Pericentriolar material 1 promotes intestinal inflammation in ulcerative colitis by activating NLRP3/gasdermin D-mediated macrophage pyroptosis.

Excessive proinflammatory cytokine release induced by pyroptosis plays a vital role in intestinal mucosal inflammation in ulcerative colitis (UC). Several pyroptosis-related factors are regulated by the centrosome. Pericentriolar material 1 (PCM1) is a primary component of centriolar satellites that is present as cytoplasmic granules around the centrosome. Our previous study revealed that PCM1 was highly expressed in UC patients, but the role of PCM1 in UC remains unknown. This study aimed to elucidate the role of PCM1 in the development of UC, especially the mechanism in pyroptosis process of UC. Clinical mucosal sample and dextran sulfate sodium (DSS)-induced colitis mouse were used to reveal the association between PCM1 and intestinal inflammation. Intestinal epithelial cell-specific PCM1-knockout mice were constructed to determine the role of PCM1 in colitis. Finally, PCM1 RNA interference and overexpression assays in THP1 cells were employed to study the molecular mechanisms of PCM1 in inflammatory responses and pyroptosis. We found that PCM1 expression was upregulated in the colonic mucosa of UC patients and positively correlated with inflammatory indicators. PCM1 expression was elevated in DSS-induced colitis mice and was reduced after methylprednisolone treatment. In the DSS colitis model, intestinal-specific PCM1-knockout mice exhibited milder intestinal inflammation and lower pyroptosis levels than wild-type mice. In cell level, PCM1 exerted a proinflammatory effect by activating the NLRP3 inflammasome and triggering subsequent gasdermin D-mediated pyroptosis to release IL-1ß and IL-18. In conclusion, PCM1 mediates activation of the NLRP3 inflammasome and gasdermin D-dependent pyroptosis, ultimately accelerating intestinal inflammation in UC. These findings revealed a previously unknown role of PCM1 in initiating intestinal mucosal inflammation and pyroptosis in UC, and this factor is expected to be a regulator in the complex inflammatory network of UC.

Achieving Ultra-Long Cycle Life of Zn Anode Using ZnSn(OH)6 Coating Layer via Desolvation Effect and Uniform Zn2+ Flux.

Aqueous zinc-ion batteries (AZIBs) are considered as a promising energy storage system because of good safety, low cost, abundant resources, and environmental friendliness. However, the bottlenecks including dendrite growth, hydrogen evolution, and corrosion seriously limit their practical application. Herein, a novel ZnSn(OH)6 coating layer with rich hydroxyl groups is employed to achieve highly stable Zn anode. The hydroxyl groups can feasibly interact with H2O molecules, contributing to the desolvation of hydrated Zn2+ and the inhibition of side reactions on Zn anode surface. Furthermore, according to the DFT calculation, the adsorption energy of Zn2+ among various sites on the surface of ZnSn(OH)6 coating layer is relatively large, which helps the uniform distribution of Zn2+ flux and the prevention of dendrite growth. Consequently, the ZnSn(OH)6@Zn anode delivers ultra-long cycle life (6770 h), low polarization voltage (27 mV), and high Coulombic efficiency (99.2% over 800 cycles) at 1 mA cm-2, 1 mAh cm-2. Besides, the assembled NaV3O8·xH2O//ZnSn(OH)6@Zn full cell can operate stably for 1500 cycles at 2 A g-1 with a high specific capacity of 144.9 mAh g-1, demonstrating an excellent application potential. This simple and effective coating layer with high electrochemical performance provides an appealing strategy for the development of rechargeable AZIBs.

Assessing social cognition in patients with schizophrenia and healthy controls using the reading the mind in the eyes test (RMET): a systematic review and meta-regression.

The reading the mind in the eyes test (RMET) - which assesses the theory of mind component of social cognition - is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91-20.60) in patients and 25.53 (95% CI 25.19-25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score - RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning.

