Superior oxidase-mimetic activity of FeCo-NC dual-atom nanozyme for smartphone-based visually colorimetric assay of organophosphorus pesticides.

A colorimetric analysis platform has been successfully developed based on FeCo-NC dual-atom nanozyme (FeCo-NC DAzyme) for the detection of organophosphorus pesticides (OPPs). The FeCo-NC DAzyme exhibited exceptional oxidase-like activity (OXD), enabling the catalysis of colorless TMB to form blue oxidized TMB (oxTMB) without the need for H2O2 involvement. By combining acid phosphatase (ACP) hydrolase with FeCo-NC DAzyme, a "FeCo-NC DAzyme + TMB + ACP + SAP" colorimetric system was constructed, which facilitated the rapid detection of malathion. The chromogenic system was applied to detect malathion using a smartphone-based app and an auxiliary imaging interferogram device for colorimetric measurements, which have a linear range of 0.05-4.0 µM and a limit of detection (LOD) as low as 15 nM in real samples, comparable to UV-Vis and HPLC-DAD detection methods. Overall, these findings present a novel approach for convenient, rapid, and on-site monitoring of OPPs.

Transcriptome-based network analysis reveals hub immune genes and pathways of hepatopancreas against LPS in Amphioctopus fangsiao.

The hepatopancreas is the biggest digestive organ in Amphioctopus fangsiao (A. fangsiao), but also undertakes critical functions like detoxification and immune defense. Generally, pathogenic bacteria or endotoxin from the gut microbiota would be arrested and detoxified in the hepatopancreas, which could be accompanied by the inevitable immune responses. In recent years, studies related to cephalopods immune have been increasing, but the molecular mechanisms associated with the hepatopancreatic immunity are still unclear. In this study, lipopolysaccharide (LPS), a major component of the cell wall of Gram-negative bacteria, was used for imitating bacteria infection to stimulate the hepatopancreas of A. fangsiao. To investigate the immune process happened in A. fangsiao hepatopancreas, we performed transcriptome analysis of hepatopancreas tissue after LPS injection, and identified 2615 and 1943 differentially expressed genes (DEGs) at 6 and 24 h post-injection, respectively. GO and KEGG enrichment analysis showed that these DEGs were mainly involved in immune-related biological processes and signaling pathways, including ECM-receptor interaction signaling pathway, Phagosome signaling pathway, Lysosome signaling pathway, and JAK-STAT signaling pathways. The function relationships between these DEGs were further analyzed through protein-protein interaction (PPI) networks. It was found that Mtor, Mapk14 and Atm were the three top interacting DEGs under LPS stimulation. Finally, 15 hub genes involving multiple KEGG signaling pathways and PPI relationships were selected for qRT-PCR validation. In this study, for the first time we explored the molecular mechanisms associated with hepatopancreatic immunity in A. fangsiao using a PPI networks approach, and provided new insights for understanding hepatopancreatic immunity in A. fangsiao.

Genetic variants in C1GALT1 are associated with gastric cancer risk and immune infiltrations.

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-ß-galactosyltransferase 1 (C1GALT1) is known to play a critical role in the development of gastric cancer, but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer susceptibility. By using the genome-wide association study data from the database of Genotype and Phenotype (dbGAP), we evaluated these associations with a logistic regression model and identified that the rs35999583 in C1GALT1 was associated with gastric cancer risk (odd ratio, 0.83; 95% confidence interval [CI], 0.75-0.92; P = 3.95 × 10 -4]. C1GALT1 mRNA expression was significantly higher in gastric tumor tissues, and gastric cancer patients with higher C1GALT1 mRNA levels had the worse overall survival rates (hazards ratio, 1.33; 95% CI, 1.05-1.68; P log-rank = 1.90 × 10 -2). Furthermore, we found that C1GALT1 copy number variations differed in various immune cells and C1GALT1 mRNA expression was positively correlated with the infiltrating levels of CD4 + T cells and macrophages. These results highlight that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 to be a promising predictor of gastric cancer susceptibility and immune status.

Childhood maltreatment and Internet addiction among Chinese adolescents: A moderated mediation model.

