Exploration of ferroptosis and necroptosis-related genes and potential molecular mechanisms in psoriasis and atherosclerosis.

Objective: Ferroptosis and necroptosis are two recently identified forms of non-apoptotic cell death. Their dysregulation plays a critical role in the development and progression of Psoriasis (PsD) and Atherosclerosis (AS). This study explores shared Ferroptosis and necroptosis-related genes and elucidates their molecular mechanisms in PsD and AS through the analysis of public databases. Methods: Data sets for PsD (GSE30999) and AS (GSE28829) were retrieved from the GEO database. Differential gene expression (DEG) and weighted gene co-expression network analysis (WGCNA) were performed. Machine learning algorithms identified candidate biomarkers, whose diagnostic values were assessed using Receiver Operating Characteristic (ROC) curve analysis. Additionally, the expression levels of these biomarkers in cell models of AS and PsD were quantitatively measured using Western Blot (WB) and real-time quantitative PCR (RT-qPCR). Furthermore, CIBERSORT evaluated immune cell infiltration in PsD and AS tissues, highlighting the correlation between characteristic genes and immune cells. Predictive analysis for candidate drugs targeting characteristic genes was conducted using the DGIdb database, and an lncRNA-miRNA-mRNA network related to these genes was constructed. Results: We identified 44 differentially expressed ferroptosis-related genes (DE-FRGs) and 30 differentially expressed necroptosis-related genes (DE-NRGs). GO and KEGG enrichment analyses revealed significant enrichment of these genes in immune-related and inflammatory pathways, especially in NOD-like receptor and TNF signaling pathways. Two ferroptosis-related genes (NAMPT, ZFP36) and eight necroptosis-related genes (C7, CARD6, CASP1, CTSD, HMOX1, NOD2, PYCARD, TNFRSF21) showed high sensitivity and specificity in ROC curve analysis. These findings were corroborated in external validation datasets and cell models. Immune infiltration analysis revealed increased levels of T cells gamma delta, Macrophages M0, and Macrophages M2 in PsD and AS samples. Additionally, we identified 43 drugs targeting 5 characteristic genes. Notably, the XIST-miR-93-5p-ZFP36/HMOX1 and NEAT1-miR-93-5p-ZFP36/HMOX1 pathways have been identified as promising RNA regulatory pathways in AS and PsD. Conclusion: The two ferroptosis-related genes (NAMPT, ZFP36) and eight necroptosis-related genes (C7, CARD6, CASP1, CTSD, HMOX1, NOD2, PYCARD, TNFRSF21) are potential key biomarkers for PsD and AS. These genes significantly influence the pathogenesis of PsD and AS by modulating macrophage activity, participating in immune regulation, and mediating inflammatory responses.

Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.

BACKGROUND: As people age, degenerative bone and joint diseases (DBJDs) become more prevalent. When middle-aged and elderly people are diagnosed with one or more disorders such as osteoporosis (OP), osteoarthritis (OA), and intervertebral disc degeneration (IVDD), it often signals the onset of prolonged pain and reduced functionality. Chronic inflammation has been identified as the underlying cause of various degenerative diseases, including DBJDs. Recently, excessive activation of pyroptosis, a form of programed cell death (PCD) mediated by inflammasomes, has emerged as a primary driver of harmful chronic inflammation. Consequently, pyroptosis has become a potential target for preventing and treating DBJDs. AIM OF REVIEW: This review explored the physiological and pathological roles of the pyroptosis pathway in bone and joint development and its relation to DBJDs. Meanwhile, it elaborated the molecular mechanisms of pyroptosis within individual cell types in the bone marrow and joints, as well as the interplay among different cell types in the context of DBJDs. Furthermore, this review presented the latest compelling evidence supporting the idea of regulating the pyroptosis pathway for DBJDs treatment, and discussed the potential, limitations, and challenges of various therapeutic strategies involving pyroptosis regulation. KEY SCIENTIFIC CONCEPTS OF REVIEW: In summary, an interesting identity for the unregulated pyroptosis pathway in the context of DBJDs was proposed in this review, which was undertaken as a spoiler of peaceful coexistence between cells in a degenerative environment. Over the extended course of DBJDs, pyroptosis pathway perpetuated its activity through crosstalk among pyroptosis cascades in different cell types, thus exacerbating the inflammatory environment throughout the entire bone marrow and joint degeneration environment. Correspondingly, pyroptosis regulation therapy emerged as a promising option for clinical treatment of DBJDs.

Polymer Mechanochemistry in Microbubbles.

