Novel Nitrophenyl Substituted Anthranilic Diamide Derivatives: Design, Synthesis, Selectivity, and Antiresistance.

Diamide insecticides have gained popularity due to their high efficacy and low toxicity to nontarget organisms. However, diamide-associated resistance has emerged recently, causing a significant reduction in their potency, thereby hindering sustainable agricultural development. Here, we explored novel diamide insecticide analogs and, using a structure-based approach, rationally designed and synthesized 28 nitrophenyl substituted anthranilic diamides. Most of the compounds showed moderate to good activity against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compounds Ia and Im showed extraordinarily high activity and their mode of action was verified on isolated neurons. Additionally, Im exhibited over 10-fold greater potency than chlorantraniliprole in a HEK293 cell line stably expressing S. frugiperda ryanodine receptors (SfRyRs) containing the resistance mutations, G4891E and I4734M. The binding modes of Im in the SfRyRs were predicted using in silico molecular docking analysis. Our novel nitrophenyl substituted anthranilic diamide derivatives provide valuable insights for the design of insecticidal RyR-targeting compounds to effectively control both wild type and diamide insecticide-resistant lepidopteran pests.

Anticancer effects of marine compounds blocking the nuclear factor kappa B signaling pathway.

The abnormal expression of nuclear factor kappa B (NF-κB) target genes is closely related to the occurrence, metastasis, and invasion of tumor cells and is an inhibitor of their apoptosis. In recent years, the unique biodiversity in the marine environment has aroused great interest. Many studies indicate that some marine compounds exert anticancer effects on most common human tumors by modulating the NF-κB signaling pathway. In this study, 26 marine compounds that reduce cancer cell survival by suppressing the NF-κB signaling pathway were reviewed. They were derived from a wide range of sources, including sponges, fungi, algae and their derivatives or metabolites. These marine compounds exert antitumor effects through the canonical, noncanonical and atypical NF-κB signaling pathways; however, most of their anticancer targets and mechanisms remain unclear, and more research is needed in the future. Our article provides comprehensive information for researchers investigating the bioactivities of marine compounds and developing marine-derived anticancer drugs.

Octreotide-mediated neurofunctional recovery in rats following traumatic brain injury. Role of H2S, Nrf2 and TNF-α.

PURPOSE: To explore the role and mechanisms of octreotide in neurofunctional recovery in the traumatic brain injury (TBI) model. METHODS: Rats were subjected to midline incision followed by TBI in the prefrontal cortex region. After 72 hours, the behavioural and neurological deficits tests were performed, which included memory testing on Morris water maze for 5 days. Octreotide (15 and 30 mg/kg i.p.) was administered 30 minutes before subjecting to TBI, and its administration was continued for three days. RESULTS: In TBI-subjected rats, administration of octreotide restored on day 4 escape latency time (ELT) and increased the time spent in the target quadrant (TSTQ) on day 5, suggesting the improvement in learning and memory. It also increased the expression of H2S, Nrf2, and cystathionine-γ-lyase (CSE) in the prefrontal cortex, without any significant effect on cystathionine-ß-synthase. Octreotide also decreased the TNF-α levels and neurological severity score. However, co-administration of CSE inhibitor (D,L-propargylglycine) abolished octreotide-mediated neurofunctional recovery, decreased the levels of H2S and Nrf2 and increased the levels of TNF-α. CONCLUSIONS: Octreotide improved the neurological functions in TBI-subjected rats, which may be due to up-regulation of H2S biosynthetic enzyme (CSE), levels of H2S and Nrf2 and down-regulation of neuroinflammation.

Design, synthesis and biological activity of diamide compounds based on 3-substituent of the pyrazole ring†.

BACKGROUND: Diamide insecticides have attracted significant attention due to their high efficacy and low toxicity to non-target organisms since they were introduced to the market. In order to tackle the problems of insecticide resistance and ecological safety, 16 novel nitrobenzene substituted anthranilic diamides with ester, hydroxyl or sulfonyl at the 3-position of the pyrazole ring were designed and synthesized. RESULTS: All of these compounds possessed good activity against the ryanodine receptor (RyR) from Spodoptera frugiperda and relatively lower activity against mammalian RyR1, showing a better insect-selectivity compared to chlorantraniliprole in a cell-based assay. The molecular docking analysis predicted the binding conformations of these compounds, which showed a good correlation between the insecticidal activity and the binding scores. In vitro studies using a calcium imaging method demonstrated that the novel compounds could not only activate the RyR but may also target the dihydropyridine receptor on the plasma membrane of insect neurons, implicating a similar but not same mode of action. CONCLUSION: Substituted anthranilic diamides with an ester at the 3-position of the pyrazole ring exhibited a promising insecticidal activity and better insect-selectivity, which provided insight into the rational design of a new generation of effective diamide insecticides.

