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This study investigated the effect of household air pollution on pregnant women with GDM, and assessed the modifying effect of a healthy lifestyle on this relationship. Household solid fuel exposure was defined as using solid fuels (coal, crop residue, and wood) for cooking and heating. Four individually modifiable lifestyle factors were assessed in early pregnancy: body mass index, diet, sleep, and vitamin D supplementation. Multifactorial logistic regression modeling was used to assess the relationship between household air pollution and GDM. A stratified analysis and additive interaction tested the effects of healthy lifestyle scores. After adjusting for potential confounders, we found that using solid fuels for heating was significantly associated with an increased risk of GDM (adjusted OR = 1.60, 95% CI 1.18–2.18). GDM risk showed a decreasing trend in the medium versus the high score group when compared to the low score group, with a consistent trend regardless of household fuel type used (adjusted OR = 0.39, 95% CI 0.27–0.57) (adjusted OR = 0.12, 95% CI 0.05–0.28), respectively. Importantly, when the healthy lifestyle score increased, exposure to household air pollution was no longer associated with a higher GDM risk. There was a negative additive interaction between exposure to household solid fuels exposure and a healthy lifestyle (FERI: −5.10 [−16.48, −2.04]; AP: −1.29 [−2.80, −0.39]; SI: −0.37 [−0.20, −0.67]). We determined that exposure to household air pollution may be an important GDM risk factor. In addition, A healthy lifestyle may have a protective effect on women with GDM exposed to indoor fuel air pollution. [ABSTRACT FROM AUTHOR]

Introduction: Despite the available secondary preventive treatments, the management of stable coronary artery disease (SCAD) remains challenging. Intermediate coronary lesion (ICL), defined as luminal stenosis between 50% and 70%, is a key stage of SCAD. However, existing therapeutic strategies are limitated in delaying plaque progression and associated with various adverse effects and economic burdens. Qing-Xin-Jie-Yu Granules (QXJYG) with proven anti-platelet, anti-inflammatory, and lipid-lowering effects may compensate for the drawbacks of current treatments and can be tested as a complementary therapy. Therefore, this study aims to investigate the efficacy and safety of QXJYG in treating ICL, with a particular focus on its impact on myocardial ischemia and plaque progression. Materials and methods: This is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 120 participants with ICL will be randomly assigned to two groups in a 1:1 ratio. In addition to basic medications, the intervention group will receive QXJYG, while the control group will receive a placebo for over 6 months, followed by a 12-month follow-up. The primary efficacy outcome is computed tomography-derived fractional flow reserve. The secondary outcomes include the degree of coronary stenosis, coronary artery calcification score, Gensini score, Seattle Angina Questionnaire score, high-sensitivity C-reactive protein, matrix metalloproteinase-9, blood lipids, and carotid artery ultrasound parameters. Major adverse cardiovascular events are recorded as endpoints. The safety outcomes include composite events of bleeding, laboratory test results, and adverse events. Clinical visits are scheduled at baseline, every 2 months during the treatment, and after a 12-month follow-up. Discussion: This trial is anticipated to yield reliable results to verify the efficacy and safety of QXJYG in the treatment of ICL, which will provide novel insights to help address the prevailing therapeutic dilemma of ICL, thereby facilitating for the management of SCAD. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200059262. Registered on April 27, 2022. [ABSTRACT FROM AUTHOR]

[Display omitted] • The catalyze activity of ADH decreases in a competitive manner with the presence of THC. • THC spontaneously enters the substrate-binding cavity of ADH. • The binding process of ADH and THC was driven by hydrogen bonds and van der Waals forces. • The secondary structure becomes loose in the presence of THC. • The interactions between THC and Val294 residue reveal the primary cause for the decrease in ADH activity. Tetrahydrocurcumin (THC), a major metabolite of curcumin, is renowned for its potent antioxidant and anti-inflammatory properties, including preventing liver injury from alcohol. Alcohol dehydrogenase (ADH), an essential enzyme in alcohol metabolism, is significant in the development of alcohol-induced diseases. Hence, enzymatic activity assays, spectroscopic methods, and computational techniques were employed in this study to explore their interaction. The results indicated that THC can competitively inhibit ADH activity, as inferred from the kinetic parameter values. Meanwhile, THC spontaneously entered the substrate-binding cavity of ADH to form a binary complex, and surrounded by Thr178, Leu57, Ile318, Leu141, Glu68, Leu116, Phe93, Val294, and Asp49. The K a value of this binding was 1.724 ± 0.017 × 104 M−1 at 298 K. This binding process was driven by hydrogen bonds and van der Waals forces; additionally, the π electrons in THC were significant for the stability of the ADH-THC complex. The presence of THC led to a decrease in the α-helix content of ADH, resulting in a looser secondary structure. Furthermore, molecular dynamic simulations revealed that Glu68, Leu116, Phe93, Val294, and Asp49 made significant contributions to the binding process. The inhibition of ADH catalytic activity may be primarily attributed to the interaction between THC and the Val294 residue. [ABSTRACT FROM AUTHOR]

Leptographium qinlingensis is one of the major fungal associates of the Chinese white pine beetle (Dendroctonus armandi) and is an active participant in the large-scale death of Pinus armandi. Beetles and associated fungi have evolved efficient systems for overcoming the toxicity of host defense chemicals, which consist of a multitude of monoterpenes and diterpenes. As fungal cytochromes (CYPs) can detoxify and degrade various xenobiotic compounds, we identified 11 CYPs from L. qinlingensis to analyze their potential function in detoxifying or degrading host chemical defense. These 11 CYPs of L. qinlingensis belong to 6 clans and cluster into 3 clades, clade 2, clade 8 and clade 10, based on their phylogenetic relationships. Moreover, we also analyzed the transcript levels of CYPs following treatment with terpenes or expression in mycelia grown on terpenoids as a carbon source. The results in this paper showed that several CYPs were upregulated after treatment with terpenes or growth on terpenoids as the only carbon source. Our research provides some insight into the function of CYPs from bark beetle symbiotic fungi in the detoxification of pine defense compounds or their relationships with the utilization of terpenoids. [ABSTRACT FROM AUTHOR]

Halogenated Organic Phosphate Esters (OPEs) are commonly found in plasticizers and flame retardants. However, they are one kind of persistent contaminants that can pose a significant threat to human health and ecosystem as new environmental estrogen. In this study, two representative halogenated OPEs, tris(1,3-dichloro-2-propyl) phosphate (TDCP) and tris(2,3-dibromopropyl) phosphate (TDBP), were selected as experimental subjects to investigate their interaction with human serum albumin (HSA). Despite having similar structures, the two ligands exhibited contrasting effects on enzyme activity of HSA, TDCP inhibiting enzyme activity and TDBP activating it. Furthermore, both TDCP and TDBP could bind to HSA at site I, interacted with Arg222 and other residues, and made the conformation of HSA unfolded. Thermodynamic parameters indicated the main driving forces between TDBP and HSA were hydrogen bonding and van der Waals forces, while TDCP was mainly hydrophobic force. Molecular simulations found that more hydrogen bonds of HSA-TDBP formed during the binding process, and the larger charge area of TDBP than TDCP could partially account for the differences observed in their binding abilities to HSA. Notably, the cytotoxicity of TDBP/TDCP was inversely proportional to their binding ability to HSA, implying a new method for determining the cytotoxicity of halogenated OPEs in vitro. [Display omitted] • The cytotoxicity of TDCP/TDBP is inversely proportional to their binding ability to HSA. • Halogenated OPEs can bind with HSA and alter the secondary structure of HSA. • TDBP can stimulate the enzyme activity characteristics of HSA while TDCP inhibits it. • The higher number of hydrogen bonds between TDBP and HSA may be the reason for its stronger binding ability than TDCP. • Compounds with higher surface electrostatic potential are more conducive to binding. [ABSTRACT FROM AUTHOR]

