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Lead contamination in the environment tends to enter the food chain and further into the human body, causing serious health issues. Herein, we proposed a Csm6-DNAzyme tandem assay (termed cDNAzyme) using CRISPR/Cas III-A Csm6 and GR-5 DNAzyme, enabling one-pot and sensitive detection of lead contamination. We found that Pb

This retrospective study aimed to develop a practical model to determine overall survival after surgery in patients with colorectal cancer according to radiomics signatures based on computed tomography (CT) images and clinical predictors.A total of 121 colorectal cancer (CRC) patients were selected to construct the model, and 51 patients and 114 patients were selected for internal validation and external testing. The radiomics features were extracted from each patient's CT images. Univariable Cox regression and least absolute shrinkage and selection operator regression were used to select radiomics features. The performance of the nomogram was evaluated by calibration curves and the c-index. Kaplan-Meier analysis was used to compare the overall survival between these subgroups.The radiomics features of the CRC patients were significantly correlated with survival time. The c-indexes of the nomogram in the training cohort, internal validation cohort and external test cohort were 0.782, 0.721, and 0.677. Our nomogram integrated the optimal radiomics signature with clinical predictors showed a significant improvement in the prediction of CRC patients' overall survival. The calibration curves showed that the predicted survival time was close to the actual survival time. According to Kaplan-Meier analysis, the 1-, 2-, and 3-year survival rates of the low-risk group were higher than those of the high-risk group.The nomogram combining the optimal radiomics signature and clinical predictors further improved the predicted accuracy of survival prognosis for CRC patients. These findings might affect treatment strategies and enable a step forward for precise medicine.

The aim of this study was to evaluate and identify the predictive value of combining CT radiomics features and clinical features to determine recurrence-free survival (RFS) and overall survival (OS) after surgery in patients with esophageal squamous cell carcinoma (ESCC).A total of 372 patients with surgically and pathologically confirmed ESCC from 2 institutions were retrospectively included. All patients from institution 1 were randomized at a 7:3 ratio into a training cohort (n=206) and an internal validation cohort (n=88), and patients from institution 2 were used as an external validation cohort (n=78). The association between the radiomics features and RFS and OS was assessed in the training cohort and verified in the validation cohort. Furthermore, the performance of the radiomics nomogram was evaluated by combining the radiomics score (rad-score) and clinical risk factors.The radiomics nomogram that combined radiomics features and clinical risk factors was better than the clinical nomogram and radiomics model alone at predicting RFS and OS in ESCC patients. All calibration curves showed significant consistency between predicted survival and actual survival.Radiomics features could be used to stratify patients with ESCC following radical resection into high- and low-risk groups. Furthermore, the radiomics nomograms provided better predictive accuracy than other predictive models and might serve as a therapeutic decision-making reference for clinicians and be used to monitor the risks of recurrence and death.

A modified method for iron-catalyzed C–C bond cleavage and amination and alkylation of nonactivated cyclic alcohols has been developed. Using FeCl3 as catalyst, the photoinduced ligand-to-metal charge transfer facilitates the generation of O-radicals from alcohols, the subsequent β-scission, and finally the radical trapping. Compared with the Fe(OR)3 catalysis, this mildly base-free system could enable the amination in a broader substrate scope with higher yields. Moreover, the C–C bond cleavage and alkylation of cyclic alcohols proceeds with electron-deficient olefins under these conditions.

Osteoarthritis, characterized by articular cartilage degradation, is the leading cause of chronic disability in older adults. Studies have indicated that circular RNAs are crucial regulators of chondrocyte development and are involved in the progression of osteoarthritis. In this study, we investigated the function and mechanism of a circular RNA and its potential for osteoarthritis therapy. The expression levels of circCREBBP, screened by circular RNA sequencing during chondrogenic differentiation in adipose tissue-derived stem cells, and TGFβ2 were significantly increased in the cartilage of patients with osteoarthritis and IL-1β-induced chondrocytes. circCREBBP knockdown increased anabolism in the extracellular matrix and inhibited chondrocyte degeneration, whereas circCREBBP overexpression led to the opposite effects. Luciferase reporter assays, rescue experiments, RNA immunoprecipitation, and RNA pulldown assays confirmed that circCREBBP upregulated TGFβ2 expression by sponging miR-1208, resulting in significantly enhanced phosphorylation of Smad1/5 in chondrocytes. Moreover, intra-articular injection of adeno-associated virus-sh-circCrebbp alleviated osteoarthritis in a mouse model of destabilization of the medial meniscus. Our findings reveal a critical role for circCREBBP in the progression of osteoarthritis and provide a potential target for osteoarthritis therapy.