Although childhood maltreatment has been suggested to play an important role in developing Internet addiction among adolescents, little is known about the mediating and moderating mechanisms underlying this association. The present study investigated (a) the mediating role of maladaptive cognitive emotion regulation strategy (MCERS) in the association between childhood maltreatment and Internet addiction, and (b) the moderating role of peer support in the relationship between childhood maltreatment and Internet addiction. A sample of 4163 Chinese adolescents (50.3 % females, Mage = 14.25, SD = 1.53) were recruited. The moderated mediation model showed that MCERS mediated the relationship between childhood maltreatment and Internet addiction. Furthermore, the mediating process was moderated by peer support. Interestingly, peer support can protect adolescents from being affected by higher levels of MCERS while it displays limited protective effect when adolescents suffered from higher levels of childhood maltreatment. These findings indicate that reducing the MCERS and enhancing peer support can contribute to the alleviation of negative influences of childhood maltreatment on Internet addiction.

Genome-wide copy number variation detection in a large cohort of diverse horse breeds by whole-genome sequencing.

Understanding how genetic variants alter phenotypes is an essential aspect of genetic research. Copy number variations (CNVs), a type of prevalent genetic variation in the genome, have been the subject of extensive study for decades. Numerous CNVs have been identified and linked to specific phenotypes and diseases in horses. However, few studies utilizing whole-genome sequencing to detect CNVs in large horse populations have been conducted. Here, we performed whole-genome sequencing on a large cohort of 97 horses from 16 horse populations using Illumina Hiseq panels to detect common and breed-specific CNV regions (CNVRs) genome-wide. This is the largest number of breeds and individuals utilized in a whole genome sequencing-based horse CNV study, employing racing, sport, local, primitive, draft, and pony breeds from around the world. We identified 5,053 to 44,681 breed CNVRs in each of the 16 horse breeds, with median lengths ranging from 1.9 kb to 8 kb. Furthermore, using Vst statistics we analyzed the population differentiation of autosomal CNVRs in three diverse horse populations (Thoroughbred, Yakutian, and Przewalski's horse). Functional annotations were performed on CNVR-overlapping genes and revealed that population-differentiated candidate genes (CTSL, RAB11FIP3, and CTIF) may be involved in selection and adaptation. Our pilot study has provided the horse genetic research community with a large and valuable CNVR dataset and has identified many potential horse breeding targets that require further validation and in-depth investigation.

A Natural Compound Containing a Disaccharide Structure of Glucose and Rhamnose Identified as Potential N-Glycanase 1 (NGLY1) Inhibitors.

N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.

NOX2 Enzyme Mimicking Nano-Networks Regulate Tumor-Associated Macrophages to Initiate Both Innate and Adaptive Immune Effects.

Macrophages, capable of both direct killing and antigen presentation, are crucial for the interplay between innate and adaptive immunity. However, strategies mainly focus on polarizing tumor-associated macrophages (TAMs) to M1 phenotype, while overlooking the inefficient antigen cross-presentation due to hyperactive hydrolytic protease within lysosomes which leads to antigen degradation. In light of the significant influence of reactive oxygen species (ROS) on TAMs' polarization and the inhibition of phagosomal proteolysis, a novel nanosystem termed OVA-Fe-GA (OFG) is engineered, drawing inspiration from the NOX2 enzyme's role. OFG integrates ovalbumin (OVA) and a network composed of Fe-gallic acid (GA), emulating the NOX2 enzyme's sequential ROS generation process ("O2 to O2 •- to H2 O2 /•OH"). Furthermore, it elucidates a biological mechanism that augments antigen cross-presentation by suppressing the expression of cysteine proteases. OFG restores the innate anti-tumor functionality of TAMs and significantly amplifies their antigen cross-presentation (4.5-fold compared to the PBS control group) in B16-OVA tumor-bearing mice. Notably, the infiltration and activity of intratumoral CD8+ T cells are enhanced, indicating an adaptive immune response. Moreover, OFG exhibits excellent photothermal properties, thereby fostering a system antitumor immune response. This study provides a promising strategy for initiating both innate and adaptive immunity via TAMs activation. This article is protected by copyright. All rights reserved.

Alternative polyadenylation-related genetic variants contribute to bladder cancer risk.

