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Benzoic acid decarboxylases offer an elegant alternative to CO2 fixation by reverse reaction-carboxylation, which is named the bio-Kolbe–Schmitt reaction, but they are unfavorable to carboxylation. Enhancing the carboxylation efficiency of reversible benzoic acid decarboxylases is restricted by the unexplained carboxylation mechanisms. The direction of reversible enzyme catalytic reactions depends on whether catalytic residues at the active center of the enzyme are protonated, which is subjected by the pH. Therefore, the forward and reverse reactions could be separated at different pH values. Reversible 2,3-dihydroxybenzoate acid decarboxylase undergoes decarboxylation at pH 5.0 and carboxylation at pH 8.6. However, it is unknown whether the interaction of enzymes with substrates and products in the forward and reverse reactions can be exploited to improve the catalytic activity of reversible enzymes in the unfavorable direction. Here, we identify a V-shaped tunnel of 2,3-dihydroxybenzoic acid decarboxylase from Aspergillus oryzae (2,3-DHBD_Ao) through which the substrate travels in the enzyme, and demonstrate that the side chain conformation of a tyrosine residue controls the entry and exit of substrate/product during reversible reactions. Together with the kinetic studies of the mutants, it is clarified that interactions between substrate/product traveling through the enzyme tunnel in 2,3-DHBD_Ao are direction-dependent. These results enrich the understanding of the interactions of substrates/products with macromolecular reversible enzymes in different reaction directions, thereby demonstrating a possible path for engineering decarboxylases with higher carboxylation efficiency. Key points: • The residue Trp23 of 2,3-DHBD_Ao served as a switch to control the entry and exit of catechol • A V-shaped tunnel of 2,3-DHBD_Ao for decarboxylation and carboxylation reactions was identified • The results provide a promising strategy for engineering decarboxylases with direction-dependent residues inside the substrate/product traveling tunnel of the enzyme [ABSTRACT FROM AUTHOR]

Although the dynamic zero-COVID policy has effectively controlled virus spread in China, China has to face challenges in balancing social-economic burdens, vaccine protection, and the management of long COVID symptoms. This study proposed a fine-grained agent-based model to simulate various strategies for transitioning from a dynamic zero-COVID policy with a case study in Shenzhen. The results indicate that a gradual transition, maintaining some restrictions, can mitigate infection outbreaks. However, the severity and duration of epidemics vary based on the strictness of the measures. In contrast, a more direct transition to reopening may lead to rapid herd immunity but necessitate preparedness for potential sequelae and reinfections. Policymakers should assess healthcare capacity for severe cases and potential long-COVID symptoms and determine the most suitable approach tailored to local conditions. [ABSTRACT FROM AUTHOR]

Leadless pacemakers with an atrioventricular synchrony algorithm represent a novel technology for patients qualified for VDD pacing. The current evidence of their performance is limited to several small-scale observational studies. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of this new technology. We systematically searched the PubMed, Embase, and Cochrane library databases from their inception to 12 September 2022. The primary efficacy outcome was atrioventricular synchrony after implantation, whereas the secondary efficacy outcome was the change in cardiac output represented by the left ventricular outflow tract velocity time integral (LVOT-VTI). The primary safety outcome was major complications related to the procedures and the algorithm. Means or mean differences with 95% confidence interval (95% CI) were combined using a random-effects model or a fixed-effects model. Finally, 8 published studies with 464 participants were included in the qualitative analysis. The pooled atrioventricular synchrony proportion was 78.9% (95% CI 71.9–86.0%), and a further meta-regression did not screen factors that contributed significantly to the heterogeneity. Additionally, a significant increase in atrioventricular synchrony of 11.3% (95% CI 7.0–15.7%, p < 0.01) was achieved in patients experiencing programming optimization. LVOT-VTI was significantly increased by 1.9 cm (95% CI 1.2–2.6, p < 0.01), compared with the VVI pacing mode. The overall incidence of complications was approximately 6.3%, with major complications related to the algorithm being extremely low. Overall, leadless pacemakers with atrioventricular synchronous pacing demonstrated favorable safety and efficacy. Future data on their long-term performance are required to facilitate their widespread adoption in clinical practice. [ABSTRACT FROM AUTHOR]

As a guide rail is the basic motion unit of precision equipment, the measurement of and compensation for its motion errors are important preconditions for precision machining and manufacturing. A targetless and simultaneous measurement method of three-degree-of-freedom (3-DOF) angular motion errors using digital speckle pattern interferometry (DSPI) is introduced in this paper. Based on the analysis of the sensitivity mechanism of DSPI to DOF errors and the formation mechanism of the phase fringes, the relationship between the angular motion errors and the distribution of the interferometric phases was established, and a new simultaneous measurement model of 3-DOF angular motion errors was further proposed. An optical setup based on a three-dimensional spatial-carrier DSPI with a right-angle symmetrical layout was used in the measurement system. Furthermore, repetitive tests, noise tests, and precision analysis were carried out to verify the performance of the system. The test results showed that the measurement resolution of the system was <1 μrad, which is capable of measuring the pitch angle, yaw angle, and roll angle at the submicron arc level simultaneously without target mirrors. The method has the advantages of no need to install cooperative targets and high measurement resolution, showing broad application prospects in many fields, including mechanical manufacturing, laser detection, aerospace, etc. [ABSTRACT FROM AUTHOR]