The relationship between exposure to certain metals and the risk of hyperuricemia (HUA) has biological plausibility, yet prior studies have presented inconsistent findings. We aim to clarify the relationship between exposure to certain metals and HUA using a systematic review and meta-analysis approach. We searched the Web of Science, Embase, MEDLINE, Pubmed, Corchrane and China National Knowledge Infrastructure databases from inception through December, 2021 in order to identify studies that assessed the relationships between metals and the risk of HUA. Data were pooled by random-effects models and expressed as pooled odds ratios (OR) and 95% confidence intervals (CIs). The risk of bias was assessed using a tool from Agency for Healthcare Research and Quality (AHRQ). Twenty eligible articles (nineteen cross-sectional studies and one cohort) were included in our analysis, involving 63,283 participants in total. The studies showed that arsenic (pooled OR = 1.702, 95% CI: 1.44, 2.011; n = 6, I

To evaluate the predictive value of intratumoral and peritumoral radiomics and radiomics nomogram for preoperative lymphovascular invasion (LVI) status and overall survival (OS) in patients with non-small cell lung cancer (NSCLC).In total, 240 NSCLC patients from our institution were randomly divided into the training cohort (n = 145) and internal validation cohort (n = 95) with a ratio of 6:4, and 65 patients from the Cancer Imaging Archive were enrolled as the external validation cohort. We extracted 1217 CT-based radiomics features from the gross tumor volume (GTV) and gross tumor volume incorporating peritumoral 3, 6, and 9 mm regions (GPTVCompared with GTV, GPTVCT-based radiomics nomogram can predict LVI and OS in patients with NSCLC and may help in making personalized treatment strategies before surgery.• Compared with GTV, GPTV

The problem of how to use large amounts of historical data for tunnel safety management has a greater practical application value. The association rule method in data mining technology can provide effective decision support for tunnel safety prevention by mining historical data. To address the problem of large data volume and sparse data items in tunnel safety management, an association rule method—Apriori algorithm—based on the Hadoop platform is proposed to improve the efficiency and accuracy of data mining in cloud environment. First, the parallel MapReduce implementation steps are analyzed on the basis of the distributed Hadoop framework. Then, the existing single-user data validation algorithm is improved by applying a multiuser parallel validation algorithm to Apriori in order to reduce the number of validations. Next, the traditional association rule Apriori algorithm is MapReduce optimized to generate a smaller set of useless candidate items. At the same time, Boolean ranking is used to optimize the way transactional data are stored in the database, reducing the number of redundant subsets and the number of times the database is connected, and shortening the task processing time. The experimental results show that the proposed method is able to mine the relationships between tunnel safety hazards and provide effective decision support for tunnel safety prevention. At the same time, the proposed method more efficiently operates than other association rule methods.

This article is concerned with the development of a new event-triggered parity space fault detection (FD) scheme. A linear discrete-time system model with varying sampling periods is presented for handling the problem of event-triggered FD and a new parity relation is established. Based on this, an event-triggered residual generator is constructed and the generated residual is completely decoupled from event-triggered transmission error. The design of the parity matrix is formulated into an optimization problem and an optimal solution of the parity matrix is obtained by using singular value decomposition. The issue of residual evaluation is also considered in the event-triggering implementation. The novelties of this article are twofold. First, a new event-triggered parity relation is obtained and the parity space-based residual signal achieves complete decoupling with the event-triggered transmission error. Second, the calculation of the parity matrix is independent of event parameters. So the design of the parity space-based residual generator and event generator can be carried out independently. Finally, a simulation example is considered to demonstrate the effectiveness of the proposed method.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for versatile diagnostic assays that can discriminate among emerging variants of the virus. Here we report the development and performance benchmarking of an inexpensive (approximately US$0.30 per test) assay for the rapid (sample-to-answer time within 30 min) colorimetric detection of SARS-CoV-2 variants. The assay, which we integrated into foldable paper strips, leverages nucleic acid strand-displacement reactions, the thermodynamic energy penalty associated with single-base-pair mismatches and the metal-ion-controlled enzymatic cleavage of urea to amplify the recognition of viral RNAs for the colorimetric readout of changes in pH via a smartphone. For 50 throat swab samples, the assay simultaneously detected the presence of SARS-CoV-2 and mutations specific to the SARS-CoV-2 variants Alpha, Beta and Gamma, with 100% concordance with real-time quantitative polymerase chain reaction and RNA sequencing. Customizable and inexpensive paper-based assays for the detection of viruses and their variants may facilitate viral surveillance.

