Selective Generation of Reactive Oxygen Species in Photocatalytic Oxidation by Tuning Porphyrin-Based COFs' Dimensionality.

Regulating the selective generation of reactive oxygen species (ROS) is a significant challenge in the field of photocatalytic oxidation, with successful approaches still being limited. Herein, we present a strategy to selectively generate singlet oxygen (1O2) and superoxide radicals (O2•-) by tuning the dimensionality of porphyrin-based covalent organic frameworks (COFs). The transformation of COFs from three-dimensional (3D) solids to two-dimensional (2D) sheets was achieved through the reversible protonation of the imine bond. Upon irradiation, both bulk and thin-layer COF-367 can transfer energy to O2 to generate 1O2. However, thin-layer COF-367 exhibited a superior performance compared to its bulk counterpart in activating O2 to form the O2•- radicals via electron transfer. After excluding the influences of the band structure, O2 adsorption energy, and frontier orbital composition attributed to the dimensionality of the COFs, it is reasonably speculated that the variance in ROS generation arises from the differential exposure ratios of the active surfaces, leading to distinct reaction pathways between the carrier and O2. This study is the first to explore the modulation mechanism of COF dimensionality on the activation of the O2 pathway, underscoring the importance of considering COF dimensionality in photocatalytic reactions.

Behavioral and economic traits reflect distinct resource acquisition strategies in tendril vines and stem twining vines.

Climbing plants are important components of tropical and many temperate forest ecosystems. Current studies regard climbing plants as a single ecological plant type and ignore the ecological differences resulting from their climbing mechanisms, which may lead to a misrepresentation of the role of climbing plants in forest dynamics. Based on behavioral traits and economic traits of climbing plants, we test the hypothesis that tendril climbers and stem twiners are characterized by different resource acquisition strategies. We quantified and compared 4 behavioral traits and 7 economic traits of four stem twining vines and four tendril vines in a temperate oak forest and further tested their differences in resource acquisition strategy. Our study found that tendril vines were scattered in a group distinct from stem twining vines along the first axes of the principal component analysis using four behavioral traits and seven economic traits, being located at the more acquisitive end with more hosts, a larger distance to length ratio of stem, higher leaf and root nitrogen concentrations, and lower leaf carbon content, while stem twining vines showed the opposite trends. These results indicate that tendril vines have a more acquisitive strategy than stem twining vines. The findings suggest a functional variability among the different climbing mechanisms, and which should be accounted for in future studies.

Mineral composition, pore structure and mechanical properties of coal measure strata rocks: A case study of Pingdingshan Coalfield.

The microstructure and mechanical properties of coal measure rocks (CMR) are critical factors in the successful geological storage of CO2. While previous research has predominantly focused on coal seams, the overlying and underlying bedrock strata are equally significant yet often overlooked. This study addresses this gap by selecting coal and adjacent strata from the Twelve Mine as representative samples. A comprehensive suite of analyses was conducted, including thin section identification, X-ray diffraction (XRD), nuclear magnetic resonance (NMR), uniaxial compression, and acoustic emission tests. These analyses were used to determine the mineralogical composition and pore structure characteristics of the CMR, elucidate the mechanical failure mechanisms of different CMR types, and explore the relationships between rock strength, mineral composition, and pore characteristics. The findings indicate that the primary minerals in coal are clay minerals, while mudstone is composed predominantly of clay minerals and quartz, sandstone is rich in quartz and feldspar, and limestone contains significant amounts of calcite. The porosity of CMR varies between 1.73 % and 10.12 %, with 82.72 % of the pores being micro- to mesopores and the remaining 17.28 % being macropores. The pore structures exhibit fractal characteristics, with the fractal dimension of mesopores ranging from 2.581 to 2.902, and that of macropores from 2.968 to 2.997. Coal predominantly fails through a combination of tensile and shear failure mechanisms, mudstone and limestone through tensile failure, and sandstone through shear failure. Furthermore, the results suggest that rock strength is positively correlated with quartz content and negatively correlated with kaolinite content and porosity. In terms of their influence on coal rock strength, the factors in descending order of impact are kaolinite, quartz, calcite, microporosity, macroporosity, dolomite, and mesoporosity. Thus, while the mechanical properties of these rocks are primarily governed by their mineralogical composition, the pore structure also plays a significant role.