The ascomycete Leptographium qinlingensis is one of the major externally living fungal associates of Dendroctonus armandi, which can kill host trees when it invades Chinese white pine (Pinus armandii). We identified and phylogenetically analysed the cytochrome P450 (CYP) genes in the transcriptome of L. qinlingensis. Furthermore, the expression profiles of six CYPs in the mycelium of L. qinlingensis grown on different media or treated with terpenoids were detected, as well as their growth rates on different nutritional media and inhibition by terpenoids. The CYP evolution predicted that most of the CYPs occurred in a putative common ancestor shared between L. qinlingensis and Grosmannia clavigera. The growth rates and inhibition test result shows that L. qinlingensis has more similarity with G. clavigera, which can retrieve nutrition from pine wood and utilize monoterpenes as the sole carbon source. CYP582C and CYP52Z4 of L. qinlingensis might be involved in the metabolism of fatty acids and detoxification of terpenes and phenolics after the analysis of their transcription levels with different treatments. [ABSTRACT FROM AUTHOR]

Objective. To compare the efficacy of three different traditional Chinese exercises (Tai Chi, Baduanjin, and Wuqinxi) combined with antihypertensive drugs (AHD) on patients with essential hypertension (EH). Method. Eight electronic databases were searched to identify randomized controlled trials (RCTs) comparing the effects of traditional Chinese fitness exercises combined with AHD and AHD alone. The analysis mainly consists of network meta-analysis (NMA) and pairwise meta-analysis. The Cochrane assessment tool was adopted to assess the risk of bias of included literatures. This study used STATA/SE 15.1 (StataCorp, 2017), R software (version 4.0.1), and Cochrane's Review Manager software (version 5.4) to conduct data analysis and figures generation. Results. A total of 30 RCTs were included in this study, of which 16 evaluated Tai Chi plus AHD versus AHD, 11 evaluated Baduanjin plus AHD versus AHD, and 3 evaluated Wuqinxi plus AHD versus AHD. No RCT compared directly among the three traditional Chinese fitness exercises. Pairwise meta-analysis showed that Tai Chi plus AHD was significantly superior to AHD alone in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP). BDJ plus AHD was statistically superior to AHD alone in reducing SBP, DBP, and endothelin (ET) and increasing nitric oxide (NO). NMA results indicated that Tai Chi plus AHD (WMD −12.42 mmHg, 95% CI: −15.29 to −9.55) and Baduanjin plus AHD (WMD −7.03 mmHg, 95% CI: −9.80 to −4.26) were superior to AHD, and Tai Chi was more effective than other traditional exercises in lowering SBP, Tai Chi plus AHD (WMD −7.56 mmHg, 95% CI: −10.15 to −4.96) and Baduanjin plus AHD (WMD −4.51 mmHg, 95% CI: −7.38 to −1.65) were superior to AHD in reducing DBP, Baduanjin plus AHD (WMD 4.26 μmol/L, 95%CI: 2.68 to 5.83) was statistically superior to AHD in increasing NO, and Tai Chi plus AHD (WMD −7.64 pg/ml, 95% CI: −10.46 to −4.83) and Baduanjin plus AHD (WMD −9.23 pg/ml, 95% CI: −10.85 to −7.61) were superior to AHD in lowering ET. Conclusion. Compared with AHD alone, both Tai Chi plus AHD and Baduanjin plus AHD showed significant benefit in regulating SBP, DBP, and ET. Among the three traditional Chinese fitness exercises, Tai Chi may be the best as an adjunctive therapy for SBP reduction. These findings provided evidence for the therapeutic benefit of either Tai Chi or Baduanjin exercise as an adjunct therapy for patients with EH. Limited by the methodological quality and quantity of included studies, results need to be interpreted with caution, and it is necessary to carry out further high-quality RCTs on traditional Chinese fitness exercise-assisted treatment of EH in the future. [ABSTRACT FROM AUTHOR]

The sensitivity of photosynthesis to temperature has been identified as a key uncertainty for projecting the magnitude of the terrestrial carbon cycle response to future climate change. Although thermal acclimation of photosynthesis under rising temperature has been reported in many tree species, whether tropospheric ozone (O3) affects the acclimation capacity remains unknown. In this study, temperature responses of photosynthesis (light‐saturated rate of photosynthesis (Asat), maximum rates of RuBP carboxylation (Vcmax), and electron transport (Jmax) and dark respiration (Rdark) of Populus tremula exposed to ambient O3 (AO3, maximum of 30 ppb) or elevated O3 (EO3, maximum of 110 ppb) and ambient or elevated temperature (ambient +5°C) were investigated in solardomes. We found that the optimum temperature of Asat (ToptA) significantly increased in response to warming. However, the thermal acclimation capacity was reduced by O3 exposure, as indicated by decreased ToptA, and temperature optima of Vcmax (ToptV) and Jmax (ToptJ) under EO3. Changes in both stomatal conductance (gs) and photosynthetic capacity (Vcmax and Jmax) contributed to the shift of ToptA by warming and EO3. Neither Rdark measured at 25°C (Rdark25) nor the temperature response of Rdark was affected by warming, EO3, or their combination. The responses of Asat, Vcmax, and Jmax to warming and EO3 were closely correlated with changes in leaf nitrogen (N) content and N use efficiency. Overall, warming stimulated growth (leaf biomass and tree height), whereas EO3 reduced growth (leaf and woody biomass). The findings indicate that thermal acclimation of Asat may be overestimated if the impact of O3 pollution is not taken into account. [ABSTRACT FROM AUTHOR]

The Chinese white pine beetle, Dendroctonus armandi Tsai & Li (Coleoptera: Curculionidae, Scolytinae), is considered the most destructive forest pest in the Qinling and Bashan Mountains of China. In recent years, winter temperature has dropped in these regions, and extremely low temperatures are hard to survive for insects. Cold hardiness becomes a crucial strategy because temperature change often leads to fluctuations in insect abundance, and the metabolism rate is a key index of resistance to cold in overwintering insects. Therefore, we investigated the relationship between the change in respiratory rate and the activity of metabolism‐related mitochondrial enzymes in D. armandi larvae under cold conditions. We found that the respiratory rate decreased, and it was matched with the activity of glutamate dehydrogenase, aconitase, and lipase during overwintering. Among the various test times under cold conditions, the respiratory rate also decreased with decreasing temperature and increased under very low temperatures. At all cold stress periods, glutamate dehydrogenase and lipase showed increased activity at higher temperatures and decreased activity under lower temperatures, but the activity of NAD‐malic enzyme, NADP‐malic enzyme, mitochondrial isocitrate dehydrogenase, and aconitase were contrary. Under all low temperatures, the activity of enzymes – except for NADP‐malic enzyme, glutamate dehydrogenase, and lipase – increased in short‐term cold stress and decreased in long‐term cold stress at 4, 0, −4, −6, −8, and −10 °C. However, at −2 °C, the activity of enzymes showed a decreasing trend in short‐term treatments and an increasing trend in long‐term treatments, except for mitochondrial isocitrate dehydrogenase. The results not only improve our understanding of the metabolic mechanism of cold adaptation in D. armandi, but also provide an important experimental basis for further study and biological pest control. [ABSTRACT FROM AUTHOR]

