorbic acid co-doping mesoporous silica for toxicity reduction

《环境科学与工程前沿（英文）》 2023年 第18卷 第4期 doi: 10.1007/s11783-024-1804-7

摘要：

● Cu-C-MSNs are developed via a co-doping step of Cu with L(+)-ascorbic acid.

关键词： Cation-π structures     Polarization electric field     Fenton-like process     Contaminants cleavage    

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Current recommendations of managing HBV infection in preconception or pregnancy

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 158-165 doi: 10.1007/s11684-014-0340-4

摘要：

Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.

关键词： antiviral therapy     Caesarean section     cirrhosis     hepatitis B     immunoprophylaxis     mother-to-child transmission     pregnancy     prevention    

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Oral administration of

Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

《农业科学与工程前沿（英文）》 2015年 第2卷 第4期   页码 318-326 doi: 10.15302/J-FASE-2015080

摘要： Garlic ( Liliaceae) has been safely used for more than 5000 years, and research on garlic extract is rapidly increasing because of its multiple biological functions. The effects of oral administration of garlic mixture (GM, water-soluble extract) on infectious bursal disease virus (IBDV)-infected specific pathogen free male white leghorn chicken were examined through histopathological, immunohistochemical, and Western blot analyses, and enzyme-linked immunosorbent assay. The results confirmed the protective effects of oral administration of 5 mg·kg BW GM (Group GM1) on bursal lesions after IBDV infection. In particular, protein expression of IBDV in the bursa decreased in Group GM1, indicating that GM administration decreased IBDV replication in the bursa. Furthermore, immunoglobulin M- and A-bearing B lymphocytes significantly increased 7 days post infection in bursae in Group GM1 ( <0.01), suggesting that the oral administration of 5 mg·kg GM offers moderate protection against B cell destruction after IBDV infection. During infection, the concentration of bursal interferon gamma (IFN-g) increased and peaked in Group GM1 earlier than in Group T (IBDV-exposed), demonstrating that GM administration prompted the production of IFN-g to protect against IBDV infection.

关键词： garlic     infectious bursal disease virus (IBDV)     antiviral effect     IgM-bearing B lymphocyte    

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A brief review of microRNA and its role in PRRSV infection and replication

Xuekun GUO,Wenhai FENG

《农业科学与工程前沿（英文）》 2014年 第1卷 第2期   页码 114-120 doi: 10.15302/J-FASE-2014022

摘要： Porcine reproductive and respiratory syndrome virus (PRRSV), a single-stranded RNA virus, mainly infects cells of monocyte/macrophage lineage. Recently, host microRNAs were shown to be capable of modulating PRRSV infection and replication by multiple ways such as targeting viral genomic RNA, targeting viral receptor and inducing antiviral response. MicroRNAs are small RNAs and have emerged as important regulators of virus-host cell interactions. In this review, we discuss the identified functions of host microRNAs in relation to PRRSV infection and propose that cellular microRNAs may have a substantial effect on cell or tissue tropism of PRRSV.

关键词： porcine reproductive and respiratory syndrome virus (PRRSV)     microRNA     antiviral     viral tropism    

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Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 502-508 doi: 10.1007/s11684-017-0590-z

摘要：

Although the efficacy of nucleos(t)ide analogue (NA) has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus (HBV) are integrated into the life cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA (cccDNA), particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen (HBsAg) that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a “para-functional cure,” a status nearly close to the functional cure of chronic hepatitis B, to distinguish the “functional cure” characterized as serum HBsAg loss with or without anti-HBs seroconversion.

