Molecular insights into the functional analysis of P450 CYP321A7 gene in the involvement of detoxification of lambda-cyhalothrin in Spodoptera frugiperda.

Fall armyworm, Spodoptera frugiperda (J. E. Smith), is a widely recognized global agricultural pest that has significantly reduced crop yields all over the world. S. frugiperda has developed resistance to various insecticides. Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides, leading to increased resistance in insect populations. However, the function of the specific P450 gene for lambda-cyhalothrin resistance in S. frugiperda was unclear. Herein, the expression patterns of 40 P450 genes in the susceptible and lambda-cyhalothrin-resistant populations were analyzed. Among them, CYP321A7 was found to be overexpressed in the resistant population, specifically LRS (resistance ratio = 25.38-fold) derived from a lambda-cyhalothrin-susceptible (SS) population and FLRS (a population caught from a field, resistance ratio = 63.80-fold). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for LRS (2.76-fold) and the FLRS (4.88-fold) as compared to SS, while no significant differences were observed in the activities of glutathione S-transferases and esterases. Furthermore, the knockdown of CYP321A7 gene by RNA interference significantly increased the susceptibility to lambda-cyhalothrin. Remarkably, the knockdown of CYP321A7 reduced the enzymatic activity of P450 by 43.7%, 31.9%, and 22.5% in SS, LRS, and FLRS populations, respectively. Interestingly, fourth-instar larvae treated with lambda-cyhalothrin at the LC30 dosage had a greater mortality rate due to RNA interference-induced suppression of CYP321A7 (with increases of 61.1%, 50.0%, and 45.6% for SS, LRS, and FLRS populations, respectively). These findings suggest a link between lambda-cyhalothrin resistance and continual overexpression of CYP321A7 in S. frugiperda larvae, emphasizing the possible importance of CYP321A7 in lambda-cyhalothrin detoxification in S. frugiperda.

Diastolic and systolic blood pressure and gout: a Mendelian randomization study.

Background: Although there is solid epidemiological evidence supporting the connection between hypertension and gout, little has been said about the relationship between diastolic and systolic blood pressure and gout, the causal relationship and direction associated are uncertain, so we aim to research the causal relationship between diastolic and systolic blood pressure and gout. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect between 2 blood pressure phenotypes (including diastolic blood pressure and systolic blood pressure) and 5 gout phenotypes (including gout, drug-induced gout, idiopathic gout, unspecified gout, and strictly defined gout) using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. Results: After the screening, we found a causal relationship between diastolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout, and a causal relationship between systolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout. Conclusion: From a genetic predisposition, controlling blood pressure may reduce the risk of gout.

Suicidal ideation in adolescents with adiponectin receptor 2 rs12342 polymorphism affected by Wenchuan earthquake.

PURPOSE: The present study was to investigate prevalence of suicidal ideation and its associations with biological and environmental factors in adolescents with different genotypes of rs12342 at adiponectin receptor 2 gene (ADIPOR2). METHODS: Suicidal ideation, biological and environmental factors were evaluated by questionnaires in 669 high school students after Wenchuan earthquake in China. ADIPOR2 rs12342 was genotyped by polymerase chain reaction-restriction fragment length polymorphism and verified by DNA sequencing. RESULTS: Female adolescents had higher prevalence of suicidal ideation than male students in AG heterozygote and GG homozygote, but not AA homozygote. Prevalence of suicidal ideation was different in male, but not female, subjects with different genotypes. Genotype and allele frequencies were significantly different between male students with and without suicidal ideation, but not the female counterparts. Family history of mental disorders, extent of damage to property, carbohydrate intake and protein intake were associated with suicidal ideation in female subjects, while ADIPOR2 rs12342, father's educational level and previous trauma experience were associated with suicidal ideation in male subjects. CONCLUSION: ADIPOR2 rs12342 is associated with and has potential to interact with environmental factors on suicidal ideation in a gender-dependent manner in youth. These findings pave a novel way and perspective for precision inferences of suicidal ideation in subjects with different genetic backgrounds. ADIPOR2 rs12342 needs to be considered when intervening suicidal ideation, especially in adolescents.

Poly(Dibenzothiophene-Terphenyl Piperidinium) for High-Performance Anion Exchange Membrane Water Electrolysis.

The anion exchange membrane water electrolysis is widely regarded as the next-generation technology for producing green hydrogen. The OH- conductivity of the anion exchange membrane plays a key role in the practical implementation of this device. Here, we present a series of Z-S-x membranes with dibenzothiophene groups. These membranes contain sulfur-enhanced hydrogen bond networks that link surrounding surface site hopping regions, forming continuous OH- conducting highways. Z-S-20 has a high through-plane OH- conductivity of 182±28 mS cm-1 and ultralong stability of 2650 h in KOH solution at 80 °C. Based on rational design, we achieved a high PGM-free alkaline water electrolysis performance of 7.12 A cm-2 at 2.0 V in a flow cell and demonstrated durability of 650 h at 2 A cm-2 at 40 °C with a cell voltage increase of 0.65 mV/h.

