Deciphering the interaction mechanism between soy protein isolate and fat-soluble anthocyanin on experiments and molecular simulations.

In this work, the acylated anthocyanin (Ca-An) was prepared by enzymatic modification of black rice anthocyanin with caffeic acid, and the binding mechanism of Ca-An to soybean protein isolate (SPI) was investigated by experiments and computer simulation to expand the potential application of anthocyanin in food industry. Multi-spectroscopic studies revealed that the stable binding of Ca-An to SPI induced the folding of protein polypeptide chain, which transformed the secondary structure of SPI trended to be flexible. The microenvironment of protein was transformed from hydrophobic to hydrophilic, while tyrosine played dominant role in quenching process. The binding sites and forces of the complexes were determined by computer simulation for further explored. The protein conformation of the 7S and 11S binding regions to Ca-An changed, and the amino acid microenvironment shifted to hydrophilic after binding. The results showed that more non-polar amino acids existed in the binding sites, while in binding process van der Waals forces and hydrogen bonding played a major role hydrophobicity played a minor role. Based on MM-PBSA analysis, the binding constants of 7S-Ca-An and 11S-Ca-An were 0.518 × 106 mol-1 and 5.437 × 10-3 mol-1, respectively. This information provides theoretical guidance for further studying the interaction between modified anthocyanins and biomacromolecules.

Response of ocean acidification to atmospheric carbon dioxide removal.

Artificial CO2 removal from the atmosphere (also referred to as negative CO2 emissions) has been proposed as a potential means to counteract anthropogenic climate change. Here we use an Earth system model to examine the response of ocean acidification to idealized atmospheric CO2 removal scenarios. In our simulations, atmospheric CO2 is assumed to increase at a rate of 1% per year to four times its pre-industrial value and then decreases to the pre-industrial level at a rate of 0.5%, 1%, 2% per year, respectively. Our results show that the annual mean state of surface ocean carbonate chemistry fields including hydrogen ion concentration ([H+]), pH and aragonite saturation state respond quickly to removal of atmospheric CO2. However, the change of seasonal cycle in carbonate chemistry lags behind the decline in atmospheric CO2. When CO2 returns to the pre-industrial level, over some parts of the ocean, relative to the pre-industrial state, the seasonal amplitude of carbonate chemistry fields is substantially larger. Simulation results also show that changes in deep ocean carbonate chemistry substantially lag behind atmospheric CO2 change. When CO2 returns to its pre-industrial value, the whole-ocean acidity measured by [H+] is 15%-18% larger than the pre-industrial level, depending on the rate of CO2 decrease. Our study demonstrates that even if atmospheric CO2 can be lowered in the future as a result of net negative CO2 emissions, the recovery of some aspects of ocean acidification would take decades to centuries, which would have important implications for the resilience of marine ecosystems.

Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression.

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1). Under the alternating magnetic field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient to trigger the opening and activation of TRPV1, and effectively impeded macrophagic inflammation and chondrocyte ferroptosis. This magnetothermal modulation of TRPV1 simultaneously attenuated synovitis and cartilage degeneration in mice incurred by destabilization of medial meniscus surgery, indicating the delayed OA progression. Furthermore, MNPs-TRPV1 with AMF exposure remarkably reduced knee pain sensitivity, alleviated the crippled gait, and improved spontaneous ambulatory activity performance in the mice OA model. Overall, this work provides a potential pathogenesis-based precise OA therapy with temporally and spatially magnetothermal modulation of TRPV1 in a controllable manner.

Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1.

Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate-stabilized gold nanorods (Cit-AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit-AuNRs. Under NIR irradiation, Cit-AuNRs@Anti-TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR-inspired Cit-AuNRs@Anti-TRPV1. Furthermore, the activation of TRPV1 by Cit-AuNRs@Anti-TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)-induced OA mice. The study reveals Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.

Air-Stable Li2S Cathodes Enabled by an In Situ-Formed Li+ Conductor for Graphite-Li2S Pouch Cells.

