Design, Synthesis, Nematicidal, and Fungicidal Activities of Novel Azo and Azoxy Compounds.

Bursaphelenchus xylophilus (B. xylophilus) and Meloidogyne are parasitic nematodes that have caused severe ecological and economic damage in pinewood and crops, respectively. Jietacins (jietacin A and B) were found to have excellent biological activity against B. xylophilus. Based on our tremendous demand for chemicals against B. xylophilus, a novel scaffold based on the azo and azoxy groups was designed, and a series of compounds were synthesized. In the bioassay, Ia, IIa, IIc, IId, and IVa exhibited higher activity against B. xylophilus in vitro than avermectin (LC50 = 2.43 µg·mL-1) with LC50 values of 1.37, 1.12, 0.889, 1.56, and 1.10 µg·mL-1, respectively. Meanwhile, Ib, Ic, IIc, and IVa showed good inhibition effects against Meloidogyne in vivo at the concentrations of 80 and 40 µg·mL-1 with inhibition rates of 89.0% and 81.6%, 95.6% and 75.7%, 96.3% and 41.2%, and 86.8% and 78.7%, respectively. In fungicidal activity in vitro, IIb and IVa exhibited excellent effect against Botryosphaeria dothidea with the inhibition of 82.59% and 85.32% at the concentration of 10 µg·mL-1, while the inhibition of Ia was 83.16% against Rhizoctonia solani at the concentration of 12.5 µg·mL-1. Referring to the biological activity against B. xylophilus, a 3D-QASR model was built in which the electron-donating group and small group at the 4-phenylhydrazine were favorable for the activity. In general, the novel azoxy compounds, especially IIc possess great potential for application in the prevention of B. xylophilus.

Synthesis, herbicidal activity and soil degradation of novel 5-substituted sulfonylureas as AHAS inhibitors.

BACKGROUND: Chlorsulfuron, metsulfuron-methyl and ethametsulfuron can damage sensitive crops in rotation pattern as a result of their long persistence in soil. To explore novel sulfonylurea (SU) herbicides with favorable soil degradation rates, four series of SUs were synthesized through a structure-based drug design (SBDD) strategy. RESULTS: The target compounds, especially Ia, Id and Ie, exhibited prospective herbicidal activity against dicotyledon oil seed rape (Brassica campestris), amaranth (Amaranthus retroflexus), monocotyledon barnyard grass (Echinochloa crusgalli) and crab grass (Digitaria sanguinalis) at a concentration of 15 a.i. g ha-1 . Additionally, Ia, Id and Ig displayed excellent inhibitory effects against AtAHAS, with Kapp i values of 59.1, 34.5 and 71.8 µm, respectively, which were much lower than that of chlorsulfuron at 149.4 µm. The π-π stack and H-bonds between the Ia conformation and AtAHAS in the molecular docking results confirmed the series of compounds to be conventional AHAS inhibitors. In alkaline soil (pH = 8.46), compounds Ia-Ig revealed various degrees of acceleration in the degradation rate compared with chlorsulfuron. Besides, compound Ia showed considerable wheat and corn safety under postemergence at the concentration of 30, 60 and even 120 a.i. g ha-1 . CONCLUSION: Overall, based on the synthetic procedure, herbicidal activity, soil degradation and crop safety, the Ia sulfonylureas series were chosen to be investigated as prospective AHAS inhibitors. The 5-dimethylamino group on SUs accelerated the degradation rate at different levels in alkaline soils which seems to be controllable in conventional cropping systems in their further application. © 2022 Society of Chemical Industry.

Magnetic Resonance Imaging Assessment of Abdominal Ectopic Fat Deposition in Correlation With Cardiometabolic Risk Factors.

