Rational design, synthesis and binding mechanisms of novel benzyl geranate derivatives as potential eco-friendly aphid repellents.

BACKGROUND: The push-pull strategy is considered as a promising eco-friendly method for pest management. Plant volatile organic compounds (PVOCs) act as semiochemicals constitute the key factor in implementing this strategy. Benzyl alcohol and geraniol, as functional PVOCs, were reported to regulate insect behavior, showing the potential application in pest control. Using geraniol as lead, a geraniol derivative 5i with fine repellent activity was discovered in our previous work. In order to explore novel, eco-friendly aphid control agents, a series of benzyl geranate derivatives was designed and synthesized using 5i as the lead and benzyl alcohol as the active fragment. RESULTS: Benzyl alcohol was firstly evaluated to have repellent activity to Acyrthosiphon pisum. Based on this repellent fragment, a series of novel benzyl geranate derivatives was rationally designed and synthesized using a scaffold-hopping strategy. Among them, compound T9, with a binding affinity (Kd = 0.43 µm) and a substantial repellency of 64.7% against A. pisum, is the most promising compound. Molecule docking showed that hydrophobic and hydrogen-bonding interactions substantially influenced the binding affinity of compounds with ApisOBP9. Additionally, T9 exhibited low-toxicity to honeybees and ladybugs. CONCLUSION: Using a simple scaffold-hopping strategy combined with active fragment benzyl alcohol, a new derivative T9, with high aphid-repellency and low-toxicity to nontarget organisms, can be considered as a novel potential eco-friendly aphid control agent for sustainable agriculture. © 2023 Society of Chemical Industry.

Efficacy and safety of IL inhibitors, TNF-α inhibitors, and JAK inhibitors in patients with ankylosing spondylitis: a systematic review and Bayesian network meta-analysis.

Background: Biologics and Janus kinase (JAK) inhibitors are commonly used to improve ankylosing spondylitis (AS) symptoms if conventional treatments are ineffective or unsuitable. This systematic review aimed to compare the therapeutic effects and safety of JAK inhibitors, tumor necrosis factor-alpha (TNF-α) inhibitors, and interleukin (IL) inhibitors in patients with AS. Methods: We retrieved literature from various databases including Web of Science, Cochrane, Embase, PubMed, China National Knowledge Infrastructure, Weipu Journal Database, SinoMed, and WanFang Data up to February 1, 2023, and evaluated the quality of the included RCTs using the Cochrane risk-of-bias tool. R 4.1.3, STATA 15.1 were employed for network meta-analyses. Results: We identified 48 eligible articles including 8,937 patients. Ten articles were rated as "low risk", 5 as "high risk", and the others as "some concerns". In terms of efficacy, IL-17, IL-6, and JAK inhibitors were compared with TNF-α inhibitors in ASAS20 (RR =0.81, 95% CI: 0.66-0.98; RR =0.57, 95% CI: 0.35-0.95; RR =0.77, 95% CI: 0.60-0.99). IL-6 inhibitors were compared with TNF-α inhibitors in ASAS5/6 (RR =0.39, 95% CI: 0.16-0.98). IL-23, JAK inhibitors were compared with TNF-α inhibitors in BASDAI50 (RR =0.35, 95% CI: 0.20-0.60; RR =0.70, 95% CI: 0.49-0.98). IL-17 inhibitors were compared with IL-23 and IL-6 inhibitors in BASFI (MD =-1.05, 95% CI: -1.65--0.51; MD =-1.46, 95% CI: -2.02--0.97). In terms of safety, IL-6 inhibitors were compared with JAK, TNF-α inhibitors in AEs (RR =1.38, 95% CI: 1.06-1.88; RR =1.30, 95% CI: 1.01-1.70). Conclusions: TNF-α inhibitors are significantly superior to both IL and JAK inhibitors, and may be the preferable option to deal with the rapid progression of AS and severe functional limitations. IL-17 inhibitors may better improve the BASDAI50 response compared with JAK, IL-23, and TNF-α inhibitors. The efficacy and safety of IL-6 inhibitors are inferior to other types of drugs, indicating the low efficacy and high risk of IL-6 inhibitors.

Associations between smoke exposure and osteoporosis or osteopenia in a US NHANES population of elderly individuals.