Terpyridine-Based Metal-Organic Cage with Enhanced Emission via Coordination-Induced Rigidity.

Realizing the regulation of photophysical properties by precisely controlling the molecular composition and configuration, thereby obtaining high-performance optical materials, remains of great significance. Due to the directionality and reversibility of the coordination bond, coordination-driven self-assembly endows the molecule with customized thermodynamically stable structures and desired properties. In this paper, a luminous metal-organic cage [Zn12L6] (S) was elaborately designed and quantitatively synthesized by self-assembly of tetrapodal TQPP chromophore-containing terpyridine ligand L with Zn2+. Complex S possessed a rigid cage-like structure, which endows a higher fluorescence quantum efficiency both in solution (∼88%) and neat solid (16%) than the corresponding ligand L. Further, using complex S as the photoactive component, two light-emitting diodes (LEDs) were successfully fabricated and the emission of pure white light (CIE coordinates: 0.3341, 0.3300) was achieved. These results afford a method to obtain enhanced luminescence performance via the formation of rigid coordination-driven supramolecular architectures.

Genome-wide selection reveals candidate genes associated with multiple teats in Hu sheep.

Increasing the number of teats in sheep helps to improve the survival rate of sheep lambs after birth. In order to analyze the candidate genes related to the formation of multiple teats in Hu sheep, the present study was conducted to investigate the genetic pattern of multiple teats in Hu sheep. In this study, based on genome-wide data from 157 Hu sheep, Fst, xp-EHH, Pi and iHS signaling were performed, and the top 5% signal regions of each analyzed result were annotated based on the Oar_v4.0 for sheep. The results show that a total of 142 SNP loci were selected. We found that PTPRG, TMEM117 and LRP1B genes were closely associated with polypodium formation in Hu sheep, in addition, among the candidate genes related to polypodium we found genes such as TMEM117, SLC25A21 and NCKAP5 related to milk traits. The present study screened out candidate genes for the formation of multiple teats at the genomic level in Hu sheep.

Single-Cell Informatics for Tumor Microenvironment and Immunotherapy.

Cancer comprises malignant cells surrounded by the tumor microenvironment (TME), a dynamic ecosystem composed of heterogeneous cell populations that exert unique influences on tumor development. The immune community within the TME plays a substantial role in tumorigenesis and tumor evolution. The innate and adaptive immune cells "talk" to the tumor through ligand-receptor interactions and signaling molecules, forming a complex communication network to influence the cellular and molecular basis of cancer. Such intricate intratumoral immune composition and interactions foster the application of immunotherapies, which empower the immune system against cancer to elicit durable long-term responses in cancer patients. Single-cell technologies have allowed for the dissection and characterization of the TME to an unprecedented level, while recent advancements in bioinformatics tools have expanded the horizon and depth of high-dimensional single-cell data analysis. This review will unravel the intertwined networks between malignancy and immunity, explore the utilization of computational tools for a deeper understanding of tumor-immune communications, and discuss the application of these approaches to aid in diagnosis or treatment decision making in the clinical setting, as well as the current challenges faced by the researchers with their potential future improvements.

Multi-functionalized Metallo-Supramolecular Spoked Wheels: Their Emission-Tunable Hierarchically Assembled System with Dye Molecules.

Supramolecular architectures with multiple emissive units are especially appealing due to their desired properties, such as artificial light harvesting and white-light emission. But fully achieving multi-wavelength photoluminescence in a single supramolecular architecture remains a challenge. In this paper, functionalized supramolecular architectures containing twelve metal centers and six pyrene moieties were nearly quantitatively synthesized by multi-component self-assembly and fully characterized by 1D and 2D nuclear magnetic resonance, dynamic light scattering, electrospray ionization mass spectrometry, traveling-wave ion mobility mass spectrometry, and transmission electron microscopy. Moreover, the hierarchical nano-assemblies were prepared by introducing anionic dyes to the positively charged self-assembled framework, which contained three luminescence centers, namely, pyrene, tpy-Cd coordination parts, and Sulforhodamine B anions. Such a hierarchically assembled system displayed tunable emission by taking full advantage of aggregation-induced emission enhancement, aggregation-caused quenching, and fluorescence resonance energy transfer effects and showed the diverse emission colors. This research provides a new insight for constructing multiple emissive metallo-supramolecular assemblies.