Polymer mechanochemistry is a promising technology to convert mechanical energy into chemical functionality by breaking covalent and supramolecular bonds site-selectively. Yet, the mechanochemical reaction rates of covalent bonds in typically used ultrasonication setups lead to reasonable conversions only after comparably long sonication times. This can be accelerated by either increasing the reactivity of the mechanoresponsive moiety or by modifying the encompassing polymer topology. Here, a microbubble system with a tailored polymer shell consisting of an N2 gas core and a mechanoresponsive disulfide-containing polymer network is presented. It is found that the mechanochemical activation of the disulfides is greatly accelerated using these microbubbles compared to commensurate solid core particles or capsules filled with liquid. Aided by computational simulations, it is found that low shell thickness, low shell stiffness and crosslink density, and a size-dependent eigenfrequency close to the used ultrasound frequency maximize the mechanochemical yield over the course of the sonication process.

Research progress of Traditional Chinese Medicine (TCM) in targeting inflammation and lipid metabolism disorder for arteriosclerosis intervention: A review.

Atherosclerosis (AS) is a chronic disease caused by inflammation and lipid deposition. Immune cells are extensively activated in the lesions, producing excessive pro-inflammatory cytokines, which accompany the entire pathological process of AS. In addition, the accumulation of lipid-mediated lipoproteins under the arterial intima is a crucial event in the development of AS, leading to vascular inflammation. Improving lipid metabolism disorders and inhibiting inflammatory reactions are the primary treatment methods currently used in medical practice to delay AS progression. With the development of traditional Chinese medicine (TCM), more mechanisms of action of the monomer of TCM, Chinese patent medicine, and compound prescription have been studied and explored. Research has shown that some Chinese medicines can participate in treating AS by targeting and improving lipid metabolism disorders and inhibiting inflammatory reactions. This review explores the research on Chinese herbal monomers, compound Chinese medicines, and formulae that improve lipid metabolism disorders and inhibit inflammatory reactions to provide new supplements for treating AS.

A study on characteristics of background gamma spectrum from LaCl3 detector in pulsed neutron logging.

The scintillator detectors such as LaCl3(Ce) play an important role in some fields of scientific research, environment, safeguards, medicine, security and industry due to its superior energy resolution and exceptional luminescence properties, etc. However, Cl element in a LaCl3 crystal produces uncertainty of determining oil saturation in pulsed neutron logging because of the background spectrum caused by secondary gamma ray from the reaction of Cl nuclei with the neutron. In this paper, we employed Monte Carlo method to simulate secondary gamma ray generated LaCl3 crystal induced by thermal neutron with different borehole and formation conditions and establish a reference spectrum of Cl element. The relations between elemental window or peak areas counts and borehole and formation conditions were also investigated. The background was obtained by combining the reaction rate derived from thermal neutron capture cross section for Cl element and neutron flux with the reference spectrum. The results indicate that the contribution of secondary gamma ray to measuring spectrum decreases with formation porosity, limestone content, borehole diameter, and water salinity increasing. Nevertheless, the relative peak areas of Cl at different energies remain constant, indicating that the logging conditions have less of an effect on the background spectrum shape. As evidenced by the measured spectra in the sandstone and limestone calibration wells processed, the peaks of Si and Ca elements are enhanced while the peaks of Cl element are weakened. After subtracting detector background, the computations of oil saturation based on calibration wells are 38% more accurate than the original method.

The exploration of shared genes and molecular mechanisms of systemic lupus erythematosus and atherosclerosis.

OBJECTIVE: Despite widespread recognition, the mechanisms underlying the relationship between systemic lupus erythematosus (SLE) and atherosclerosis (AS) are still unclear. Our study aimed to explore the shared genetic signature and molecular mechanisms of SLE and AS using a bioinformatics approach. METHODS: Gene expression profiles of GSE50772 (contains peripheral blood mononuclear cells from 61 SLE patients and 20 normal samples) and GSE100927 (contains 69 AS plaque tissue samples and 35 control samples) were downloaded from the Gene Expression Database (GEO) before the differentially expressed genes were obtained using the "limma" package in R. The differential genes were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the DAVID online platform to annotate their functions. The intersection targets of PPI and WGCNA were used as key shared genes for SLE and AS with their diagnostic value as shared genes being verified through ROC curves. Finally, Cytoscape 3.7.2 software was used to construct a miRNA-mRNA network map associated with the shared genes. RESULTS: A total of 246 DEGs were identified, including 189 upregulated genes and 57 downregulated genes, which were mainly enriched in signaling pathways such as TNF signaling pathway, IL-17 signaling pathway, and NF-kB signaling pathway. The molecular basis for the relationship between SLE and AS may be the aforementioned signaling pathways. Following ROC curve validation, the intersection of PPI and WGCNA, as well as AQP9, CCR1, CD83, CXCL1, and FCGR2A, resulted in the identification of 15 shared genes. CONCLUSION: The study provided a new perspective on the common molecular mechanisms between SLE and AS, and the key genes and pathways that were identified as being part of these pathways may offer fresh perspectives and suggestions for further experimental research.

