In Silico Prediction of Quercetin Analogs for Targeting Death-Associated Protein Kinase 1 (DAPK1) Against Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that greatly affects the health and life quality of the elderly population. Existing drugs mainly alleviate symptoms but fail to halt disease progression, underscoring the urgent need for the development of novel drugs. Based on the neuroprotective effects of flavonoid quercetin in AD, this study was designed to identify potential AD-related targets for quercetin and perform in silico prediction of promising analogs for the treatment of AD. Database mining suggested death-associated protein kinase 1 (DAPK1) as the most promising AD-related target for quercetin among seven protein candidates. To achieve better biological effects for the treatment of AD, we devised a series of quercetin analogs as ligands for DAPK1, and molecular docking analyses, absorption, distribution, metabolism, and excretion (ADME) predictions, as well as molecular dynamics (MD) simulations, were performed. The energy for drug-protein interaction was predicted and ranked. As a result, quercetin-A1a and quercetin-A1a1 out of 19 quercetin analogs exhibited the lowest interaction energy for binding to DAPK1 than quercetin, and they had similar dynamics performance with quercetin. In addition, quercetin-A1a and quercetin-A1a1 were predicted to have better water solubility. Thus, quercetin-A1a and quercetin-A1a1 could be promising agents for the treatment of AD. Our findings paved the way for further experimental studies and the development of novel drugs.

Electrophysiological Characteristics of Inhibitive Control for Adults with Different Physiological or Psychological Obesity.

Individuals exhibiting high scores on the fatness subscale of the negative-physical-self scale (NPSS-F) are characterized by heightened preoccupation with body fat accompanied by negative body image perceptions, often leading to excessive dieting behaviors. This demographic constitutes a considerable segment of the populace in China, even among those who are not obese. Nonetheless, scant empirical inquiries have delved into the behavioral and neurophysiological profiles of individuals possessing a healthy body mass index (BMI) alongside elevated NPSS-F scores. This study employed an experimental paradigm integrating go/no-go and one-back tasks to assess inhibitory control and working memory capacities concerning food-related stimuli across three adult cohorts: those with normal weight and low NPSS-F scores, those with normal weight and high NPSS-F scores, and individuals classified as obese. Experimental stimuli comprised high- and low-caloric-food pictures with concurrent electroencephalogram (EEG) and photoplethysmogram (PPG) recordings. Individuals characterized by high NPSS-F scores and normal weight exhibited distinctive electrophysiological responses compared to the other two cohorts, evident in event-related potential (ERP) components, theta and alpha band oscillations, and heart rate variability (HRV) patterns. In essence, the findings underscore alterations in electrophysiological reactivity among individuals possessing high NPSS-F scores and a healthy BMI in the context of food-related stimuli, underscoring the necessity for increased attention to this demographic alongside individuals affected by obesity.

Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

[Research progress on the neural mechanism of the regulation of social isolation on innate behaviors].

Innate behavior is mainly controlled by genetics, but is also regulated by social experiences such as social isolation. Studies in animal models such as Drosophila and mice have found that social isolation can regulate innate behaviors through the changes at the molecular level, such as hormone, neurotransmitter, neuropeptide level, and at the level of neural circuits. In this review, we summarized the research progress on the regulation of social isolation on various animal innate behaviors, such as sleep, reproduction and aggression by altering the expression of conserved neuropeptides and neurotransmitters, hoping to deepen the understanding of the key and conserved signal pathways that regulate innate behavior by social isolation.

Association between Hypertrophic Cardiomyopathy and Variations in Sarcomere Gene and Calcium Channel Gene in Adults.

