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Despite the importance of soil bacterial and fungal communities for ecosystem services and human welfare, how their ecological networks respond to climatic aridity have yet been evaluated. Here, we collected soil samples from 47 sites across 2500 km in coastal and inland areas of eastern Australia with contrasting status of aridity. We found that the diversity of both bacteria and fungi significantly differed between inland and coastal soils. Despite the significant differences in soil nutrient availability and stoichiometry between the inland and coastal regions, aridity was the most important predictor of bacterial and fungal community compositions. Aridity has altered the potential microbial migration rates and further impacted the microbial assembly processes by increasing the importance of stochasticity in bacterial and fungal communities. More importantly, ecological network analysis indicated that aridity enhanced the complexity and stability of the bacterial network but reduced that of the fungal network, possibly due to the contrasting impacts of aridity on the community-level habitat niche breadth and overlaps. Our work paves the way towards a more comprehensive understanding of how climate changes will alter soil microbial communities, which is integral to predicting their long-term consequences for ecosystem sustainability and resilience to future disturbances.

The production of platelets is tightly regulated by thrombopoietin (THPO). Mutations in the THPO gene cause thrombocytopenia. Although mice lacking Thpo present with thrombocytopenia, predicting phenotypes and pathogenicity of novel THPO mutations in mice is limited. Zebrafish can be a powerful tool for fast validation and study of candidate genes of human hematological diseases and have already been used as a model of human thrombocytopenia.We aim to investigate the role of Thpo in zebrafish thrombopoiesis and to establish a Thpo-deficient zebrafish model. The model could be applied for illustrating the clinically discovered human THPO variants of which the clinical significance is not known and to evaluate the effect of THPO receptor agonists (THPO-Ras), as well as a screening platform for new drugs.We generated a thpo loss-of-function zebrafish model using CRISPR/Cas9. After disruption of zebrafish thpo, thpoZebrafish with the mutation thpo

Pancreatic ductal adenocarcinoma (PDAC) usually presents infrequent infiltration of T lymphocytes. The known immune-checkpoint inhibitors to date focus on activating T cells and manifest limited effectiveness in PDAC. SIGLEC15 was identified as a novel tumor-associated macrophage (TAM)-related immune-checkpoint in other cancer types, while its immunosuppressive role and clinical significance remained unclear in PDAC. In our study, SIGLEC15 presented immunosuppressive relevance in PDAC via bioinformatic analysis and expressed on TAM and PDAC cells. SIGLEC15

Burning lignocellulosic biomass wastes in an outdoor atmosphere has placed heavy burden on ecological environment and increased risk on human health. Converting solid agricultural wastes into functional materials is a research hotspot. In this study, N-doped and CoO-loaded carbocatalyst (CoO-N/BC) was successfully synthesized from the cotton stalk biomass via a simple synthesis process of impregnation and carbonization. Compared with cotton stalk biomass derived pristine biochar, the CoO-N/BC possessed a higher specific surface area (466.631 m2 g-1 vs 286.684 m2 g-1) as well as a better catalytic performance in the activation of peroxymonosulfate (PMS) for CIP degradation. The superior catalytic efficiency was ascribed to the directional flow of electrons on the well-organized carbon network of CoO-N/BC, which accelerated electron migration and improved electron conduction ability. Based on the results of radical quenching experiment and electron paramagnetic resonance (EPR), both radical and non-radical process conjointly led to the stepwise decomposition of CIP, and singlet oxygen (1O2) mediated non-radical pathway was discovered to play a dominant role. Besides, the carbon-bridge mediated non-radical pathway was proved to accelerate this degradation process through the experiments of prolong the time of adding CIP at different time intervals. Nitrogen doped sites and CoO active sites as well as defects formed in sp2-hybridized carbon network were supposed to be the active sites for PMS. Furthermore, EIS and LSV were employed to confirm the electron transfer mediated non-radical process of reaction system. This work provides a modified strategy for the disposition of lignocellulosic biomass wastes and illuminates the underlying mechanism of heterogeneous catalysis by CoO-N/BC.