Organocatalytic Enantioselective Synthesis of Inherently Chiral Calix[4]arenes.

Inherently chiral calix[4]arenes are an excellent structural scaffold for enantioselective synthesis, chiral recognition, sensing, and circularly polarized luminescence. However, their catalytic enantioselective synthesis remains challenging. Herein, we report an efficient synthesis of inherently chiral calix[4]arene derivatives via cascade enantioselective cyclization and oxidation reactions. The three-component reaction features a broad substrate scope (33 examples), high efficiency (up to 90 % yield), and excellent enantioselectivity (>95 % ee on average). The potential applications of calix[4]arene derivatives are highlighted by their synthetic transformation and a detailed investigation of their photophysical and chiroptical properties.

Enantioselective Nickel-Catalyzed Denitrogenative Transannulation En Route to N-N Atropisomers.

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.

Size effects and electronic properties of zinc-doped boron clusters Zn B n (n = 1-15).

CONTEXT: To gain a deeper understanding of zinc-doped boron clusters, theoretical calculations were performed to investigate the size effects and electronic properties of zinc-doped boron clusters. The study of the electronic properties, spectral characteristics, and geometric structures of Zn B n (n = 1-15) is of great significance in the fields of semiconductor materials science, material detection, and improving catalytic efficiency. The results indicate that Zn B n (n = 1-15) clusters predominantly exhibit planar or quasi-planar structures, with the Zn atom positioned in the outer regions of the B n framework. The second stable structure of Zn B 3 is a three-dimensional configuration, indicating that the structures of zinc-doped boron clusters begin to convert from the planar or quasi-planar structures to the 3D configurations. The second low-energy structure of Zn B 15 is a novel configuration. Relative stability analyses show that the Zn B 12 has better chemical stability than other clusters with a HOMO-LUMO gap of 2.79 eV. Electric charge analysis shows that part electrons on zinc atoms are transferred to boron atoms, and electrons prefer to cluster near the B n framework. According to the electron localization function, it gets harder to localize electrons as the equivalent face value drops, and it's challenging to see covalent bond formation between zinc and boron atoms. The spectrograms of Zn B n (n = 1-15) exhibit distinct properties and notable spectral features, which can be used as a theoretical basis for the identification and confirmation of boron clusters doped with single-atom transition metals. METHODS: The calculations were performed using the ABCluster global search technique combined with density functional theory (DFT) methods. The selected low-energy structures were subjected to geometric optimization and frequency calculations at the PBE0/6-311 + G(d) level to ensure structural stability and eliminate any imaginary frequencies. To acquire more precise relative energies, we performed single-point energies calculations for the low-lying isomers of Zn B n (n = 1-15) at the CCSD(T)/6-311 + G(d)//PBE0/6-311 + G(d) level of theory. All calculations were performed using Gaussian 09 software. To facilitate analysis, we utilized software tools such as Multiwfn, and VMD.

Palladium-catalyzed asymmetric carbene coupling en route to inherently chiral heptagon-containing polyarenes.

Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial. However, originate chirality from the distorted structure around heptagon-containing polyarenes is largely overlooked, the enantioselective construction of all-carbon heptagon-containing polyarenes remains a challenge. Herein, we present a highly enantioselective synthesis route for fabricating all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross-coupling of benzyl bromides and N-arylsulfonylhydrazones. A wide range of nonplanar, saddle-shaped tribenzocycloheptene derivatives are efficiently prepared in high yields with excellent enantioselectivities using this approach. In addition, stereochemical stability experiments show that these saddle-shaped tribenzocycloheptene derivatives have high inversion barriers.

Cure Kinetics and Thermal Decomposition Behavior of Novel Phenylacetylene-Capped Polyimide Resins.

Based on a novel phenylacetylene capped polyimide (PI) with unique high-temperature resistance, its curing kinetics and thermal decomposition behavior were investigated. The curing mechanism and kinetics were studied by differential scanning calorimetry (DSC), and the activation energy (Ea) and pre-exponential factor (A) of the curing reaction were calculated based on the Kissinger equation, Ozawa equation, and Crane equation. According to the curve of conversion rate changing with temperature, the relationship between the dynamic reaction Ea and conversion rate (α) was calculated by the Friedman equation, Starink equation, and Ozawa-Flynn-Wall (O-F-W) equation, and the reaction Ea in different stages was compared with the results of molecular dynamics. Thermogravimetric analysis (TGA) and a scanning electron microscope (SEM) were used to analyze the thermal decomposition behavior of PI resins before and after curing. Temperatures at 5% and 20% mass loss (T5%, T20%), peak decomposition temperature (Tmax), residual carbon rate (RW), and integral process decomposition temperature (IPDT) were used to compare the thermal stability of PI resins and cured PI resins. The results display that the cured PI has excellent thermal stability. The Ea of the thermal decomposition reaction was calculated by the Coats-Redfern method, and the thermal decomposition behavior was analyzed. The thermal decomposition reaction of PI resins at different temperatures was simulated by molecular dynamics, the initial thermal decomposition reaction was studied, and the pyrolysis mechanism was analyzed more comprehensively and intuitively.