Ascorbate in leaf apoplast (ASCapo) reacts with ozone (O3) and thereby reduces O3 flux reaching plasmalemma (Fpl). Some studies have shown significant protection of cells from O3 by ASCapo, while others have questioned its efficacy. Hypothesizing that the protection by ASCapo depends on other variables, we quantified determinants of O3 detoxification with a model of O3 transport and reaction in apoplast. The model determines ascorbic acid concentration in apoplast (AAapo) using measured values of O3 concentration (co), leaf tissue ascorbic acid concentration (AAleaf), cell wall thickness (L3), apoplastic pH (pHapo), and stomatal conductance (Gsw). We compared the measured and model‐estimated AAapo in leaves of peach (Prunus persica) grown in open‐top chambers under non‐filtered air (NF) and elevated (EO3: NF + 80 ppb) O3 concentrations. The estimated AAapo in individual leaves agreed well with the measured values (R2 =.91). Analyses of the simulation results yielded the following findings: (a) The efficacy of O3 reduction with ASCapo as quantified by fractional reduction (ϕ3) of O3 flux at the surface of plasmalemma (Fpl) was lowered from 70% in NF to 40% in EO3 due to the reduction of L3. The EO3 reduced AAapo, but the lower Gsw and L3 in EO3 increased AAapo resulting in no significant change in AAapo due to EO3. ϕ3 can be calculated with measured values of AAapo and L3, and Fpl can be estimated with the measurement‐based ϕ3. (b) When c0 is increased, Fpl increased curvilinearly with the increase of Fst: nominal O3 flux via stomatal diffusion, exhibiting apparent threshold on Fst. The deviation of Fpl from Fst became greater when L3, pHapo, and AAleaf were increased. The quantification of ϕ3 and Fpl using leaf traits shall facilitate the understanding of the mechanisms of differential plant sensitivity to O3 and improve quantification of the O3 impacts on plants. [ABSTRACT FROM AUTHOR]

Two contrasting rapeseed (Brassica napus L.) genotypes, Qinyou 8 (drought-sensitive) and Q2 (drought-tolerant), were studied under drought stress with or without pretreatment with melatonin to (i) explore whether melatonin enhances drought resistance by regulating root growth and (ii) determine the relationship between the belowground and aboveground responses to melatonin under drought stress. Results show that the light-saturated rate of photosynthesis (P n), stomatal conductance (g s), water use efficiency (WUE) and chlorophyll content were decreased by drought for Qinyou 8, whereas drought only decreased P n and chlorophyll content for Q2. Drought decreased actual photochemical efficiency in saturated light (F v '/F m '), actual photochemical efficiency (PhiPSⅡ), quenching of photochemical efficiency (qL) and electron transport rate (ETR) in Qinyou 8. However drought only decreased F v '/F m ' and qL in Q2. Drought increased malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2) contents in the roots of both genotypes. Melatonin had no significant additional effects on root guaiacol peroxidase (POD) and superoxide dismutase (SOD) activities, but enhanced root catalase (CAT) activity of droughted plants further. Melatonin promoted taproot and lateral root growth under drought stress. Melatonin also promoted stomatal opening resulting in enhanced photosynthesis in the two genotypes. The two mechanisms induced by melatonin synergistically enhance drought resistance of rapeseed as indicated by enhanced gas exchange parameters under melatonin pretreatment. The findings provide evidence for a physiological role of melatonin in improving drought resistance, especially in belowground parts. Image 1 • Melatonin promoted taproot and a lateral root growth and root CAT activity under drought. • Melatonin promoted stomata opening under drought. • The enhanced root growth by melatonin may contribute to preventing stomata from closing. [ABSTRACT FROM AUTHOR]

Abstract To investigate whether nitrogen (N) load affects the ozone (O 3) stomatal flux-effect relationship for birch biomass, three-year old birch saplings were exposed to seven different O 3 profiles (24 h mean of 35–66 ppb) and four different N loads (10, 30, 50 and 70 kg ha−1 yr−1) in precision-controlled hemispherical glasshouses (solardomes) in 2012 and 2013. Stomatal conductance (g s) under optimal growth conditions was stimulated by enhanced N supply but was not significantly affected by enhanced O 3 exposure. Birch root, woody (stem + branches) and total biomass (root + woody) were not affected by the Phytotoxic Ozone Dose (POD 1 SPEC) after two seasons of O 3 exposure, and enhanced N supply stimulated biomass production independent of POD 1 SPEC (i.e. there were no POD 1 SPEC × N interactions). There was a strong linear relationship between the stem cross-sectional area and tree biomass at the end of the experiment, which was not affected by O 3 exposure or N load. Enhanced N supply stimulated the stem cross-sectional area at the end of season 2, but not at the end of season 1, which suggests a time lag before tree biomass responded to enhanced N supply. There was no significant effect of POD 1 SPEC on stem cross-sectional area after either the first or second growing season of the experiment. Contrasting results reported in the literature on the interactive impacts of O 3 and N load on tree physiology and growth are likely due to species-specific responses, different duration of the experiments and/or a limitation of the number of O 3 and N levels tested. Graphical abstract Unlabelled Image Highlights • O 3 flux-effect relationships investigated for birch at 7 O 3 profiles and 4 N loads • g s under optimal conditions was stimulated by N but not affected by O 3. • O 3 flux-effect relationships for biomass were not affected by N supply. • O 3 reduced stem cross-sectional area after the first season only. • N stimulation of stem cross-sectional area increased in the second season. [ABSTRACT FROM AUTHOR]

Polyethylene glycol (PEG) based formulation and polyvinylchloride (PVC) tubing are frequently used for drug delivery and administration. The compatibility of a parenteral drug microdose formulation in intravenous infusion (IV) devices was studied to support the clinical determination of absolute bioavailability by the microdosing method. The investigational microdose formulation containing PEG was found prone to significant loss of potency within hours of storage in the PVC IV tubing due to degradation. Degradation occurred only when both PEG and PVC tubing were present. The degradation product could not be detected by LC/MS due to the significant interference from the high concentration of PEG (4%) matrix and the extremely low level of drug (0.6 ppm). To obtain structural information of the degradation impurity and understand the cause of the degradation, a simple heart-cutting 2D-LC/MS approach was utilized to effectively separate the impurity from the complex PEG oligomers and overcome the matrix interference, enabling mass spectrometric analysis of the impurity. An oxidation- dominated mechanism was proposed in which the combination of PEG auto-oxidation and dehydrochlorination of the PVC tubing yielded an oxidative environment that enhanced radical propagation and accelerated degradation of the investigational parent drug. [ABSTRACT FROM AUTHOR]