Waste cotton textile-derived cellulose composite porous film with enhanced piezoelectric performance for energy harvesting and self-powered sensing.

Integrating flexible piezoelectric nanogenerators (PENGs) into wearable and portable electronics offers promising prospects for motion monitoring. However, it remains a significant challenge to develop environmentally friendly PENGs using biodegradable and cost-effective natural polymers for mechanical energy harvesting and self-powered sensing. Herein, reduced graphene oxide (rGO) and barium titanate (BTO) were introduced into regenerated cellulose pulp to fabricate a composite porous film-based PENG. The incorporation of rGO not only increased the electrical conductivity of the porous film but also enhanced the dispersibility of BTO. Moreover, the unique pore structure of the composite porous film improved the polarization effect of the air inside the pores, thereby greatly boosting the overall piezoelectric performance. The piezoelectric coefficient of the resulting composite porous film reaches up to 41.5 pC·N-1, which is comparable to or higher than those reported in similar studies. Consequently, the PENG assembled from this cellulose/rGO/BTO composite porous film (CGB-PENG) achieved an output voltage of 47 V, a current of 4.6 µA, and a power density of 30 µW·cm-2, approximately three times the output voltage and ten times the power density of similar studies. This work presents a feasible approach for the fabrication of high-performance cellulose-based PENGs derived from recycled waste cotton textiles.

Functional characterization of Arabidopsis hydroxynitrile lyase in response to abiotic stress and the regulation of flowering time.

BACKGROUND: Hydroxynitrile lyases (HNLs) are a class of hydrolytic enzymes from a wide range of sources, which play crucial roles in the catalysis of the reversible conversion of carbonyl compounds derived from cyanide and free cyanide in cyanogenic plant species. HNLs were also discovered in non-cyanogenic plants, such as Arabidopsis thaliana, and their roles remain unclear even during plant growth and reproduction. METHODS AND RESULTS: The pattern of expression of the HNL in A. thaliana (AtHNL) in different tissues, as well as under abiotic stresses and hormone treatments, was examined by real-time quantitative reverse transcription PCR (qRT-PCR) and an AtHNL promoter-driven histochemical ß-glucuronidase (GUS) assay. AtHNL is highly expressed in flowers and siliques, and the expression of AtHNL was dramatically affected by abiotic stresses and hormone treatments. The overexpression of AtHNL resulted in transgenic A. thaliana seedlings that were more tolerance to mannitol and salinity. Moreover, transgenic lines of A. thaliana that overexpressed this gene were less sensitive to abscisic acid (ABA). Altered expression of ABA/stress responsive genes was also observed in hnl mutant and AtHNL-overexpressing plants, suggesting AtHNL may play functional roles on regulating Arabidopsis resistance to ABA and abiotic stresses by affecting ABA/stress responsive gene expression. In addition, the overexpression of AtHNL resulted in earlier flowering, whereas the AtHNL mutant flowered later than the wild type (WT) plants. The expression of the floral stimulators CONSTANS (CO), SUPPRESSOR OF OVER EXPRESSION OF CO 1 (SOC1) and FLOWERING LOCUS T (FT) was upregulated in plants that overexpressed AtHNL when compared with the WT plants. In contrast, expression of the floral repressor FLOWERING LOCUS C (FLC) was upregulated in AtHNL mutants and downregulated in plants that overexpressed AtHNL compared to the WT plants. CONCLUSION: This study revealed that AtHNL can be induced under abiotic stresses and ABA treatment, and genetic analysis showed that AtHNL could also act as a positive regulator of abiotic stress and ABA tolerance, as well as flowering time.

Mitochondrial targeted modification and anticancer mechanism of natural product ergosterol peroxide.