INTRODUCTION: Calcium channel gene variations have been reported to be associated with hypertrophic cardiomyopathy (HCM) in family, but the relationship between calcium channel gene variations and HCM remains undefined in the population. METHODS: A total of 719 HCM unrelated patients were initially enrolled. Finally, 371 patients were identified based on inclusion and exclusion criteria, including 145 patients with gene negative, 28 patients with a single rare calcium channel gene variation (calcium gene variation), 162 patients with a single pathogenic/likely pathogenic sarcomere gene variation (sarcomere gene variation) and 36 patients with a single pathogenic/likely pathogenic sarcomere gene variation and a single rare calcium channel gene variation (double gene variations). Then the demographic, electrocardiographic, echocardiographic, and follow-up data were collected. RESULTS: Patients with double gene variations were at an earlier age and had more percent of family history of HCM, and had thicker walls, higher left ventricular outflow tract pressure gradient, more pathological Q waves, and more bundle branch blocks as compared with those with single sarcomere gene variation. During the follow-up period, patients with double gene variations had more primary endpoints than the other three groups (p = 0.0013). Multivariate analysis showed that double gene variations were the independent predictor of primary endpoint events in patients (HR: 4.82, 95% CI: 1.77-13.2; p = 0.002). CONCLUSION: We found that patients with double gene variations had more severe HCM phenotype and prognosis. The pathogenesis effects of sarcomere gene variation and calcium channel gene variation may be cumulative in HCM populations.

Immobilization of Coprinus comatus with magnetic alginate hydrogel microsphere for improving the antioxidant activity of fermentation products.

Coprinus comatus is an edible mushroom and its fermented product possesses antioxidant activity. In this study, to further enhance the antioxidant activity and improve the reusability of the strain, calcium alginate hydrogel was used as the carrier for embedding and immobilizing Coprinus comatus. The effects of CaCl2 concentration, sodium alginate concentration, microsphere diameter, and the amount of magnetic particle on the antioxidant activity of fermented products were investigated. The results showed that the magnetic immobilized microsphere prepared by 2.50% CaCl2, 2.00% sodium alginate and 0.50% Fe3O4 had the best fermentation antioxidant activity (EC50 was 0.43 ± 0.01 mg/mL) when the diameter was 5 mm, which increased by 24.56% compared to the initial activity. Besides, the microsphere showed strong reusability, the antioxidant activity was still better than the free strain after being used five times. This study not only enhanced the antioxidant activity of Coprinus comatus fermented product through immobilization, but also provided an effective method for microbial fermentation.

Novel Pt(IV) complexes containing salvigenin ligand reverse cisplatin-induced resistance by inhibiting Rap1b-mediated cancer cell stemness in esophageal squamous cell carcinoma treatments.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that is highly susceptible to metastasis, recurrence and resistance, and few therapeutic targets have been identified and proven effective. Herein, we demonstrated for the first time that Rap1b can positively regulate ESCC cell stemness, as well as designed and synthesized a novel class of Pt(IV) complexes that can effectively inhibit Raplb. In vitro biological studies showed that complex-1 exhibited stronger cytotoxicity than cisplatin and oxaliplatin against a variety of ESCC cells, and effectively reversed cisplatin-induced resistance of TE6 cells by increasing cellular accumulation of platinum and inhibiting cancer cell stemness. Significantly, complex-1 also exhibited strong ability to reversal cisplatin-induced cancer cell resistance and inhibit tumor growth in TE6/cDDP xenograft mice models, with a tumor growth inhibition rate of 73.3 % at 13 mg/kg and did not show significant systemic toxicity. Overall, Rap1b is a promising target to be developed as an effective treatment for ESCC. Complex-1, as the first Pt(IV) complex that can strongly inhibit Rap1b, is also worthy of further in-depth study.

Comparison of the RF-CL and CACS-CL models to estimate the pretest probability of obstructive coronary artery disease and predict prognosis in patients with stable chest pain and diabetes mellitus.