Purpose: Ectopic fat accumulation and abdominal fat distribution may have different cardiometabolic risk profiles. This study aimed to assess the associations between various magnetic resonance imaging (MRI)-acquired fat depots and cardiometabolic risk factors. Methods: A total of 320 subjects with median age of 59 years, 148 men and 172 women, were enrolled in the study. Visceral adipose tissue (VAT) area and fat fraction (FF), subcutaneous adipose tissue (SAT) area and FF at the L1-L2 levels, preperitoneal adipose tissue (pPAT) area and FF, hepatic FF, pancreatic FF, and intramuscular FF were assessed by MRI FF maps. The associations of various MRI-acquired fat depots with blood pressure, glucose, and lipid were examined using sex-stratified linear regression. Logistic regression stratified by sex was used to analyze the association of various MRI-acquired fat depots with the risk of hypertension, T2DM, and dyslipidemia. Results: The intraclass correlation coefficient (ICC) values were >0.9, which suggested good interobserver and intraobserver agreement. VAT area, V/S, hepatic fat, pancreatic fat, and pPAT rather than SAT area were significantly associated with multiple cardiometabolic risk factors (all p < 0.05). However, the patterns of these correlations varied by sex and specific risk factors. Also, VAT and SAT FF were only significantly associated with multiple cardiometabolic risk factors in women (all p < 0.05). Conclusions: VAT, hepatic fat, pancreatic fat, and pPAT were associated with cardiovascular metabolic risk factors independent of BMI. The patterns of these correlations were related to gender. These findings further the understanding of the association between ectopic fat deposition and cardiometabolic risk factors and help to better understand the obesity heterogeneity.

Two new threonine-containing metabolites from fungus Curvularia inaequalis strain HS-FG-257.

Two new threonine-containing metabolites, N-[4-hydroxy-3-prenyl-benzoyl]-L-threonine (1) and N-[2,2-dimethyl-2H-chromene-6-carbonyl]-L-threonine (2), were isolated from the fermentation broth of the soil fungus Curvularia inaequalis strain HS-FG-257. Their structures were elucidated through the interpretation of HR-ESIMS and extensive NMR spectroscopic data. Both compounds exhibited no cytotoxic activity against the test cell lines A549 and HCT-116.

Hepatic fat quantification of magnetic resonance imaging whole-liver segmentation for assessing the severity of nonalcoholic fatty liver disease: comparison with a region of interest sampling method.

BACKGROUND: Accurate and early assessment of the hepatic fat content is crucial for patients with nonalcoholic fatty liver disease (NAFLD). For years, magnetic resonance imaging (MRI) has been considered the optimal noninvasive method for the assessment of fat accumulation. To avoid time-consuming manual placement of multiple regions of interest (ROI), the use of whole-liver segmentation has been proposed to measure liver fat, mainly for heterogeneous fat deposition. However, it remains uncertain whether the hepatic mean fat fraction (FF) obtained by whole-liver segmentation with the inclusion of intrahepatic vasculature is consistent with the traditional ROI sampling method. In this study, we assessed the accuracy of hepatic mean FF obtained by whole-liver segmentation in patients of NAFLD with different severities using the ROI sampling method as a reference standard. METHODS: Hepatic FFs were measured by whole-liver segmentation and the ROI sampling method (reference standard) using MRI scanning with the iterative decomposition of water and fat with echo an asymmetry at least-square estimation-iron quantification (IDEAL-IQ) sequence. SPSS version 25.0 software was used to analyze the correlation and consistency of data between the two methods. RESULTS: There was a strong correlation in hepatic FF between whole-liver segmentation and the ROI sampling method in healthy, mild, and moderate steatosis patients (r = 0.943, 0.990, and 0.961, respectively). Bland-Altman analysis showed a small bias of +0.50±0.27 and +0.05±0.30, which indicated a small overestimation when using whole-liver segmentation in healthy subjects and mild NAFLD patients. The 95% limits of agreement ranged from +1.02 to -0.03, and from +0.65 to -0.55, respectively. However, a small bias of -0.96±0.77 was also evident, which indicated a small underestimation when using whole-liver segmentation in moderate NAFLD patients. The 95% limits of agreement ranged from +0.56 to -2.48. CONCLUSIONS: Due to inclusion of the intrahepatic vasculature, whole-liver segmentation has some effects on hepatic FF assessment in patients with different NAFLD severities; yet, it does not significantly affect the assessment of whole-liver FF in MRI FF maps.