Ovarian cancer remains a challenge to decrease mortality and improve diagnostic efficiency in gynecological cancers. To develop a delivery system capable of efficient cancer cell targeting and delivering novel efficacious therapeutics, we assembled folic acid (FA) conjugated ultrafine iron oxide nanoparticles (uIONP) with encapsulation of DNA topoisomerase inhibitor SN38, which target ovarian cancer cells with over-expression of folate receptor alpha (FRα) and deliver SN38 to induce apoptosis. The assembled FA-uIONP-SN38 exhibited higher drug loading efficiency than the larger counterparts with core diameters more than 10 nm. The targeting specificity of FA-uIONP-SN38 for SKOV-3 cancer cells was validated, with HEK293 kidney cells and Raw264.7 macrophages as non-targeted cell line control. It was found that more SKOV-3 cancer cells were killed due to apoptosis by FA-uIONP-SN38 at the same SN38 dosages compared with uIONP-SN38 and free SN38, respectively. The delivery of this inhibitor to SKOV-3 cancer cells by FRα-targeted FA-uIONP carrier was enhanced by about 10-folds with less cytotoxicity comparing to the free drug SN38. The developed FA-uIONP-SN38 holds a great potential as a theranostic approach in treating ovarian cancer.

Globally, chronic obstructive pulmonary disease(COPD) is the third leading cause of death. Necroptosis is a programmed regulated necrosis and contributes to the progression of lung disease. However, the function of necroptosis in COPD needs to be further elucidated. This study aimed to unravel the role of necroptosis in COPD via bioinformatics analysis and experimental validation. The GSE38974 and GSE8581 datasets were downloaded from the GEO database. Identified of differentially expressed genes(DEGs) from GSE38974. The GO, KEGG and GSEA enrichment analyses for DEGs.Differentially expressed genes of necroptosis(NR-DEGs) were obtained by combining DEGs and 159 necroptosis-related genes and the GO and KEGG were performed. The AUC values of NR-DEGs were assessed in the GSE38974 dataset and further were verified in the GSE8581 dataset. To further verify NR-DEGs in CSE-induced BEAS-2B cells by using RT-qPCR. The level of immune cell infiltration was quantified by ssGSEA analysis and the correlation analysis was performed between NR-DEGs and immune cell infiltration. We identified 646 DEGs and acquired 5 NR-DEGs(IL1B, IL-33, TNFAIP3, TNFRSF1A and CHMP4B) by combining 646 DEGs and 159 necroptosis-related genes. The GO, KEGG and GSEA enrichment analyses for the DEGs and NR-DEGs mainly involved in regulating of inflammatory response, cytokine-mediated signaling pathway, cytokine activity, receptor ligand activity and necroptosis. The AUC values of the NR-DEGs were 0.797, 0.971, 0.908, 1 and 1 from GSE38974 dataset and further were verified in the GSE8581 dataset were 0.741 and 0.737. The results of RT-qPCR showed that mRNA expression levels of IL1B and TNFAIP3 were up-regulated compared with control group(P

Previous studies demonstrated that reward circuit plays an important role in smoking. The differences of functional and structural connectivity were found among several brain regions such as nucleus accumbens, thalamus and frontal lobe. However, few studies focused on functional connectivity in whole-brain voxel level of young smokers. In this study, intrinsic connectivity contrast (ICC) was used to perform voxel-based whole-brain analyses in 55 young smokers and 55 matched non-smokers to identify brain regions with significant group differences. ICC results showed that the connectivity of young smokers in Medial Frontal Cortex (MedFC) showed a significantly lower trend compared with the non-smokers. The seed-based functional connectivityanalysis about MedFC indicated that young smokers showed reduced connectivity between the MedFC and left hippocampus, left amygdala compared to non-smokers. In addition, correlation analysis showed that the ICC of MedFC in young smokers was significantly negatively correlated with Fagerstrom Test for Nicotine Dependence (FTND) and Questionnaire on Smoking Urges (QSU). The functional connectivity of the MedFC was significantly negatively correlated with Pack_years. Moreover, the mediation analysis indicated that ICC of MedFC completely mediated FTND and QSU of young smokers. The results suggest that nicotine accumulation may affect the conmunication of the frontal lobe with the whole brain to some extent, leading to changes in smoking cravings. These results demonstrate the importance of whole-brain analysis and highlight the effectiveness of a completely data-driven approach to the problem. The above research also provides in-depth insights into the mechanism of adolescent smoking addiction and related intervention treatment.