Aberrant alternative polyadenylation (APA) events play an important role in cancers, but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer. Previous genome-wide association study performed APA quantitative trait loci (apaQTL) analyses in bladder cancer, and identified 17 955 single nucleotide polymorphisms (SNPs). We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways, high mutational burden, and immune infiltration. Association analysis showed that apaQTL-associated SNPs rs34402449 C>A, rs2683524 C>T, and rs11540872 C>G were significantly associated with susceptibility to bladder cancer (rs34402449: OR = 1.355, 95% confidence interval [CI]: 1.159-1.583, P = 1.33 × 10 -4; rs2683524: OR = 1.378, 95% CI: 1.164-1.632, P = 2.03 × 10 -4; rs11540872: OR = 1.472, 95% CI: 1.193-1.815, P = 3.06 × 10 -4). Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer ( P trend = 2.87 × 10 -12). We found that PRR13, being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines, was more highly expressed in bladder cancer tissues than in adjacent normal tissues. Moreover, the rs2683524 T allele was correlated with shorter 3' untranslated regions of PRR13 and increased PRR13 expression levels. Collectively, our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome in Shaziling Pig Testicular Development.

RNA N6-methyladenosine (m6A) modification is one of the principal post-transcriptional modifications and plays a dynamic role in testicular development and spermatogenesis. However, the role of m6A in porcine testis is understudied. Here, we performed a comprehensive analysis of the m6A transcriptome-wide profile in Shaziling pig testes at birth, puberty, and maturity. We analyzed the total transcriptome m6A profile and found that the m6A patterns were highly distinct in terms of the modification of the transcriptomes during porcine testis development. We found that key m6A methylated genes (AURKC, OVOL, SOX8, ACVR2A, and SPATA46) were highly enriched during spermatogenesis and identified in spermatogenesis-related KEGG pathways, including Wnt, cAMP, mTOR, AMPK, PI3K-Akt, and spliceosome. Our findings indicated that m6A methylations are involved in the complex yet well-organized post-transcriptional regulation of porcine testicular development and spermatogenesis. We found that the m6A eraser ALKBH5 negatively regulated the proliferation of immature porcine Sertoli cells. Furthermore, we proposed a novel mechanism of m6A modification during testicular development: ALKBH5 regulated the RNA methylation level and gene expression of SOX9 mRNA. In addition to serving as a potential target for improving boar reproduction, our findings contributed to the further understanding of the regulation of m6A modifications in male reproduction.

Achieving smartphone-based colorimetric assay for Hg2+ with a bimetallic site strategy based on Hg2+-triggered oxidase-like catalytic activity of NSC/Co6Ni3S8 nanocomposite.

Modulation of the nanozyme's catalytic activity is crucial for its real applications in detecting target analytes. Herein, we fabricated the nanocomposite (NSC/Co6Ni3S8) of N, S co-doped carbon and Co6Ni3S8 by a facile sol-gel approach. Compared to NSC/Ni9S8, NSC/Co6Ni3S8 with bimetallic active sites displayed better enzyme-mimetic activity. This nanocomposite could catalyze O2 to form ·O2- and oxidize colorless 3, 3', 5, 5'-tetramethylbenzidine (TMB) into blue oxTMB. The other two free radicals (h+ and ·OH) played minor roles during the catalytic reaction. Hg2+ could integrate with S2- to form HgS and the surface charges of O2 were transferred to Hg2+ to promote O2 adsorption. DFT theoretical calculations highlight that the main reasons for the enhancing effect of Hg2+ on color development results from electron transfer and increased adsorption energy of O2 molecules onto the surface of NSC/Co6Ni3S8. By employing the oxidase-like activity of NSC/Co6Ni3S8 and Hg2+-triggered promoting effect, a colorimetric sensing platform was established for Hg2+ assay with a linear range of 10-200 µg/L and detection limit of 3 µg/L. Through integration with a smartphone-based APP "Thing Identify" software, a visual colorimetric assay for Hg2+ was constructed with a detection limit of 5 µg/L. Compared to the data detected by the mercury vapor meter, the relative recoveries of 92.4-108.1% evidenced the higher accuracy of this smartphone-based visual detection. Overall, the NSC/Co6Ni3S8-based colorimetric assay is convenient, rapid, and visual, and can be applied for routine monitoring of Hg2+ in real-world waters under outdoor conditions.

Integrated analysis of circRNA, lncRNA, miRNA and mRNA to reveal the ceRNA regulatory network of postnatal skeletal muscle development in Ningxiang pig.