Backbone N-methylation of peptides: Advances in synthesis and applications in pharmaceutical drug development.

Peptide-based drugs have garnered considerable attention in recent years owing to their increasingly crucial role in the treatment of diverse diseases. However, the limited pharmacokinetic properties of peptides have hindered their full potential. One prominent strategy for enhancing the druggability of peptides is N-methylation, which involves the addition of a methyl group to the nitrogen atom of the peptide backbone. This modification significantly improves the stability, bioavailability, receptor binding affinity and selectivity of peptide drug candidates. In this review, we provide a comprehensive overview of the advancements in synthetic methods for N-methylated peptide synthesis, as well as the associated limitations. Moreover, we explore the versatile effects of N-methylation on various aspects of peptide properties. Furthermore, we emphasize the efforts dedicated to N-methylated peptide pharmaceuticals that have successfully obtained marketing approval.

Advances in Extraction, Purification, and Analysis Techniques of the Main Components of Kudzu Root: A Comprehensive Review.

Kudzu root (Pueraria lobate (Willd.) Ohwi, KR) is an edible plant with rich nutritional and medicinal values. Over the past few decades, an ample variety of biological effects of Pueraria isoflavone have been evaluated. Evidence has shown that Pueraria isoflavone can play an active role in antioxidant, anti-inflammatory, anti-cancer, neuroprotection, and cardiovascular protection. Over 50 isoflavones in kudzu root have been identified, including puerarin, daidzein, daidzin, 3'-hydroxy puerarin, and genistein, each with unambiguous structures. However, the application of these isoflavones in the development of functional food and health food still depends on the extraction, purification and identification technology of Pueraria isoflavone. In recent years, many green and novel extraction, purification, and identification techniques have been developed for the preparation of Pueraria isoflavone. This review provides an updated overview of these techniques, specifically for isoflavones in KR since 2018, and also discusses and compares the advantages and disadvantages of these techniques in depth. The intention is to provide a research basis for the green and efficient extraction, purification, and identification of Pueraria isoflavone and offers investigators a valuable reference for future studies on the KR.

The Research Progress of Extraction, Purification and Analysis Methods of Phenolic Compounds from Blueberry: A Comprehensive Review.

Blueberry is the source of a variety of bioactive substances, including phenolic compounds, such as anthocyanins, pterostilbene, phenolic acids, etc. Several studies have revealed that polyphenols in blueberry have important bioactivities in maintaining health, such as antioxidant and anti-tumor activities, immune regulation, the prevention of chronic diseases, etc. Therefore, these phenolic compounds in blueberries have been widely used in the field of healthcare, and the extraction, isolation, and purification of phenolic compounds are the prerequisites for their utilization. It is imperative to systematically review the research progress and prospects of phenolic compounds present in blueberries. Herein, the latest progress in the extraction, purification, and analysis of phenolic compounds from blueberries is reviewed, which can in turn provide a foundation for further research and usage of blueberries.

Photoelectrochemical determination of diclofenac using oriented single-crystalline TiO2 nanoarray modified with molecularly imprinted polypyrrole.