Background: The most appropriate tool for estimating the pretest probability (PTP) of obstructive coronary artery disease (CAD) in patients with diabetes mellitus (DM) and stable chest pain (SCP) remains unknown. Therefore, we aimed to validate and compare two recent models, namely, the risk factor-weighted clinical likelihood (RF-CL) model and coronary artery calcium score (CACS)-weighted clinical likelihood (CACS-CL) model, in these patient populations. Methods: A total of 1,245 symptomatic patients with DM, who underwent CACS and coronary computed tomographic angiography (CCTA) scan, were identified and followed up. PTP of obstructive CAD for each patient was estimated using the RF-CL model and CACS-CL model, respectively. Area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess the performance of models. The associations of major adverse cardiovascular events (MACE) with risk groups were evaluated using Cox proportional hazards regression. Results: Compared with the RF-CL model, the CACS-CL model revealed a larger AUC (0.856 vs. 0.782, p = 0.0016), positive IDI (12%, p < 0.0001) and NRI (34%, p < 0.0001), stronger association to MACE (hazard ratio: 0.26 vs. 0.38) and less discrepancy between observed and predicted probabilities, resulting in a more effective risk assessment to optimize downstream clinical management. Conclusion: Among patients with DM and SCP, the incorporation of CACS into the CACS-CL model resulted in a more accurate estimation for PTP and prediction of MACE. Utilizing the CACS-CL model, instead of the RF-CL model, might have greater potential to avoid unnecessary and omissive cardiovascular imaging testing with minimal cost.

Comparison of the specific energies of sinusoidal VCS cutter rings and CCS cutter rings in breaking rock-like materials based on the FEM.

Disc cutters are essential for full-section hard-rock tunnel boring machines. The performance of these devices directly affects tunnel engineering costs and duration. This paper proposes a sinusoidal variable cross-section (VCS) cutter ring and design method and establishes a digital model. Rock-like materials are simulated with a finite element model, and the model validity is verified via rock simulation mechanics tests. A disc cutter rolling rock simulation model for a linear cutting machine is also established, and simulation tests are performed for single- and three-cutter rolling using sinusoidal VCSs and constant cross-section (CCS) cutter models, respectively. The stress and energy changes for the cutters and rock-like material damage area were compared via simulation, confirming that some sinusoidal VCS cutter rings do less work on rock-like materials and cause larger crushing areas under the same engineering parameters; therefore, these cutter rings have smaller specific energies. The sinusoidal VCS cutter ring performance is 7% greater than that of CCS on average under single-cutter simulation, and the intermediate cutter performance of the intermediate cutter is 9% greater than that of CCS on average under three-cutter simulation. Thus, sinusoidal VCS cutter rings offer improved rock damage performance, and further research and application of this technology will improve the working efficiency of tunnel boring machines.

Series of Viologen-Based Metal-Organic Polyhedra with Photo/Electrochromic Behavior for Inkless Printing and UV Detection.

The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.

Resident tissue macrophages: Key coordinators of tissue homeostasis beyond immunity.

Resident tissue macrophages (RTMs) encompass a highly diverse set of cells abundantly present in every tissue and organ. RTMs are recognized as central players in innate immune responses, and more recently their importance beyond host defense has started to be highlighted. Despite sharing a universal name and several canonical markers, RTMs perform remarkably specialized activities tailored to sustain critical homeostatic functions of the organs they reside in. These cells can mediate neuronal communication, participate in metabolic pathways, and secrete growth factors. In this Review, we summarize how the division of labor among different RTM subsets helps support tissue homeostasis. We discuss how the local microenvironment influences the development of RTMs, the molecular processes they support, and how dysregulation of RTMs can lead to disease. Last, we highlight both the similarities and tissue-specific distinctions of key RTM subsets, aiming to coalesce recent classifications and perspectives into a unified view.

Feeding adaptation of François' langurs (Trachypithecus francoisi) to the fragmented limestone habitats in Southwest China.