Introduction: The development of skeletal muscle is regulated by regulatory factors of genes and non-coding RNAs (ncRNAs). Methods: The objective of this study was to understand the transformation of muscle fiber type in the longissimus dorsi muscle of male Ningxiang pigs at four different growth stages (30, 90, 150, and 210 days after birth, n = 3) by histological analysis and whole transcriptome sequencing. Additionally, the study investigated the expression patterns of various RNAs involved in muscle fiber transformation and constructed a regulatory network for competing endogenous RNA (ceRNA) that includes circular RNA (circRNA)/long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA). Results: Histomorphology analysis showed that the diameter of muscle fiber reached its maximum at 150 days after birth. The slow muscle fiber transformation showed a pattern of initial decrease followed by an increase. 29,963 circRNAs, 2,683 lncRNAs, 986 miRNAs and 22,411 mRNAs with expression level ≥0 were identified by whole transcriptome sequencing. Furthermore, 642 differentially expressed circRNAs (DEc), 505 differentially expressed lncRNAs (DEl), 316 differentially expressed miRNAs (DEmi) and 6,090 differentially expressed mRNAs (DEm) were identified by differential expression analysis. Functions of differentially expressed mRNA were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). GO enrichment analysis indicates that 40 known genes and 6 new genes are associated with skeletal muscle development. Additionally, KEGG analysis shows that these genes regulate skeletal muscle development via MAPK, FoxO, Hedgehog, PI3K-Akt, Notch, VEGF and other signaling pathways. Through protein-protein interaction (PPI) and transcription factor prediction (TFP), the action mode of skeletal muscle-related genes was explored. PPI analysis showed that there were stable interactions among 19 proteins, meanwhile, TFP analysis predicted 22 transcription factors such as HMG20B, MYF6, MYOD1 and MYOG, and 12 of the 19 interacting proteins were transcription factors. The regulatory network of ceRNA related to skeletal muscle development was constructed based on the correlation of various RNA expression levels and the targeted binding characteristics with miRNA. The regulatory network included 31 DEms, 59 miRNAs, 667 circRNAs and 224 lncRNAs. conclusion: Overall, the study revealed the role of ceRNA regulatory network in the transformation of skeletal muscle fiber types in Ningxiang pigs, which contributes to the understanding of ceRNA regulatory network in Ningxiang pigs during the skeletal muscle development period.

Genome-Wide Assessment of Runs of Homozygosity by Whole-Genome Sequencing in Diverse Horse Breeds Worldwide.

In the genomes of diploid organisms, runs of homozygosity (ROH), consecutive segments of homozygosity, are extended. ROH can be applied to evaluate the inbreeding situation of individuals without pedigree data and to detect selective signatures via ROH islands. We sequenced and analyzed data derived from the whole-genome sequencing of 97 horses, investigated the distribution of genome-wide ROH patterns, and calculated ROH-based inbreeding coefficients for 16 representative horse varieties from around the world. Our findings indicated that both ancient and recent inbreeding occurrences had varying degrees of impact on various horse breeds. However, recent inbreeding events were uncommon, particularly among indigenous horse breeds. Consequently, the ROH-based genomic inbreeding coefficient could aid in monitoring the level of inbreeding. Using the Thoroughbred population as a case study, we discovered 24 ROH islands containing 72 candidate genes associated with artificial selection traits. We found that the candidate genes in Thoroughbreds were involved in neurotransmission (CHRNA6, PRKN, and GRM1), muscle development (ADAMTS15 and QKI), positive regulation of heart rate and heart contraction (HEY2 and TRDN), regulation of insulin secretion (CACNA1S, KCNMB2, and KCNMB3), and spermatogenesis (JAM3, PACRG, and SPATA6L). Our findings provide insight into horse breed characteristics and future breeding strategies.

Genetic variation and domestication of horses revealed by 10 chromosome-level genomes and whole-genome resequencing.