A novel molecular imprint photoelectrochemical (PEC) sensor has been prepared based on oriented single-crystalline TiO2 nanoarray (TNA) material for sensitive detection of diclofenac (DCF). The TNA obtained by the one-step hydrothermal method was characterized by XRD, SEM, and TEM. Polypyrrole film was formed on the TNA by electrochemical method, and DCF was imprinted on the polymer film as the template molecule. After the removal of DCF, there appeared lots of specific recognition sites that matched template molecules. The experimental results demonstrated that the constructed PEC sensor has good sensitivity and selectivity for the detection of DCF, which can be attributed to the high photoelectric conversion efficiency of TNA and the high selectivity of molecular imprinting technology. The fabricated PEC sensor showed a wide detection range (0.05-1000 µM) and a low limit of detection (0.0034 µM) for DCF, as well as good repeatability and stability. The proposed PEC sensor provided an effective strategy in the monitoring of environmental pollutants.

Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone ß-Subunit Promoted Reproductive Functions in Mice.

A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-ß-(34−37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-ß-(37−49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-ß-(37−49) and hFSH-ß-(34−49), created by merging hFSH-ß-(34−37) and hFSH-ß-(37−49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 µg/g BW ip of hFSH-ß-(37−49) or hFSH-ß-(34−49) hastened (p < 0.05) puberty, whereas the same treatments given daily for 4 d promoted (p < 0.05) the gonadal steroidogenesis and gamete formation. In addition of either peptide to the in vitro cell cultures, promoted (p < 0.05) the proliferation of primary murine granulosa cells and the estradiol production by upregulating the expression of Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 µg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-ß-(34−49) was a more potent (p < 0.05) reproductive modulator than hFSH-ß-(37−49), both in vivo and in vitro. We concluded that hFSH-ß-(37−49) and especially hFSH-ß-(34−49), have the potential for reproductive modulation.

Research progress on the protective effects of aucubin in neurological diseases.

CONTEXT: Aucubin (AU), an iridoid glycoside that is one of the active constituents of Eucommia ulmoides Oliv. (EUO) (Eucommiaceae), a traditional Chinese medicine, has been extensively studied in the management of neurological diseases (NDs). However, a comprehensive review of its effects and mechanisms in this regard is currently not available. OBJECTIVE: To compile the protective effects and mechanisms of AU in NDs and provide a basis for further research. METHODS: We used 'aucubin' as the 'All Fields' or 'MeSH' in PubMed, Web of Science and China National Knowledge Infrastructure without any limitation to search all relevant articles as comprehensively as possible; we selected the articles on AU treatment of NDs for summary. RESULTS: Studies reviewed herein reported that AU improved the symptoms or prognosis of Parkinson's disease, Alzheimer's disease, intracerebral haemorrhage, diabetic encephalopathy, epilepsy, anxiety and depression, and traumatic brain injury. The pharmacological mechanisms involved in repairing neuronal loss were postulated to include increasing γ-aminobutyric acid (GABA) content in the synapse, promoting differentiation of neural precursor cells into GABAergic neurons, providing antioxidant and anti-neuroinflammation activities, as well as enhancing autophagy and anti-apoptotic actions. DISCUSSION AND CONCLUSIONS: The protective effects of AU on some NDs have been confirmed. According to the pharmacological effects, AU is also highly likely to have protective effects on other NDs, which can be realized by further in vivo and in vitro basic research, and clinical trials. In the future, AU may be used for clinical prevention or treatment of patients with neurological diseases.

microRNA-454-mediated NEDD4-2/TrkA/cAMP axis in heart failure: Mechanisms and cardioprotective implications.