The thermal deactivation of diesel soot particles exerts a significant influence on the control strategy for the regeneration of diesel particulate filters (DPFs). This work focused on the changes in the surface functional groups, carbon chemical state, and graphitization degree during thermal treatment in an inert gas environment at intermediate temperatures of 600°C, 800°C, and 1000°C and explore the chemical species that were desorbed from the diesel soot surface during thermal treatment using a thermogravimetric analyser coupled with a gas-chromatograph mass spectrometer (TGA-GC/MS). The surface functional groups and carbon chemical state were characterized using Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The graphitization degree was evaluated by means of Raman spectroscopy (RS). The concentrations of aliphatic C–H, C–OH, C=O, and O–C=O groups are reduced for diesel soot and carbon black when increasing the thermal treatment temperature, while the sp2/sp3 hybridized ratio and graphitization degree enhance. These results provide comprehensive evidence of the decreased reactivity of soot samples. Among oxygenated functional groups, the percentage reduction during thermal treatment is the largest for the O–C=O groups owing to its worst thermodynamic stability. TGA-GC/MS results show that the aliphatic and aromatic chains and oxygenated species would be desorbed from the soot surface during 1000°C thermal treatment of diesel soot. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been highly recommended for glycemic control and weight reduction. However, evidence has accumulated that GLP-1 RAs treatment is related to an increase in heart rate, which could potentially induce cardiac arrhythmias. This study aims to investigate the association of GLP-1 RAs therapy with incident arrhythmias in diabetic and obese patients. Methods: MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception up to May 25, 2022. Randomized controlled trials (RCTs) comparing GLP-1 RAs with placebo or active control for adults with type 2 diabetes or obesity were included. The outcomes of interest were prespecified as incident atrial fibrillation (AF), atrial flutter (AFL), ventricular arrhythmias (VAs), and sudden cardiac death (SCD). Mantel-Haenszel relative risk (MH-RR) with a corresponding 95% confidence interval (95% CI) was estimated using a fixed-effects model. Results: A total of 56 RCTs involving 79,720 participants (44,028 GLP-1 RAs vs 35,692 control: mean age 57.3 years) were included from 7692 citations. GLP-1 RAs use overall did not significantly increase the risk of AF (RR 0.97, 95% CI 0.83–1.12), AFL (RR 0.83, 95% CI 0.59–1.17), VAs (RR 1.24, 95% CI 0.92–1.67), and SCD (RR 0.89, 95% CI 0.67–1.19), compared with controls. In further subgroup analyses, we observed an increasing trend toward incident AF with dulaglutide (RR 1.40, 95% CI 1.03–1.90) while an inverse trend with oral semaglutide (RR 0.43, 95% CI 0.21–0.87). Additionally, higher doses of GLP-1 RAs (RR 1.63, 95% CI 1.11–2.40) and higher baseline BMI (RR 1.60, 95% CI 1.04–2.48) might significantly increase the risk of VAs. No significant differences were identified in other subgroup analyses. Conclusions: GLP-1 RAs therapy was not associated with an overall higher risk of arrhythmias, demonstrating an assuring cardiovascular safety profile. Further studies are required to determine whether the potential antiarrhythmic or arrhythmogenic effect of GLP-1 RAs is drug-specific and varies from doses or baseline BMI. Trial registration: PROSPERO Identifier: CRD42022339389. [ABSTRACT FROM AUTHOR]

Laser speckle contrast imaging (LSCI) is a real-time, full-field, non-contact optical imaging technique that has been widely used in blood flow imaging. However, its practical applications are limited due to its low signal-to-noise ratio (SNR) and low image contrast. In this study, a fusion denoising algorithm based on homomorphic transform and block-matching and 3D transform-domain collaborative filtering algorithm is proposed to reduce noise and improve image contrast. The reliability and applicability of the proposed method were evaluated by a phantom experiment and two in vivo experiments. The results show that the proposed algorithm can effectively remove the noise and enhance the image contrast. Consequently, the SNR is increased, the dynamic range of LSCI is expanded, and the estimation accuracy of blood flow is improved. [ABSTRACT FROM AUTHOR]

In many countries, governments have implemented non-pharmaceutical techniques to limit COVID-19 transmission. Restricting human mobility is one of the most common interventions, including lockdown, travel restrictions, working from home, etc. However, due to the strong transmission ability of the virus variants, further rounds of interventions, including a strict lockdown, are not considered as effective as expected. The paper aims to understand how the lockdown policy and pandemics changed human mobility in the real scenario. Here we focus on understanding the mobility changes caused by compliance with restrictions and risk perceptions, using a mobility index from the Google report during three strict lockdown periods in Leeds, the largest city in the county of West Yorkshire, England, from March 2020 to March 2021. The research uses time-varying z-scores and Principal Component Analysis (PCA) to simulate how local people dynamically process and perceive health risks based on multi-dimensional daily COVID-19 reports first. Further modelling highlights exponentially increasing policy non-compliance through the duration of lockdown, probably attributable to factors such as mental anxiety and economic pressures. Finally, the proposed nonlinear regression model examines the mobility changes caused by the population's dynamic risk perceptions and lockdown duration. The case study model in Leeds shows a good fit to the empirical mobility data and indicates that the third lockdown policy took effect much slower than the first. At the same time, the negative impact of the epidemic on population mobility decayed by 40% in the third lockdown period in contrast with the first lockdown. The risk perception estimation methods could reflect that the local population became increasingly accustomed to the COVID-19 situation, and local people rationally evaluated the risks of COVID in the third lockdown period. The results demonstrate that simulated risk perceptions and policy decay could explain urban mobility behaviour during lockdown periods, which could be a reference for future decision-making processes. [ABSTRACT FROM AUTHOR]

Irreversible perturbations in Langevin dynamics have been widely recognized for their role in accelerating convergence in simulations of multi-modal distributions π (θ) . A commonly used and easily computed standard irreversible perturbation is J ∇ log π (θ) , where J is a skew-symmetric matrix. However, Langevin dynamics employing a fixed-scale standard irreversible perturbation encounter a trade-off between local exploitation and global exploration, associated with small and large scales of standard irreversible perturbation, respectively. To address this trade-off, we introduce the adaptive irreversible perturbations Langevin dynamics, where the scale of the standard irreversible perturbation changes adaptively. Through numerical examples, we demonstrate that adaptive irreversible perturbations in Langevin dynamics can enhance performance compared to fixed-scale irreversible perturbations. [ABSTRACT FROM AUTHOR]

Pulse diagnosis is one of the four diagnostic methods of traditional Chinese medicine. However it suffers from the lack of objective and efficient detection method. We propose a noncontact optical method to detect human wrist pulse, aiming at the precise determination of the temporal and spatial distributions of pulse. The method uses the spatial-carrier digital speckle pattern interferometry (DSPI) to measure the micro/nanoscale skin displacement dynamically. Significant improvements in DSPI measurement have been made to allow the DSPI to detect the comprehensive information of the arterial pulsation at locations of Cun, Guan, and Chi. The experimental results prove that the spatiotemporal distributions of pulse can be obtained by the proposed method. The obtained data can be further used to describe most of the pulse parameters such as rate, rhythm, depth, length, width, and contour. [ABSTRACT FROM AUTHOR]