This study aimed to explore the role of circular-CDC like kinase 1 (circ-CLK1) in the pathogenesis of oral squamous cell carcinoma (OSCC). Circ-CLK1 expression levels were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of circ-CLK1 knockdown on the viability and apoptosis of OSCC cells were determined using the cell counting kit-8 (CCK-8) assay, EdU staining, flow cytometry, and Western blotting. StarBase and TargetScan were used to predict targeting relationships, which were then confirmed by the dual luciferase reporter assay and RNA pull-down assay. We found that the expression of circ-CLK1 was significantly higher in OSCC patients and cell lines. Inhibition of circ-CLK1 reduced the viability and proliferation of OSCC cells while enhancing their apoptosis. However, inhibiting miR-18b-5p or overexpression of Y-box protein 2 (YBX2) can reverse the effect of circ-CLK1 knockdown on OSCC cells. Therefore, circ-CLK1 inhibited the apoptosis of OSCC cells through the miR-18b-5p/YBX2 axis, and these findings suggest that circ-CLK1 could be a potential therapeutic target for OSCC patients.

To evaluate the addition of digital breast tomosynthesis (DBT) in the diagnosis of breast lesions in symptomatic young Chinese women (≤30 years) diagnosed with Breast Imaging Reporting and Data System (BI-RADS) category 4 or 5 on ultrasound, and demonstrate the potential use of combining DBT with ultrasound.This retrospective analysis included 5 years of digital mammography (DM) and DBT data (January 2015 to July 2020). In total, 768 DBT and DM examinations were performed in 713 young women. The results were determined by pathological assessment. Diagnostic performance was measured based on the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic area under the curve (AUC).Compared with DM alone, DBT + DM increased the sensitivity from 82.5% to 93.2%, specificity from 70.8% to 84%, accuracy from 74% to 86.5%, NPV from 93.6% to 97.4% (all p0.01). The AUC of DBT + DM (0.946, 95% confidence interval [CI]: 0.927-0.960) was greater than that of DM (0.884, 95% CI: 0.859-0.905; p0.001). The differences in the BI-RADS category distributions of malignant and benign lesions were both statistically significant (p0.001). DM alone led to 36 false-negative diagnoses, whereas the inclusion of DBT identified breast cancer in 22 of those cases. There were 4.9% (10/206) false-negative diagnoses in ultrasound. After adding DBT, four breast cancers were detected. An additional six breast cancers were diagnosed by biopsy based on an assessment of BI-RADS 4A by DBT/DM.DBT + DM significantly improves the diagnostic performance in this young population, especially in young people with higher breast density. Moreover, DBT is an effective supplementary examination to ultrasound.

Background Cancer-associated fibroblasts (CAFs) are critically involved in gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanism by which CAFs promote chemotherapy resistance remains unexplored. Here, we explored the role of circRNAs in CAF-induced GEM resistance in PDAC. Methods circRNA sequencing and quantitative real-time PCR (qRT–PCR) were utilized to screen CAF-specific circRNAs. The effects of CAF circFARP1 expression on GEM resistance in tumor cells were assessed in vitro and in vivo. RNA-seq, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays were used to screen the downstream target and underlying mechanism of circFARP1. Results circFARP1 (hsa_circ_0002557), a CAF-specific circRNA, was positively correlated with GEM chemoresistance and poor survival in an advanced PDAC cohort. Silencing or overexpressing circFARP1 in CAFs altered the ability of CAFs to induce tumor cell stemness and GEM resistance via leukemia inhibitory factor (LIF). Mechanistically, we found that circFARP1 directly binds with caveolin 1 (CAV1) and blocks the interaction of CAV1 and the E3 ubiquitin-protein ligase zinc and ring finger 1 (ZNRF1) to inhibit CAV1 degradation, which enhances LIF secretion. In addition, circFARP1 upregulated LIF expression by sponging miR-660-3p. Moreover, high circFARP1 levels were positively correlated with elevated serum LIF levels in PDAC and poor patient survival. Decreasing circFARP1 levels and neutralizing LIF significantly suppressed PDAC growth and GEM resistance in patient-derived xenograft models. Conclusions The circFARP1/CAV1/miR-660-3p/LIF axis is critical for CAF-induced GEM resistance in PDAC. Hence, circFARP1 may be a potential therapeutic target for PDAC.