Ergosterol peroxide (EP) isolated from the edible medicinal fungus Pleurotus ferulae has a wide range of anti-tumor activity, but poor water solubility and low bioavailability limit further application. In this study, EP was structurally modified using triphenylphosphine (TPP+), which combines mitochondrial targeting, amphiphilicity, and cytotoxicity. A series of TPP+-conjugated ergosterol peroxide derivatives (TEn) with different length linker arms were synthesized. The structure-activity relationship showed that the anticancer activity of TEn gradually decreased with the elongation of the linker arm. The compound TE3 has the optimal and broadest spectrum of antitumor effects. It mainly through targeting mitochondria, inducing ROS production, disrupting mitochondrial function, and activating mitochondria apoptosis pathway to exert anti-cervical cancer activity. Among them, TPP+ only acted as a mitochondrial targeting group, while EP containing peroxide bridge structure served as an active group to induce ROS. In vivo experiments have shown that TE3 has better anti-cervical cancer activity and safety than the first-line anticancer drug cisplatin, and can activate the immune response in mice. Although TE3 exhibits some acute toxicity, it is not significant at therapeutic doses. Therefore, TE3 has the potential for further development as an anti-cervical cancer drug.

Study of the Immune Infiltration and Sonic Hedgehog Expression Mechanism in Synovial Tissue of Rheumatoid Arthritis-Related Interstitial Lung Disease under Machine Learning CIBERSORT Algorithm.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is one of the common complications in patients with RA, which affects their quality of life. The CIBERSORT algorithm is widely employed to determine the proportion of immune cells (ICs) in diseased tissues, while the Sonic Hedgehog (Shh) signaling pathway, as an imperative regulatory factor, has also attracted attention in the pathology of RA-ILD. This work was to explore the mechanisms of RA-ILD immune infiltration and synovial tissue (ST) Shh expression based on the CIBERSORT algorithm. The differential genes of RA-ILD were subjected to pathway enrichment analysis using R language. The content and proportion of 22 types of ICs in RA-ILD lung tissues were analyzed using machine learning-based CIBERSORT algorithm. Meanwhile, immunoblotting was employed to detect and analyze the expression of Shh, Smoothened (Smo), and bone morphogenetic proteins (BMPs) proteins in ST samples from RA-ILD and Ctrl groups (RA patients without ILD). The hub target genes in the protein network associated with RA-ILD include BSG, CCL2, CTLA4, FGFBP1, GLI1, HHIP, HLA-DRB1, IFNAR1, IL17A, IL23A, IL-6, INPP4A, LILRB1, MUC5B, PADI4, PPM1A, PTCH1, PTPN22, RSPO4, Shh, SMO, STAT4, SUFU, TAOK2, TIMP2, and TWSG1, which are involved in multiple pathways, such as B cell regulation, transcription factors of the Shh pathway, and ST immune tolerance-related pathways. In the immunological analysis of RA-ILD using the CIBERSORT algorithm, HLA (r = - 0.26), PTPN22 (r = - 0.36), STAT4 (r = - 0.18), IL-6 (r = - 0.17), CTLA4 (r = - 0.27), and PADI4 (r = - 0.21) were all found to exhibit negative correlations with CD4+T cells (P < 0.05). Monocytes were found to be more abundant in RA-ILD patients' serum versus the Ctrl group. Shh, Smo, and BMP expressions were drastically lower in the RA-ILD group versus Ctrl group (P < 0.05). Significant immune cell infiltration was observed in the lung tissues of RA-ILD patients. Further analysis utilizing the CIBERSORT algorithm revealed alterations in the proportions of different IC subtypes, indicating their association with disease severity and prognosis. Moreover, there was a significant decrease in the expression levels of Shh, Smo, and BMP. These findings underscore the importance of immune cells in the pathophysiology of RA-ILD and suggest a potential involvement of the Shh signaling pathway in the pathogenesis of RA-ILD.

Primary biliary cholangitis has causal effects on systemic rheumatic diseases: a Mendelian randomization study.

BACKGROUND: An association has been observed between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs) in observational studies, however the exact causal link remains unclear. We aimed to evaluate the causal effects of PBC on SRDs through Mendelian randomization (MR) analysis. METHODS: The genome-wide association study (GWAS) summary data were obtained from MRC IEU OpenGWAS and FinnGen databases. Independent genetic variants for PBC were selected as instrumental variables. Inverse variance weighted was used as the main approach to evaluate the causal effects of PBC on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and polymyositis (PM). Horizontal pleiotropy and heterogeneity were measured by MR‒Egger intercept test and Cochran's Q value, respectively. RESULTS: PBC had causal effects on SS (OR = 1.177, P = 8.02e-09), RA (OR = 1.071, P = 9.80e-04), SLE (OR = 1.447, P = 1.04e-09), SSc (OR = 1.399, P = 2.52e-04), MCTD (OR = 1.306, P = 4.92e-14), and PM (OR = 1.416, P = 1.16e-04). Based on the MR‒Egger intercept tests, horizontal pleiotropy was absent (all P values > 0.05). The robustness of our results was further enhanced by the leave-one-out method. CONCLUSIONS: Our research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.