Understanding the genetic variations of the horse (Equus caballus) genome will improve breeding conservation and welfare. However, genetic variations in long segments, such as structural variants (SVs), remain understudied. We de novo assembled 10 chromosome-level three-dimensional horse genomes, each representing a distinct breed, and analysed horse SVs using a multi-assembly approach. Our findings suggest that SVs with the accumulation of mammalian-wide interspersed repeats related to long interspersed nuclear elements might be a horse-specific mechanism to modulate genome-wide gene regulatory networks. We found that olfactory receptors were commonly loss and accumulated deleterious mutations, but no purge of deleterious mutations occurred during horse domestication. We examined the potential effects of SVs on the spatial structure of chromatin via topologically associating domains (TADs). Breed-specific TADs were significantly enriched by breed-specific SVs. We identified 4199 unique breakpoint-resolved novel insertions across all chromosomes that account for 2.84 Mb sequences missing from the reference genome. Several novel insertions might have potential functional consequences, as 519 appeared to reside within 449 gene bodies. These genes are primarily involved in pathogen recognition, innate immune responses and drug metabolism. Moreover, 37 diverse horses were resequenced. Combining this with public data, we analysed 97 horses through a comparative population genomics approach to identify the genetic basis underlying breed characteristics using Thoroughbreds as a case study. We provide new scientific evidence for horse domestication, an understanding of the genetic mechanism underlying the phenotypic evolution of horses, and a comprehensive genetic variation resource for further genetic studies of horses.

CaCO3 powder-mediated biomineralization of antigen nanosponges synergize with PD-1 blockade to potentiate anti-tumor immunity.

Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of "antigen multi-copy display" and "calcium carbonate (CaCO3) biomineralization" to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4+ T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.

[Recent advances in the development and application of effervescence-assisted microextraction techniques].

Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. This is commonly achieved using methods such as vortexing, centrifugation, and dilution, among others. The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples.

The association of childhood maltreatment with Internet addiction: the serial mediating effects of cognitive emotion regulation strategies and depression.

OBJECTIVES: Childhood maltreatment, cognitive emotion regulation strategies (CERSs), and depression can be important in adolescents' Internet addiction. The current study aims to investigate the direct effect of childhood maltreatment on Internet addiction and its indirect effects via CERSs and depression. PARTICIPANTS AND SETTING: 4091 adolescents (age M = 13.64, SD = 1.59; 48.9 % males) were recruited from a public school in China. METHODS: In a cross-sectional design, participants completed the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Cognitive Emotion Regulation Questionnaire-Short version (CERQ-Short), the Self-Rating Depression Scale (SDS), and the Internet Addiction Test (IAT). A latent structural equation model was used to test the hypotheses. RESULTS: After controlling for age, childhood maltreatment was directly associated with adolescents' Internet addiction (ß = 0.12, p < 0.001). Meanwhile, the serial mediating effect via maladaptive CERSs and depression was 0.02 (95 % CI [0.01, 0.04]), and via adaptive CERSs and depression was 0.001 (95 % CI [0.0004, 0.002]), demonstrating significant serial mediating role of CERSs and depression in this relationship. No gender difference was observed. CONCLUSIONS: The findings suggest that maladaptive CERSs and depression can be potential mechanisms relating childhood maltreatment to adolescents' Internet addiction, while adaptive CERSs can be a less influential factor for reducing Internet addiction.

Ultrafine V2O5-anchored 3D N-doped carbon nanocomposite with augmented dual-enzyme mimetic activity for evaluating total antioxidant capacity.

Total antioxidant capacity (TAC) can be evaluated by detecting the content of antioxidants, such as ascorbic acid, based on the enzyme-mimetic activity of nanomaterials. Herein, we fabricated a 3D-V2O5/NC nanocomposite using a self-templating strategy, which achieved ultrafine particles (∼2.5 nm), a porous carbon layer, large specific surface area (152.4 m2/g), N-doping and heterogeneous structure. The strong catalytic activity of 3D-V2O5/NC resulted from the integrated effect between the ultrafine structure of V2O5 nanoparticles and the 3D porous nitrogen-doped carbon framework, effectively increasing the number of active sites. This nanozyme presented a higher catalytic activity than its components or precursors in the nanocomposite (e.g., VN/NC, NC, V2O5, and VO2/g-C3N4). ROS scavenging experiments confirmed that the dual enzyme-like activity of 3D-V2O5/NC (catalase-like and oxidase-like) resulted from their co-participation of ‧O2-, h+ and ‧OH, among which ‧O2- played a crucial role in the catalytic color reaction. By virtue of the 3D-V2O5/NC nanoenzyme activity and TMB as a chromogenic substrate, the mixed system of 3D-V2O5/NC + TMB + H2O2 provided a low detection limit (0.03 µM) and suitable recovery (93.0-109.5%) for AA. Additionally, a smartphone-based colorimetric application was developed employing "Thing Identify" software to evaluate TAC in beverages. The colorimetric sensor and smartphone-detection platform provide a better or comparable analytical performance for TAC assessment in comparison to commercial ABTS test kits. The newly developed smartphone-based colorimetric platform presents several prominent advantageous, such as low cost, simple/rapid operation, and feasibility for outdoor use.