Octreotide-mediated neurofunctional recovery in rats following traumatic brain injury. Role of H2S, Nrf2 and TNF-α

ABSTRACT Purpose: To explore the role and mechanisms of octreotide in neurofunctional recovery in the traumatic brain injury (TBI) model. Methods: Rats were subjected to midline incision followed by TBI in the prefrontal cortex region. After 72 hours, the behavioural and neurological deficits tests were performed, which included memory testing on Morris water maze for 5 days. Octreotide (15 and 30 mg/kg i.p.) was administered 30 minutes before subjecting to TBI, and its administration was continued for three days. Results: In TBI-subjected rats, administration of octreotide restored on day 4 escape latency time (ELT) and increased the time spent in the target quadrant (TSTQ) on day 5, suggesting the improvement in learning and memory. It also increased the expression of H2S, Nrf2, and cystathionine-γ-lyase (CSE) in the prefrontal cortex, without any significant effect on cystathionine-β-synthase. Octreotide also decreased the TNF-α levels and neurological severity score. However, co-administration of CSE inhibitor (D,L-propargylglycine) abolished octreotide-mediated neurofunctional recovery, decreased the levels of H2S and Nrf2 and increased the levels of TNF-α. Conclusions: Octreotide improved the neurological functions in TBI-subjected rats, which may be due to up-regulation of H2S biosynthetic enzyme (CSE), levels of H2S and Nrf2 and down-regulation of neuroinflammation.

Knowledge, attitudes and practices related to seeking medical eyecare services by adults with moderate-to-severe visual impairment in rural Yueqing, Wenzhou, China: a cross-sectional survey.

AIM: To evaluate the knowledge, attitudes, and practices regarding eye-care seeking practices of visually impaired adults in a rural area Yueqing, and explore factors influencing their behavior. METHODS: A stratified sampling method was used to select 48 villages in Yueqing, from which 2400 people were selected to receive vision screenings conducted by oculists during a household visit. Those presenting visual acuity ≥0.5 logMAR in either eye completed a self-designed questionnaire investigating their knowledge about medical eye-care seeking, attitudes about eye health and eye-care-seeking behavior. RESULTS: Totally 165 people with moderate-to-severe visual impairment were identified (6.9%, 165/2400), and 146 eligible participants were recruited (response rate: 88.4%, mean age: 68.6±15.0y), among which 88 (60.3%) were female. They had 82 (56.2%) and 64 (43.8%) monocular and binocular visual impairments respectively. A total of 67 (45.9%) subjects demonstrated a high knowledge level about medical eye-care seeking and 88 (60.3%) had self-rated poor vision, with 23 (15%) receiving regular vision checks. The 105 (71.9%) subjects had never been to hospital for an eye examination. "No need" and "schedule conflicts" were the main reasons for not seeking eye care. Having extensive knowledge of medical eye-care seeking was positively associated with high education levels (OR=3.73, P=0.045) and negatively correlated with older age (OR=0.97, P=0.043). Both the self-perceived vision condition (OR=2.59, P=0.03) and regular vision check behavior (OR=6.50, P<0.01) were related with seeking eye care services. CONCLUSION: In rural Yueqing, intervention is required to increase public knowledge about seeking medical eye care among people with moderate-to-severe visual impairment, especially for the elderly and poorly education. Regular vision checks may be useful to promote their medical eye-care utilization.

Validity and feasibility of a self-administered home vision examination in Yueqing, China: a cross-sectional study.

