GLIS1 alleviates cell senescence and renal fibrosis through PGC1-α mediated mitochondrial quality control in kidney aging.

Mitochondrial dysfunction is implied as a crucial factor in age-related chronic kidney disease. It is confirmed that Gli-like transcription factor 1 (GLIS1) is involved in age-related renal fibrosis, however, the correlation between mitochondrial disturbances and GLIS1-driven kidney aging are not clearly clarified. Thus, we investigated the regulatory mechanism of GLIS1 in the homeostasis of mitochondrial quality control both in vivo and in vitro. The lower expression of GLIS1 was identified in natural and accelerated kidney aged models, accompanied by the dysfunctions of mitochondrial quality control, including enhanced mitochondrial fission, reduced mitochondrial biogenesis and mitophagy, whereas, GLIS1 could maintain mitochondrial stability by interacting with peroxisome proliferator-activated receptor γ coactivator-1α (PGC1-α). Additionally, the over-expressed GLIS1 inhibited extracellular matrix accumulation and alleviated renal fibrosis while siGLIS1 inhibited PGC1-α transcription, as well as affecting its mitochondria-protective functions. Collectively, we demonstrated that GLIS1 mediated mitochondrial quality control through targeting PGC1-α in kidney aging, which might be a promising therapeutic target for attenuating cell senescence and age-related renal fibrosis.

Development and validation of an HPLC-MS/MS method for the simultaneous analysis of volatile organic compound metabolites, hydroxylated polycyclic aromatic hydrocarbons, and 8-hydroxy-2'-deoxyguanosine in human urine.

Humans are widely and concurrently exposed to volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). However, few studies have reported the internal co-exposure levels of these chemicals in occupational and general populations. Specifically, the associations revealed between the urinary levels of metabolites of VOCs (mVOCs), hydroxylated PAHs (OH-PAHs), and oxidative stress biomarkers for humans remain limited. In this study, a method based on solid-phase extraction (SPE) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous analysis of 22 mVOCs, 12 OH-PAHs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human urine samples. The method was validated with all target analyte accuracies and precisions in the range of 76 %-120 % and 1 %-14 % at three levels of spiked urine samples, respectively. The limit of detection (LOD) and limit of quantification (LOQ) of the target analytes were 0.01-0.34 ng/mL and 0.01-7.57 ng/mL, respectively. And the method was applied to measure urinary levels of target analytes from 38 petrochemical workers in Guangzhou, South China. Except for 3-hydroxy-benzo[a]pyrene, all target analytes were detected in the urine samples. The average levels were 0.05-12.6 ng/mL for individual OH-PAHs, 0.20-73620 ng/mL for individual mVOCs, and 1.00 ng/mL for 8-OHdG. Additionally, 3-hydroxy-phenanthrene, 1-hydroxy-pyrene, 6-hydroxy-chrysene, N-acetyl-S-(trichlorovinyl)-L-cysteine, 2-methylhippuric acid, thiodiacetic acid, trans, trans-Muconic acid, and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine had statistically significant positive effects on 8-OHdG levels, while 1-hydroxy-naphthalene, 1,2-dihydroxybenzene, and hippuric acid showed a negative effect on 8-OHdG, indicating these metabolites could lead to synergistic or antagonistic oxidative DNA damage. This study provides a robust analytical method that permits a comprehensive assessment of co-exposure to PAHs and VOCs and their potential adverse health effects.

Study of an Ultrasensitive Label-Free Electrochemiluminescent Immunosensor Fabricated with a Composite Electrode for Detecting the Glutamate Decarboxylase Antibody.