Caffeic acid phenethyl ester (CAPE) is the bioactive constituent of propolis from honeybee hives and is well known for its anti-inflammatory, anticarcinogenic, antioxidant, and immunomodulatory properties. Herein, we revisited the cellular mechanism underlying the diverse biological effects of CAPE. We demonstrated that XPO1/CRM1, a major nuclear export receptor, is a cellular target of CAPE. Through nuclear export functional assay, we observed a clear shift of XPO1 cargo proteins from a cytoplasmic localization to nucleus when treated with CAPE. In particular, we showed that CAPE could specifically target the non-catalytic and conserved Cys528 of XPO1 through the means of mass spectrometric analysis. In addition, we demonstrated that the mutation of Cys528 residue in XPO1 could rescue the nuclear export defects caused by CAPE. Furthermore, we performed position-restraint molecular dynamics simulation to show that the Michael acceptor moiety of CAPE is the warhead to enable covalent binding with Cys528 residue of XPO1. The covalent modulation of nuclear export by CAPE may explain its diverse biological effects. Our findings may have general implications for further investigation of CAPE and its structural analogs. [ABSTRACT FROM AUTHOR]

The covalent modification of intrinsically nucleophilic cysteine in proteins is crucial for diverse biochemical events. Bioinformatics approaches may prove useful in the design and discovery of covalent molecules targeting the cysteine in proteins to tune their functions and activities. Herein, we describe the Cysteinome, the first online database that provides a rich resource for the display, search and analysis of structure, function and related annotation for proteins with targetable cysteine as well as their covalent modulators. To this end, Cysteinome compiles 462 proteins with targetable cysteine from 122 different species along with 1217 covalent modulators curated from existing literatures. Proteins are annotated with a detailed description of protein families, biological process and related diseases. In addition, covalent modulators are carefully annotated with chemical name, chemical structure, binding affinity, physicochemical properties, molecule type and related diseases etc. The Cysteinome database may serve as a useful platform for the identification of crucial proteins with targetable cysteine in certain cellular context. Furthermore, it may help biologists and chemists for the design and discovery of covalent chemical probes or inhibitors homing at functional cysteine of critical protein targets implicated in various physiological or disease process. The Cysteinome database is freely available to public at http://www.cysteinome.org/ . [ABSTRACT FROM AUTHOR]

In this work, the particulate matter less than 10 μm (PM 10) emissions from a medium-sized passenger vehicle's front brake wear were studied using a finite element analysis (FEA) and experimental approaches. The world harmonised light-duty vehicle test procedure-brake (WLTP-B) cycle was chosen to simulate real-world driving. An electrical low-pressure impactor (ELPI+) was used to count the brake wear particles on a brake dynamometer sealed in a chamber. In addition, a machine learning method, namely, extreme gradient boosting (XGBoost), was employed to capture the feature importance rankings of braking conditions contributing to brake wear PM 10 emissions. The simulated PM 10 emissions were quite consistent with the measured ones, with an overall relative error of 9%, indicating that the proposed simulation approach is promising to predict brake wear PM 10 during the WLTP-B cycle. The simulated and experimental PM 10 emission factors during the WLTP-B cycle were 6.4 mg km−1 veh−1 and 7.0 mg km−1 veh−1, respectively. Among the 10 trips of the WLTP-B cycle, the measured PM 10 of trip #10 was the largest contributor, accounting for 49% of total PM 10 emissions. On the other hand, the XGBoost results revealed that the top five most important factors governing brake wear PM 10 emissions were dissipation energy, initial braking speed, final rotor temperature, braking power, and deceleration rate. From the perspective of friendly driving behaviour and regulation, limiting severe braking and high-speed braking has the potential to reduce PM 10 emissions from brake wear. [ABSTRACT FROM AUTHOR]

• A novel method of roll angle measurement using digital shearography is proposed. • The new method outperforms the DSPI method a lot in measurement speed and anti-interference capability. An approach to non-contact, fast, and precision measurement of small roll angle using digital shearography is introduced. The roll angles are determined directly by recording the interferometric phase changes when using a dual-beam digital shearography to measure tested surfaces. Phase at a point rather than full-field phase distribution is used to calculate the roll angle, so global image processing is no longer needed and the measurement speed becomes much faster. The proposed approach is robust due to the nature of digital shearography, making it a promising method in field applications. The theoretical measurement resolution of the method is from 1.5 µrad to deep sub-microradian, which can compete with the best resolution of the existing methods. [ABSTRACT FROM AUTHOR]

Cell lysates were subjected to immunoblotting. gl We next examined the biological consequences of dp53m-RA-mediated p53-R175H degradation in cancer cells. dp53m-RA treatment dramatically inhibited the proliferation of p53-R175H-expressing H1299 cells and SKBR3 cells. Moreover, the proteasome inhibitor MG132 completely blocked dp53m-RA-induced p53-R175H degradation (Figure 2J), and dp53m-RA treatment increased polyubiquitination of p53-R175H over p53-WT (Figure 2K). To the Editor: I TP53 i encodes the tumour suppressor protein p53, a master regulator of genomic integrity and cell survival, and is the most frequently mutated gene.[1] p53 mutant proteins are stabilised and can acquire dominant-negative or oncogenic gain-of-function activities, thereby promoting malignant transformation, metastasis and chemoresistance.[[2]] Proteolysis targeting chimeras (PROTACs) that hijack cellular ubiquitin-proteasome machinery for targeted protein degradation have shown considerable promise in targeting previously undruggable proteins.[[4]] However, PROTACs targeting p53 mutants have not yet been reported, probably due to difficulty in identifying a suitable binder for these mutants. [Extracted from the article]

Digital shearography has become a competitive tool for vibration analysis due to its capability of full-field, high resolution, and high-speed measurements. Many stroboscopic shearographic systems have been developed in recent years. However, they are only suitable for vibration analysis of a small area. This paper presents a shearographic system that was developed to carry out the vibration analysis of a large-area object whose area is 1 m or even bigger. The system can use both time-average and stroboscopic illumination methods to analyze the forced vibration distribution. The setup of the system is introduced and experimental results are presented. [ABSTRACT FROM AUTHOR]