Relief of Extracellular Matrix Deposition Repression by Downregulation of IRF1-Mediated TWEAK/Fn14 Signaling in Keloids.

Keloids represent a fibrotic disorder characterized by the excessive deposition of extracellular matrix (ECM). However, the mechanisms through which ECM deposition in keloids is regulated remain elusive. In this study, we found that the expression of both TWEAK and its cognate receptor Fn14 was significantly downregulated in keloids and that TWEAK/Fn14 signaling repressed the expression of ECM-related genes in keloid fibroblasts. The IRF1 gene was essential for this repression, and the TWEAK/Fn14 downstream transcription factor p65 directly bound to the promoter of the IRF1 gene and induced its expression. Furthermore, in patients with keloid, the expression of TWEAK and Fn14 was negatively correlated with that of ECM genes and positively correlated with that of IRF1. These observations indicate that relief of TWEAK/Fn14/IRF1-mediated ECM deposition repression contributes to keloid pathogenesis, and the identified mechanism and related molecules provide potential targets for keloid treatment in the future.

Labeling Assembly of Hydrophilic Methionine into Nanoparticle for Mild-Heat Mediated Immunometabolic Therapy.

Methionine metabolism has a significant impact on T cells' survival and activation even in comparison to arginine, a well-documented amino acid in metabolic therapy. However, hydrophilic methionine is hardly delivered into TME due to difficult loading and rapid diffusion. Herein, the labeling assembly of methionine into nanoparticle is developed to overcome high hydrophilicity for mild-heat mediated immunometabolic therapy. The strategy is to first label methionine with protocatechualdehyde (as the tag) via reversible Schiff-base bond, and then drive nanoassembly of methionine (MPC@Fe) mediated by iron ions. In this fashion, a loading efficiency of 40% and assembly induced photothermal characteristics can be achieved. MPC@Fe can accumulate persistently in tumor up to 36 h due to tumor-selective aggregation in acidic TME. A mild heat of 43 °C on tumor by light irradiation stimulated the immunogenic cell death and effectively generated CD8+ T cells. Notably, MPC@Fe assisted by mild heat promoted 4.2-fold of tumor-infiltrating INF-γ+ CD8+ T cells, leading to an inhibition ratio of 27.3-fold versus the free methionine. Such labeling assembly provides a promising methionine delivery platform to realize mild heat mediated immunometabolic therapy, and is potentially extensible to other amino acids.

Dynamic tagging to drive arginine nano-assembly to metabolically potentiate immune checkpoint blockade therapy.

L-arginine metabolism is essential for the activation, survival, and effector function of the T lymphocytes and critical in eliminating tumors via T-cell-mediated immunotherapy, such as immune checkpoint blockade (ICB). Unfortunately, efficient delivery of hydrophilic L-arginine to the tumor microenvironment (TME) has met tremendous difficulties because of the limited loading efficacy and rapid diffusion. Inspired by the small-molecule prodrug nanoassemblies with ultrahigh drug-loading, we screen out aromatic aldehydes compounds to be used as dynamic tags to decorate L-arginine (reversible imine). Nano-Arginine (ArgNP, 104 nm) was created based on dynamic tag-mediated self-assembly. Molecular dynamics simulations indicate that the driving force of this self-assembly process is intermolecular hydrogen bonds, π-π stacking, and cation-π interactions. Notably, ArgNP metabolic synergy with anti-PD-L1 antibody (aPDL1) can promote tumor-infiltrating T cells (3.3-fold than aPDL1), resulting in a tumor inhibition ratio of 2.6-fold than aPDL1. Besides, such a strategy efficiently reduces the myeloid-derived suppressor cells, increases the M1-macrophages against the tumor, and induces the production of memory T cells. Furthermore, this synergistic therapy effectively restrains lung metastasis and prolongs mouse survival (60% survival ratio). The study highlights the dynamic tags strategy with facility and advance to deliver L-arginine that can metabolically promote ICB therapy.