Spatiotemporal Evolution and Spatial Analysis of Ecological Environmental Quality in the Longyangxia to Lijiaxia Basin in China Based on GEE.

The upper reaches of the Yellow River are critical ecological barriers within the Yellow River Basin (YRB) that are crucial for source conservation. However, environmental challenges in this area, from Longyangxia to Lijiaxia, have emerged in recent years. To assess the ecological environment quality (EEQ) evolution from 1991 to 2021, we utilized remote sensing ecological indices (RSEIs) on the Google Earth Engine (GEE) platform. Spatial autocorrelation and heterogeneity impacting EEQ changes were examined. The results of this study show that the mean value of the RSEIs fluctuated over time (1991: 0.70, 1996: 0.77, 2001: 0.67, 2006: 0.71, 2011: 0.68, 2016: 0.65, and 2021: 0.66) showing an upward, downward, and then upward trend. The mean values of the overall RSEI are all at 0.65 and above. Most regions showed no significant EEQ change during 1991-2021 (68.59%, 59.23%, and 55.78%, respectively). Global Moran's I values (1991-2021) ranged from 0.627 to 0.412, indicating significant positive correlation between EEQ and spatial clustering, and the LISA clustering map (1991-2021) shows that the area near Longyangxia Reservoir shows a pattern of aggregation, dispersion, and then aggregation again. The factor detection results showed that heat was the most influential factor, and the interaction detection results showed that greenness and heat had a significant effect on regional ecosystem distribution. Our study integrates spatial autocorrelation and spatial heterogeneity and combines them with reality to provide an in-depth discussion and analysis of the Longyangxia to Lijiaxia Basin. These findings offer guidance for ecological governance, vegetation restoration, monitoring, and safeguarding the upper Yellow River's ecological integrity.

NK-92 cells activated by IL-2 inhibit the progression of endometriosis in vitro.

BACKGROUND: Interleukin (IL)-2 is a key cytokine capable of modulating the immune response by activating natural killer (NK) cells. This study was recruited to explore the therapeutic potential of IL-2-activated NK-92 cells in endometriosis in vitro. METHODS: Ectopic endometrial stromal cells (EESCs) were isolated and co-cultured with IL-2-activated NK-92 cells at varying effector-to-target (E:T) ratios (1:0 [Control], 1:1, 1:3, and 1:9). The viability, cytotoxicity, and cell surface antigen expression of IL-2-activated NK-92 cells were assessed. The viability, apoptosis, invasion, and migration ability of EESCs co-cultured with NK-92 cells at different ratios were evaluated. The apoptosis-related proteins, invasion and migration-related proteins as well as MEK/ERK pathway were examined via western blot. Each experiment was repeated three times. RESULTS: IL-2 activation enhanced NK-92 cytotoxicity in a concentration-dependent manner. Co-culturing EESCs with IL-2-activated NK-92 cells at E:T ratios of 1:1, 1:3, and 1:9 reduced EESC viability by 20%, 45%, and 70%, respectively, compared to the control group. Apoptosis rates in EESCs increased in correlation with the NK-92 cell proportion, with the highest rate observed at a 1:9 ratio. Moreover, EESC invasion and migration were significantly inhibited by IL-2-activated NK-92 cells, with a 60% reduction in invasion and a 50% decrease in migration at the 1:9 ratio. Besides, the MEK/ERK signalling pathway was down-regulated in EESCs by IL-2-activated NK-92 cells. CONCLUSION: IL-2-activated NK-92 cells exhibit potent cytotoxic effects against EESCs. They promote EESC apoptosis and inhibit viability, invasion, and migration through modulating the MEK/ERK signalling pathway.

Endometriosis is a common chronic systemic disease affecting approximately 190 million women worldwide. However, clinical treatments for endometriosis remain challenging due to the scarcity of high-quality scientific evidence and conflicting available guidelines. This research was designed to explore whether interleukin (IL)-2 affected the progression of endometriosis by modulating endometrial stromal cell apoptosis and natural killer (NK) cell-mediated cytotoxicity, thereby providing new therapeutic methods for endometriosis.