Limestone forests are an unusual habitat for primates, especially fragmented limestone habitats. However, while some research has been conducted on François' langurs (Trachypithecus francois) in these habitats, there is still a need to improve the understanding of their behavioral adaptations to the fragmented limestone habitat. We collected data on the diet of François' langurs in a fragmented limestone habitat in Encheng National Nature Reserve, southwestern Guangxi, China using instantaneous scanning sampling, and their feeding adaptations to the fragmented forest were examined. The results indicated that a total of 101 species of plants were consumed by the langurs. They also fed on two non-plant components, including cliff minerals and at least one species of insect. The langurs ate a higher number of food species in Encheng when compared with the other geographic populations, and they maintained a high level of food diversity and ate more vines. Moreover, they were highly selective in their use of vegetation in their home range, and fewer plants provided a high-quality food source. During the season when food resources were scarce, the consumption of fruits and young leaves decreased as their availability decreased. This led to the use of other food components, such as mature leaves and seeds. The findings support that François' langurs adjust their feeding behavior to cope with seasonal and micro-variations in their dietary requirements and to adapt to their particular environment.

The multifaceted role of macrophage mitophagy in SiO2-induced pulmonary fibrosis: A brief review.

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

Comparison of the effect of tea shoots during different seasons in Arma chinensis (Hemiptera: Pentatomidae) reared on Ectropis grisescens (Lepidoptera: Geometridae) pupae.

In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age-stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.

The Neural Correlates of Food Preference among Music Kinds.

The calorie and taste choices of food have been shown to be related to the external environment, including music. Previous studies have mostly focused on manipulating basic auditory parameters, with few scholars exploring the impact of complex musical parameters on food selection. This study explored the effects of different kinds of music (classical, rock, jazz, and hip-hop) on food liking based on the calories (high and low) and taste (sweet and salty) using event-related potentials (ERPs). Twenty-four participants (8 males, 16 females) were recruited from Southwest University, China to participate in the food liking task using a Likert seven-point rating and simultaneously recording EEG signals (N2, P2, N3, and LPC). This study used repeated-measures analyses of covariances and found that the score of the high-calorie foods was greater than that of the low-calorie foods. Additionally, results revealed that the score in classical music was greatest for sweet foods, while there was no difference among music kinds in the salty foods. The ERP results showed that P2 amplitudes were greater for sweet foods than those for the salty foods. N2 amplitudes for the salty foods were greater than those for the sweet foods during rock music; in addition, N2 amplitudes during hip-hop music were greatest for sweet foods. However, N2 amplitudes during rock music were the greatest for salty foods. The results also revealed that N2 amplitudes during hip-hop music were greater than those during jazz music. This study provides unique operational insights for businesses.

A Paternò-Büchi Reaction of Aromatics with Quinones under Visible Light Irradiation.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

Advances in biotin biosynthesis and biotechnological production in microorganisms.

Biotin, also known as vitamin H or B7, acts as a crucial cofactor in the central metabolism processes of fatty acids, amino acids, and carbohydrates. Biotin has important applications in food additives, biomedicine, and other fields. While the ability to synthesize biotin de novo is confined to microorganisms and plants, humans and animals require substantial daily intake, primarily through dietary sources and intestinal microflora. Currently, chemical synthesis stands as the primary method for commercial biotin production, although microbial biotin production offers an environmentally sustainable alternative with promising prospects. This review presents a comprehensive overview of the pathways involved in de novo biotin synthesis in various species of microbes and insights into its regulatory and transport systems. Furthermore, diverse strategies are discussed to improve the biotin production here, including mutation breeding, rational metabolic engineering design, artificial genetic modification, and process optimization. The review also presents the potential strategies for addressing current challenges for industrial-scale bioproduction of biotin in the future. This review is very helpful for exploring efficient and sustainable strategies for large-scale biotin production.

NRSN2 promotes the malignant behavior of HPV-transfected laryngeal carcinoma cells through AMPK/ULK1 pathway mediated autophagy activation.

Neurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.