Bark beetles oxidize the defensive allelochemicals of their host trees both to detoxify them and convert them into components of their pheromone systems which were catalyzed by cytochrome P450 enzymes (CYPs) and occur in different tissues of the insect. We study P450 genes in the Chinese white pine beetle ( Dendroctonus armandi ), and some bio-information analysis was done for the full-length deduced amino acid sequences. The tissue specificity of these P450 genes was determined in three tissues (antenna, gut and reproductive organs). Differential expression of the P450 genes was observed between sexes, and within these significant differences exposed to stimuli (α-pinene (1:1 racemic mix), (S)-(−)-α-pinene, (S)-(−)-β-pinene, (+)-3-carene, (±)-limonene and turpentine oil) at 24 h. Increased expression of P450 genes suggested that they play a role in the detoxification of monoterpenes released by the host trees. The different transcript accumulation patterns of these bark beetle P450 genes provided insight into ecological interactions of D . armandi with its host pine. [ABSTRACT FROM AUTHOR]

Bark beetles oxidize the defensive allelochemicals from their host trees to both detoxify and convert these materials into components of their pheromone system. The ability of this insect to adapt to its chemical environment might be explained by the action of major detoxification enzymes such as cytochrome P450s (or CYPs). Sixty-four sequences coding for P450s were identified, and most of the transcripts were found to be expressed in the larvae, pupae and adults of Dendroctonus armandi . To gain information on how these genes help D. armandi overcome the host defense, differential transcript levels of the CYP genes were observed between sexes and within the sexes. Significant differences were observed among developmental stages, in feeding on the phloem of Pinus armandi and in exposure to stimuli ((±)-α-pinene, (S)-(−)-α-pinene, (S)-(−)-β-pinene, (+)-3-carene, (±)-limonene and turpentine oil) for 8 h. We investigated the effect of sex and generations on the survivorship of individual D. armandi that were exposed to host volatiles at concentrations comparable to constitutive and induced levels of defense using fumigant exposure to understand the ability of the beetles to tolerate host defensive chemicals. The differential transcript accumulation patterns of CYP genes of these bark beetle provided insight into the ecological interactions of D. armandi with its host pine. [ABSTRACT FROM AUTHOR]

We isolated two full-length cDNAs encoding 3-hydroxy-3-methyl-glutaryl coenzyme A synthase ( HMG-S ) and 3-hydroxy-3-methylglutaryl coenzyme A reductase ( HMG-R ) from the Chinese white pine beetle ( Dendroctonus armandi ), and carried out some bioinformatic analysis on the full-length nucleic acid sequences and deduced amino acid sequences. Differential expression of the DaHMG-S and DaHMG-R genes was observed between sexes (emerged adults), and within these significant differences among development stage, tissue distribution, fed on phloem of Pinus armandi and topically applied juvenile hormone (JH) III. Increase of DaHMG-S and DaHMG-R mRNA levels in males suggested that they may play a role in mevalonate pathway. Information from the present study might contribute to understanding the relationship between D. armandi and its semiochemical production. [ABSTRACT FROM AUTHOR]

A sensitive analytical method using mixed mode HPLC separation coupled with charged aerosol detection (CAD) was developed for quantitative analysis of lithium. The method is capable of separating lithium ion from different drug matrices and other ions in a single run thus eliminating the organic matrix and ionic analyte interferences without extensive sample preparation such as derivatization and extraction. The separation space and chromatographic conditions are defined by systematic studies of the retention behaviors of lithium and potential interfering ions and different type of pharmaceutical APIs (active pharmaceutical ingredients) under reversed-phase, HILIC and cation/anion exchange mechanisms. Compared to other current analytical techniques for lithium analysis, the presented method provides a new approach and demonstrates high sensitivity (0.02 ng for LOD and 0.08 ng for LOQ in both standard and sample solution). The method has been validated for pharmaceutical samples and can be potentially applied to biological, food and environmental samples. [ABSTRACT FROM AUTHOR]

Abstract: A mixed-mode chromatography coupled with charged aerosol detector (CAD) method was developed in this work to simultaneously determine pharmaceutical counterions including both inorganic ions and organic ions in the forms of cations and anions. 25 commonly used pharmaceutical ions were studied and simultaneously separated within 20min by this single method. A silica based mixed-mode column with reversed-phase/cation-exchange/anion-exchange modes was used. It provides reversed-phase, strong cation-exchange and weak anion-exchange properties at the same time. It also provides the HILIC behavior at high percentage of organic solvent. The effects of mobile-phase organic strength, buffer ions, ionic strength, pH and column temperature have been investigated to optimize the method as well as to understand the retention and separation mechanisms. Conventional HPLC system was used and no special chromatography system is needed. The presented method has been employed successfully for screening and quantitative analysis of counterions, unknown ionic impurities and salts in active pharmaceutical ingredients and in process control samples with excellent accuracy, precision and sensitivity. This method provides a simple, fast and generic approach to speed up pharmaceutical research and development process and enhance lab efficiency. The similar methodologies can be applied to other ion analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: The bark beetle is the most well-known pest in coniferous trees worldwide. These insects only leave the host pine bark when they disperse to locate a new host. Determining how Dendroctonus armandi overcome the trees' terpene-based defense systems has been the key problem in the study of bark beetles. Therefore, the aim of this study was to discover the molecular mechanism of insect detoxification enzymes' ability to confer resistance to terpenes. For this purpose, the genes of cytochrome P450s, glutathione S-transferases, and carboxylesterases were studied in beetles given diets containing terpenes. The results suggest that beetles express different genes in response to terpenoids, and the responses of multiple detoxifying enzymes indicate these insects' adaption to their chemical environment. Bark beetles overcome the toxic terpenoids produced by pine trees by both detoxifying and converting them into a pheromone system. Detoxification enzymes such as cytochrome P450s, glutathione S-transferases, and carboxylesterases are involved in the ability of Dendroctonus armandi to adapt to its chemical environment. Ten genes from these three major classes of detoxification enzymes were selected to study how these enzymes help D. armandi to respond to the host defenses. The expression profile of these detoxification enzyme genes was observed in adult beetles after feeding on different types of diet. Significant differences were observed between two types of seminatural diet containing the phloem of pines, and a purely artificial diet containing five monoterpenes ((−)-α-pinene, (−)-β-pinene, (+)-3-carene, (±)-limonene, and turpentine oil) also caused differential transcript levels in the detoxification enzyme genes. The results suggest that monoterpenes enter the beetles through different routes (i.e., respiratory and digestive systems) and cause the expression of different genes in response, which might be involved in pheromone metabolism. In addition, the xenobiotic metabolism in bark beetles should be considered as a system comprising multiple detoxifying enzymes. [ABSTRACT FROM AUTHOR]