Using Li2S cathodes instead of S cathodes presents an opportunity to pair them with Li-free anodes (e.g., graphite), thereby circumventing anode-related issues, such as poor reversibility and safety, encountered in Li-S batteries. However, the moisture-sensitive nature of Li2S causes the release of hazardous H2S and the formation of insulative by-products, increasing the manufacturing difficulty and adversely affecting cathode performance. Here, Li4SnS4, a Li+ conductor that is air-stable according to the hard-soft acid-base principle, is formed in situ and uniformly on Li2S particles because Li2S itself participates in Li4SnS4 formation. When exposed to air (20% relative humidity), the protective Li4SnS4 layer maintains its components and structure, thus contributing to the enhanced stability of the Li2S@Li4SnS4 composite. In addition, the Li4SnS4 layer can accelerate the sluggish conversion of Li2S because of its favorable interfacial charge transfer, and continuously confine lithium polysulfides owing to its integrity during electrochemical processes. A graphite-Li2S pouch cell containing a Li2S@Li4SnS4 cathode is constructed, which shows stable cyclability with 97% capacity retention after 100 cycles. Hence, combining a desirable air-stable Li2S cathode and a highly reversible Li-free configuration offers potential practical applications of graphite-Li2S full cells.

Organic Intercalation Induced Kinetic Enhancement of Vanadium Oxide Cathodes for Ultrahigh-Loading Aqueous Zinc-Ion Batteries.

Vanadium-based oxides have attracted much attention because of their rich valences and adjustable structures. The high theoretical specific capacity contributed by the two-electron-transfer process (V5+ /V3+ ) makes it an ideal cathode material for aqueous zinc-ion batteries. However, slow diffusion kinetics and poor structural stability limit the application of vanadium-based oxides. Herein, a strategy for intercalating organic matter between vanadium-based oxide layers is proposed to attain high rate performance and long cycling life. The V3 O7 ·H2 O is synthesized in situ on the carbon cloth to form an open porous structure, which provides sufficient contact areas with electrolyte and facilitates zinc ion transport. On the molecular level, the added organic matter p-aminophenol (pAP) not only plays a supporting role in the V3 O7 ·H2 O layer, but also shows a regulatory effect on the V5+ /V4+ redox process due to the reducing functional group on pAP. The novel composite electrode with porous structure exhibits outstanding reversible specific capacity (386.7 mAh g-1 , 0.1 A g-1 ) at a high load of 6.5 mg cm-2 , and superior capacity retention of 80% at 3 A g-1 for 2100 cycles.

Unraveling Exogenous DNA Processing in Cas4-Lacking Crispr Systems: A Novel Bypass Pathway Explored.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems are widely distributed adaptive immune systems found in prokaryotes. The process involves three main stages: adaptation, expression, and interference. While the adaptation stage has been extensively studied, there is still an incomplete understanding of the mechanisms underlying the capture, trimming, and integration of exogenous DNA. For instance, Cas4, a CRISPR-Cas protein with endonuclease activity, is responsible for selecting and processing protospacer adjacent motif (PAM) sequences. However, some CRISPR isoforms lack Cas4 activity, relying on other enzymes for adaptive immunity. Recently, Wang et al. presented a novel model of exogenous DNA processing in a type I-E CRISPR system lacking Cas4 in a Nature article. This model integrates protospacer processing into CRISPR arrays through fine-tuned synthases formed by DnaQ-like exonuclease (DEDDh) and Cas1-Cas2 complexes. Their study introduces a novel model, shedding new light on the evolution of CRISPR adaptive immunity. This perspective comprehensively examines the fundamental process of CRISPR adaptive immunity, detailing both the classical pathway mediated by Cas4 and the alternative pathway mediated by DEDDh. Furthermore, a thorough evaluation of Wang et al.'s work is conducted, highlighting its strengths, weaknesses, and existing research challenges.

Interface Engineering with Dynamics-Mechanics Coupling for Highly Reactive and Reversible Aqueous Zinc-Ion Batteries.

