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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]

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]

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]

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]

The Chinese white pine beetle (Dendroctonus armandi Tsai and Li) is the causal organism for the colossal death of the Chinese white pine (Pinus armandi Fr). We investigated the change of monoterpenes in the stem pholem and xylem in P. armandi saplings at 4 days, 8 days, and 30 days after treatment using treatment (MeJa + Tween-20 and Tween-20 as control) and untreated. GC-MS analysis found that the total monoterpene concentrations in the pholem and xylem in MeJa-treated saplings increased significantly compared with control or untreated saplings. Additionally, the proportions of β-pinene in the stem pholem, β-myrcene in the stem xylem, and limonene + β-phellandrene in both pholem and xylem of MeJa-treated saplings were increased significantly compared with control or untreated saplings. Based on our results, we suggest that by increasing the total concentration of monoterpene and the concentrations of β-myrcene, β-pinene and limonene + β-phellandrene maybe play an important defensive role against insect pests in P. armandi defense.

A generic static headspace gas chromatographic (HSGC) method for determining common residual solvents in pharmaceuticals is described. The method is simple and readily adaptable to diversified drug substances or drug [...]

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]

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]

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]

Lipopolysaccharides (LPSs) released by gut microbiota are correlated with the pathophysiology of osteoarthritis (OA). Exercise remodels the composition of gut microbiota. The present study investigated the hypothesis that wheel-running exercise prevents knee OA induced by high-fat diet (HFD) via reducing LPS from intestinal microorganisms. Male C57BL/6 J mice were treated with sedentary or wheel-running exercise, standard diet (13.5% kcal) or HFD (60% kcal), berberine or not according to their grouping. Knee OA severity, blood and synovial fluid LPS, cecal microbiota, and TLR4 and MMP-13 expression levels were determined. Our findings reveal that HFD treatment decreased gut microbial diversity. Increase in endotoxin-producing bacteria, decrease in gut barrier-protecting bacteria, high LPS levels in the blood and synovial fluid, high TLR4 and MMP-13 expression levels, and severe cartilage degeneration were observed. By contrast, voluntary wheel running caused high gut microbial diversity. The gut microbiota were reshaped, LPS levels in the blood and synovial fluid and TLR4 and MMP-13 expression levels were low, and cartilage degeneration was ameliorated. Berberine treatment reduced LPS levels in the samples, but decreased the diversity of intestinal flora with similar changes to that caused by HFD. In conclusion, unlike taking drugs, exercising can remodel gut microbial ecosystems, reduce the circulating levels of LPS, and thereby contribute to the relief of chronic inflammation and OA. Our findings showed that moderate exercise is a potential therapeutic approach for preventing and treating obesity-related OA. [ABSTRACT FROM AUTHOR]

The Chinese white pine beetle (Dendroctonus armandi) is undoubtedly one of the most important pests causing ecological damage in the Qinling Mountains. When bark beetles invade conifers, they must overcome host tree defenses, including primary resistance and induced resistance responses. Moreover, this induced resistance occurs following herbivory by bark beetles. Bark beetles have a corresponding defense mechanism for degrading toxic compounds, and glutathione S-transferases (GSTs) can catalyze the binding of endogenous substances that reduce glutathione (GSH) to various harmful electrophilic substrates, increasing their solubility and facilitating their excretion from cells. In this experiment, we successfully obtained sixteen full-length sequences of D. armandi , which belonged to four GST categories (delta, epsilon, sigma, and theta). The transcript levels of sixteen GSTs in D. armandi were compared at four developmental stages (larvae, pupae, teneral adults, and adults), three different tissues (antennae, gut, and reproductive organs), and under various levels of terpenoid stimuli during feeding on phloem tissue to evaluate the various relevant modes of action. This study aids in the understanding of the interaction between monoterpenes and beetles, and beetles' detoxification through GSTs. [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]