• An AEX method was developed for sgRNA as an alternative to IP-RPLC and HILIC. • Temperature-dependent AEX reveals the complex higher-order structure (HOS) of sgRNAs. • The HOS of sgRNA differs from other nucleic acids, providing additional chemical stability for sgRNA. Large synthetic oligonucleotides such as guide ribonucleic acid (gRNA), a critical reagent in clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing, have complex higher order structures (HOS) inherent in their design. In this study, we first developed a generic anion exchange chromatography (AEX) method for the comprehensive analysis of a 100mer single guide ribonucleic acid (sgRNA) impurity profiling. AEX demonstrated superior resolution compared to other common chromatographic methods employed for sgRNA analysis, such as Ion-Pairing Reversed Phase Liquid Chromatography (IP-RPLC) and Hydrophilic Interaction Chromatography (HILIC). Moreover, we discovered AEX's potential in probing the HOS of RNAs by adjusting the temperature and using organic additives. Our study also highlighted that sgRNA possesses a unique HOS distinctly different from other therapeutic nucleic acids, such as antisense oligonucleotides and messenger RNAs. [ABSTRACT FROM AUTHOR]

Background: 11β-hydroxylase deficiency (11β-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11β-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11β-OHD. Methods: Peripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants. Results: Early onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM_000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269–143,957,579 (hg19) with the insertion of 'ACAG' (NM_000497.4:c.954 + 78_980delinsACAG), which was in trans with CYP11B1: c.281 C > T. Conclusions: Our study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11β-OHD genetic diagnosis and carrier sequencing. [ABSTRACT FROM AUTHOR]

The Chinese white pine beetle, Dendroctonus armandi Tsai and Li, is a serious native pest in the Qinling Mountains of China. exo -Bevicomin, as the main component of bark beetle pheromone, is released by the female D. armandi. In this paper, we identified two genes encoding, (Z)-6-nonen-2-ol dehydrogenase and CYP6CR, that are known to be involved in xo-brevicomin synthesis to improve the understanding of exo -brevicomin biosynthesis in the Chinese white pine beetle. The two protiens had high homology with their orthologs in the exo -brevicomin biosynthesis pathway from D. ponderosae. The expression profiles of CYP6CR12 and DaZnoDH in D. armandi females are closely correlated with exo -brevicomin biosynthesis. The expression levels of CYP6CR12 and DaZnoDH are also regulated by feeding behavior and juvenile hormone levels. Since they are also expressed in males, CYP6CR12 and DaZnoDH are not only important for exo -brevicomin biosynthesis that this might be potential role for the semichemical biosysthesis pathways. Unlabelled Image • The two genes were identified as CYP6CR12 and DaZnoDH from the Chinese white pine beetle. • The expression levels of CYP6CR12 and DaZnoDH are regulated by feeding behavior and juvenile hormone levels. • CYP6CR12 and DaZnoDH are important for exo-brevicomin biosynthesis, as well as other semiochemical biosynthesis. [ABSTRACT FROM AUTHOR]

The potential association between coal-burning arsenic exposure and type 2 diabetes (T2D) was examined through a case control study, conducted in coal-burning arsenic poisoning areas in the Guizhou Province. This study included patients diagnosed with type 2 diabetes. Control subjects without type 2 diabetes were recruited randomly after gender and age 1:1 matching. All subjects completed questionnaire surveys and underwent physical examination and whole blood arsenic level testing. The whole blood arsenic level was associated with a significant increase in the risk of type 2 diabetes (75th versus 25th, adjusted OR = 1.76, 95% CI: 1.03–3.01). However, a nonlinear relationship was observed between the blood arsenic level and type 2 diabetes. The risk of type 2 diabetes increased with blood arsenic levels above 3.69 μg/L (Log As ≥0.57). The subgroup analysis revealed that blood arsenic levels were associated with significantly increased risk of type 2 diabetes in people who ever smoked (P <.05), particularly those who smoked ≥15 years (adjusted OR = 3.15, 95% CI: 1.9–7.28). Therefore, prolonged arsenic exposure, even at a low level, is associated with a higher prevalence of type 2 diabetes in a nonlinear pattern. Blood arsenic levels less than 3.69 μg/L may be considered safe with respect to the risk of T2D. However, smoking, particularly smoking ≥15 years, may be associated with the development of diabetes in patients with arsenic exposure. • Coal-burning arsenic exposure is associated with T2D. • Prolonged arsenic exposure, is associated with T2D in a nonlinear pattern. • Smoking may be associated with T2D onset in patients with arsenic exposure. [ABSTRACT FROM AUTHOR]

Euwallacea interjectus, a recently discovered pest in poplar plantations, poses a significant economic threat due to its role in causing widespread tree mortality. This pest's cryptic behaviour has hindered research and control efforts, making laboratory rearing a valuable tool for studying its development and biology. We investigated the development period and biological characteristics of E. interjectus using artificial diets and fungal medium. Our findings revealed that the development time for eggs, larvae, and pupae averages approximately 6, 18, and 6 days, respectively. Notably, first and second instar larvae displayed peak moulting periods at 3.45 ± 0.64 SD and 7.92 ± 1.77 SD days, respectively. Furthermore, we measured head capsule widths of postmolt larvae, yielding values of 318.02 ± 7.38 SD μ m for first-instar larvae, 403.01 ± 11.08 SD μ m for second-instar larvae, and 549.54 ± 20.74 SD μ m for third-instar larvae. Our research also uncovered a positive correlation between the number of progeny (eggs, larvae, pupae, and adults) and the mean length of the gallery system. Interestingly, the haplodiploid reproductive strategy did not significantly affect the number of offspring produced by the foundress. Additionally, we observed that foundresses displayed higher fecundity when subjected to nutrient-rich diets as compared to nutrient-poor diets. Our results will deepen our understanding of the biology of E. interjectus and provide criteria for larval instar classification. Additionally, managing nutrient availability within the colony could be considered a viable approach to regulating population size. [ABSTRACT FROM AUTHOR]

Introduction: Aging is characterized by the deterioration of a wide range of functions in tissues and organs, and Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Hypothyroidism occurs when there is insufficient production of thyroid hormones (THs) by the thyroid. The relationship between hypothyroidism and aging as well as AD is controversial at present. Methods: We established an animal model of AD (FAD4T) with mutations in the APP and PSEN1 genes, and we performed a thyroid function test and RNA sequencing (RNA-Seq) of the thyroid from FAD4T and naturally aging mice. We also studied gene perturbation correlation in the FAD4T mouse thyroid, bone marrow, and brain by further single-cell RNA sequencing (scRNA-seq) data of the bone marrow and brain. Results: In this study, we found alterations in THs in both AD and aging mice. RNA-seq data showed significant upregulation of T-cell infiltration- and cell proliferation-related genes in FAD4T mouse thyroid. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that upregulated genes were enriched in the functional gene modules of activation of immune cells. Downregulated energy metabolism-related genes were prominent in aging thyroids, which reflected the reduction in THs. GSEA showed a similar enrichment tendency in both mouse thyroids, suggesting their analogous inflammation state. In addition, the regulation of leukocyte activation and migration was a common signature between the thyroid, brain, and bone marrow of FAD4T mice. Conclusions: Our findings identified immune cell infiltration of the thyroid as the potential underlying mechanism of the alteration of THs in AD and aging. Plain Language Summary: In order to prove the relationship between alteration of thyroid hormones (THs) and Alzheimer's disease (AD), as well as aging, we established animal models of AD and naturally aging and performed thyroid function test and bulk RNA sequencing. We also studied gene perturbation correlation in AD mouse thyroid, bone marrow, and brain by further single-cell RNA sequencing (scRNA-seq) data of the bone marrow and brain. Our findings identified immune cell infiltration of the thyroid as the potential underlying mechanism of the alteration of THs in AD and aging. [ABSTRACT FROM AUTHOR]