The practical application of AZIBs is hindered by problems such as dendrites and hydrogen evolution reactions caused by the thermodynamic instability of Zinc (Zn) metal. Modification of the Zn surface through interface engineering can effectively solve the above problems. Here, sulfonate-derivatized graphene-boronene nanosheets (G&B-S) composite interfacial layer is prepared to modulate the Zn plating/stripping and mitigates the side reactions with electrolyte through a simple and green electroplating method. Thanks to the electronegativity of the sulfonate groups, the G&B-S interface promotes a dendrite-free deposition behavior through a fast desolvation process and a uniform interfacial electric field mitigating the tip effect. Theoretical calculations and QCM-D experiments confirmed the fast dynamic mechanism and excellent mechanical properties of the G&B-S interfacial layer. By coupling the dynamics-mechanics action, the G&B-S@Zn symmetric battery is cycled for a long-term of 1900 h at a high current density of 5 mA cm-2 , with a low overpotential of ≈30 mV. Furthermore, when coupled with the LMO cathode, the LMO//G&B-S@Zn cell also exhibits excellent performance, indicating the durability of the G&B-S@Zn anode. Accordingly, this novel multifunctional interfacial layer offers a promising approach to significantly enhance the electrochemical performance of AZIBs.

A Note on the Mixing Factor of Polar Codes.

Over binary-input memoryless symmetric (BMS) channels, the performance of polar codes under successive cancellation list (SCL) decoding can approach maximum likelihood (ML) algorithm when the list size L is greater than or equal to 2MF, where MF, known as mixing factor of code, represents the number of information bits before the last frozen bit. Recently, Yao et al. showed the upper bound of the mixing factor of decreasing monomial codes with length n=2m and rate R≤12 when m is an odd number; moreover, this bound is reachable. Herein, we obtain an achievable upper bound in the case of an even number. Further, we propose a new decoding hard-decision rule beyond the last frozen bit of polar codes under BMS channels.

The bound state in the continuum in flexible terahertz metasurfaces enabled sensitive biosensing.

The combination of a flexible device and novel electromagnetic resonances offers new dimensions to manipulate electromagnetic waves and promises new device functionalities. In this study, we experimentally demonstrate a flexible metasurface that can support the bound state in the continuum (BIC) in the terahertz regime. The metasurface consists of toroidal dipole resonant units on top of the flexible polyimide substrate, which can support a terahertz Friedrich-Wintgen BIC resonance, and the resonance characteristics can be tuned by changing the parameters of the coupling unit among two resonant modes. The BIC resonances under different bending conditions are analyzed and compared, showing decent mechanical robustness. The sensing application is demonstrated by combining Fetal Bovine Serum with the flexible BIC metasurface. The measured minimum detectable concentration is 0.007 mg mL-1. Benefiting from the mechanical flexibility and BIC resonance characteristics, our approach can effectively manipulate terahertz waves and have potential applications in the realization of multifunctional and flexible photonic devices.

Stress stimulation maintaining by genipin crosslinked hydrogel promotes annulus fibrosus healing.