OBJECTIVE: To investigate the validity and feasibility of a self-administered home vision examination programme in China. DESIGN: Cross-sectional study. SETTING: Yueqing, China. PARTICIPANTS: A two-stage convenience sampling procedure was used to randomly select 600 households from 30 communities participating in the Yueqing Eye Study (YES). The aim of YES is to encourage home-based vision screening, reporting of visual acuity (VA) annually through social media and encouraging people to attend follow-up clinic appointments as a way to improve eye care access for adults with VA ≤+0.5 log of the minimum angle of resolution (logMAR). INTERVENTIONS: Household screeners (one per household) who tested other family members' VA completed a questionnaire on family structure, demographic information and knowledge about screening procedures. Other family members then underwent confirmatory VA testing by researchers. OUTCOME MEASURES: The completion rate of home-based VA screening, its sensitivity and specificity were used to evaluate validity. Factors that determined whether families participated in the self-VA screening were used to evaluate feasibility. RESULTS: 345 (66%) of the 523 (87.2%) households with valid data form their home-based vision examinations also were retested by researchers. There was no statistically significant difference in scores on the family-administerd or researcher-administerd VA test (VA≤+0.5 logMAR, p=0.607; VA >+0.5 logMAR, p=0.612). The sensitivity and specificity of home-based vision screening were 80.5% (95% CI 70.2% to 86.9%) and 95.1% (95% CI 92.6% to 96.8%), respectively. 14.7% (77/523) of tested respondents had VA ≤+0.5 logMAR. Predictors of performing home screening for VA remaining in regression models included higher economic status ('fair and above' vs 'poor': OR 1.74; 95% CI 1.08 to 2.76; p=0.022), age (<45 years vs ≥45 years: OR 0.46; 95% CI 0.25 to 0.85; p=0.014) and living in a nuclear (OR 5.17; 95% CI 2.86 to 9.36; p<0.001) or extended family (OR 8.37; 95% CI 4.93 to 14.20; p<0.001). CONCLUSION: Self-administered home vision screening is reliable and highly accepted by Chinese adults.

Recyclable ferromagnetic chitosan nanozyme for decomposing phenol.

Decomposing phenol and phenolic compounds to purify the environment is a focus of social attention. The use of ferromagnetic nanoparticles (MNP) to degrade phenol and phenolic compounds possesses many advantages and has received extensive attention. However, the unsatisfied catalyst activity and stability of MNP hamper its industrial applications. To improve MNP's properties, a ferromagnetic chitosan nanozyme (MNP@CTS) was synthesized via an improved hydrothermal method and molecular self-assembly technology. Its particle size was 11.76 nm, polydispersity index (PDI) was 0.073, surface zeta potential was 40.34 mV, saturation magnetization value was 35.28 emu g-1 and coercivity value was 17.56 Oe. The catalytic condition was extensively optimized among a range of pH and temperature, as well as initial concentrations of the substrate and H2O2, and MNP@CTS removed over 95% phenol from an aqueous solution within 5 h under the optimum conditions. Moreover, MNP@CTS was stable and could be regenerated for reuse for at least ten rounds. Thus, our findings open up a wide spectrum and lay a foundation of environmental friendly applications of MNP@CTS, showing several attractive features, such as easy preparation, low cost, excellent catalytic activity, good stability and reusability.

The pyrolysis behaviors of phosphorus-containing organosilicon compound modified ammonium polyphosphate with different phosphorus-containing groups, and their different flame-retardant mechanisms in polyurethane foam.

Two phosphorus-containing organosilicon compounds (PCOCs) with similar structure but different phosphorus-containing groups (phenyl phosphate group, PCOC1; phenylphosphoryl group, PCOC2) were synthesized. They were used to modify ammonium polyphosphate (APP), and the products obtained were coded as MAPP1 and MAPP2. Then MAPP1 and MAPP2 were respectively incorporated into low-density rigid polyurethane foam (LD-RPUF). The pyrolysis behavior of these two kinds of MAPP was investigated. Results showed that PCOC2, with the phenylphosphoryl group, induced the decomposition of APP, leading to early and rapid decomposition of MAPP2 with the release of NH3 in a short time and the formation of crosslinked structure quickly. Simultaneously, the phosphorus of MAPP2 was all retained in the condensed phase. In contrast, PCOC1, with the phenyl phosphate group, also induced the decomposition of APP. However, not all the phosphorus-containing groups of MAPP1 were retained in the condensed phase; some of the phosphorus was released into the gas phase in the form of PO2· and PO· free radicals. Evaluation of the flame-retardant effect by means of the cone calorimeter test demonstrated that MAPP2 had better flame-retardant properties in the LD-RPUF system, including the reduction of peak heat release rate, total heat release, and total smoke release. Moreover, the char yield of LD-RPUF/MAPP2 was more than that of LD-RPUF/MAPP1. Macro and micro photographs showed that MAPP2 can promote the LD-RPUF matrix to form an intumescent char layer with more complete and stable foam during the combustion process compared with MAPP1. Finally, a possible flame-retardant mechanism of MAPP1 and MAPP2 in LD-RPUF is proposed.