Abstract We investigated the effects of elevated ozone (O 3) concentration on leaf nitrogen (N), a key determinant of plant photosynthesis, with two clones of poplar grown in open-top chambers. We focus on the difference between mass-based leaf N concentration (N mass) and area-based one (N area) in their responses to elevated O 3 , and the allocation of N to different leaf components: photosynthetic apparatus, cell walls, and others under elevated O 3 level. Our results showed that elevated O 3 significantly increased N mass , but reduced N area and leaf mass per area (LMA). The two clones showed no difference in N mass response to O 3 , but the more sensitive clone showed greater reduction of N area and LMA due to O 3. We also found positive relationships between N area and photosynthetic parameters, e.g. light-saturated photosynthetic rate (A sat). Furthermore, elevated O 3 significantly reduced photosynthetic N-use efficiency (PNUE) and leaf N allocation to photosynthetic components, while increasing N allocation to cell walls and other components. We concluded that plants invested more N in cell walls and other components to resist O 3 damages at the expense of photosynthetic N. The change of N allocation in plant leaves in response to elevated O 3 could have an impact on ecological processes, e.g. leaf litter decomposition. Graphical abstract Unlabelled Image Highlights • Ozone exposure-response relationships for leaf N concentration were established. • E-O 3 increased N mass of leaf, but reduced N area. • E-O 3 reduced leaf N allocation to photosynthesis (productivity). • E-O 3 increased leaf N allocation to cell walls (defense). [ABSTRACT FROM AUTHOR]

• Generic HILIC method was developed for gRNA analysis with mechanism revealed. • Suppressing surface charge is critical on HILIC separation of large RNAs. • HILIC-MS allows intact mass analysis of gRNAs without ion pairing reagents. • Low temperature HILIC is able to monitor gRNA aggregation formation. In this study, we aimed to develop a hydrophilic interaction liquid chromatography (HILIC) method for the analysis of single guide ribonucleic acid (sgRNA), a critical reagent used in CRISPR genome editing. Our results showed that effective profiling of sgRNA can be achieved by suppressing the surface charge of the stationary phase in HILIC. We identified hydrogen bonding as the primary retention mechanism with potential weak partitioning in HILIC separation of large oligonucleotides like 100-mer sgRNA. Moreover, we demonstrated that direct coupling of HILIC with mass spectrometry (MS) allows the intact mass analysis of sgRNA and its impurities with minimal adduct present. Finally, we characterized the post peak shown in the low temperature HILIC and identified it as sgRNA aggregates. Our findings provide valuable insight into the characterization of sgRNA and highlight the potential of HILIC-MS as a powerful analytical tool for relatively large oligonucleotide analysis. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine-disrupting compound, and the binding mechanism of BPA with carrier proteins has drawn widespread attention. Halogen substitutions can significantly impact the properties of BPA, resulting in various effects for human health. Here, we selected tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) to investigate the interaction between different halogen-substituted BPAs and human serum albumin (HSA). TBBPA/TCBPA spontaneously occupied site I and formed stable binary complexes with HSA. Compared to TCBPA, TBBPA has higher binding affinity to HSA. The effect of different halogen substituents on the negatively charged surface area of BPA was an important reason for the higher binding affinity of TBBPA to HSA compared to TCBPA. Hydrogen bonds and van der Waals forces were crucial in the TCBPA–HSA complex, while the main driving factor for the formation of the TBBPA–HSA complex was hydrophobic interactions. Moreover, the presence of TBBPA/TCBPA changed the secondary structure of HSA. Amino acid residues such as Lys199, Lys195, Phe211, Arg218, His242, Leu481, and Trp214 were found to play crucial roles in the binding process between BPA compounds and HSA. Furthermore, the presence of halogen substituents facilitated the binding of BPA compounds with HSA. [ABSTRACT FROM AUTHOR]

The sensitivity of Chinese soybean cultivars to ambient ozone (O 3 ) in the field is unknown, although soybean is a major staple food in China. Using ethylenediurea (EDU) as an O 3 protectant, we tested the gas exchange, pigments, antioxidants and biomass of 19 cultivars exposed to 28 ppm·hr AOT40 (accumulated O 3 over an hourly concentration threshold of 40 ppb) over the growing season at a field site in China. By comparing the average biomass with and without EDU, we estimated the cultivar-specific sensitivity to O 3 and ranked the cultivars from very tolerant (< 10% change) to highly sensitive (> 45% change), which helps in choosing the best-suited cultivars for local cultivation. Higher lipid peroxidation and activity of the ascorbate peroxidase enzyme were major responses to O 3 damage, which eventually translated into lower biomass production. The constitutional level of total ascorbate in the leaves was the most important parameter explaining O 3 sensitivity among these cultivars. Surprisingly, the role of stomatal conductance was insignificant. These results will guide future breeding efforts towards more O 3 -tolerant cultivars in China, while strategies for implementing control measures of regional O 3 pollution are being implemented. Overall, these results suggest that present ambient O 3 pollution is a serious concern for soybean in China, which highlights the urgent need for policy-making actions to protect this critical staple food. [ABSTRACT FROM AUTHOR]

Background: Endosonographers are highly dependent on the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to develop a deep‐learning radiomics (DLR) model based on endoscopic ultrasonography (EUS) images for identifying PDAC and to explore its true clinical benefit. Methods: A retrospective data set of EUS images that included PDAC and benign lesions was used as a training cohort (N = 368 patients) to develop the DLR model, and a prospective data set was used as a test cohort (N = 123 patients) to validate the effectiveness of the DLR model. In addition, seven endosonographers performed two rounds of reader studies on the test cohort with or without DLR assistance to further assess the clinical applicability and true benefits of the DLR model. Results: In the prospective test cohort, DLR exhibited an area under the receiver operating characteristic curves of 0.936 (95% confidence interval [CI], 0.889–0.976) with a sensitivity of 0.831 (95% CI, 0.746–0.913) and 0.904 (95% CI, 0.820–0.980), respectively. With DLR assistance, the overall diagnostic performance of the seven endosonographers improved: one endosonographer achieved a significant expansion of specificity (p =.035,) and another achieved a significant increase in sensitivity (p =.038). In the junior endosonographer group, the diagnostic performance with the help of the DLR was higher than or comparable to that of the senior endosonographer group without DLR assistance. Conclusions: A prospective test cohort validated that the DLR model based on EUS images effectively identified PDAC. With the assistance of this model, the gap between endosonographers at different levels of experience narrowed, and the accuracy of endosonographers expanded. The deep‐learning radiomics model improved the diagnostic accuracy, sensitivity, and specificity of all endosonographers in the test cohort. With the aid of our model, the decision‐making accuracy of all endosonographers was further improved. The deep learning radiomics model is a tool with clinical application potential that can assist endosonographers in pancreatic ductal adenocarcinoma diagnosis. [ABSTRACT FROM AUTHOR]