Curcumin is the major constituent of turmeric plant, an ancient spice widely used in Indian cuisine and traditional herbal medicine. Recently, the potential medical use of curcumin as anti-cancer and anti-inflammatory agent has set off an upsurge in research into the mechanism for its broad biological effects. We showed that CRM1, an important nuclear exportin, is a cellular target of curcumin by serious experimental and theoretical investigation. Using a nuclear export functional assay, we observed a clear and rapid shift of cargo proteins from a cytoplasmic localization to the nucleus when treated with curcumin or its structural analogue dibenzylideneacetone ( DBA). We demonstrated that curcumin could specifically target the conserved Cys528 of CRM1 through mass spectrometric analysis and in vivo experiments. Furthermore, computational modeling has revealed that curcumin could be correctly docked into the hydrophobic pocket of CRM1 judged from shape complementarity and putative molecular interactions. The Michael acceptor moiety on curcumin is within the appropriate distance to enable Michael reaction with Cys residue of CRM1. More importantly, we showed that nuclear retention of FOXO1 could be observed in the presence of Leptomycin B ( LMB) or curcumin whereas in cells expressing the CRM1-Cys528 mutant, only a cytoplasmic localization was observed. The inhibition of nuclear traffic by curcumin may account for its myriad of biological effects, particularly for its therapeutic properties in cancer and inflammatory diseases. Our findings may have important implications for further clinical investigation of curcumin. [ABSTRACT FROM AUTHOR]

Abstract: Precise measurement of the spatial derivative of displacement using digital shearography depends on well-calibrated phase shifts. However, due to time drift or a change in the position of the phase shifter, the previously calibrated results may not be applicable for the measurements. In this paper, we introduce a Michelson-interferometer-based digital shearographic setup, with an in situ phase shift calibration, that precisely measures the displacement derivatives. For the optical arrangement, a small number of optical parts are introduced into the existing Michelson interferometer to carry out the in situ calibration of the phase shifter. The calibration can be carried out anytime without changing the optical arrangement. This feature easily recalibrates the digital shearography, eliminating the influence of the phase shift error. [Copyright &y& Elsevier]

Docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from Streblus asper, and some of its derivatives and Na+/K+-ATPase have been investigated. In addition, binding between (+)-strebloside and its aglycone, strophanthidin, and several of their other molecular targets, including FIH-1, HDAC, KEAP1 and MDM2 (negative regulators of Nrf2 and p53, respectively), NF-κB, and PI3K and Akt1, have been inspected and compared with those for digoxin and its aglycone, digoxigenin. The results showed that (+)-strebloside, digoxin, and their aglycones bind to KEAP1 and MDM2, while (+)-strebloside, strophanthidin, and digoxigenin dock to the active pocket of PI3K, and (+)-strebloside and digoxin interact with FIH-1. Thus, these cardiac glycosides could directly target HIF-1, Nrf2, and p53 protein–protein interactions, Na+/K+-ATPase, and PI3K to mediate their antitumor activity. Overall, (+)-strebloside seems more promising than digoxin for the development of potential anticancer agents. [ABSTRACT FROM AUTHOR]

Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3′a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin's cytotoxicity and interactions with Na+/K+-ATPase. The docking profiles for digoxin and several derivatives and Na+/K+-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na+/K+-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na+/K+-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Soybean products were prepared from germinated soybeans as raw materials. • Germination increased the aglycone isoflavones content in soymilk and soymilk gel. • Protein dissolution was improved in soymilk after germination. • Germination reduced the strength of soymilk gel. • Germination improved the water-holding capacity of soymilk gel. Germination holds the key to nutritional equilibrium in plant grains. In this study, the effect of soybean germination on the processing of soymilk (SM) and glucono-δ-lactone (GDL) induced soymilk gel (SG) was investigated. Germination promoted soybean sprout (SS) growth by activating the energy metabolism system. The energy metabolism was high during the three-day germination and was the most vigorous on the second day of germination. After germination, protein dissolution was improved in SM, and endogenous enzymes produced small molecule proteins. Small molecule proteins were more likely to aggregate to produce SM protein particles. Germination increased the water-holding capacity of SG induced by GDL but weakened the strength. Furthermore, the dynamic fluctuations in isoflavone content were closely monitored throughout the processing of soybean products, including SS, SM, and SG. Although the total amount of isoflavones in SM and SG processed from germinated soybeans decreased, a significant enrichment in the content of aglycone isoflavones was observed. The content of aglycone isoflavones in SG processed from germinated soybeans on the second day of germination was 736.17 ± 28.49 µg/g DW, which was 83.19 % higher than that of the control group. This study demonstrates that germination can enhance the nutritional value of soybean products, providing innovative opportunities for the development of health-promoting soybean-based products. [ABSTRACT FROM AUTHOR]

A method of simultaneous and precision measurement of yaw and pitch based on digital speckle pattern interferometry is proposed. The relationship between the yaw/pitch and phase distribution is analyzed in detail, resulting in the establishment of the yaw and pitch simultaneous measurement model. A plane fitting method is proposed to separate the two angle motions from a single phase map. The proposed method enjoys the advantages of being free of cooperative target, high-resolution measurement, and compact optical setup. Experimental results show the mean absolute error of the measurement is <1 μrad. [ABSTRACT FROM AUTHOR]

Previous studies found that Vitamin E (VE) could recruit protein kinase B (Akt1) to the membrane by targeting its unconventional lipid-binding site, which led to the dephosphorylation of Akt1 at Ser473, eventually deactivating the enzyme. A series of VE-like compounds with varying types and lengths of the linker groups are designed to study the VE-driven membrane recruitment of Akt1 using a combined molecular docking and molecular dynamics (MD) simulation approach. We find that the linker groups with only one methylene linker and multiple hydrogen bond donors are optimal for achieving a balance between binding to the protein and partitioning into the membrane to form a stable protein-ligand-membrane ternary complex. These polar linkers are found to form stable hydrogen bonds with the lipid head groups during the MD simulations, which turns out critical for ensuring that the chromanol ring of the VE-like compounds resides above the membrane surface to fully engage in the protein. Our results reveal the molecular determinants of the linker groups for VE derivatives' ability to anchor Akt1 to the membrane. These findings will facilitate the design of membrane interfacial compounds to recruit specific proteins to the membrane to modulate the protein function. • Vitamin E derivatives for Akt1 inactivation. • Computational design of membrane interfacial binders. • Molecular determinants of Vitamin E derivatives for membrane recruitment. [ABSTRACT FROM AUTHOR]