The current study aimed to investigate the mechanism by which miR-454 influences the progression of heart failure (HF) in relation to the neural precursor cell expressed, developmentally downregulated 4-2 (NEDD4-2)/tropomyosin receptor kinase A (TrkA)/cyclic adenosine 3',5'-monophosphate (cAMP) axis. Sprague-Dawley rats were used to establish a HF animal model via ligation of the left anterior descending branch of the coronary artery. The cardiomyocyte H9c2 cells were treated with H2 O2 to stimulate oxidative stress injury in vitro. RT-qPCR and Western blot assay were subsequently performed to determine the expression patterns of miR-454, NEDD4-2, TrkA, apoptosis-related proteins and cAMP pathway markers. Dual-luciferase reporter gene assay coupled with co-immunoprecipitation was performed to elucidate the relationship between miR-454, NEDD4-2 and TrkA. Gain- or loss-of-function experiments as well as rescue experiments were conducted via transient transfection (in vitro) and adenovirus infection (in vivo) to examine their respective functions on H9c2 cell apoptosis and myocardial damage. Our results suggested that miR-454 was aberrantly downregulated in the context of HF, while evidence was obtained suggesting that it targeted NEDD4-2 to downregulate NEDD4-2 in cardiomyocytes. miR-454 exerted anti-apoptotic and protective effects on cardiomyocytes through inhibition of NEDD4-2, while NEDD4-2 stimulated ubiquitination and degradation of TrkA protein. Furthermore, miR-454 activated the cAMP pathway via the NEDD4-2/TrkA axis, which ultimately suppressed cardiomyocyte apoptosis and attenuated myocardial damage. Taken together, the key findings of the current study highlight the cardioprotective role of miR-454, which is achieved through activation of the cAMP pathway by impairing NEDD4-2-induced TrkA ubiquitination.

Design, synthesis and biological evaluation of novel dithiocarbamate-substituted diphenylaminopyrimidine derivatives as BTK inhibitors.

Bruton's tyrosine kinase (BTK) has emerged as an attractive target related to B-lymphocytes dysfunctions, especially hematologic malignancies and autoimmune diseases. In our study, a series of diphenylaminopyrimidine derivatives bearing dithiocarbamate moieties were designed and synthesized as novel BTK inhibitors for treatment of B-cell lymphoma. Among all these compounds, 30ab (IC50 = 1.15 ±â€¯0.19 nM) displays similar or more potent inhibitory activity against BTK than spebrutinib (IC50 = 2.12 ±â€¯0.32 nM) and FDA approved drug ibrutinib (IC50 = 3.89 ±â€¯0.57 nM), which is attributed to close binding of 30ab with BTK predicted by molecular docking. In particular, 30ab exhibits enhanced anti-proliferative activity against B-lymphoma cell lines at the IC50 concentration of 0.357 ±â€¯0.02 µM (Ramos) and 0.706 ±â€¯0.05 µM (Raji), respectively, almost 10-fold better than ibrutinib and spebrutinib. In addition, 30ab displays stronger selectivity on B-cell lymphoma over other cancer cell lines than spebrutinib. Furthermore, 30ab efficiently blocks BTK downstream pathways and results in apoptosis of cancer cells. In vivo xenograft model evaluation demonstrates the significant efficacy and broad safety margin of 30ab in treatment of B-cell lymphoma. We propose that compound 30ab is a candidate for further study and development based on our current findings.

Efficient Synthesis of Furfural from Biomass Using SnCl4 as Catalyst in Ionic Liquid.

Furfural is a versatile platform molecule for the synthesis of various chemicals and fuels, and it can be produced by acid-catalyzed dehydration of xylose derived from renewable biomass resources. A series of metal salts and ionic liquids were investigated to obtain the best combination of catalyst and solvent for the conversion of xylose into furfural. A furfural yield of 71.1% was obtained at high xylose loading (20 wt%) from the single-phasic reaction system whereby SnCl4 was used as catalyst and ionic liquid 1-ethyl-3-methylimidazolium bromide (EMIMBr) was used as reaction medium. Moreover, the combined catalyst consisting of 5 mol% SnCl4 and 5 mol% MgCl2 also produced a high furfural yield (68.8%), which was comparable to the furfural yield obtained with 10 mol% SnCl4. The water⁻organic solvent biphasic systems could improve the furfural yield compared with the single aqueous phase. Although these organic solvents could form biphasic systems with ionic liquid EMIMBr, the furfural yield decreased remarkably compared with the single EMIMBr phase. Besides, the EMIMBr/SnCl4 system with appropriate water was also efficient to convert xylan and lignocellulosic biomass corn stalk into furfural, obtaining furfural yields as high as 57.3% and 54.5%, respectively.