Antibody testing for the glutamic acid decarboxylase 65 antibody (GADA) is widely used as a golden standard for autoimmune diabetes diagnosis, while current methods for antibody testing are not sensitive enough for clinical usage. Here, a label-free electrochemiluminescent (ECL) immunosensor for detecting GADA in autoimmune diabetes is fabricated and investigated. In the designed immunosensor, a composite film including the multiwalled carbon nanotubes (MWCNTs), zinc oxide (ZnO), and Au nanoparticles (AuNPs) was prepared through nanofabrication processes to improve the performance of sensor. The MWCNTs, which can provide a larger specific surface area, ZnO as a good photocatalytic material, and AuNPs that can enhance the ECL signal of luminol and immobilize the GAD65 antigen were applied to prefunctionalize indium tin oxide (ITO) glass based on a nanofabrication process. The GADA concentration was detected using the ECL immunosensor after incubating with GAD65 antigen-coated prefunctionalized ITO glass. After a direct immunoreaction, it is found that the degree of decreased ECL intensity has a good linear regression toward the logarithm of the GADA concentration in the range of 0.01 to 50 ng mL-1 with a detection limit down to 10 pg mL-1. Human serum samples positive or negative for GADA all nicely fell in the expected area. The fabricated immunosensor with excellent sensitivity, specificity, and stability has potential capability for clinical usage in GADA detection.

Flower-like molybdenum disulfide/cobalt ferrite composite for the extraction of benzotriazole UV stabilizers in environmental samples.

Benzotriazole UV stabilizers (BUVSs) are a class of emerging contaminants of concern; the development of rapid and convenient monitoring method for these trace-level pollutants in waters is of crucial significance in environmental science. Here, a novel magnetic flower-like molybdenum disulfide/cobalt ferrite nanocomposite (MoS2/CoFe2O4) was synthesized by hydrothermal reaction. Compared with the conventional Fe3O4-based magnetic composites, the proposed material just required a minimum consumption of Co/Fe towards the equivalent of MoS2 while providing superior magnetization performance. Taking advantages of high adsorption capacity, extraordinary stability, and repeatability in construction, MoS2/CoFe2O4 was applied to the extraction to BUVSs. The enrichment factors of three BUVSs were in the range 164-193 when 20 mL of environmental water sample was loaded on 40 mg of the adsorbent. MoS2/CoFe2O4 could be regenerated and recycled at least 10 cycles of adsorption/desorption with recoveries of 80.1-111%. The method of MoS2/CoFe2O4-based extraction coupled with high-performance liquid chromatography-variable wavelength detector was applied to the monitoring of BUVSs in seawater, lake water, and wastewater, which gave detection limits (S/N = 3) of 0.023-0.030 ng·mL-1 and recoveries of 80.1-110%. The intra-day and inter-day precisions (relative standard deviation, RSDs, n = 3) were in the range 1.6-7.5% and 3.2-11.5%, respectively. The approach is an alternative for efficient and sensitive extraction and determination of trace-level environmental pollutants in waters.

Phase stability and electronic structure of CsPbCl3 under hydrostatic stress and anion substitution.

Perovskites based on CsPbX3 (X = Cl, Br, I) have promising applications in solar cells, light-emitting diodes, and photodetectors. In this paper, the phase stability of inorganic metal halide perovskite CsPbCl3 under hydrostatic pressure and anion substitution is studied using density functional theory (DFT), and this modification is explained by the interaction of the octahedrons and transformation of the bond-orbital coupling. In addition, two space groups, P4/mbm and Amm2, which are stable under stress, are subjected to anion substitution; then, the structural stability and band gap change of CsPbCl3-yXy (X = Br, I; y = 0, 1, 2, 3) are analyzed after applying stress; finally, the electronic structures and optical properties of the six most stable components are presented. The effect of stress and anions on the components' optoelectronic properties is closely linked with the crystal's structural alteration mechanism. These results show that stress and anion modulation can significantly change the optoelectronic properties of materials, which make these materials have broad application prospects. Furthermore, stress can be used as an effective tool for screening the most stable material structure.

Rubidium ions doping to improve the photoluminescence properties of Mn doped CsPbCl3perovskite quantum dots.

All-inorganic cesium lead halide CsPbX3(X = Cl, Br, I) perovskite quantum dots (PQDs) have shown promising potential in current Mini/Micro-LED display applications due to their excellent photoluminescence performance. However, lead ions in PQDs are easily to leak owing to the unstable structure of PQDs, which hinders their commercial applications. Herein, we adopt Rb+ions co-doping strategy to regulate the doping characteristics of Mn2+ions in CsPbCl3PQDs. The synthesized CsPbCl3:(Rb+, Mn2+) PQDs possess enhanced photoluminescence quantum yield of 71.1% due to the reduction of intrinsic defect states and Mn-Mn or Mn-traps in co-doped PQDs. Moreover, the white light emission of CsPb(Cl/Br)3:(Rb+, Mn2+) PQDs is achieved by anion exchange reaction and the constructed WLED exhibits the CIE coordinate of (0.33, 0.29) and the correlated color temperature of 5497 K. Benefiting from the substitution strategy, these doped CsPbX3PQDs can be widely used as fluorescence conversion materials for the construction of Mini/Micro-LED.