A memristive-photoconductive transduction methodology for accurately nondestructive memory readout.

Crossbar resistive memory architectures enable high-capacity storage and neuromorphic computing, accurate retrieval of the stored information is a prerequisite during read operation. However, conventional electrical readout normally suffer from complicated process, inaccurate and destructive reading due to crosstalk effect from sneak path current. Here we report a memristive-photoconductive transduction (MPT) methodology for precise and nondestructive readout in a memristive crossbar array. The individual devices present dynamic filament form/fuse for resistance modulation under electric stimulation, which leads to photogenerated carrier transport for tunable photoconductive response under subsequently light pulse stimuli. This coherent signal transduction can be used to directly detect the memorized on/off states stored in each cell, and a prototype 4 * 4 crossbar memories has been constructed and validated for the fidelity of crosstalk-free readout in recall process.

Transcriptome and metabolome reveal the effects of ABA promotion and inhibition on flavonoid and amino acid metabolism in tea plant.

Flavonoids (especially anthocyanins and catechins) and amino acids represent a high abundance of health-promoting metabolites. Although we observed abscisic acid accumulation in purple leaves and low levels in albino tea leaves, the specific mechanism behind its impact on flavor compounds remains unclear. In this study, we treated tea leaves with exogenous abscisic acid and abscisic acid biosynthesis inhibitors (Flu), measured physiological indicators and conducted comprehensive transcriptomic and metabolomic analyses to elucidate the potential mechanisms underlying color change. Our results demonstrate that abscisic acid treatment induces purple coloration, while Flu treatment causes discoloration in tea leaves. Metabolomic analysis revealed higher levels of four anthocyanins and six catechins in the group treated with abscisic acid in comparison with the control group. Additionally, there was a notable increase in 15 amino acids in the Flu-treated group. Notably, the levels of flavonoids and amino acids showed an inverse relationship between the two treatments. Transcriptomic comparison between the treatments and the control group revealed upregulation of differentially expressed genes encoding dihydroflavonol reductase and uridine diphosphate-glycose flavonoid glycosyltransferase in the abscisic acid-treated group, leading to the accumulation of identified anthocyanins and catechins. In contrast, differentially expressed genes encoding nitrate reductase and nitrate transporter exhibited elevated expression in the group treated with Flu, consequently facilitating the accumulation of amino acids, specifically L-theanine and L-glutamine. Furthermore, our co-expression network analysis suggests that MYB and bHLH transcription factors may play crucial roles in regulating the expression of differentially expressed genes involved in the biosynthesis of flavonoids and amino acids. This study provides insights for targeted genetic engineering to enhance the nutritional and market value of tea, together with the potential application of purple and albino tea leaves as functional beverages. It also offers guidance for future breeding programs and production.

The effect of different drying temperatures on flavonoid glycosides in white tea: A targeted metabolomics, molecular docking, and simulated reaction study.

Drying is an important stage used to improve the quality of white tea (WT). However, the effect of the drying temperature on the key taste compounds in WT remains unclear. In this study, targeted metabolomics, molecular docking, and a simulated reaction were used to investigate the transformation mechanism of flavonoid glycosides (FGs) in WT during drying at 60, 80, and 100 °C and its impact on taste. There were 45 differential FGs in WT at three drying temperatures. Compared with the withering samples for 48 h, the total FGs contents at three drying temperatures showed a decreasing trend, with quercetin-3-O-galactoside and kaempferol-3-O-glucoside showing the most degradation. These results were confirmed via a simulated drying reaction of FGs standards. Drying at 80 and 100 °C contributed to the formation of flavonoid-C-glycosides, but only trace amounts of these compounds were observed. In addition, nine key taste FGs were selected using dose-over-threshold values. These FGs regulated the taste of WT, mainly by binding to taste receptors via hydrogen bond, hydrophobic and electrostatic interactions. Finally, the taste acceptability of WT dried at 60 °C was found to be the highest, as this method could properly reduce the contents of FGs, weaken the bitterness and astringency, and retain the sweet and umami taste. This study revealed for the first time the transformation mechanism of sensory-active FGs affected by drying temperature, which provides a novel perspective for the analysis of the formation mechanism of the unique flavor of WT and the optimization of this process.