Objective: To explore the repair effect of tissue engineering for annulus fibrosus (AF) injury in stress-stimulation environment. Methods: Non-adhesive fibrinogen (Fib) representing the repair with non-stress stimulation and adhesive hydrogel of fibrinogen, thrombin and genipin mixture (Fib-T-G) representing the repair with stress stimulation were prepared to repair the AF lesion. The relationship between adhesion and stress stimulation was studied in rheological measurements, tension tests and atomic force microscopy (AFM) experiments. The repair effect of stress stimulation was studied in designed acellular AF scaffold models with fissures and defects. The models were repaired by the two different hydrogels, then implanted subcutaneously and cultured for 21 â€‹d in rats. Histology and qPCR of COL1A1, COL2A1, aggrecan, RhoA, and ROCK of the tissue engineering of the interface were evaluated afterward. Moreover, the repair effect was also studied in an AF fissure model in caudal disc of rats by the two different hydrogels. Discs were harvested after 21 â€‹d, and the disc degeneration score and AF healing quality were evaluated by histology. Result: In interfacial stress experiment, Fib-T-G hydrogel showed greater viscosity than Fib hydrogel (24.67 â€‹± â€‹1.007 vs 459333 â€‹± â€‹169205 â€‹mPa â€‹s). Representative force-displacement and sample modulus for each group demonstrate that Fib-T-G group significantly increased the interfacial stress level and enhanced the modulus of samples, compared with Fib group (P â€‹< â€‹0.01). The Fib-T-G group could better bond the interface to resist the loading strain force with the broken point at 1.11 â€‹± â€‹0.10 â€‹N compared to the Fib group at 0.12 â€‹± â€‹0.08 â€‹N â€‹(P â€‹< â€‹0.01). Focusing on the interfacial healing in acellular AF scaffold model, compared with Fib â€‹+ â€‹MSCs group, the fissure and defect were connected closely in Fib-T-G â€‹+ â€‹MSCs group (P â€‹< â€‹0.01). Relative higher gene expression of COL2A1 and RhoA in Fib-T-G â€‹+ â€‹MSCs group than Fib â€‹+ â€‹MSCs group in AF fissure and AF defect model (P â€‹< â€‹0.05). The immunohistochemistry staining showed more positive staining of COL2A1 and RhoA in Fib-T-G â€‹+ â€‹MSCs group than in Fib â€‹+ â€‹MSCs group in both AF fissure and AF defect models. The degree of disc degeneration was more severe in Fib â€‹+ â€‹MSCs group than Fib-T-G â€‹+ â€‹MSCs group in vivo experiment (11.80 â€‹± â€‹1.11 vs 7.00 â€‹± â€‹1.76, P â€‹< â€‹0.01). The dorsal AF defect in Fib-T-G â€‹+ â€‹MSCs group (0.02 â€‹± â€‹0.01 â€‹mm2) was significantly smaller than that (0.13 â€‹± â€‹0.05 â€‹mm2) in Fib â€‹+ â€‹MSCs group (P â€‹< â€‹0.05). Immunohistochemical staining showed more positive staining of COL2A1 and Aggrecan in Fib-T-G â€‹+ â€‹MSCs group than in Fib â€‹+ â€‹MSCs group. Conclusion: Genipin crosslinked hydrogel can bond the interface of AF lesions and transfer strain force. Stress stimulation maintained by adhesive hydrogel promotes AF healing. The translational potential of this article: We believe the effect of stress stimulation could be concluded through this study and provides more ideals in mechanical effects for further research, which is a key technique for repairing intervertebral disc in clinic. The adhesive hydrogel of Fib-T-G+MSCs has low toxicity and helps bond the interface of AF lesion and transfer strain force, having great potential in the repair of AF lesion.

The ratio of monocyte count and high-density lipoprotein cholesterol mediates the association between urinary tungsten and cardiovascular disease: a study from NHANES 2005-2018.

Tungsten (W) is an emerging contaminant that can damage multiple systems in humans. However, studies of its effects on cardiovascular disease (CVD) are limited. The monocyte count to high-density lipoprotein cholesterol ratio (MHR) is a composite inflammatory index of great concern in recent years, derived from lipid and cell inflammation parameters, that is used to indicate the risk of CVD. This study aimed to investigate the association between urinary W and CVD in the general population and compare the mediating effects of lipids, cell inflammatory parameters, and MHR to find a better target for intervention. We analyzed data from 9137 (≥ 20 years) participants in the National Health and Nutrition Examination Survey (NHANES), from 2005 to 2018. Restricted cubic splines (RCS) and survey-weighted generalized linear models (SWGLMs) were used to assess the relationship between W and CVD. Mediated analyses were used to explore lipids, cell inflammatory parameters, and MHR in the possible mediating pathways between W and CVD. In SWGLM, we found that W enhances the risk of CVD, especially congestive heart failure (CHF), coronary heart disease (CHD), and angina pectoris (AP). Women, higher age groups (≥ 55 years), and those with hypertension were vulnerable to W in the subgroup analysis. Mediation analysis showed that monocyte count (MC), white blood cell count (WBC), high-density lipoprotein cholesterol (HDL), and MHR played a mediating role between W and CVD in proportions of 8.49%, 3.70%, 5.18%, and 12.95%, respectively. In conclusion, our study shows that urinary W can increase the risk of CVD, especially for CHF, CHD, and AP. Women, older age groups, and people with hypertension seem to be more vulnerable to W. In addition, MC, WBC, HDL, and MHR mediated the association between W and CVD, especially MHR, which suggests that we should consider it as a priority intervention target in the future.

The global burden of schizophrenia and the impact of urbanization during 1990-2019: An analysis of the global burden of disease study 2019.