Rehabilitation and pharmacotherapy of neuromyelitis optica spectrum disorder: A case report.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating autoimmune disease that affects the central nervous system. It typically manifests as optic neuritis or extensive longitudinal myelitis, with or without the presence of anti-aquaporin protein 4 autoantibodies (immunoglobulin G). CASE SUMMARY: We report the case of a 45-year-old woman with a history of Sjogren's syndrome who was diagnosed with NMOSD accompanied by spinal cord injury and left calf intermuscular vein thrombosis. The patient received hormone shock and gamma globulin therapy in the acute phase and standard rehabilitation treatment during convalescence. Upon discharge, the patient was able to control urination and defecation, stand independently, and walk short distances with the aid of a walker. CONCLUSION: This case suggests that pharmacotherapy and standard rehabilitation treatment can improve the prognosis of NMSOD patients.

Controllable Soil Degradation Rate of 5-Substituted Sulfonylurea Herbicides as Novel AHAS Inhibitors.

Chlorsulfuron has been applied in wheat fields as a recognized herbicide worldwide, yet it was officially banned in China since 2014 for its soil persistence problem. On the basis of our previous research that 5-dimethylamino distinctively accelerated degradation rate in soils, a modified amino moiety (Ia-c) and monosubstituted amino group (Id-e) were introduced onto the fifth position of the benzene ring in sulfonylurea structures, as well as heterocyclic amino substituents (If-g) to seek a suitable soil degradation rate during such an in situ crop rotation system. Referring to the biological data and ScAHAS inhibition and ScAHAS docking results, they turned out to be AHAS inhibitors with high potent herbicidal activities. The various influence on soil degradation rate along with crop safety indicated that different substituents on the fifth position have exerted an apparent impact. Their united study of structure-activity-safety-degradation relationship has great potential to provide valuable information for further development of eco-friendly agrochemicals.

Two new tenvermectins from a genetically engineered strain Streptomyces avermitilis MHJ1011.

Two new tenvermectins, tenvermectins C (1) and D (2), were isolated from Streptomyces avermitilis MHJ1011. Their structures were determined by extensive spectroscopic analysis and by comparison with a related known compound, tenvermectin A. Compounds 1 and 2 exhibited potent nematocidal and acaricidal activities against Bursaphelenchus xylophilus and Tetranychus cinnabarinus.

New macrocyclic lactones with acaricidal and nematocidal activities from a genetically engineered strain Streptomyces bingchenggensis BCJ60.

Two new macrocyclic lactones, 4,25-diethyl-4,25-demethyl-milbemycin ß3 (1) and 27-formaldehyde-milbemycin ß14 (2), were isolated from a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. The acaricidal and nematocidal capacities of compounds 1 and 2 were evaluated against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, respectively. The results showed that the two new macrocyclic lactones 1 and 2 possessed potent acaricidal and nematocidal activities.

New milbemycin metabolites from the genetically engineered strain Streptomyces bingchenggensis BCJ60.

Two new milbemycin derivatives, 27-methoxylmilbemycin α31 (1) and 27-oxomilbemycin α31 (2), were isolated from the genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined by 1D NMR, 2D NMR and HR-ESI-MS spectral analysis, and comparison with previous reports. The acaricidal and nematocidal capacities of compounds 1 and 2 were evaluated against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, respectively. The results showed that the two new macrocyclic lactones 1 and 2 possessed potent acaricidal and nematocidal activities.

Synthesis, biological activities and structure-activity relationships for new avermectin analogues.