Genetically predicted body fat mass and distribution with diabetic kidney disease: A two-sample Mendelian randomization study.

The aim of this study is to apply a Mendelian randomization (MR) design to investigate the potential causal associations between the body mass index (BMI), body fat mass such as trunk fat mass and waist circumference (WC), and diabetic kidney disease (DKD). A two-sample MR study was conducted to obtain exposure and outcome data from previously published studies. The instrumental variables for BMI, trunk fat mass, and WC were selected from genome-wide association study datasets based on summary-level statistics. The random-effects inverse-variance weighted (IVW) method was used for the main analyses, and the weighted median and MR-Egger approaches were complementary. In total, three MR methods suggested that genetically predicted BMI, trunk fat mass, and WC were positively associated with DKD. Using IVW, we found evidence of causal relationships between BMI [odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.47-2.69; p = 7.89 × 10-6], trunk fat mass (OR = 1.80; 95% CI, 1.28-2.53; p = 6.84 × 10-4), WC (OR = 2.48; 95% CI, 1.40-4.42; p = 1.93 × 10-3), and DKD. MR-Egger and weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts showed no directional pleiotropic effects involving the aforementioned variables and DKD. Our MR analysis supported the causal effect of BMI, trunk fat mass, and WC on DKD. Individuals can substantially reduce DKD risk by reducing body fat mass and modifying their body fat distribution.

Lightweight convolutional neural network for aircraft small target real-time detection in Airport videos in complex scenes.

Airport aircraft identification has essential application value in conflict early warning, anti-runway foreign body intrusion, remote command, etc. The scene video images have problems such as small aircraft targets and mutual occlusion due to the extended shooting distance. However, the detection model is generally complex in structure, and it is challenging to meet real-time detection in air traffic control. This paper proposes a real-time detection network of scene video aircraft-RPD (Realtime Planes Detection) to solve this problem. We construct the lightweight convolution backbone network RPDNet4 for feature extraction. We design a new core component CBL module(Conv (Convolution), BN (Batch Normalization), RELU (Rectified Linear Units)) to expand the range of receptive fields in the neural network. We design a lightweight channel adjustment module block by adding separable depth convolution to reduce the model's structural parameters. The loss function of GIou loss improves the convergence speed of network training. the paper designs the four-scale prediction module and the adjacent scale feature fusion technology to fuse the adjacent features of different abstract levels. Furthermore, a feature pyramid structure with low-level to high-level is constructed to improve the accuracy of airport aircraft's small target detection. The experimental results show that compared with YOLOv3, Faster-RCNN, and SSD models, the detection accuracy of the RPD model improved by 5.4%, 7.1%, and 23.6%; in terms of model parameters, the RPD model was reduced by 40.5%, 33.7%, and 80.2%; In terms of detection speed, YOLOv3 is 8.4 fps while RPD model reaches 13.6 fps which is 61.9% faster than YOLOv3.

Multi-extraction system with identical supported semi-liquid membrane: Enhanced stability for coextraction of acidic and basic drugs.

Coextraction of different groups of analytes is vital for saving sample volumes and simplifying analytical procedures in bioanalysis. Conventionally, coextraction was achieved by using multi-extraction systems with different supported liquid membranes (SLMs). However, the different membrane solvents tended to diffuse into the aqueous solutions and the other SLM to reach distribution equilibrium during extraction process, causing the system instability. In this work, a stable multi-extraction system (integration of liquid-phase microextraction and electromembrane extraction, LPME/EME) based on the identical supported semi-liquid membrane (SsLM) was developed. Principally, the state of distribution equilibrium of the membrane solvent (polypropylene glycol with molecular weight 4000) in SsLM could be reached at the beginning of extraction, which enhanced the coextraction stability. With this multi-extraction system, acidic and basic analytes were simultaneously extracted from practical biological samples. The extraction recoveries of the six model drugs in undiluted urine samples were over 70%. Followed by LC-MS/MS, the limits of quantification (LOQs) were in the range of 5-10 ng mL-1. The multi-extraction system using the identical SsLM in this study shows promising potential in construction of other stable multi-extraction systems (e.g., LPME/LPME and EME/EME) in the future, which will greatly benefit the group separation of analytes in complicated biological samples.