BACKGROUND AND HYPOTHESIS: The burden of schizophrenia is increasing. Assessing the global distribution of schizophrenia and understanding the association between urbanization factors and schizophrenia are crucial. STUDY DESIGN: We conducted a two-stage analysis utilizing public data from GBD (global burden of disease) 2019 and the World Bank. First, the distribution of schizophrenia burden at the global, regional, and national levels as well as temporal trends was analyzed. Then, four composite indicators of urbanization (including demographic, spatial, economic, and eco-environment urbanization) were constructed from ten basic indicators. Panel data models were used to explore the relationship between urbanization indicators and the burden of schizophrenia. RESULTS: In 2019, there were 23.6 million people with schizophrenia, an increase of 65.85% from 1990, and the country with the largest ASDR (age-standardized disability adjusted life years rate) was the United States of America, followed by Australia, and New Zealand. Globally, the ASDR of schizophrenia rose with the sociodemographic index (SDI). In addition, six basic urbanization indicators including urban population proportion, employment in industry/services proportion, urban population density, the population proportion in the largest city, GDP, and PM2.5 concentration were positively associated with ASDR of schizophrenia, with the largest coefficients being urban population density. Overall, demographic, spatial, economic, and eco-environment urbanization all had positive effects on schizophrenia, and the estimated coefficients indicated that demographic urbanization was the most significant influence. CONCLUSIONS: This study provided a comprehensive description of the global burden of schizophrenia and explored urbanization as a factor contributing to the variation in the burden of schizophrenia, and highlighted policy priorities for schizophrenia prevention in the context of urbanization.

Characterization of airborne microplastics at different workplaces of the poly(ethylene:propylene:diene) (EPDM) rubber industry.

Microplastics (MPs) as an emerging air pollutant have received widespread attention, but research on airborne MPs at occupational sites is still limited, especially in the rubber industry. Hence, indoor air samples were collected from three production workshops and an office of a rubber factory producing automotive parts to analyze the characteristics of airborne MPs in different workplaces of this industry. We found MP contamination in all air samples from the rubber industry, and the airborne MPs at all sites mainly showed small-sized (< 100 µm) and fragmented characteristics. The abundance and source of MPs at various locations is primarily related to the manufacturing process and raw materials of the workshop. The abundance of MPs in the air was higher in workplaces where production activities are involved than in office (360 ± 61 n/m3), of which the highest abundance of airborne MPs was in the post-processing workshop (559 ± 184 n/m3). In terms of types, a total of 40 polymer types were identified. The post-processing workshop has the largest proportion of injection-molded plastic ABS, the extrusion workshop has a greater proportion of EPDM rubber than the other locations, and the refining workshop has more MPs used as adhesives, such as aromatic hydrocarbon resin (AHCR).

A Potential Lead for Insect Growth Regulator: Design, Synthesis, and Biological Activity Evaluation of Novel Hexacyclic Pyrazolamide Derivatives.

Ecdysone receptor (EcR) and chitinase play a critical role in the molting stage of insect pests. Each of them is considered a promising target for the development of novel insect growth regulators (IGRs). In the present paper, a total of 24 (23 novel) hexacyclic pyrazolamide derivatives were designed and synthesized by reducing the heptacycle and inserting small flexible linkers on the basis of the previously discovered dual-target compound D-27 acting simultaneously on EcR and Ostrinia furnacalis chitinase (OfChtI). Their insecticidal activities against Plutella xylostella, Spodoptera frugiperda, and Ostrinia furnacalis larvae were evaluated. The results revealed that the insecticidal activity was not significantly enhanced when the heptacycle on the pyrazole ring was reduced to a hexacycle. However, the insertion of an additional methylene spacer between the substituted phenyl ring and the amide bond can improve the insecticidal activity. Among the derivatives, the most potent compound, 6j, exhibited promising insecticidal activities against P. xylostella and S. frugiperda. Further protein binding assays and molecular docking indicated that 6j could target both EcR and OfChtI, and is a potential lead compound for IGRs. The present work provides valuable clues for the development of new dual-target IGRs.

Rational design and identification of novel thiosemicarbazide derivatives as laccase inhibitors.