Two new glycosides from the fruits of Forsythia suspense.

Two new glycosides suspensaside C (1) and 2,3,5,6-tetrahydro-jacaranone-4-O-ß-D-glucopyranoside (2), together with four known compounds suspensaside A (3), rengynic acid-1'-O-ß-D-glucopyranoside (4), forsythoside A (5), and rengynic acid (6), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. The structures of 1 and 2 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HR-ESI-MS. All isolates were tested for their cytotoxicities against five human cancer cell lines (A549, Colo-205, Hep-3B, HL60, and KB). Compound 3 exhibited cytotoxicity against HL-60, Hep-3B, and A549 cancer cell lines.

Stochastic dynamical analysis for the complex infectious disease model driven by multisource noises.

This paper mainly studies the dynamical behavior of the infectious disease model affected by white noise and Lévy noise. First, a stochastic model of infectious disease with secondary vaccination affected by noises is established. Besides, the existence and uniqueness of the global positive solution for the stochastic model are proved based on stochastic differential equations and Lyapunov function, then the asymptotic behavior of the disease-free equilibrium point is studied. Moreover, the sufficient conditions for the extinction of the disease are obtained and the analysis showed that different noise intensity could affect the extinction of infectious disease on different degree. Finally, the theoretical results are verified by numerical simulation and some suggestions have been put forward on how to prevent the spread of diseases are presented.

Stochastic Analysis for the Dual Virus Parallel Transmission Model with Immunity Delay.

In this article, the qualitative properties of a stochastic dual virus parallel transmission model with immunity delay are analyzed. First, we use Lyapunov theory to study the existence and uniqueness of the global positive solution of the proposed model. Second, the threshold values of the persistence and extinction of two viruses were obtained. Finally, the numerical simulation verifies the theoretical results. The results show that the immunity delay and the intensity of noise have important effects on the two diseases spreading in parallel.

Artesunate inhibits macrophage-like phenotype switching of vascular smooth muscle cells and attenuates vascular inflammatory injury in atherosclerosis via NLRP3.

Inflammation is one of the main pathogenic factors of atherosclerosis (AS), and the phenotypic transformation of macrophages in human vascular smooth muscle cells (HVSMCs) contributes to the inflammatory injury of blood vessels and the formation of atherosclerotic plaques. Artesunate reportedly exerts anti-inflammatory activity against AS. Herein, we aimed to explore the artesunate-mediated anti-inflammatory and HVSMC phenotypic switch effects against AS and elucidate potential underlying mechanisms. In vitro, artesunate decreased expression of NLRP3, caspase-1, and interleukin (IL)- 1ß. Artesunate significantly inhibited low-density lipoprotein (LDL) expression in HVSMCs and macrophages. In vivo, artesunate reduced atherosclerotic plaque formation in high-fat diet (HFD)-fed ApoE-/- mice, as well as decreased NLRP3 and CD68 expression in atherosclerotic plaques. Artesunate decreased serum levels of triglycerides and increased high-density lipoprotein levels in HFD-med mice; however, serum levels of total cholesterol and LDL were unaltered. Treatment with artesunate substantially increased α-smooth muscle actin expression in aortic tissues while inhibiting expression levels of NLRP3, IL-1ß, heparinase, matrix metalloproteinase 9, and Krüppel-like factor 4 (KLF4). Collectively, our findings suggest that artesunate-mediated effects may involve inhibition of the ERK1/2/NF-κB/IL-1ß pathway in HVSMCs via the downregulation of NLRP3 expression. Thus, artesunate could serve as a novel strategy to treat AS by inhibiting AS plaque formation and suppressing macrophage-like phenotype switching of HVSMCs.