A tri-color Michelson-type spatial phase-shift digital shearography is introduced to measure three displacement gradients, including one out-of-plane component and two in-plane components, simultaneously. By using this setup, three shearograms are recorded simultaneously in a single frame. The high-frequency components of these shearograms are then separated in the frequency domain due to their different spatial frequencies which are produced by the use of three lasers with different wavelength, yielding three individual phase maps with which the three displacement gradients are solved. The detailed capability of the proposed approach is described by theoretical discussion as well as experimental demonstration. [ABSTRACT FROM AUTHOR]

The Aedes aegypti mosquito serves as a major vector for viral diseases, such as dengue, chikungunya, and Zika, which are spreading across the globe and threatening public health. In addition to increased vector transmission, the prevalence of insecticide-resistant mosquitoes is also on the rise, thus solidifying the need for new, safe and effective insecticides to control mosquito populations. We recently discovered that cinnamodial, a unique drimane sesquiterpene dialdehyde of the Malagasy medicinal plant Cinnamosma fragrans, exhibited significant larval and adult toxicity to Ae. aegypti and was more efficacious than DEET–the gold standard for insect repellents–at repelling adult female Ae. aegypti from blood feeding. In this study several semi-synthetic analogues of cinnamodial were prepared to probe the structure-activity relationship (SAR) for larvicidal, adulticidal and antifeedant activity against Ae. aegypti. Initial efforts were focused on modification of the dialdehyde functionality to produce more stable active analogues and to understand the importance of the 1,4-dialdehyde and the α,ß-unsaturated carbonyl in the observed bioactivity of cinnamodial against mosquitoes. This study represents the first investigation into the SAR of cinnamodial as an insecticide and antifeedant against the medically important Ae. aegypti mosquito. Author summary: Aedes mosquitoes are the primary carriers of Zika, dengue, chikungunya, and yellow fever viruses around the globe. Given the emergence of insecticide-resistance in this genus and unprecedented 'globalization' of mosquito-borne viruses, new chemicals to control these mosquitoes (e.g., insecticides, repellents) are urgently needed. In the continuation of our search for new and safe natural product derived insecticides, we generated semi-synthetic derivatives of cinnamodial (CDIAL), previously identified as an insect antifeedant, repellent and insecticide, to give insights into the important features of the molecule that can contribute to the observed activities. Since the antifeedant and repellent activity of CDIAL are found to be mediated by modulation of a sensory receptor (TRPA1) in the mosquito, we developed a structural model to understand how CDIAL interacts with TRPA1 and to explain the difference in activities of CDIAL and the prepared derivatives. Our findings aid in the development of plant-derived insecticides to control the Ae. aegypti mosquito and justify continued efforts using TRPA1 as a target for new mosquito repellents. [ABSTRACT FROM AUTHOR]

A temporal 4-step polarization phase-shifting technique for digital speckle pattern interferometry (DSPI) with one fixed and two rotatable polarizers is proposed. The fixed polarizer is used to filter out the reflected object beam in one polarization direction, and the two rotatable polarizers are used to perform the 4 times phase shifts. The Jones derivation illustrates the object surface phase distribution can be derived from the 4 speckle pattern interferograms, which are bright, gloomy, bright, and gloomy successively. The experiment shows that the proposed temporal polarization phase-shifting technique is able to extract the phase change caused by a tiny out-of-plane displacement. Unlike the PZT-driven phase-shifting, the polarization phase-shifting in this method is stable and accurate in the long term. [ABSTRACT FROM AUTHOR]

Sulforaphene (LFS-01) is the major chemical constituent of Raphanus sativu s, a medicinal herb used for over a thousand years in traditional Chinese medicine. Here we identified that LFS-01 can selectively eradicate lymphoma cells while sparing normal lymphocytes by triggering concomitant mitophagy and apoptosis. We demonstrated that LFS-01 can retain Nrf2 in the nucleus by covalently modulating CRM1 and consequently upregulate p62/SQSTM1, an essential structural component of the autophagosomes during mitophagic process. We found that LFS-01 treatment also stimulated AMPK and thereby inhibited the mTOR pathway. On the contrary, we revealed that AMPK inhibition can severely impair the LFS-01-mediated mitophagy. Transcriptomic studies confirmed that 15 autophagy-associated genes such as p62/SQSTM1 , VCP and BCL2 were differentially expressed after LFS-01 treatment. Furthermore, protein interactome network analysis revealed that the events of apoptosis and the assembly of autophagy vacuole were significant upon LFS-01 exposure. Lastly, we found that LFS-01 exhibited strong efficacy in xenograft mouse model yet with the lack of apparent toxicity to animals. We concluded that LFS-01 triggered mitophagic cell death via CRM1-mediated p62 overexpression and AMPK activation. Our findings provide new insights into the mechanism of action for LFS-01 and highlight its potential applications in treating major human diseases. [ABSTRACT FROM AUTHOR]

The regulatory mechanism of tautomycetin (TMC) biosynthesis remains largely unknown, although it has been of great interest to the pharmaceutical industry. Our previous study showed that intracellular adenosine triphosphate (inATP) level is negatively correlated with secondary metabolite biosynthesis in various Streptomyces spp. In this study, by exogenous treatment of ATP, we also found a negative correlation between TMC biosynthesis and inATP level in Streptomyces griseochromogenes ( S. griseochromogenes ). However, the underlying mechanism remains unclear. TmcN, a pathway-specific transcriptional regulator of TMC biosynthetic genes, was previously revealed as a large ATP-binding LuxR (LAL) family protein. The predicted amino acid sequence of TmcN shows highly conserved Walker A and B binding motifs, which suggest an ATPase function of TmcN. We therefore hypothesized that the ATPase domain of TmcN may play a role in sensing endogenous pool of ATP, and is thus involved in the ATP regulation of TMC biosynthesis. To test the hypothesis, we first explored the key residue that affects the ATPase activity of TmcN by amino acid sequence alignment and structural simulation. After that, we disrupted tmcN gene in S. griseochromogenes , and the tmcN or site-direct-mutated tmcN were re-introduced to get the complementary and ATPase domain disrupted strains. The transcription level of tmcN , TMC yield, and inATP, as well as the effect of ATP on TMC production of different mutants were evaluated. Deletion of tmcN or site-direct mutation of ATPase domain of TmcN in S. griseochromogenes significantly reduced the TMC production, and it was not affected by exogenous ATP treatment. In addition, a relatively high level of inATP was detected in tmcN deletion and site-direct mutation strains. Our results here suggested that TmcN, especially its ATPase domain, is involved in consuming of endogenous ATP pool and thus plays pivotal role in connecting the primary and secondary metabolite in S. griseochromogenes . [ABSTRACT FROM AUTHOR]