Successive liquid-phase microextraction of acidic and basic analytes.

Practical biological and environmental samples always contain both acidic and basic substances, and the samples are always precious. Thus, separation of analytes with different nature from the same sample was of great significance. Successive liquid phase microextraction (sLPME) of acidic and basic analytes under optimal extraction conditions was therefore proposed for the first time. The concept of sLPME was proved by using three acidic analytes (naproxen, flurbiprofen and diclofenac) and three basic analytes (haloperidol, fluoxetine and sertraline) as model analytes, and using polypropylene glycol with an average molecular weight of 4000 (PPG4000) as SLM. The recoveries of all target analytes by sLPME were similar to that by individual LPME due to good affinity of PPG4000 to both acidic and basic analytes. Under optimal extraction conditions, the recoveries for all analytes by sLPME from urine samples were in the range of 62%-95%. Moreover, combined with LC-MS/MS, such sLPME approach was also evaluated with urine samples. The matrix effect of sLPME-LC-MS/MS at different levels for all analytes ranged from -14.1%-13.2%. The linear ranges with R2 > 0.996 were 5-1000 ng mL-1 for basic analytes, and 20-1000 ng mL-1 for acidic analytes except diclofenac (1-1000 ng mL-1). The repeatability and accuracy at four levels were in the range of 3%-10% and 86%-120%, respectively. The limit of detection (LOD, S/N = 3) and limit of quantification (LOQ, S/N = 10) were found to be 0.07-0.49 ng mL-1 and 0.25-1.63 ng mL-1, respectively. Finally, the strategy for constructing a sLPME system was further confirmed with urine, plasma and saliva using another two versatile SLM solvents possessing high affinity to both acidic and basic analytes. Successive LPME enabled separation of acidic and basic analytes from the same sample under optimum extraction conditions for all target analytes. Thus, we believe that the sLPME system will become a potent platform for forensic toxicology analysis, food science, environmental analysis and epidemiology study.

Ultrasound-assisted electromembrane extraction with supported semi-liquid membrane.

Electromembrane extraction (EME), involving the migration of charged analytes across a supported liquid membrane (SLM) with an external power supply, is a promising sample preparation method in analytical chemistry. However, the presence of boundary double layers at the SLM/solution interfaces often restricts extraction efficiency. To avoid this, the current work proposed an ultrasound-assisted EME (UA-EME) method based on a novel type of supported semi-liquid membrane (SsLM). The characterizations showed that the SsLM was stable under ultrasound conditions. Ultrasound was found to reduce the boundary double layers and thus increase the mass transfer. Major operational parameters in UA-EME including ultrasound power density, temperature, applied voltage and extraction time were optimized with haloperidol, fluoxetine, and sertraline as model analytes. Under the optimal conditions, extraction recoveries of model analytes in water samples were in the range of 66.8%-91.6%. When this UA-EME method was coupled with LC-MS/MS for detection of the target analytes in human urine samples, the linear range of the analytical method was 10-1000 ng mL-1, with R2 > 0.997 for all analytes. The limits of detection (LOD) and limits of quantification (LOQ) were in the range of 1.7-2.1 ng mL-1 and 5.7-6.7 ng mL-1, respectively. The UA-EME expands the application field of ultrasound chemistry and will be very important in development of stable and fast sample preparation systems in the future.

Disruption of MAP7D1 Gene Function Increases the Risk of Doxorubicin-Induced Cardiomyopathy and Heart Failure.