Nonnegligible Contribution of Nonlymphoid Tissue to Viral Reservoir During the Short-Term Early cART in SIVmac239-Infected Chinese Rhesus Macaques.

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.

Identification of novel mammalian viruses in tree shrews ( Tupaia belangeri chinensis).

The Chinese tree shrew ( Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.

Stable Anion Exchange Membrane Bearing Quinuclidinium for High-performance Water Electrolysis.

Anion exchange membranes (AEMs) are core components in anion exchange membrane water electrolyzers (AEM-WEs). However, the stability of functional quaternary ammonium cations, especially under high temperatures and harsh alkaline conditions, seriously affects their performance and durability. Herein, we synthesized a 1-methyl-3,3-diphenylquinuclidinium molecular building unit. Density functional theory (DFT) calculations and accelerated aging analysis indicated that the quinine ring structure was exceedingly stable, and the SN2 degradation mechanism dominated. Through acid-catalyzed Friedel-Crafts polymerization, a series of branched poly(aryl-quinuclidinium) (PAQ-x) AEMs with controllable molecular weight and adjustable ion exchange capacity (IEC) were prepared. The stable quinine structure in PAQ-x was verified and retained in the ex situ alkaline stability. Furthermore, the branched polymer structure reduces the swelling rate and water uptake to achieve a tradeoff between dimensional stability and ionic conductivity, significantly improving the membrane's overall performance. Importantly, PAQ-5 was used in non-noble metal-based AEM-WE, achieving a high current density of 8 A cm-2 at 2 V and excellent stability over 2446 h in a gradient constant current test. Based on the excellent alkaline stability of this diaryl-quinuclidinium group, it can be further considered as a multifunctional building unit to create multi-topological polymers for energy conversion devices used in alkaline environments.

A dynamic panel threshold model analysis on heterogeneous environmental regulation, R&D investment, and enterprise green total factor productivity.

Environmental regulations are important means to influence manufacturing enterprise green development. However, there are two completely different conclusions both in theoretical and in empirical research, namely the "Follow Cost" theory and the "Porter Hypothesis". The nonlinear mechanism needs to be considered. Therefore, this study aims to explain the threshold impact of heterogeneous environmental regulations on enterprise green total factor productivity. Environmental regulations are divided into different sub-categories, then based on the panel data of 1220 Chinese manufacturing listed companies from 2011 to 2020, this paper uses threshold regression model to examine the impact of heterogeneous environmental regulations on Chinese manufacturing enterprise Green Total Factor Productivity. The empirical results show that: (1) Command-controlled, market-incentive and voluntary-agreement environmental regulation all have a significant nonlinear impact on enterprise Green Total Factor Productivity. (2) Enterprise R&D investment plays a threshold role in the impact. (3) There are industry and equity type differences in the impact process. This study focuses on the micro level of enterprises and tests the threshold mechanism, which make some theoretical complement to previous researches. The research results are not only beneficial for the government to propose appropriate environmental regulatory policies, but also for enterprises to achieve green growth through heterogeneous R&D investment.

Opportunities and Challenges for Inhalable Nanomedicine Formulations in Respiratory Diseases: A Review.

Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system.

High stability of EEG spectral power across polysomnography and multiple sleep latency tests in good sleepers and chronic insomniacs.

To assess the stability of electroencephalographic (EEG) spectral features across overnight polysomnography (PSG) and daytime multiple sleep latency tests (MSLTs) in chronic insomniacs (CIs) and normal controls (NCs). A total of 20 NCs and 22 CIs underwent standard PSG and MSLTs. Spectral analyses were performed on EEG data from PSG and MSLTs and absolute and relative power in central, frontal and occipital channels were obtained for wake (W) and non-rapid eye movement sleep stage 1 and 2 (N1, N2). Intraclass correlation coefficients (ICCs) were used to assess the stability of EEG spectral power across PSG and MSLTs for W, N1 and N2. The absolute power of all frequency bands except delta exhibited high stability across PSG and MSLTs in both NCs and CIs (ICCs ranged from 0.430 to 0.978). Although delta absolute power was stable in NCs during N1 and N2 stages (ICCs ranged from 0.571 to 0.835), it tended to be less stable in CIs during W and sleep stages (ICCs ranged from 0.042 to 0.807). We also observed lower stability of relative power compared to absolute power though the majority of relative power outcomes maintained high stability in both groups (ICCs in relative power ranged from 0.044 to 0.962). Most EEG spectral bandwidths across PSG and MSLT in W, N1 and N2 show high stability in good sleepers and chronic insomniacs. EEG signals from either an overnight PSG or a daytime MSLT may be useful for reliably exploring EEG spectral features during wakefulness or sleep.