BACKGROUND: Laccase is a key enzyme in the fungal 1,8-dihydroxynaphthalene (DHN) melanin biosynthesis pathway, which is a potential target for the control of pathogenic fungi. In our previous work, compound a2 was found with higher inhibition activity against laccase and antifungal activity than laccase inhibitor PMDD-5Y. The introduction of hydrogen-bonded receptors in the amino part was found to be beneficial in improving laccase inhibitory activity by target-based-biological rational design. In this work, the hydrogen-bonded receptors morpholine and piperazine were introduced for structure optimization to enhancing biological activity. RESULTS: Enzyme activity tests indicated that all target compounds had inhibitory activity against laccase, and some compounds exhibited better activity against laccase than a2, it was further verified that the introduction of hydrogen-bonded receptors in the amino portion could enhance the laccase inhibitory activity of target compounds. Most compounds showed excellent antifungal activities in vitro. Compound m14 displayed good activity against Magnaporthe oryzae both in vitro and in vivo. The scanning electron microscopy (SEM) analysis showed that the mycelium of M. oryzae treated with m14 were destroyed. Molecular docking revealed the binding mode between laccase and target compounds. CONCLUSION: Thirty-eight compounds were synthesized and showed good inhibitory activity against laccase, the introduction of morpholine and piperazine in the amino part was beneficial to improve antifungal activity and laccase activity. Further validation of laccase as a potential target for rice blast control, while m14 can be used as a candidate compound for the control of rice blast. © 2023 Society of Chemical Industry.

Design, Synthesis, and Biological Activity of Novel Benzo[d][1,3]dioxole-6-benzamide Derivatives: Multichitinase Inhibitors as Potential Insect Growth Regulator Candidates.

Insect growth regulators (IGRs) disrupt normal development of physiological processes in insects and are recognized as green insecticides. Insect chitinases play a crucial role in cuticle degradation during molting, and OfChtI, OfChtII, and OfChi-h are the prospective targets for discovering new insecticides as IGRs. In our previous study, we identified the lead compound a12 as a promising multitarget inhibitor. Herein, we used the binding modes of a12 with three chitinases to recognize the critical interactions and residues favorable to the bioactivity. Subsequently, to improve the bioactivity of inhibitors via enhanced the interactions with important residues, a series of benzo[d][1,3]dioxole-6-benzamide derivatives were rationally designed and synthesized, and their inhibitory activities against Ostrinia furnacalis (O. furnacalis) chitinases, as well as insecticidal activities against O. furnacalis and Plutella xylostella (P. xylostella) were investigated. Among them, compound d29 acted simultaneously on OfChtI, OfChtII, and OfChi-h with Ki values of 0.8, 11.9, and 2.3 µM, respectively, a significant improvement over the inhibitory activity of the lead compound a12. Moreover, d29 exhibited superior activity than a12 against two lepidopteran pests by interfering with normal insect growth and molting, indicating that d29 is a potential lead candidate for novel IGRs with a multichitinase mechanism. The present study revealed that simultaneous inhibition on multiple chitinases could achieve excellent insecticidal activity. The elucidation of inhibition mechanisms and molecular conformations illustrated the interactions with the three chitinases, as well as the discrepancy in bioactivity, which will be beneficial for future work to improve the potency of bioactivity as IGRs for pest control in sustainable agriculture.

Dual-Function Smart Windows Using Polymer Stabilized Cholesteric Liquid Crystal Driven with Interdigitated Electrodes.

In this study, we present an electrically switchable window that can dynamically transmit both visible light and infrared (IR) light. The window is based on polymer stabilized cholesteric liquid crystals (PSCLCs), which are placed between a top plate electrode substrate and a bottom interdigitated electrode substrate. By applying a vertical alternating current electric field between the top and bottom substrates, the transmittance of the entire visible light can be adjusted. The cholesteric liquid crystals (CLC) texture will switch to a scattering focal conic state. The corresponding transmittance decreases from 90% to less than 15% in the whole visible region. The reflection bandwidth in the IR region can be tuned by applying an in-plane interdigital direct current (DC) electric field. The non-uniform distribution of the in-plane electric field will lead to helix pitch distortion of the CLC, resulting in a broadband reflection. The IR reflection bandwidth can be dynamically adjusted from 158 to 478 nm. The electric field strength can be varied to regulate both the transmittance in the visible range and the IR reflection bandwidth. After removing the electric field, both features can be restored to their initial states. This appealing feature of the window enables on-demand indoor light and heat management, making it a promising addition to the current smart windows available. This technology has considerable potential for practical applications in green buildings and automobiles.