Background: Breast cancer metastasis to the bone can be exacerbated by osteoporosis, is associated with poor long-term survival, and has limited therapeutic options. Sclerostin (SOST) is an endogenous inhibitor of bone formation, and an attractive target for treatment of osteoporosis. However, it is unclear whether SOST can be used as a therapeutic target for bone metastases of breast cancer, and whether small molecule compounds that target SOST in breast cancer cells can inhibit breast cancer bone metastasis. Methods: SOST expression in 442 breast cancer tissues was characterized by immunohistochemistry and statistically analyzed for the association with breast cancer bone metastases. Bone metastatic breast cancer SCP2 cells were induced for SOST silencing or overexpression and their bone metastatic behaviors were tested in vitro and in vivo. To identify potential therapeutics, we screened inhibitors of the interaction of SOST with STAT3 from a small chemical molecule library and tested the inhibitory effects of one inhibitor on breast cancer growth and bone metastasis in vitro and in vivo. Results: We found that up-regulated SOST expression was associated with breast cancer bone metastases and worse survival of breast cancer patients. SOST silencing significantly reduced the bone metastatic capacity of SCP2 cells. SOST interacted with STAT3 to enhance the TGF-β/KRAS signaling, increasing both tumor growth and bone metastasis. Treatment with one lead candidate, S6, significantly inhibited the growth of breast-cancer organoids and bone metastasis in mice. Conclusions: Our findings highlight a new class of potential therapeutics for treatment of bone metastasis in breast cancer. [ABSTRACT FROM AUTHOR]

The nonlinear bending of the sandwich plates with graphene nanoplatelets (GPLs) reinforced porous composite (GNRPC) core and two metal skins subjected to different boundary conditions and various loads, such as the concentrated load at the center, linear loads with different slopes passing through the center, linear eccentric loads, uniform loads, and trapezoidal loads, has been presented. The popular four-unknown refined theory accounting for the thickness stretching effects has been employed to model the mechanics of the sandwich plates. The governing equations have been derived from the nonlinear Von Karman strain–displacement relationship and principle of virtual work with subsequent solution by employing the classical finite element method in combination with the Newton downhill method. The convergence of the numerical results has been checked. The accuracy and efficiency of the theory have been confirmed by comparing the obtained results with those available in the literature. Furthermore, a parametric study has been carried out to analyze the effects of load type, boundary conditions, porosity coefficient, GPLs weight fraction, GPLs geometry, and concentrated load radius on the nonlinear central bending deflections of the sandwich plates. In addition, the numerical results reveal that the adopted higher order theory can significantly improve the simulation of the transverse deflection in the thickness direction. [ABSTRACT FROM AUTHOR]

This study aims to investigate the quality changes of germinated soybeans during refrigerated storage (4 °C), with an emphasis on the stimulatory effect of refrigeration on their special functional compounds. After germinating for two days, germinated soybeans were stored at 4 °C for seven days, while the germinated soybeans stored at 25 °C served as control group. The results showed that refrigerated storage significantly affected the physiological changes in germinated soybeans. The weight loss rate, browning rate, malondialdehyde (MDA) content and H 2 O 2 content all decreased dramatically during refrigerated storage compared to the control group. The total phenolic and total flavonoid contents of germinated soybeans under refrigeration exhibited a trend of increasing and then decreasing over time. Additionally, during refrigerated storage, the total isoflavone content reached a peak of 8.72 g/kg on the fifth day, in which the content of daidzein and glycitin increased by 45% and 49% respectively, when compared with the control group. Moreover, the content of γ-aminobutyric acid (GABA) peaked on the first day, and kept a high level during storage. In which, the refrigerated group was 2.35-, 2.88-, 1.67-fold respectively after storage for three to seven days. These results indicated that refrigeration stimulated the biosynthesis of isoflavones and GABA in germinated soybeans during storage. More importantly, there was a sequential difference in the timing of the stimulation of the two functional components under refrigeration. • Germinated soybeans under refrigeration had a higher content of isoflavone and GABA. • Malonyl daidzin and malonyl genistein were dominant isoflavones in the germinated soybeans. • Accumulation of GABA content was faster than that of isoflavone during storage. [ABSTRACT FROM AUTHOR]

The hydrophobicity of a support plays a critical role in the catalytic efficiency of immobilized lipases. 3-aminopropyltriethoxysilane (APTES)-modified silica clay (A-SC) was coupled with silane coupling agents of different alkyl chains (methyl triethoxysilane, vinyl triethoxysilane, octyl triethoxysilane, and dodecyl triethoxysilane) to prepare a series of hydrophobic support for lipase immobilization. The lipases were immobilized onto the support by conducting glutaraldehyde cross-linking processes. The results showed that the activity of the immobilized biocatalyst increased with hydrophobicity. The hydrolytic activity of Lip-Glu-C12-SC (contact angle 119.8°) can reach 5900 U/g, which was about three times that of Lip-Glu-A-SC (contact angle 46.5°). The immobilized lipase was applied as a biocatalyst for biodiesel production. The results showed that the catalytic yield of biodiesel with highly hydrophobic Lip-Glu-C12-SC could be as high as 96%, which is about 30% higher than that of Lip-Glu-A-SC. After being recycled five times, the immobilized lipase still maintained good catalytic activity and stability. This study provides a good strategy to improve the efficiency of immobilized lipases, showing great potential for future industrial application on biodiesel production. [ABSTRACT FROM AUTHOR]