Increased cAMP-PKA signaling pathway activation is involved in up-regulation of CTLA-4 expression in CD4+ T cells in acute SIVmac239-infected Chinese rhesus macaques.

Human immunodeficiency virus-1 (HIV-1) infection can cause chronic activation, exhaustion, and anergy of the immune system. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint molecule, which plays an important role in immune homeostasis and disease. CTLA-4 expression is elevated in HIV-1-infected patients and is associated with disease progression. However, the mechanism controlling expression of CTLA-4 in HIV-1 infection is poorly characterized. In this study, we used a SIV-infected Chinese rhesus macaque (ChRM) model to explore CTLA-4 expression in SIV infection. Results showed that SIV infection significantly increased CTLA-4 expression in all T cell subsets, especially central memory T cells. CTLA-4+CD4+ T cell frequency was significantly associated with disease progression markers. Activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway regulated CTLA-4 expression in CD4+T cells, as confirmed by stimulation with dibutyryl cyclic adenosine monophosphate, forskolin, and 3-isobutyl-1-methylxanthine, and inhibition with H-89 ex vivo. Simultaneously, cAMP concentration in PBMCs and PKA activity in both PBMCs and CD4+ T cells were increased in acute SIV-infected ChRMs, accompanied by an increase in adenylate cyclase 6 expression and a decrease in cAMP-phosphodiesterase 3A (PDE3A), PDE4B, and PDE5A expression in PBMCs. In addition, selective inhibition of PDE4B and PDE5A activity enhanced CTLA-4 expression in CD4+ T cells. These results suggest that SIV infection alters cAMP metabolism and increases cAMP-PKA signaling pathway activation, which up-regulates the expression of CTLA-4 in acute SIVmac239-infected ChRMs. Thus, regulation of the cAMP-PKA signaling pathway may be a potential strategy for the restoration of T cell function and therapy for AIDS.

Association of food insecurity with successful aging among older Indians: study based on LASI.

PURPOSE: Whether food insecurity (FI), a social determinant of health, is linked with successful aging (SA) in the older generation remains uncertain. This study explored the association of FI with SA among older Indians. METHODS: Data were collected from the Longitudinal Ageing Study in India (LASI) wave 1 (2017-2018). Older adults (≥ 60 years) who completed both the FI and the SA surveys were selected. FI was indicated by the lack of access to enough food in the past year. SA was determined by five components: (1) low probability of diseases; (2) low probability of disability; (3) high cognitive functionality; (4) low probability of depression; and (5) active social engagement. The association of FI and SA was assessed using multivariable logistic regression adjusted for potential covariates. Subgroup analyses were performed to evaluate interactions with age, sex, alcohol use, smoking, and place of residence. RESULTS: 27,579 participants met the eligibility criteria. Overall prevalence was 7.13% for FI and 19.41% for SA. Following full adjustment, FI was inversely associated with SA (OR 0.56; 95% CI 0.49-0.65) and with each of SA's five components. No significant interactions of FI and SA were observed in subgroup analyses stratified by age, sex, alcohol use, smoking, or place of residence. CONCLUSIONS: FI was inversely associated with SA among older Indians. These findings need to be validated by future studies which should also explore potential underlying mechanisms, and whether interventions decreasing FI might increase SA.

Organocatalytic Enantioselective Synthesis of Seven-Membered Ring with Inherent Chirality.

Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).

Novel Triazolopyridine-Based BRD4 Inhibitors as Potent HIV-1 Latency Reversing Agents.

Bromodomain-containing protein 4 (BRD4) inhibitors have been proven to be a promising option for anti-HIV-1 latency therapeutics. We herein describe the design, synthesis, and anti-HIV-1 latency bioevaluation of triazolopyridine derivatives as BRD4 inhibitors. Among them, compound 13d displayed favorable HIV-1 reactivation and prominent safety profile without triggering abnormal immune activation. It exerted strong synergism when combined with the PKC activator prostratin and has the same BRD4-targeting latency mechanism as observed with JQ1, by stimulating Tat-dependent HIV-1 elongation. Besides, it neither affected the antiviral efficacies of antiviral drugs nor caused secondary infections to uninfected cells and the latency reversing potency of 13d, in turn, was not affected by different classes of antiviral drugs.