In an effort to discover new molecules with good insecticidal activities, more than 40 new avermectin derivatives were synthesized and evaluated for their biological activities against three species of arachnids, insects and nematodes, namely, Tetranychus Cinnabarinus, Aphis craccivora and Bursaphelenchus xylophilus. All the tested compounds showed potent inhibitory activities against three insect species. Notably, the majority of compounds exhibited high selectivity against T. cinnabarinus, some of which were much better in comparison with avermectin. Especially compounds 9j (LC50: 0.005 µM) and 16d (LC50: 0.002 µM) were 2.5- and 4.7-fold more active than avermectin (LC50: 0.013 µM), respectively, against T. cinnabarinus. Moreover, compounds 9b, 9d-f, 9h, 9j, 9l, 9n, 9p, 9r, 9v and 17d showed superior activities with LC50 values of 2.959-5.013 µM compared to that of 1 (LC50: 6.746 µM) against B. xylophilus. Meanwhile, the insecticidal activities of compounds 9f, 9g, 9h, and 9m against A. craccivora were 7-8 times better than that of avermectin, with LC50 values of 7.744, 5.634, 6.809, 7.939 and 52.234 µM, respectively. Furthermore, QSAR analysis showed that the molecular shape, size, connectivity degree and electronic distribution of avermectin analogues had substantial effects on insecticidal potency. These preliminary results provided useful insight in guiding further modifications of avermectin in the development of potential new insecticides.

Three new 16-membered macrolide compounds from a genetically engineered strain S. avermitilis MHJ1011.

Three new 16-membered macrolide compounds, 13α-O-α-l-oleandrosyl milbemycin ß3 (1), 13α-O-α-l-oleandrosyl-25-ethyl milbemycin ß3 (2), 13α-O-α-l-oleandrosyl-25-isopropyl milbemycin ß3 (3), were isolated from the genetically engineered strains Streptomyces avermitilis MHJ1011. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. Both compounds 1-3 displayed impressive acaricidal activity against larval mites with the IC50 values of 0.0327, 0.0276 and 0.0235mg/L, respectively, which are higher than those of 13α-hydroxy milbemycin ß3 and 13α-hydroxy-25-ethyl milbemycin ß3.

Three new milbemycins from a genetically engineered strain S. avermitilis MHJ1011.

Three new ß-class milbemycins, 13α-hydroxy-4-ethy1 milbemycin ß3 (1), 13α-hydroxy-25-ethy1 milbemycin ß3 (2), 13α-hydroxy milbemycin ß3 (3), were isolated from the broth of the genetically engineered strains Streptomyces avermitilis MHJ1011, whose aveA1 gene was replaced by milA1 gene seamlessly. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. These three compounds, especially compound 1, exhibited potent acaricidal activity.

Detection of gallbladder stones by dual-energy spectral computed tomography imaging.

AIM: To evaluate the detectability of gallbladder stones by dual-energy spectral computed tomography (CT) imaging. METHODS: Totally 217 patients with surgically confirmed gallbladder stones were retrospectively analyzed who underwent single-source dual-energy CT scanning from August 2011 to December 2013. Polychromatic images were acquired. And post-processing software was used to reconstruct monochromatic (40 keV and 140 keV) images, and calcium-lipid pair-wise base substance was selected to acquire calcium base images and lipid base images. The above 5 groups of images were evaluated by two radiologists separately with 10-year experience in CT image reading. In the 5 groups of images, the cases in the positive group and negative group were counted and then the detection rate was calculated. The inter-observer agreement on the scoring results was analyzed by Kappa test, and the scoring results were analyzed by Wilcoxon test, with P < 0.05 indicating that the difference was statistically significant. The stone detection results of the 5 groups of images were analyzed by χ(2) test. RESULTS: There was good inter-observer agreement (κ = 0.772). In 217 patients with gallbladder stones, there was a statistically significant difference in stone visualization between spectral images (40 keV, 140 keV, calcium base and lipid base images) and polychromatic images (P < 0.05). 40 keV monochromatic images were better than 140 keV monochromatic images (4.90 ± 0.35 vs 4.53 ± 1.15, P < 0.05), and calcium base images were superior to lipid base images (4.91 ± 0.43 vs 4.77 ± 0.63, P < 0.05), but there was no statistically significant difference between 40 keV monochromatic images and calcium base images (4.90 ± 0.35 vs 4.91 ± 0.43, P > 0.05). In 217 gallbladder stone patients, there were 21, 3, 28, 5 and 12 negative stone cases in polychromatic images, 40 keV images, 140 keV images, calcium base images and lipid base images, respectively, and the differences among the five groups were statistically significant (P < 0.05). CONCLUSION: Monochromatic images and base substance images have a good clinical prospect in the iso-density stone detection.