• Inhibition of spontaneous coal combustion is best when the wall-to-core ratio of microencapsulated inhibitors is 4:1. • Reduction of free hydroxyl groups in coal samples after addition of microencapsulated inhibitor. • The addition of inhibitors increases the interaction energy of the system. • The hydroxyl group in the inhibitor interacts with the oxygen atoms in the water molecule more strongly. In order to solve the shortcomings of traditional inhibitors, which are easy to be interfered by the outside world during the inhibition process and the active ingredients are easy to be oxidized and invalidated, microencapsulated inhibitors were developed. In this study, we prepared microencapsulated inhibitors of varying wall-to-core ratios using a composite phase of polyethylene glycol 20,000 (PEG-20000) and octenyl amyl succinate (OSAS) as the wall material and a lauryl glucoside (APG-12) and butyl hydroxyanisole (BHA) phase as the core material. After thoroughly mixing the microcapsule inhibitor with coal samples, simultaneous thermal analyzer (TG/DSC) and a temperature-programmed system were used to evaluate the resisting qualities of the produced microencapsulated inhibitors. The results of the temperature programmed experiment showed that the overall CO release from the blocked coal samples was less than that of the original coal. According to thermogravimetric results, the most effective inhibition occurred when the wall/core ratio of the microcapsule inhibitor was 4:1. This also resulted in a reduction of the maximum coal weight loss rate from 1.34 to 0.96 %/min and an increase in the maximum coal weight loss temperature from 477.4 to 507.6 °C. The microencapsulated inhibitor melts in the wall at 57.4 °C, enabling temperature-sensitive intelligent control of core release. Following heating the raw and inhibited coal samples to 100 and 200 °C, respectively, Fourier infrared spectroscopy was conducted. At these temperatures, the amounts of ether bonds increased by 20.4 and 22.6 %, and the number of free hydroxyl groups decreased by 12.8 and 2.7 %, respectively, in the inhibited coal samples. Finally, molecular dynamics theory was applied to investigate the inhibitory mechanism. The prepared microcapsule retardant effectively inhibited the spontaneous combustion reaction of coal, suggesting this microcapsule inhibitor could be manufactured as a novel inhibitor for coal spontaneous combustion. [ABSTRACT FROM AUTHOR]

Background: Heat Shock Proteins 70 (HSP70s) in insects act on a diverse range of substrates to assist with overcoming extreme high temperatures. MaltHSP70-2, a member of HSP70s, has been characterized to involve in the thermotolerance of Monochamus alternatus in vitro, while quantification and localization of MaltHSP70-2 in various tissues and its functional analysis in vivo remain unclear. Results: In this study, temporal expression of MaltHSP70-2 indicated a long-last inductive effect on MaltHSP70-2 expression maintained 48 hours after heat shock. MaltHSP70-2 showed a global response to heat exposure which occurring in various tissues of both males and females. Particularly in the reproductive tissues, we further performed the quantification and localization of MaltHSP70-2 protein using Western Blot and Immunohistochemistry, suggesting that enriched MaltHSP70-2 in the testis (specifically in the primary spermatocyte) must be indispensable to protect the reproductive activities (e.g., spermatogenesis) against high temperatures. Furthermore, silencing MaltHSP70-2 markedly influenced the expression of other HSP genes and thermotolerance of adults in bioassays, which implied a possible interaction of MaltHSP70-2 with other HSP genes and its role in thermal resistance of M. alternatus adults. Conclusions: These findings shed new insights into thermo-resistant mechanism of M. alternatus to cope with global warming from the perspective of HSP70s functions. [ABSTRACT FROM AUTHOR]

Monochamus alternatus , the dominant vector of Bursaphelenchus xylophilus (Aphelenchida: Aphelenchoididae), has caused immense damage to forest resources. In China, this vector was native to the southern regions but has spread northward recently. To adapt to more challenging environments in the northern winter, M. alternatus has evolved an intricate strategy for overwintering, which remains largely unknown. Herein, we compared the transcriptome data of the overwintering and non-overwintering larvae of M. alternatus larvae to investigate the molecular mechanisms in overwintering. A total of 53.10 GB clean bases and 28, 245 unigenes were obtained by RNA-seq. Analysis of 2597 upregulated and 2429 downregulated unigenes, as well as the enrichment of DEGs showed that many genes and pathways were jointly involved in the overwintering period. Besides, the accuracy of the RNA-seq data was tested by using qPCR experiment involving 13 selected genes. The results revealed that the overwintering process relied largely on the energy allocation trade-off. Specifically, overwintering M. alternatus inhibited energy-intensive activities, such as growth and molting, detoxification, and trehalose transport, and the reserved energy was skewed towards the synthesis of antifreeze compounds and immune response to cope with the deleterious effects of winter. [ABSTRACT FROM AUTHOR]

A substantial increase in the occurrence of extremely high‐ or low‐temperature events caused by global climate change has imposed pressure on the survival and reproduction of invertebrates. Hyphantria cunea (H. cunea; Lepidoptera: Arctiidae) is a worldwide defoliator and has become a major forestry and agricultural pest during the past three decades in China. The thermal and cold tolerance has directly affected the population and geographical distribution of H. cunea, which remains poorly understood. Here, we examined the thermal tolerance of H. cunea larvae and discovered that they could endure extremely high temperatures, as demonstrated by median lethal times (Ltim50) of 103.3 hr at 37°C, 62.0 hr at 40°C and even 14.5 hr at 43°C. To further explore the molecular evidence of the physiological response to heat and cold, we cloned and characterized six small heat shock proteins (sHSPs). These proteins possessed the conserved α‐domain of the sHSP family at the C‐terminus and various N‐terminal domains. Phylogenetic analysis showed that the HCsHSPs presented a close evolutionary relationship with sHSP genes in noctuidae species. Four sHSPs in H. cunea were sensitive to heat stress, and only HCsHSP28.7 was induced by cold stress. The expression level of HCsHSPs peaked at 40°C and decreased in treatment at 45°C. HCsHSP20.0 transcripts were abundant in the cuticle after heat shock, and HCsHSP28.7 was most enriched in the fat body after cold shock. In addition, an equal molecular weight of the HCsHSP20.0 protein could completely protect malate dehydrogenase (MDH) from thermal aggregation. Recombinant HCsHSP28.7 E. coli cells exhibited tolerance to cold stress. Overall, our results demonstrate that HCsHSPs, especially HCsHSP20.0 and HCsHSP28.7, are vital genes in the adaptation of H. cunea larvae to extreme conditions in the context of global climate change. [ABSTRACT FROM AUTHOR]