Background: Tobacco exposure is considered to be a risk factor for reduced bone mineral density (BMD), which may result in osteopenia. Cotinine, a metabolite of nicotine, is commonly utilized as a marker of tobacco exposure. Nevertheless, there are limited clinical data on the associations between osteoporosis (OP) or osteopenia and smoking status or serum cotinine level. Methods: We thoroughly examined the NHANES cross-sectional data from 2005 to 2010, 2013 to 2014, and 2017 to 2018. Multivariate logistic regression models were applied to assess the associations among smoking status and serum cotinine levels as well as OP and osteopenia. The relationships between serum cotinine level and OP and osteopenia were also assessed using the restricted cubic spline (RCS) method. Results: A total of 10,564 participants were included in this cross-sectional study. The mean age of the study population was 64.85 ± 9.54 years, and the patients were predominantly male (51.9%). We found that the relationships between higher serum cotinine levels (≥3 ng/ml) and the prevalence of osteoporosis (Model 1: OR=2.27 [1.91-2.69]; Model 2: OR=2.03 [1.70-2.43]; Model 3: OR=2.04 [1.70-2.45]; all p for trend <0.001) remained significant after adjustment for covariates by applying the lowest serum cotinine levels (<0.05 ng/ml) as the reference. Similar results were observed for current smokers, who were more likely to develop OP compared with nonsmokers (Model 1: OR=2.30 [1.90-2.79]; Model 2: OR=2.16 [1.77-2.64]; Model 3: OR=2.16 [1.77-2.65]). Moreover, higher serum cotinine levels were found to be strongly and positively correlated with the prevalence of osteopenia (OR=1.60 [1.42-1.80]). A similar relationship was observed between current smokers and the prevalence of osteopenia compared with nonsmokers (OR=1.70 [1.49-1.94]). RCS regression also showed that serum cotinine levels were nonlinearly and positively correlated with OP and osteopenia, with inflection points of 5.82 ng/ml and 3.26 ng/ml, respectively. Conclusion: This study showed that being a smoker was associated with the prevalence of OP or osteopenia compared with being a nonsmoker and that there was a strong nonlinear positive dose-response relationship between serum cotinine levels and OP and osteopenia.

Taming Chiral Quaternary Stereocenters via Remote H-Bonding Stereoinduction in Palladium-Catalyzed (3+2) Cycloadditions.

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

Association of hormone replacement therapy and the risk of knee osteoarthritis: A meta-analysis.

BACKGROUND: The relationship between hormone replacement therapy (HRT) and osteoarthritis is controversial in epidemiological studies. With the aim of better understanding the effect of HRT use, this first meta-analysis was implemented to explore the association of HRT and knee OA. METHODS: A series of data is retrieved from Web of Science, PubMed, and Embase databases to observe the association of HRT and knee osteoarthritis up to December 2021. Two separated reviewers chose the research, extracted the data, and evaluated the study quality. Pooled estimates of 95% CI and HRs were acquired through a random-effects model. RESULTS: Finally, there existed 13 pieces of research, containing one case-control research, four cross-sectional pieces of research, as well as eight cohort pieces of research, involving 2573,164 participants. The overall results showed that the use of HRT was related to a raised risk of knee OA (HR = 1.24, 95% CI 1.07-1.45). And the pooled analysis showed a statistically significant raised risk of knee joint replacement (HR = 1.30, 95% CI 1.09-1.54) when using HRT. In addition, the outcome exhibits the raised knee OA risk for the present users of HRT (HR = 1.40, 95% CI 1.16-1.68) according to HRT status. In the past users of HRT, the augment of knee OA risk was not statistically evident (HR = 1.16, 95% CI 0.94-1.42). CONCLUSION: We observed that HRT use was related to a raised knee OA risk. Furthermore, future studies might focus on relevant mechanistic to verify our observed associations.

Treatment of the saline-alkali soil with acidic corn stalk biochar and its effect on the sorghum yield in western Songnen Plain.

Due to biochar could improve the physical and chemical properties of soil and promote crop growth, it is widely used in soil remediation, especially in saline soil. However, it is rarely studied of the application of acidic biochar in saline-alkali land. A field experiment with acidic corn stalk biochar (ACSBC) as a soil amendment was carried out in the western Songnen Plain of China. ACSBC (0, 0.15, 0.3, 0.45, 0.6, 0.75, 1, 6 and 15 t ha-1) was added to the topsoil to evaluate the combined effects on soil and sorghum yield. During the seeding and harvest period, the content of soil water, nutrient elements, cation exchange capacity (CEC), organic matter (OM), soluble cations (K+, Ca2+, Mg2+) increased, Na+ content showed opposite trend. However, soil pH decreased averagely with 0.3 and 1.0 during the seeding and harvest period respectively, salinity decreased with 19.37% and 18.14%, exchange sodium percentage (ESP) decreased with 37.08% and 37.04%. The sorghum yield increased 32.98% averagely, significantly by 51.37% and 47.33% with the 0.6 and 1 t ha-1 of ACSBC treatments respectively. These experimental results show that proper application of ACSBC in saline-alkali soil can effectively improve soil properties and increase sorghum yield.