The main active substances of Schisandra chinensis are lignans. Lignans are largely composed of schisandrin B (Sch B), which has a very high biphenyl cyclooctene content. This study was designed to evaluate the ability of Sch B to repair the particulate matter 2.5 (PM2.5)-induced THP-1 cell injury and determine the underlying mechanism of Sch B action. The results showed that Sch B significantly inhibited interleukin-1ꞵ (IL-1ꞵ) secretion and reduced PM2.5-caused cell pyroptosis. Mechanistically, Sch B reduced both cell membrane damage and the release of inflammatory factors via active reduction of caspase-1 enzyme activity and subsequent inhibition of gasdermin D (GSDMD) cleavage to N-GSDMD. In addition, Sch B treatment promoted the transcription of ALG2, ALIX, TSG101, and CHMP4B and membrane repair via ESCRT-III. Thus, we demonstrated that Sch B, the main active component of S. chinensis extracts, has anti-PM2.5 effect and elucidated the underlying mechanism of Sch B effects against THP-1 cell pyroptosis.

Poly(butylene adipate-co-terephthalate) (PBAT), a polyester made of terephthalic acid (TPA), 1,4-butanediol, and adipic acid, is extensively utilized in plastic production and has accumulated globally as environmental waste. Biodegradation is an attractive strategy to manage PBAT, but an effective PBAT-degrading enzyme is required. Here, we demonstrate that cutinases are highly potent enzymes that can completely decompose PBAT films in 48 h. We further show that the engineered cutinases, by applying a double mutation strategy to render a more flexible substrate-binding pocket exhibit higher decomposition rates. Notably, these variants produce TPA as a major end-product, which is beneficial feature for the future recycling economy. The crystal structures of wild type and double mutation of a cutinase from Thermobifida fusca in complex with a substrate analogue are also solved, elucidating their substrate-binding modes. These structural and biochemical analyses enable us to propose the mechanism of cutinase-mediated PBAT degradation.

Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. Methods This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. Results ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. Conclusions ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

The intestine is a site of immune cell priming at birth. Therefore, spatial transcriptomes were performed to define how the transcriptomic landscape was spatially organized in the posterior intestine of Sebastes schlegelii following Edwardsiella piscicida infection. In the healthy condition, we identified a previously unappreciated molecular regionalization of the posterior intestine. Following bacterial infection, most immune-related genes were identified in mucosa layer. Moreover, investigation of immune-related genes and genes in immune-related KEGG pathways based on spatial transcriptomes shed light on which sections of these genes are in the posterior intestine. Meanwhile, the high expression of genes related to regeneration also indicated that the posterior intestine was responding to the invasion of pathogens by constantly proliferating new cells. In addition, the increasing microbiota communities indicated that these bacteria maintained posterior intestine integrity and shaped the mucosal immune system. Taken together, spatial transcriptomes and microbiota compositions have significant implications for understanding the immune mechanism that responds to E. piscicida infection in the posterior intestine of S. schlegelii , which also provides a theoretical basis for the spatial distribution of immune genes and changes in bacterial flora in other teleosts in the process of resisting pathogens.

Pneumocystis jirovecii is an opportunistic fungus that can cause severe and potentially fatal Pneumocystis pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic polymorphisms of P. jirovecii at eight different loci, including six nuclear genes (ITS, 26S rRNA, sod, dhps, dhfr and β-Tub) and two mitochondrial genes (mtLSU-rRNA and cyb) in three PCP cases, including two patients with HIV infection and one without HIV infection in Shanxi Province, P.R. China. The gene targets were amplified by PCR followed by sequencing of plasmid clones. The HIV-negative patient showed a coinfection with two genotypes of P. jirovecii at six of the eight loci sequenced. Of the two HIV-positive patients, one showed a coinfection with two genotypes of P. jirovecii at the same two of the six loci as in the HIV-negative patient, while the other showed a single infection at all eight loci sequenced. None of the three drug target genes (dhfr, dhps and cyb) showed mutations known to be potentially associated with drug resistance. This is the first report of genetic polymorphisms of P. jirovecii in PCP patients in Shanxi Province, China. Our findings expand our understanding of the genetic diversity of P. jirovecii in China.