• CV quenched the intrinsic fluorescence of pepsin in a combined mechanism. • The conformational change of pepsin was induced by CV. • Electrostatic interaction was nonnegligible for the stability of CV-pepsin binding process. • Tyr75, Tyr189 and Asp215 residues made a great contribution towards the binding process. • The activity of pepsin was activated by CV. As a well-known triphenylmethane dye, crystal violet (CV) has received extensive concerns owing to its harmful influence on human health. Pepsin is a digestive enzyme in the stomach that plays a crucial part in several physiological and pathological process. This research aimed to use spectroscopic experiments, computer simulation and enzyme activity assays to investigate the influence of CV on the functions and structure of pepsin from the perspective of binding. Fluorescence and UV–vis spectra confirmed the complex formation between CV and pepsin. K a was in the order of 104 M−1, implying a moderate affinity between CV and pepsin. Multi non-covalent interactions played a crucial part in this binding process. The conformational alterations of pepsin caused by CV were reflected in β-sheet content reducing, and the presence of CV caused an activation of pepsin. The outcomes of molecular docking indicated that the interaction of Tyr75/Tyr189 with CV is the major cause for the fluorescence quenching phenomenon of pepsin. For molecular dynamics (MD) simulation, the CV-pepsin and free pepsin systems reached equilibrium in 40 ns. In addition, the compactness of pepsin changed after interacting with CV, which was in line with the results of solvent experiment. From the above results, CV has effects on the properties of pepsin, which may provide novel insights into the toxicological study of CV. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Finite mesophyll conductance (g m) reduces the rate of CO 2 diffusion from the leaf intercellular space to the chloroplast and constitutes a major limitation of photosynthesis in trees. While it is well established that g m is decreased by stressors such as drought and high temperature, few studies have investigated if the phytotoxic air pollutant ozone (O 3) affects g m. We quantified the relative importance of three different types of limitations of photosynthesis in poplar trees exposed to elevated O 3 : decreases in stomatal conductance, g m and biochemical photosynthetic capacity. The O 3 -induced reductions in light-saturated net photosynthesis were linked to significant declines in g m and biochemical photosynthetic capacity (in particular carboxylation). There was no significant effect of O 3 on stomatal conductance. Of the O 3 -induced limitations on photosynthesis, g m limitation was by far the most important (−16%) while biochemical limitation (−8%) was rather small. Both limitations grew in magnitude over the study period and varied in response to leaf-specific O 3 exposure. Our findings suggest that declines in g m may play a key role in limiting photosynthesis of plants exposed to elevated O 3 , an effect hitherto overlooked. Graphical abstract Unlabelled Image Highlights • The photosynthetic response to elevated ozone was investigated in poplar trees. • Ozone exposure reduced leaf mesophyll conductance and carboxylation capacity. • Stomatal conductance was unaffected by elevated ozone. • The overall photosynthetic limitation increased with exposure time. • The main ozone-induced limitation to photosynthesis was reduced mesophyll conductance. [ABSTRACT FROM AUTHOR]

We comprehensively investigated the biodiversity of fungal communities in different developmental stages of Trypophloeus klimeschi and the difference between sexes and two generations by high throughput sequencing. The predominant species found in the intestinal fungal communities mainly belong to the phyla Ascomycota and Basidiomycota. Fungal community structure varies with life stage. The genera Nakazawaea, Trichothecium, Aspergillus, Didymella, Villophora, and Auricularia are most prevalent in the larvae samples. Adults harbored high proportions of Graphium. The fungal community structures found in different sexes are similar. Fusarium is the most abundant genus and conserved in all development stages. Gut fungal communities showed notable variation in relative abundance during the overwintering stage. Fusarium and Nectriaceae were significantly increased in overwintering mature larvae. The data indicates that Fusarium might play important roles in the survival of T. klimeschi especially in the overwintering stage. The authors speculated that Graphium plays an important role in the invasion and colonization of T. klimeschi. The study will contribute to the understanding of the biological role of the intestinal fungi in T. klimeschi, which might provide an opportunity and theoretical basis to promote integrated pest management (IPM) of T. klimeschi. [ABSTRACT FROM AUTHOR]

[Display omitted] • POM inserted to the subdomain IIA (site I) of HSA through H-bonds and van der Waals forces. • The secondary structure of HSA was changed by POM. • Leu198, Lys199 and Trp214 made a great contribution towards the binding process. • π electrons in POM were important for the stability of HSA-POM complex. • The therapeutic efficiency of molecular glue drugs could be assessed through the K a of serum albumin-molecular glue complex. Pomalidomide (POM) has been discovered as a new molecular-glue-type degraders in recent years. It is a potent immunomodulatory drug and is used for the treatment of recrudescent and intractable multiple myeloma (MM). The interaction between POM and human serum albumin (HSA) was studied by multiple spectral techniques, molecular docking technique, and molecular dynamics simulation in this research. POM and HSA formed a complex with one binding stoichiometry. Site I was the binding site of POM to HSA and the binding constant was (6.180 ± 0.009) × 103 M−1 (293 K). Based on the thermodynamic results, the binding process was exothermic and spontaneous. Van der Waals forces and H-bonds were the chief driving forces. The conformational changes in HSA induced by POM were reflected in β-turn content increasing and α-helix content reducing. The results of computer simulation were consistent with that of the multiple spectral experiments. In addition, the results of molecular docking indicated π electrons in POM were also vital for the stability of HSA-POM complex. Molecular dynamics simulation showed that Leu198, Lys199 and Trp214 played a contributing role in the binding process, and the fluorescence of HSA quenched by POM might be attributed to the reduction in the accessible surface area values of Trp214. This research is aimed at better understanding the effects of molecular-glue-type degraders on human health, and it is helpful in clinical treatment of MM. [ABSTRACT FROM AUTHOR]

Cold hardiness becomes a crucial strategy because temperature change often leads to fluctuations in insect abundance., The present study investigated the relationship between cold-tolerance ability in overwintering Chinese white pine beetle Dendroctonus armandi Tsai and Li larvae and physiological body indices aiming to determine the possible overwintering strategy from September 2013 to May 2014., Supercooling points ( SCP) differed significantly across months, showing a precipitous drop in December 2013 and January 2014. The maximum monthly mean supercooling point was −1.7 ± 0.4 ° C (15 September 2013) and the minimum monthly mean was −7.5 ± 0.2 ° C (15 January 2014). The SCP tended to decrease as the ambient temperature decreased until January, before increasing until the end of the winter., Glycerol, sorbitol and trehalose contents showed a significant negative correlation with the SCP., The latter results indicate that the cold tolerance ability of the larvae is enhanced by exposure to 4.0 ° C., Dendroctonus armandi larvae decreased their mortality at −8.0 ° C after cold acclimation at 4.0 ° C for 24 h. [ABSTRACT FROM AUTHOR]

• PER bound with ctDNA to form a binary complex. • Hydrogen bonds and van der Waals force worked in the binding process. • PER embedded in the ctDNA minor groove rich of A-T bases. • PER-DNA system equilibrated after 100 ns. • DC-9, DT-19, and DT-20 contributed a lot to stabilizing PER-DNA complex. Perampanel (PER) is the first drug to treat epilepsy by blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In the current study, the interaction of PER and calf thymus DNA (ctDNA) was explored through various spectroscopic techniques and computer modelling. According to the UV-vis titration results, PER combined with ctDNA via groove binding, which was also confirmed by thermal melting, salt effect, ssDNA/dsDNA quenching, and competitive experiments. The dominant forces were hydrogen bond and van der Waals force. And the binding constant obtained was 6.97 × 103 M−1 at 298 K. According to the data from FTIR assays and computer modelling, PER was embedded in the minor groove of ctDNA rich in A and T bases. In the simulation of 200 ns, the PER-DNA system reached equilibrium at about 100 ns. The structure of DNA became loose when a stable binary complex with PER was formed. The energy decomposition indicated that DC-9, DT-19, and DT-20 bases played a main role in this complex-forming. In summary, this study contributed to understanding the interaction mechanism of PER and ctDNA. [Display omitted] [ABSTRACT FROM AUTHOR]