关键词： chronic hepatitis B     serum HBV RNA     nucleos(t)ide analogs     virological response     para-functional cure    

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BIOINSECTICIDES AS FUTURE MAINSTREAM PEST CONTROL AGENTS: OPPORTUNITIES AND CHALLENGES

《农业科学与工程前沿（英文）》 2022年 第9卷 第1期   页码 82-97 doi: 10.15302/J-FASE-2021404

摘要：

Bioinsecticides are naturally-occurring substances from different sources that control insect pests. Ideal bioinsecticides should have low toxicity to non-target organisms. They should also be easily degraded in sewage treatment works and natural environments, highly effective in small quantities and affect target pests only. Public concerns about possible side-effects of synthetic pesticides have accelerated bioinsecticide research and development. However, to develop bioinsecticides into mainstream products, their high production costs, short shelf-life and often uncertain modes of action need to be considered. This review summarizes current progress on bioinsecticides which are categorized as biochemical insecticides and their derivatives, plant-incorporated protectants, and microbial bioinsecticides. The current constraints that prevent bioinsecticides from being widely used are discussed and future research directions are proposed.

 

关键词： biochemical insecticide / bioinsecticide / microbial bioinsecticides / plant-incorporated protectant / RNA insecticide    

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Leaching toxicity characteristics of municipal solid waste incineration bottom ash

Khamphe PHOUNGTHONG,Yi XIA,Hua ZHANG,Liming SHAO,Pinjing HE

《环境科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 399-411 doi: 10.1007/s11783-015-0819-5

摘要： The continuously increasing production of municipal solid waste incineration bottom ash (MSWIBA) has promoted its utilization as construction material and raised environmental concern. The physico-chemical properties and leaching behavior of MSWIBA were studied, and ecotoxicological testing using a luminescent bacterium bioassay was performed to assess the ecological pollution risks associated with its leached constituents. The MSWIBA was leached by two types of leachants, H SO /HNO and HAc solution, at different liquid to solid ratios and contact times. The concentrations of heavy metals and anions in the leachates were analyzed. Multivariate statistical analyses, including principle component analysis, Pearson's correlation analysis and hierarchical cluster analysis, were used to evaluate the contributions of the constituents to the toxicity ( ) of the MSWIBA leachate. The statistical analyses of the ecotoxicological results showed that the Ba, Cr, Cu, Pb, F and total organic carbon (TOC) concentrations were closely correlated with the value, and these substances were the main contributors to the ecotoxicity of the MSWIBA leachate. In addition, the cluster of these variables indicated similar leaching behaviors. Overall, the research demonstrated that the ecotoxicological risks resulting from MSWIBA leaching could be assessed before its utilization, which provides crucial information for the adaptation of MSWIBA as alternative materials.

关键词： Municipal solid waste incineration     bottom ash     alternative material     leaching tests     toxicity     Vibrio qinghaiensis (Q67)    

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Advances in newly developing therapy for chronic hepatitis C virus infection

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 166-174 doi: 10.1007/s11684-014-0334-2

摘要：

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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标题 作者 时间 类型 操作

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

期刊论文

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

Wentao XU, Hao TIAN, Hongjian SONG, Yuxiu LIU, Yongqiang LI, Qingmin WANG

期刊论文

Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

期刊论文

Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

期刊论文

Field scale measurement of greenhouse gas emissions from land applied swine manure

Devin L. Maurer, Jacek A. Koziel, Kelsey Bruning

期刊论文

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

期刊论文

ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

期刊论文

Enhanced Fenton-like process over Cu/L(+)-ascorbic acid co-doping mesoporous silica for toxicity reduction

期刊论文

Current recommendations of managing HBV infection in preconception or pregnancy

null

期刊论文

Oral administration of

Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

期刊论文

A brief review of microRNA and its role in PRRSV infection and replication

Xuekun GUO,Wenhai FENG

期刊论文

Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

期刊论文

BIOINSECTICIDES AS FUTURE MAINSTREAM PEST CONTROL AGENTS: OPPORTUNITIES AND CHALLENGES

期刊论文

Leaching toxicity characteristics of municipal solid waste incineration bottom ash

Khamphe PHOUNGTHONG,Yi XIA,Hua ZHANG,Liming SHAO,Pinjing HE

期刊论文

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文