Current clinical agents for autoimmunity disorders treatment often cause substantial adverse effects and safety concerns, owing to non-specific immune modulation. Due to the prominent contribution of effector T cells in pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), and preferential location of co-stimulatory receptor-ligand pair OX40-OX40L at the inflamed sites, selectively targeting autoaggressive T cells by blockade OX40-OX40L, might represent an alternative strategy. Herein, we developed a new strategy to antagonize OX40-OX40L interaction by engineering a cell membrane derived nanovesicles (NVs) expressing OX40 receptors (OX40 NVs), and explored their potential for autoimmune disorders therapy. OX40 NVs showed specific binding capability to inflamed HUVECs in vitro, it also possessed distinct arthritic-targeting capacity in RA inflamed joints, and preferential accumulation in IBD inflamed colon. OX40 NVs efficiently suppressed the progression of both RA and IBD diseases through reducing CD4+OX40+ T cells population, and proinflammatory cytokines (i.e., TNF-α and IL-1β), while reinforcing Tregs immune-suppressive effect, with superior therapeutic efficacy than anti-OX40L. Additionally, dexamethasone (DEX) loading can further enhance the potential of OX40 NVs for RA treatment. Owing to their preferential localization to inflamed sites, and potent immune-suppression ability, targeting OX40-OX40L blockade by OX40 NVs for autoimmune therapy is highly promising.

Ductal carcinoma in situ with microinvasion (DCIS-MI) is a subtype of breast cancer with a good prognosis, for which both breast conserving surgery plus radiotherapy (BCS + RT) and mastectomy are feasible surgical methods, but no clear conclusion has been made on the choice of these treatments. We used the Surveillance, Epidemiology and End Results database to extract 5432 DCIS-MI patients. Participants were divided into the BCS + RT group and the mastectomy group. We compared the overall survival (OS) and breast cancer-specific survival (BCSS) of the two groups using the Kaplan–Meier method and Cox regressions before and after propensity score matching (PSM). Before PSM, both univariate and multivariate analyses showed that BCS + RT group had significantly higher OS and BCSS compared with patients in the mastectomy group (P P P = 0.017). In addition, the subgroup analysis showed that BCS + RT is at least equivalent to mastectomy with respect to OS and BCSS in any subgroup. For patients with DCIS-MI, the prognosis of BCS + RT was superior to mastectomy.

Ventricular arrhythmias are the primary arrhythmias that cause sudden cardiac death. In current clinical and preclinical research, the discovery of new therapies and their translation is hampered by the lack of consistency in diagnostic criteria for distinguishing between ventricular tachycardia (VT) and ventricular fibrillation (VF). This study develops a new set of features, similarity maps, for discrimination between VT and VF using deep neural network architectures. The similarity maps are designed to capture the similarity and the regularity within an ECG trace. Our experiments show that the similarity maps lead to a substantial improvement in distinguishing VT and VF.

The diagnosis of atypical cystic meningioma is difficult because of the atypical MRI findings.This paper reported a case of atypical cystic meningioma and described the detailed MRI findings,which would provide valuable imaging evidence for the localization and classification of cystic meningioma.