Cooperative Ligand-Promoted P(III)-Directed Ruthenium-Catalyzed Remote Meta-C-H Alkylation of Tertiary Phosphines.

Herein, we disclose a ruthenium-catalyzed meta-selective C-H activation of phosphines by using intrinsic P(III) as a directing group. 2,2,6,6-Tetramethylheptane-3,5-dione acts as the ligand and exhibits an excellent performance in boosting the meta-alkylation. The protocol allows an efficient and straightforward synthesis of meta-alkylated tertiary phosphines. Several meta-alkylated phosphines were evaluated for Pd-catalyzed Suzuki coupling and found to be superior to commercially available ortho-substituted phosphines. The practicability of this methodology is further demonstrated by the synthesis of difunctionalized phosphines.

Remote and Selective C(sp2)-H Olefination for Sequential Regioselective Linkage of Phenanthrenes.

Biphenylcarboxylic acid with two competing C(sp2)-H sites was designed for site selective C(sp2)-H functionalization by developing carboxylic acids assisted remote and selective olefination via 7-membered palladacycle. Mechanism investigation and DFT calculations reveal a kinetics-determined process, which could be utilized to explore a variety of remote site selectivity. The practicability of this method was highlighted by the precise construction of phenathrene under sequential site selectivity.

Antifungal activity of water-soluble products obtained following the liquefaction of cornstalk with sub-critical water.

Cornstalks are the leftover leaves and stems in a field after corn harvest. They are a potential biomass resource but are underutilized in agricultural production systems. To examine the chemical components in cornstalks and their corresponding functions, blocky cornstalks were treated in water at temperatures of 190, 210, 230, 250, and 270 °C in a high-pressure reactor. Water-soluble products (WSPs) were extracted from these treatments, and their chemical compositions were analyzed using gas chromatography-mass spectrometry (GC-MS), and their antifungal activities were determined using a bioassay. It was found that WSPs contained 28.7-40.1% phenols, 27.9-36.6% ketones, 0-2.6% alcohols, 4.9-10.1% esters, 5.4-7.8% organic acids, 1.3-12% aldehydes, and 5.5-18.4% of other organic compounds such as nitrogen- and sulfur-containing compounds, furan compounds, and benzene compounds. The inhibition the growth of the plant pathogen Fusarium oxysporum by WSPs was affected by temperature. WSP-270 (obtained at 270 °C) exhibited the best growth-inhibition efficacy. Under a biomicroscope, WSP-270-treated F. oxysporum showed a deformed and swollen hypha, and an increased number of bifurcations, as well as an expansion of growing apexes of new bifurcations. Therefore, the antifungal activity of WSPs could be used to manage soilborne plant pathogens.

Carboxylate-Assisted Pd(II)-Catalyzed ortho-C-H and Remote C-H Activation: Economical Synthesis of Pyrano[4,3- b]Indol-1(5 H)-ones.

An original Pd(II)-catalyzed domino two C-H activations strategy has been designed to synthesize pyrano[4,3- b]indol-1(5 H)-one motifs from inexpensive and commercially available olefins and heteroaromatic acids by carboxylate-directed sequential ortho-C-H alkenylation and remote C-H lactonization. Importantly, this protocol overcomes the selectivity for carboxylic acids with acrylates of the conventional Michael addition-type process. Preliminary studies of mechanism indicate that both aryl and olefinlic C-H activations may participate in this catalytic system.

Facile synthesis of unnatural ß-germyl-α-amino amides via Pd(ii)-catalyzed primary and secondary C(sp3)-H bond germylation.

Pd(ii)-Catalyzed direct C(sp3)-H germylation of α-AA derivatives with the assistance of a bidentate auxiliary for the efficient synthesis of ß-germyl-α-amino amides is reported. This protocol features good generality for primary and secondary C-H bonds of aliphatic amides. Mechanistic studies show that a crucial five-membered palladacycle intermediate may play a key role in this process.

Monoprotected Amino Acid (MPAA) Ligand Enabled C-H Alkynylation of Phenyl Acetic Acid.

A weakly carboxylate-directed palladium(II)-catalyzed ortho-C-H alkynylation of diverse phenylacetic acids promoted by monoprotected amino acid ligand enabled is reported. The reaction has a broad substrate scope including α-secondary, tertiary, and quaternary phenylacetic acids. Notably, the direct ortho-C-H alkynylation of α-quaternary phenylacetic acids and chiral α-tertiary phenylacetic acids was achieved for the first time. Moreover, this method could be used for simple and efficient gram-scale synthesis and diversification of an anti-inflammatory drug.