Doxorubicin is a cornerstone chemotherapeutic drug widely used to treat various cancers; its dose-dependent cardiomyopathy, however, is one of the leading causes of treatment-associated mortality in cancer survivors. Patients' threshold doses leading to doxorubicin-induced cardiomyopathy (DIC) and heart failure are highly variable, mostly due to genetic variations in individuals' genomes. However, genetic susceptibility to DIC remains largely unidentified. Here, we combined a genetic approach in the zebrafish (Danio rerio) animal model with a genome-wide association study (GWAS) in humans to identify genetic susceptibility to DIC and heart failure. We firstly reported the cardiac and skeletal muscle-specific expression and sarcomeric localization of the microtubule-associated protein 7 domain-containing protein 1b (Map7d1b) in zebrafish, followed by expression validation in mice. We then revealed that disruption of the map7d1b gene function exaggerated DIC effects in adult zebrafish. Mechanistically, the exacerbated DIC are likely conveyed by impaired autophagic degradation and elevated protein aggregation. Lastly, we identified 2 MAP7D1 gene variants associated with cardiac functional decline and heart failure in cancer patients who received doxorubicin therapy. Together, this study identifies MAP7D1 as a clinically relevant susceptibility gene to DIC and heart failure, providing useful information to stratify cancer patients with a high risk of incurring severe cardiomyopathy and heart failure after receiving chemotherapy.

Enrichments/Derichments of Root-Associated Bacteria Related to Plant Growth and Nutrition Caused by the Growth of an EPSPS-Transgenic Maize Line in the Field.

During the past decades, the effects of the transgenic crops on soil microbial communities have aroused widespread interest of scientists, which was mainly related to the health and growth of plants. In this study, the maize root-associated bacterial communities of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) transgenic glyphosate-tolerant (GT) maize line CC-2 (CC2) and its recipient variety Zhengdan958 (Z958) were compared at the tasseling and flowering stages by high-throughput sequencing of V3-V4 hypervariable regions of 16S rRNA gene (16S rDNA) amplicons via Illumina MiSeq. In addition, real-time quantitative PCR (qPCR) was also performed to analyze the nifH gene abundance between CC2 and Z958. Our results showed no significant difference in alpha/beta diversity of root-associated bacterial communities at the tasseling or flowering stage between CC2 and Z958 under field growth conditions. The relative abundances of the genera Bradyrhizobium and Bacillus including species B. cereus and B. muralis were significantly lower in the roots of CC2 than that of Z985 under field conditions. Both these species are regarded as plant growth promoting bacteria (PGPB), as they belong to both nitrogen-fixing and phosphate-solubilizing bacterial genera. The comparison of the relative abundance of nitrogen-fixing/phosphate-solubilizing bacteria at the class, order or family levels indicated that only one class Bacilli, one order Bacillales and one family Bacillaceae were found to be significantly lower in the roots of CC2 than that of Z985. These bacteria were also enriched in the roots and rhizospheric soil than in the surrounding soil at both two stages. Furthermore, the class Betaproteobacteria, the order Burkholderiales, the family Comamonadaceae, and the genus Acidovorax were significantly higher in the roots of CC2 than that of Z985 at the tasseling stage, meanwhile the order Burkholderiales and the family Comamonadaceae were also enriched in the roots than in the rhizospheric soil at both stages. Additionally, the nifH gene abundance at the tasseling stage in the rhizosphere soil also showed significant difference. The relative abundance of nifH gene was higher in the root samples and lower in the surrounding soil, which implicated that the roots of maize tend to be enriched in nitrogen-fixing bacteria.

Novel Podophyllotoxin Derivatives as Potential Tubulin Inhibitors: Design, Synthesis, and Antiproliferative Activity Evaluation.

A number of podophyllotoxin derivatives (3A-3J) had been designed and synthesized, and their biological activities were evaluated in this study. Moreover, the antiproliferation activities of these compounds against four human cancer cell lines (HepG2, HeLa, A549, and MCF-7) were also tested. The results indicated that the most promising compound 3D displayed potent inhibitory activity over the four human cancer cell lines and was further demonstrated to have potent tubulin polymerization inhibitory effects without damaging the non-cancer cells. Additionally, 3D was verified to effectively interfere with tubulin and could prevent the mitosis of cancer cells, leading to cell cycle arrest and eventually inducing apoptosis in a dose- and time-dependent manner. Moreover, the Western blotting and siRNA results showed that Bcl-2 was downregulated in HepG2 cells treated with 3D. Finally, the molecular docking simulation results revealed that 3D could fit well in the colchicine-binding pocket. Taken together, this study has provided certain novel antitubulin agents for possible cancer chemotherapy.