Built environment and schizophrenia re-hospitalization risk in China: A cohort study.

BACKGROUND: Built environment exposure, characterized by ubiquity and changeability, has the potential to be the prospective target of public health policy. However, little research has been conducted to explore its impact on schizophrenia. This study aimed to investigate the association between built environmentand and schizophrenia rehospitalization by simultaneously considering substantial built environmental exposures. METHODS: We recruited eligible schizophrenia patients from Hefei, Anhui Province, China between 2017 and 2019. The main outcome for this study was the time interval until the first recurrent hospital admission occurred within one year after discharge. For each included subject, we estimated the built environment exposures, including population density, walkability, land use mix, green and blue space, public transportation accessibility and road traffic indicator. Lasso (Least Absolute Shrinkage and Selection Operator) analysis was used to select the key variables. Multivariable Cox regression model was applied to obtain hazard ratio (HR) and its corresponding 95% confidence intervals (CI). Further, we also evaluated the joint effects of built environment characteristics on rehospitalization for schizophrenia by Quantile g-computation model. RESULTS: A total of 1564 hospitalized schizophrenia patients were enrolled, with 347 patients (22.2%) had a rehospitalization within one-year after discharge. Multivariable Cox regression analysis indicated that the re-hospitalization rate for schizophrenia would be higher in areas with a high population density (HR: 1.10, 95%CI: 1.04-1.16). Nonetheless, compared to the reference (Q1), participants who lived in a neighborhood with the highest walkability and NDVI (Normalized Difference Vegetation Index) (Q4) had a 76% and 47% lower risk of re-hospitalization within one year (HR:0.24, 95%CI: 0.13-0.45; and 0.53, 95%CI:0.32-0.85), respectively. Moreover, quantile-based g-computation analyses revealed that increased walkability and green space significantly eliminated the adverse effects of population density increases on schizophrenia patients, with a HR ratio of 0.61 (95%CI:0.48,0.79) per one quartile change at the same time. CONCLUSION: Our study provides scientific evidence for the significant role of built environment in schizophrenia rehospitalization, suggesting that optimizing the built environment is required in designing and building a healthy city.

Mechanical stimulation promotes MSCs healing the lesion of intervertebral disc annulus fibrosus.

Mesenchymal stem cells (MSCs) and scaffolds offer promising perspectives for annulus fibrosus (AF) repair. The repair effect was linked to features of the local mechanical environment related to the differentiation of MSCs. In this study, we established a Fibrinogen-Thrombin-Genipin (Fib-T-G) gel which is sticky and could transfer strain force from AF tissue to the human mesenchymal stem cells (hMSCs) embedded in the gel. After the Fib-T-G biological gel was injected into the AF fissures, the histology scores of intervertebral disc (IVD) and AF tissue showed that Fib-T-G gel could better repair the AF fissure in caudal IVD of rats, and increase the expression of AF-related proteins including Collagen 1 (COL1), Collagen 2 (COL2) as well as mechanotransduction-related proteins including RhoA and ROCK1. To clarify the mechanism that sticky Fib-T-G gel induces the healing of AF fissures and the differentiation of hMSCs, we further investigated the differentiation of hMSCs under mechanical strain in vitro. It was demonstrated that both AF-specific genes, including Mohawk and SOX-9, and ECM markers (COL1, COL2, aggrecan) of hMSCs were up-regulated in the environment of strain force. Moreover, RhoA/ROCK1 proteins were also found to be significantly up-regulated. In addition, we further -demonstrated that the fibrochondroinductive effect of the mechanical microenvironment process could be significantly blocked or up-regulated by inhibiting the RhoA/ROCK1 pathway or overexpressing RhoA in MSCs, respectively. Summarily, this study will provide a therapeutic alternative to repair AF tears and provide evidence that RhoA/ROCK1 is vital for hMSCs response to mechanical strain and AF-like differentiation.