Mild construction of robust FeS-based electrode for pH-universal hydrogen evolution at industrial current density.

The development of fast and mild preparation of transition metal electrocatalysts for efficient and ultra-stable water electrolysis in wide pH range electrolytes is essential for hydrogen energy supply. Herein, ultrathin and metastable FeS nanolayer self-supported on 3D porous iron foam (IF) substrate is fabricated via one-step mild sulfurization etching for only 2 h to obtain FeS@IF electrode, which achieves efficient and long-term hydrogen evolution in alkaline simulated seawater (1.0 M KOH + 0.5 M NaCl), neutral electrolyte (1.0 M PBS) and other corrosive systems. The overpotentials are only 63 mV and 78 mV to drive 10 mA cm-2 during hydrogen evolution in 1.0 M KOH + 0.5 M NaCl and 1.0 M PBS, respectively. Additionally, the FeS@IF electrode continuously catalyzes for over 600 h at 0.2-0.4 A cm-2 in 1.0 M PBS with negligible performance loss, partly attributed to FeS nanolayer firmly etching on the surface and the formation of corrosion-resistant ultrathin nano fan-like iron sulfide oxide (FeOxSy). This uniformly-distributed morphology helps to facilitate the interfacial electron transmission between active species and substrate, expose more active sites, and provide moderate channels for the rapid liberation of gas bubbles and mass transfer. This work proposes a novel strategy for developing efficient and stable catalysts for hydrogen production in wide pH range systems.

Multiplexed sensing of biomolecules with optically detected magnetic resonance of nitrogen-vacancy centers in diamond.

In the past decade, a great effort has been devoted to develop new biosensor platforms for the detection of a wide range of analytes. Among the various approaches, magneto-DNA assay platforms have received extended interest for high sensitive and specific detection of targets with a simultaneous manipulation capacity. Here, using nitrogen-vacancy quantum centers in diamond as transducers for magnetic nanotags (MNTs), a hydrogel-based, multiplexed magneto-DNA assay is presented. Near-background-free sensing with diamond-based imaging combined with noninvasive control of chemically robust nanotags renders it a promising platform for applications in medical diagnostics, life science, and pharmaceutical drug research. To demonstrate its potential for practical applications, we employed the sensor platform in the sandwich DNA hybridization process and achieved a limit of detection in the attomolar range with single-base mismatch differentiation.

A new algorithm for evaluating reservoir density based on X-ray logging technology.

Rock density is an important parameter to provide critical information for evaluating both conventional and unconventional reservoirs. During the drilling process, it's a huge challenge to eliminating the negative effects of irregular mud cake formed in drilling fluid deposition to evaluating reservoir information accurately. However, the calibration of density measurement by correction charts would usually generate large errors, and the parameters that need to be corrected are often unpredictable. Therefore, based on the X-ray density logging technology, while eliminating the radioactive hazards of the isotope gamma source (137Cs), a new method is proposed to address the problem through the energy spectrum information from four detectors. Theoretically, this method would analyze the role of X-rays in the dual media of formation and mud cake and then integrate the energy spectrum information from four detectors, while using Newton iterative inversion to invert the parameters about formation and mud cake. As a result, the evaluation of reservoir parameters can be achieved without correcting the mud cake. In verifying the effectiveness of this method, a simulation example shows the high accuracy of X-ray density inversion for multiple parameters. This research provides an X-ray density inversion algorithm to realize the simultaneous calculation of formation and mud cake parameters, which is of great significance for guiding hydrocarbon exploration and production.

Activation of the Catalytic Activity of Thrombin for Fibrin Formation by Ultrasound.

The regulation of enzyme activity is a method to control biological function. We report two systems enabling the ultrasound-induced activation of thrombin, which is vital for secondary hemostasis. First, we designed polyaptamers, which can specifically bind to thrombin, inhibiting its catalytic activity. With ultrasound generating inertial cavitation and therapeutic medical focused ultrasound, the interactions between polyaptamer and enzyme are cleaved, restoring the activity to catalyze the conversion of fibrinogen into fibrin. Second, we used split aptamers conjugated to the surface of gold nanoparticles (AuNPs). In the presence of thrombin, these assemble into an aptamer tertiary structure, induce AuNP aggregation, and deactivate the enzyme. By ultrasonication, the AuNP aggregates reversibly disassemble releasing and activating the enzyme. We envision that this approach will be a blueprint to control the function of other proteins by mechanical stimuli in the sonogenetics field.