Diagnostic Significance of Diffusion-Weighted MRI in Renal Cancer.

BACKGROUND: This study aimed to investigate whether diffusion-weighted imaging (DWI) could contribute to the discrimination between benign and malignant renal cancer. METHODS: We searched the PubMed electronic database for eligible studies. STATA 12.0 software was used for statistical analysis. The SMD and 95% CI were calculated. RESULTS: Decreased ADC signal was seen in all renal cancer patients (cancer tissue versus normal tissue: SMD = 1.63 and 95% CI = 0.96~2.29, P < 0.001; cancer tissue versus benign tissue: SMD = 2.22 and 95% CI = 1.53~2.90 and P < 0.001, resp.). MRI machine type-stratified analysis showed that decreased ADC signal was found by all included MRI machine types in cancer tissues compared with benign cancer tissues (all P < 0.05). The ADC values of renal cancer patients were significantly lower than those of normal controls for all included P values (all P < 0.05), and there was a decreased ADC signal at b-500, b-600, b-1000, b-500, and 1000 gradients compared with benign cancer tissues (all P < 0.05). CONCLUSION: Our study concluded that decreased ADC signal presented in DWI may be essential for the differential diagnosis of renal cancer.

Synthesis, biological activities, and quantitative structure-activity relationship (QSAR) study of novel camptothecin analogues.

In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-to-excellent activity against three insect species tested, with LC50 values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure-activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and  of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents.

Gene Replacement for the Generation of Designed Novel Avermectin Derivatives with Enhanced Acaricidal and Nematicidal Activities.

Avermectin (AVM) and ivermectin (IVM) are potent pesticides and acaricides which have been widely used during the past 30 years. As insect resistance to AVM and IVM is greatly increasing, alternatives are urgently needed. Here, we report two novel AVM derivatives, tenvermectin A (TVM A) and TVM B, which are considered a potential new generation of agricultural and veterinary drugs. The molecules of the TVMs were designed based on structure and pharmacological property comparisons among AVM, IVM, and milbemycin (MBM). To produce TVMs, a genetically engineered strain, MHJ1011, was constructed from Streptomyces avermitilis G8-17, an AVM industrial strain. In MHJ1011, the native aveA1 gene was seamlessly replaced with milA1 from Streptomyces hygroscopicus. The total titer of the two TVMs produced by MHJ1011 reached 3,400 mg/liter. Insecticidal tests proved that TVM had enhanced activities against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, as desired. This study provides a typical example of exploration for novel active compounds through a new method of polyketide synthase (PKS) reassembly for gene replacement. The results of the insecticidal tests may be of use in elucidating the structure-activity relationship of AVMs and MBMs.

Apparent diffusion coefficient measurement by diffusion weighted magnetic resonance imaging is a useful tool in differentiating renal tumors.

BACKGROUND: To determine the clinical value of apparent diffusion coefficient (ADC) measurement by diffusion weighted magnetic resonance imaging (DW-MRI) in differentiating renal tumors. METHODS: Electronic databases were searched using combinations of keywords and free words relating to renal tumor, ADC and DW-MRI. Based on carefully selected inclusion and exclusion criteria, relevant case-control studies were identified and the related clinical data was acquired. Statistical analyses were performed using STATA 12.0 (Stata Corporation, College station, TX). RESULTS: Sixteen case-control studies were ultimately included in the present meta-analysis. These 16 high quality studies contained a combined total of 438 normal renal tissues and 832 renal tumor lesions (597 malignant and 235 benign). The results revealed that ADC values of malignant renal tumor tissues were markedly lower than normal renal tissues and benign renal tumor tissues. ADC values of benign renal tumor tissues were also significantly lower than normal renal tissue. CONCLUSIONS: ADC measurement by DW-MRI provided clinically useful information on the internal structure of renal tumors and could be an important radiographic index for differentiation of malignant renal tumors from benign renal tumors.