β-secretase ( BACE-1) is a potential target for the treatment of Alzheimer's disease ( AD). Despite its potential, only few compounds targeting BACE have entered the clinical trials. Herein, we describe the identification of Gefitinib as a potential lead compound for BACE through an integrated approach of structural bioinformatics analysis, experimental assessment and computational analysis. In particular, we performed ELISA and western analysis to assess the effect of Gefitinib using N2a human APP695 cells. In addition, we investigated the binding mechanism of Gefitinib with BACE through molecular docking coupled with molecular dynamics simulations. The computational analyses revealed that hydrophobic contact is a major contributing factor to the binding of Gefitinib with BACE. The results obtained in the study have rendered Gefitinib as a putative lead compound for BACE. Further optimization studies are warranted to improve its potency and pharmacological properties against BACE for potential AD treatment. [ABSTRACT FROM AUTHOR]

Background: Activation of nuclear factor-kappa B (NF-κΒ) through DNA damage is one of the causes of tumor cell resistance to radiotherapy. Chromosome region 1 (CRM1) regulates tumor cell proliferation, drug resistance, and radiation resistance by regulating the nuclear-cytoplasmic translocation of important tumor suppressor proteins or proto-oncoproteins. A large number of studies have reported that inhibition of CRM1 suppresses the activation of NF-κΒ. Thus, we hypothesize that the reversible CRM1 inhibitor S109 may induce radiosensitivity in glioblastoma (GBM) by regulating the NF-κΒ signaling pathway. Methods: This study utilized the cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and colony formation assay to evaluate the effect of S109 combined with radiotherapy on the proliferation and survival of GBM cells. The therapeutic efficacy of S109 combined with radiotherapy was evaluated in vivo to explore the therapeutic mechanism of S109-induced GBM radiosensitization. Results: We found that S109 combined with radiotherapy significantly inhibited GBM cell proliferation and colony formation. By regulating the levels of multiple cell cycle- and apoptosis-related proteins, the combination therapy induced G1 cell cycle arrest in GBM cells. In vivo studies showed that S109 combined with radiotherapy significantly inhibited the growth of intracranial GBM and prolonged survival. Importantly, we found that S109 combined with radiotherapy promoted the nuclear accumulation of IκΒα, and inhibited phosphorylation of p65 and the transcriptional activation of NF-κΒ. Conclusion: Our findings provide a new therapeutic regimen for improving GBM radiosensitivity as well as a scientific basis for further clinical trials to evaluate this combination therapy. [ABSTRACT FROM AUTHOR]

Acetoin is an important physiological metabolite excreted by microbes. Its functions include avoiding acidification, participating in regulation of the NAD+/NADH ratio, and storing carbon. Acetolactate decarboxylase is a well-characterized anabolic enzyme involved with 3-hydroxy butanone (acetoin). It catalyzes conversion of the (R)- and (S)-enantiomers of acetolactate to generate the single product, (R)-acetoin. In addition to the X-ray crystal structure of acetolactate decarboxylase from Bacillus brevis, although the enzyme is widely present in microorganisms, very few atomic structures of acetolactate decarboxylase are reported. In this paper, we solved and reported a 1.5 Å resolution crystal structure of acetolactate decarboxylase from Bacillus subtilis. Dimeric assembly is observed in the solved structure, which is consistent with the elution profile conducted by molecular filtration. A zinc ion is coordinated by highly conserved histidines (191, 193, and 204) and conserved glutamates (62 and 251). We performed kinetic studies on acetolactate decarboxylase from Bacillus subtilis using circular dichroism, allowing the conversion of acetolactate to chiral acetoin for real-time tracking, yielding a Km value of 21 mM and a kcat value of 2.2 s−1. Using the two enantiomers of acetolactate as substrates, we further investigated the substrate preference of acetolactate decarboxylase from Bacillus subtilis by means of molecular docking and dynamic simulation in silico. The binding free energy of (S)-acetolactate was found to be ~ 30 kcal/mol greater than that of (R)-acetolactate, indicating a more stable binding for (S)-acetolactate. [ABSTRACT FROM AUTHOR]

Phase map filtering is considered an indispensable process in the measurement delivered by speckle interferometric optics. For recent measurements, quite a lot of scenarios require an optimized time consumption. A notable feature of the raw phase map is the 2 π modulo of the phase distribution, as retrieved by the inverse tangent operation. Instead of employing the filtering method directly on the phase fringe pattern, the wrapped phase is converted into the sine–cosine domain with its sine and cosine components, and then the filtering method is applied to them. However, it is the nature of the sine–cosine filtering framework that consumes approximately 70% calculation resources for the recalculation of the intermediate phase map and the sine/cosine components at every loop, which limits the temporal property of related measurement. To address the issues of efficiency and quality at the same time, a new filtering domain is proposed, namely the complex amplitude domain filtering framework. The filtering is conducted at the stage of recovering the complex amplitude without calculating the intermediate phase map at every loop. The merit of complex amplitude domain filtering is that it has a good filtering efficiency to remove the speckle noise, preserves the details of the sharp edge in the phase-wrapped area at the same time, and no additional phase shift is generated during the filtering. Most of the existing filters and strategies used in the sine–cosine filtering domain can be directly applied in the proposed complex amplitude domain. Preliminary experiments show that, compared to the sine–cosine domain filtering, the proposed complex amplitude domain filtering accelerates the filtering process by at least 40% at no cost of filtering quality, and particularly shows a better filtering performance with the partial differential equations (PDE) noise reduction method. • Speckle suppression speed at least 40% faster than filtering in sine–cosine domain. • Preserving details of sharp edges at phase jumping area in phase measurement. • Existing filters being readily and effectively applied in complex amplitude domain. • No artificial phase shift generated during complex amplitude domain filtering. [ABSTRACT FROM AUTHOR]

This paper presents a simple spatial phase shift shearography based on the Michelson interferometer. A novel digital shearography set-up with a large angle of view, which is based on a 4 f system is demonstrated. In the system, the Michelson interferometer is used as a shearing device to generate a shearing distance by tilting a small angle in one of the two mirrors. In fact spherical wave fronts become plane after going through the first lens in 4 f system. Tilting the mirror in the Michelson interferometer also generates spatial carrier frequency. Sinusoid fitting method is applied to evaluate the phase. This system can generate a phase map of shearography by using only a single image. The effects of shearing angle, the choice of algorithm and comparison result are discussed in detail. The theory and the application are presented. [ABSTRACT FROM AUTHOR]