Disinfection and post-disinfection conditions drive bacterial and viral evolution across the environment and host.

Water disinfection practices have long been established as a critical engineering intervention for controlling pathogen transmission and safeguarding individual and public health. However, recent discoveries have unveiled the significant role disinfection and post-disinfection play in accelerating the development of resistance to disinfectants and antimicrobial drugs within bacterial and viral communities in the environment. This phenomenon, in turn, may facilitate the emergence of persistent microbes and those with new genetic characteristics. These microbes may thrive in host environments with increased infectivity and resistance, posing challenges to current medical treatments and jeopardizing human health. In this perspective, we illuminate the intricate interplay between aquatic environments, microbes, and hosts and how microbial virulence evolves across the environment and host under the pressure of disinfection and post-disinfection conditions. We aim to draw attention to the previously overlooked potential risks associated with disinfection in driving the virulence evolution of bacteria and viruses, establish connections between pathogens in diverse environments and hosts within the overarching framework of the One Health concept, and ultimately provide guidelines for advancing future water disinfection technologies to effectively curb the spread of infectious diseases.

Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Induce Fetal Wound Healing Features Revealed by Single-Cell RNA Sequencing.

The potential of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hucMSC-EVs) in wound healing is promising, yet a comprehensive understanding of how fibroblasts and keratinocytes respond to this treatment remains limited. This study utilizes single-cell RNA sequencing (scRNA-seq) to investigate the impact of hucMSC-EVs on the cutaneous wound microenvironment in mice. Through rigorous single-cell analyses, we unveil the emergence of hucMSC-EV-induced hematopoietic fibroblasts and MMP13+ fibroblasts. Notably, MMP13+ fibroblasts exhibit fetal-like expressions of MMP13, MMP9, and HAS1, accompanied by heightened migrasome activity. Activation of MMP13+ fibroblasts is orchestrated by a distinctive PIEZO1-calcium-HIF1α-VEGF-MMP13 pathway, validated through murine models and dermal fibroblast assays. Organotypic culture assays further affirm that these activated fibroblasts induce keratinocyte migration via MMP13-LRP1 interactions. This study significantly contributes to our understanding of fibroblast heterogeneities as well as intercellular interactions in wound healing and identifies hucMSC-EV-induced hematopoietic fibroblasts as potential targets for reprogramming. The therapeutic targets presented by these fibroblasts offer exciting prospects for advancing wound healing strategies.

TRIM21-mediated ubiquitylation of TAT suppresses liver metastasis in gallbladder cancer.

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.

Mitochondria-targeted fluorescent probe for simultaneously imaging viscosity and sulfite in inflammation models.

Many diseases in the human body are related to the overexpression of viscosity and sulfur dioxide. Therefore, it is essential to develop rapid and sensitive fluorescent probes to detect viscosity and sulfur dioxide. In the present work, we developed a dual-response fluorescent probe (ES) for efficient detection of viscosity and sulfur dioxide while targeting mitochondria well. The probe generates intramolecular charge transfer by pushing and pulling the electron-electron system, and the ICT effect is destroyed and the fluorescence quenched upon reaction with sulfite. The rotation of the molecule is inhibited in the high-viscosity system, producing a bright red light. In addition, the probe has good biocompatibility and can be used to detect sulfite in cells, zebrafish and mice, as well as upregulation of viscosity in LPS-induced inflammation models. We expect that the dual response fluorescent probe ES will be able to detect viscosity and sulfite efficiently, providing an effective means of detecting viscosity and sulfite-related diseases.

Causal association between systemic lupus erythematosus and primary biliary cholangitis: A bidirectional Mendelian randomization study.