DNA hybridization as a general method to enhance the cellular uptake of nanostructures.

The biomedical application of nanoparticles (NPs) for diagnosis and therapy is considerably stalled by their inefficient cellular internalization. Many strategies to overcome this obstacle have been developed but are not generally applicable to different NP systems, consequently underlining the need for a universal method that enhances NP entry into cells. Here we describe a method to increase NP cellular uptake via strand hybridization between DNA-functionalized NPs and cells that bear the respective complementary sequence incorporated into the membrane. By this, the NPs bind efficiently to the cellular surface enhancing internalization of three completely different NP types: DNA tetrahedrons, gold (Au) NPs, and polystyrene (PS) NPs. We show that our approach is a simple and generalizable strategy that can be applied to virtually every functionalizable NP system.

Four-Dimensional Deoxyribonucleic Acid-Gold Nanoparticle Assemblies.

Organization of gold nanoobjects by oligonucleotides has resulted in many three-dimensional colloidal assemblies with diverse size, shape, and complexity; nonetheless, autonomous and temporal control during formation remains challenging. In contrast, living systems temporally and spatially self-regulate formation of functional structures by internally orchestrating assembly and disassembly kinetics of dissipative biomacromolecular networks. We present a novel approach for fabricating four-dimensional gold nanostructures by adding an additional dimension: time. The dissipative character of our system is achieved using exonuclease III digestion of deoxyribonucleic acid (DNA) fuel as an energy-dissipating pathway. Temporal control over amorphous clusters composed of spherical gold nanoparticles (AuNPs) and well-defined core-satellite structures from gold nanorods (AuNRs) and AuNPs is demonstrated. Furthermore, the high specificity of DNA hybridization allowed us to demonstrate selective activation of the evolution of multiple architectures of higher complexity in a single mixture containing small and larger spherical AuNPs and AuNRs.

lncRNA-XIST protects the hypoxia-induced cardiomyocyte injury through regulating the miR-125b-hexokianse 2 axis.

Ischemic injury in the heart is associated with low oxygen, leading to the damage of cardiomyocytes. The lncRNA-XIST is known to involve in post-ischemia myocardial remodeling. However, the roles and mechanism of XIST in the hypoxia-induced cardiomyocyte are still under investigation. Moreover, studies that elucidated the impaired glucose metabolism present new hallmark of ischemic cardiovascular injury. The objective of this study is to investigate the effects of lncRNA-XIST on cardiomyocyte injury under hypoxia. Here, we demonstrate that the XIST expressions of cardiomyocyte line, H9c2 were apparently suppressed by long-time hypoxia exposure under low glucose supply. On the contrary, miRNA-125b showed reverse expression pattern to XIST. We identified that XIST functioned as a ceRNA of miR-125b to downregulate its expression in both cell line and rat primary cardiomyocyte. Under low glucose supply, H9c2 cells exhibited increased susceptibility to hypoxia. We observed overexpression of XIST significantly elevated glycose metabolism rate under hypoxia, but overexpression of miR-125b inhibited glycose metabolism rate of cardiomyocyte under hypoxia. The glycolysis enzyme, hexokinase 2 (HK2) was validated as a direct target of miR-125b, which binds to the 3'-UTR region of HK2 mRNA in cardiomyocytes. Moreover, inhibition of miR-125b significantly protected the hypoxia-induced cardiomyocyte injury through restoration of glucose metabolism. Finally, we demonstrated that transfection of miR-125b in lncRNA-XIST overexpressed H9c2 cells effectively abolished the XIST-activated glucose metabolism and cardiomyocyte protection under hypoxia. The present study illustrates roles of the XIST-miR-125b-HK2 axis in the hypoxia-induced cardiomyocyte injury and proposes that maintaining glucose metabolism might be an effective approach for protection of cardiomyocyte injury.

Total Synthesis of the Flavonoid Natural Product Houttuynoid A.

The first total synthesis of the antiviral flavonoid houttuynoid A (1) has been achieved from aryl ketone 6 and benzofuran aldehyde 5 in nine linear steps. The C6-C3-C6 structure of the flavonoid was synthesized by an I2-catalyzed oxa-Michael addition of a chalcone intermediate, generated by the Claisen-Schmidt condensation of 5 and 6. This work provides a method for the synthesis of houttuynoids and provides a reference for the synthesis of the remaining members of the houttuynoid family.