Identification of Major Rhizobacterial Taxa Affected by a Glyphosate-Tolerant Soybean Line via Shotgun Metagenomic Approach.

The worldwide commercial cultivation of transgenic crops, including glyphosate-tolerant (GT) soybeans, has increased widely during the past 20 years. However, it is accompanied with a growing concern about potential effects of transgenic crops on the soil microbial communities, especially on rhizosphere bacterial communities. Our previous study found that the GT soybean line NZL06-698 (N698) significantly affected rhizosphere bacteria, including some unidentified taxa, through 16S rRNA gene (16S rDNA) V4 region amplicon deep sequencing via Illumina MiSeq. In this study, we performed 16S rDNA V5-V7 region amplicon deep sequencing via Illumina MiSeq and shotgun metagenomic approaches to identify those major taxa. Results of these processes revealed that the species richness and evenness increased in the rhizosphere bacterial communities of N698, the beta diversity of the rhizosphere bacterial communities of N698 was affected, and that certain dominant bacterial phyla and genera were related to N698 compared with its control cultivar Mengdou12. Consistent with our previous findings, this study showed that N698 affects the rhizosphere bacterial communities. In specific, N698 negatively affects Rahnella, Janthinobacterium, Stenotrophomonas, Sphingomonas and Luteibacter while positively affecting Arthrobacter, Bradyrhizobium, Ramlibacter and Nitrospira.

[Diffusion flux of partial pressure of dissolved carbon dioxide in Wan'an reservoir in spring].

In order to understand the emission of greenhouse gases (CO2) from the river-type reservoir, this study investigated the partial pressure of CO2 [p(CO2)], in the surface water, inflow waters, outflow waters of the Wan'an reservoir in China in the May 2009. p(CO2) in the inflow water, outflow water were calculated from titration method, and the surface water p(CO2) was measured underway using a continuous measurement system (equilibrator-NDIR system). Results showed that the inflow water from the Zhangshui, Meijiang, Taojiang have higher p(CO2) than atmosphere level, with the values of 211.5, 91.7, 259.7 Pa respectively. p(CO2) in the surface water of the incoming section of Wan'an reservoir was between 180-210 Pa, and in the middle section and central section near the dam, p(CO2) in the surface water were about 140-180 Pa and 70-110 Pa. In the outflow waters, p(CO2) reached to 176.2 Pa, higher than that in central section. As a result, it can be concluded that the surface water, inflow waters, outflow waters in the Wan'an reservoir are all the source to CO2. However there is clear evidence showing that the reservoir indeed has a role in mitigating the CO2 emission in this case.

Mutation of an X chromosome in aggressive angiomyxoma: Report of a case and review of the literature.

► Cytogenetic analysis performed on peripheral blood showed a similar abnormal chromosomal complement in tumor tissue. ► Thus, mutation of an X chromosome appears to be confined to the neoplasm. ► This anomaly has not been previously described in aggressive angiomyxoma.

Synthesis and antiviral activities of chiral thiourea derivatives containing an alpha-aminophosphonate moiety.

Starting from benzaldehyde 1, the title compounds 8 were synthesized in six steps. Benzaldehyde 1 was reacted with ammonium hydroxide, and the resulting imine was then treated with dialkyl phosphite 3 to give dialkyl N-(arylmethylene)-1-amino-1-aryl methylphosphonates 4. Phosphonates 4 were then easily hydrolyzed to give dialkyl 1-amino-1-aryl-methylphosphonates 6, which on treatment with triethylamine, carbon disulfide, and phosphorus oxychloride provided 7. Target compounds 8 were then prepared by the reaction of 7 with substituted chiral amine. The structures were clearly verified by spectroscopic data (IR, (1)H, (13)C, and (31)P NMR, and elemental analysis). The bioassay of these compounds revealed them as antivirally active. It was found that title compounds 8g, 8e, 8k, and 8m had the same curative effects of TMV (inhibitory rate = 54.8, 50.5, 50.4, and 50.4%, respectively) as the commercial product Ningnanmycin (56.2%). This would appear to be the first report of the synthesis and antiviral activity of chiral thiourea derivatives containing an alpha-aminophosphonate moiety.