This study quantifies the change in traffic flow on the M25 motorway in the UK due to the COVID-19 outbreak. Moreover, the impact of the change in traffic flow on non-exhaust PM 2.5 and PM 10 emissions for different categories of vehicle was explored. During the year of the COVID-19 outbreak (March 2020 to February 2021), the total traffic flows of passenger cars (PCs), light goods vehicles (LGVs), heavy goods vehicles (HGVs), and long HGVs on the M25 motorway decreased by 38.6%, 27.6%, 15.9% and 7.2%, respectively, in comparison to the previous year. Correspondingly, the total mass of non-exhaust emissions (PM 2.5 and PM 10) of PCs, LGVs, HGVs, and long HGVs reduced by 38.7%, 27.3%, 16.2% and 7%, respectively. The traffic flows per year before and during the COVID-19 outbreak of long HGVs were 87.2% and 80.7% less than those of PCs. Correspondingly, the long HGVs emitted 10.2% less but 36.3% more PM 2.5 emissions, as well as 10.9% and 66.7% more PM 10 emissions than the latter, indicating that long HGVs contribute much more to non-exhaust particles than PCs. In addition, it was found that resuspension of road dust on the M25 motorway was the largest contributor to air pollution among non-exhaust emissions, followed by road wear, tyre wear, and brake wear particles. [Display omitted] • Traffic flow was quantified on the M25 before and during the year of the outbreak. • Total non-exhaust PM 2.5 and PM 10 mass of four categories of vehicles were evaluated. • Long HGVs emitted the most non-exhaust particles, followed by HGVs, LGVs and PCs. • Resuspension of road dust was the largest contributor to non-exhaust particles. [ABSTRACT FROM AUTHOR]

As the most common fungal pathogen of humans, severe drug resistance has emerged in the clinically isolated Candida albicans , which lead to the urgency to develop novel antifungal agents. Here, four our previously characterized cathelicidins (cathelicidin-BF, Pc-CATH1, Cc-CATH2, Cc-CATH3) were selected and their antifungal activities against C. albicans were evaluated in vitro and in vivo using amphotericin B and LL-37 as control. Results showed that all four cathelicidins could eradicate standard and clinically isolated C. albicans strains with most MIC values ranging from 1 to 16 μg/ml, in less than 0.5 h revealed by time-kill kinetic assay. Four peptides only exhibited slight hemolytic activity with most HC 50 > 200 μg/ml, and retained potent anti- C. albicans activity at salt concentrations below and beyond physiological level. In animal experiment, 50 mg/kg administration of the four cathelicidins could significantly reduce the fungal counts in a murine oral candidiasis model induced by clinically isolated C. albicans . The antibiofilm activity of cathelicidin-BF, the most potent among the five peptides was evaluated, and result showed that cathelicidin-BF strongly inhibited C. albicans biofilm formation at 20 μg/ml. Furthermore, cathelicidin-BF also exhibited potent anti- C. albicans activity in established biofilms as measured by metabolic and fluorescent viability assays. Structure-function analyses suggest that they mainly adopt an α-helical conformations, which enable them to act as a membrane-active molecule. Altogether, the four cathelicidins display great potential for antifungal agent development against candidiasis. [ABSTRACT FROM AUTHOR]

A new non-cytotoxic [(+)-17β-hydroxystrebloside (1)] and two known cytotoxic [(+)-3′-de- O -methylkamaloside (2) and (+)-strebloside (3)] cardiac glycosides were isolated and identified from the combined flowers, leaves, and twigs of Streblus asper collected in Vietnam, with the absolute configuration of 1 established from analysis of its ECD and NMR spectroscopic data and confirmed by computational ECD calculations. A new 14,21-epoxycardanolide (3a) was synthesized from 3 that was treated with base. A preliminary structure-activity relationship study indicated that the C-14 hydroxy group and the C-17 lactone unit and the established conformation are important for the mediation of the cytotoxicity of 3. Molecular docking profiles showed that the cytotoxic 3 and its non-cytotoxic analogue 1 bind differentially to Na+/K+-ATPase. Compound 3 docks deeply in the Na+/K+-ATPase pocket with a sole pose, and its C-10 formyl and C-5, C-14, and C-4′ hydroxy groups may form hydrogen bonds with the side-chains of Glu111, Glu117, Thr797, and Arg880 of Na+/K+-ATPase, respectively. However, 1 fits the cation binding sites with at least three different poses, which all depotentiate the binding between 1 and Na+/K+-ATPase. Thus, 3 was found to inhibit Na+/K+-ATPase, but 1 did not. In addition, the cytotoxic and Na+/K+-ATPase inhibitory 3 did not affect glucose uptake in human lung cancer cells, against which it showed potent activity, indicating that this cardiac glycoside mediates its cytotoxicity by targeting Na+/K+-ATPase but not by interacting with glucose transporters. [ABSTRACT FROM AUTHOR]

The overuse of insecticides with limited modes of action has led to resistance in mosquito vectors. Thus, insecticides with novel modes of action are needed. Secondary metabolites in Madagascan plants of the genus Cinnamosma (Canellaceae) are commonly used in traditional remedies and known to elicit antifeedant and toxic effects in insect pests. Here we test the hypothesis that extracts of Cinnamosma sp. enriched in drimane sesquiterpenes are toxic and/or antifeedant to the yellow fever mosquito Aedes aegypti. We show that the bark and root extracts, which contain a higher abundance of drimane sesquiterpenes compared to leaves, were the most efficacious. Screening isolated compounds revealed cinnamodial to be the primary driver of adulticidal activity, whereas cinnamodial, polygodial, cinnafragrin A, and capsicodendrin contributed to the larvicidal activity. Moreover, an abundant lactone (cinnamosmolide) in the root extract synergized the larvicidal effects of cinnamodial. The antifeedant activity of the extracts was primarily contributed to cinnamodial, polygodial, and cinnamolide. Parallel experiments with warburganal isolated from Warburgia ugandensis (Canellaceae) revealed that aldehydes are critical for—and a hydroxyl modulates—insecticidal activity. Our results indicate that plant drimane sesquiterpenes provide valuable chemical platforms for developing insecticides and repellents to control mosquito vectors. [ABSTRACT FROM AUTHOR]