Anti-biofilm effect of novel thiazole acid analogs against Pseudomonas aeruginosa through IQS pathways.

IQS has been proven to be a new quorum sensing (QS) system against bacterial biofilm formation, which is activated in the common phosphate-limiting environment of infected tissues taking over the central las system. Up to now, numerous biofilm inhibitors which function by affecting traditional QS system have been reported. However, no compound has been reported to exert anti-biofilm activity through IQS system. Herein, various novel IQS derivatives were synthesized by the reaction of thiazole-4-carboxylic acid with different linear alcohols (R-OH) or amines (R-NH2). IQS derivatives with four carbon chain length of R group were found to present the best biofilm inhibition activity. Compound B-11 as the model molecule was observed to inhibit biofilm formation only under phosphate-limiting condition, and increase in B-11 concentration significantly reduced the expression of rhlA-gfp and pqsA-gfp, but lasB-gfp. Moreover, B-11 reduced production of virulence factors of rhamnolipid and pyocyanin under phosphate limitation. These observations indicated that the synthesized compounds possessed the anti-biofilm activity through IQS pathways rather than traditional QS pathways, which pave a path for future molecular design against bacterial biofilm formation.

A two-photon excitable and ratiometric fluorogenic nitric oxide photoreleaser and its biological applications.

We report for the first time the development of a two-photon excitable NO photoreleaser, CNNO, for ratiometric imaging and tracking of NO release in live cells. CNNO exhibits the merits of spatiotemporal control in both the site-specific NO release in the selected cell culture region and the controllable vasodilation of mouse aorta ex vivo.

New molecular insights into the tyrosyl-tRNA synthase inhibitors: CoMFA, CoMSIA analyses and molecular docking studies.

Drug resistance caused by excessive and indiscriminate antibiotic usage has become a serious public health problem. The need of finding new antibacterial drugs is more urgent than ever before. Tyrosyl-tRNA synthase was proved to be a potent target in combating drug-resistant bacteria. In silico methodologies including molecular docking and 3D-QSAR were employed to investigate a series of newly reported tyrosyl-tRNA synthase inhibitors of furanone derivatives. Both internal and external cross-validation were conducted to obtain high predictive and satisfactory CoMFA model (q 2 = 0.611, r 2pred = 0.933, r 2m = 0.954) and CoMSIA model (q 2 = 0.546, r 2pred = 0.959, r 2m = 0.923). Docking results, which correspond with CoMFA/CoMSIA contour maps, gave the information for interactive mode exploration. Ten new molecules designed on the basis of QSAR and docking models have been predicted more potent than the most active compound 3-(4-hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one (15) in the literatures. The results expand our understanding of furanones as inhibitors of tyrosyl-tRNA synthase and could be helpful in rationally designing of new analogs with more potent inhibitory activities.

Simultaneous Fluorescence and Chemiluminescence Turned on by Aggregation-Induced Emission for Real-Time Monitoring of Endogenous Superoxide Anion in Live Cells.

Biological sensors with simultaneous turn-on signals of fluorescence (FL) and chemiluminescence (CL) triggered by one single species are supposed to integrate spatiotemporally resolved FL imaging with dynamic CL sensing into one luminescent assay. Efficiently increased accuracy can be expected based on complementary information simultaneously obtained from two independent modes, which is crucial in disease detection and diagnosis. However, very few examples can be found to date because of the key challenges in the rational design of sensing structures. Herein, aggregation-induced emission (AIE) was employed to develop a novel organic platform TPE-CLA with simultaneous turn-on FL/CL signals specifically modulated by O2•- in cells, which can be attributed to the activation of AIE resulted from the decreasing solubility after recognition. Using imidazopyrazinone (CLA) as the reactive motif and tetraphenylethene (TPE) as FL/CL enhancing skeleton, TPE-CLA is sensitive enough to image native O2•- in Raw264.7 cells and lipopolysaccharide stimulated O2•- in mice. Endogenous O2•- in HL-7702 cells induced by acetaminophen (APAP) was uninterruptedly monitored for 7200 s with CL and the results were further confirmed by FL imaging. Accordingly, TPE-CLA turns out to be a reliable candidate for real-time and continuous monitoring of endogenous O2•- in live cells. The strategy utilizing AIE to accomplish the FL/CL dual detection is expected to extend the application of AIE as reaction-activated biosensors.