An association has been observed between systemic lupus erythematosus (SLE) and primary biliary cholangitis (PBC) in observational studies, however, the exact causal link remains unclear. We aim to evaluate the causal relationships between SLE and PBC through bidirectional Mendelian randomization (MR). Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables from publicly accessible genome-wide association studies (GWAS) in European populations. The PBC and SLE GWAS data were obtained from the MRC IEU Open GWAS database, consisting of 24,510 and 14,267 samples, respectively. After a series of quality control and outlier removal, inverse variance weighted was used as the primary approach to evaluate the causal association between SLE and PBC. The horizontal pleiotropy and heterogeneity were examined by the MR-Egger intercept test and Cochran Q value, respectively. Seven SNPs were included to examine the causal effect of SLE on PBC. Genetically predicted SLE may increase the risk of PBC development, with an odds ratio (OR) of 1.324 (95% confidence interval [CI] 1.220 ∼ 1.437, P ˂ .001). Twenty SNPs were included to explore the causal effect of PBC on SLE. Genetically predicted PBC may increase the risk of SLE development, with an OR of 1.414 (95% CI 1.323 ∼ 1.511, P ˂ .001). Horizontal pleiotropy and heterogeneity were absent (P > .05) among SNPs. The robustness of our results was further enhanced by using the leave-one-out method. Our research has provided new insights into SLE and PBC, indicating bidirectional causal associations between the 2 diseases. These findings offer valuable contributions to future clinical studies.

Finite element analysis of different carbon fiber reinforced polyetheretherketone dental implants in implant-supported fixed denture.

OBJECTIVES: The purpose of this study is to determine the feasibility of polyetheretherketone-based dental implants, and analyze the stress and strain around different kinds of dental implants by finite element analysis. METHODS: The radiographic data was disposed to models in Mimics 19.0. 3D models of implants, crowns and jawbones were established and combined in SolidWorks 2018. Appling axial and oblique loads of 100 N, cloud pictures were exported in Ansys Workbench 18.0 to calculate and analyze the stress and strain in and around different implants. RESULTS: Oblique load tended to deliver more stress to bone tissue than axial load. The uniformity of stress distribution was the best for 30% short carbon fiber reinforced polyetheretherketone implants at axial and buccolingual directions. Stress shielding phenomenon occurred at the neck of 60% continuous carbon fiber reinforced polyetheretherketone and titanium implants. Stress concentration appeared in PEEK implants and the load of bone tissue would aggravate. CONCLUSIONS: 30% short carbon fiber reinforced polyetheretherketone implants demonstrate a more uniform stress distribution in bone-implant contact and surrounding bone than titanium. Stress shielding and stress concentration may be avoided in bone-implant interface and bone tissue. Bone disuse-atrophy may be inhibited in PEEK-based implants.

A DNA typing panel of 201 genetic markers for degraded samples: development and validation.

With the increasing number of complex forensic cases in recent years, it's more important to combine the different types of genetic markers such as short tandem repeats (STRs), single nucleotide polymorphisms (SNPs), insertion/deletion polymorphisms (InDels), and microhaplotypes (MHs) to provide more genetic information. In this study, we selected totally 201 genetic markers, including 24 autosomes STRs (A-STRs), 24 Y chromosome STRs (Y-STRs), 110 A-SNPs, 24 Y-SNPs, 9 A-InDels, 1 Y-InDel, 8 MHs, and Amelogenin to establish the HID_AM Panel v1.0, a Next-Generation Sequencing (NGS) detection system. According to the validation guidelines of the Scientific Working Group on DNA Analysis Methods (SWGDAM), the repeatability, accuracy, sensitivity, suitability for degraded samples, species specificity, and inhibitor resistance of this system were assessed. The typing results on 48 STRs and Amelogenin of this system were completely consistent with those obtained using capillary electrophoresis. This system accurately detected 79 SNPs as parallelly confirmed by a FGx sequencer with the ForenSeq™ DNA Signature Prep Kit. Complete allele typing results could be obtained with a DNA input of no less than 200 pg. The detection success rate of this system was significantly higher than that of the GlobalFiler™ kit when the degradation index of mock degraded sample was greater than 15.87. When the concentration of hematin in the amplification system was ≤40 µmol/L, indigo blue was ≤2 mmol/L, or humic acid was ≤15 ng/µL, amplification was not significantly inhibited. The system barely amplified the DNA extract from duck, mouse, cow, rabbit, and chick. The detection rate of STRs on routine samples of this panel is 99.74%, while all the SNPs, InDels, and MHs were successfully detected. In summary, we setup a NGS individual typing panel including 201 genetic markers with the high accuracy, sensitivity, species specificity, and inhibitors resistance, which is applicable for individual identification of degraded samples.