BACKGROUND Evaluating tumor-infiltrating lymphocytes (TILs) in patients with breast cancer using radiomics has been rarely explored. PURPOSE To establish a radiomics nomogram based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for preoperatively evaluating TIL level. STUDY TYPE Retrospective. POPULATION A total of 154 patients with breast cancer were divided into a training cohort (N = 87) and a test cohort (N = 67), who were further divided into low TIL (

Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown previously that insulin receptor substrate 2 (IRS2), a molecule highly critical to insulin resistance and metabolism, has an anti-inflammatory role in Th2-skewed lung inflammation and pulmonary vascular remodeling. Here, we investigated the hypothesis that IRS2 has an immunomodulatory role in human and experimental PH. Expression analysis showed that IRS2 was significantly decreased in the pulmonary vasculature of patients with pulmonary arterial hypertension and in rat models of PH. In mice, genetic ablation of IRS2 enhanced the hypoxia-induced signaling pathway of Akt and Forkhead box O1 (FOXO1) in the lung tissue and increased pulmonary vascular muscularization, proliferation, and perivascular macrophage recruitment. Furthermore, mice with homozygous IRS2 gene deletion showed a significant gene dosage-dependent increase in pulmonary vascular remodeling and right ventricular hypertrophy in response to hypoxia. Functional studies with bone marrow-derived macrophages isolated from homozygous IRS2 gene-deleted mice showed that hypoxia exposure led to enhancement of the Akt and ERK signaling pathway followed by increases in the pro-PH macrophage activation markers, vascular endothelial growth factor-A and arginase 1. Our data suggest that IRS2 contributes to anti-inflammatory effects by regulating macrophage activation and recruitment, which may limit the vascular inflammation, remodeling, and right ventricular hypertrophy that are seen in PH pathology. Restoring the IRS2 pathway may be an effective therapeutic approach for the treatment of PH and right heart failure.

This work aimed to study the application of pelvic floor dynamic images of magnetic resonance imaging (MRI) based on the particle swarm optimization (PSO) algorithm in female stress urinary incontinence (SUI). 20 SUI female patients were selected as experimental group, and another 20 healthy females were taken as controls. PSO algorithm, K-nearest neighbor (KNN) algorithm, and back propagation neural network (BPNN) algorithm were adopted to construct the evaluation models for comparative analysis, which were then applied to 40 cases of female pelvic floor dynamic MRI images. It was found that the model proposed had relatively high prediction accuracy in both the training set (87.67%) and the test set (88.46%). In contrast to the control group, there were considerable differences in abnormal urethral displacement, urethral length changes, bladder prolapse, and uterine prolapse in experimental patients ( P < 0.05 ). After surgery, the change of urethral inclination angle was evidently reduced ( P < 0.05 ). To sum up, MRI images can be adopted to assess the occurrence of female SUI with abnormal urethral displacement, shortening of urethra length, bladder prolapse, and uterine prolapse. After surgery, the abnormal urethral movement was slightly improved, but there was no obvious impact on bladder prolapse and uterine prolapse.

Solitary pulmonary nodules (SPNs) are commonly found in imaging technologies, but are plagued by high false-positive rates.We aimed to identify metabolic alterations in SPN etiology and diagnosis using less invasive plasma metabolomics and lipidomics.In total, 1160 plasma samples were obtained from healthy volunteers (n = 280), benign SPNs (n = 157) and malignant SPNs (stage I, n = 723) patients enrolled from 5 independent centers. Gas chromatography-triple quadrupole mass spectrometry (GC‒MS) and liquid chromatography-Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry (LC‒MS) were used to analyze the samples for untargeted metabolomics and lipidomics.GC‒MS-based metabolomics revealed 1336 metabolic features, while LC‒MS-based lipidomics revealed 6088 and 2542 lipid features in the positive and negative ion modes, respectively. The metabolic and lipidic characteristics of healthy vs. benign or malignant SPNs exhibited substantial pattern differences. Of note, benign and malignant SPNs had no significant variations in circulating metabolic and lipidic markers and were validated in four other centers. This study demonstrates evidence of early metabolic alterations that can possibly distinguish SPNs from healthy controls, but not between benign and malignant SPNs.

This study was conducted to ascertain whether people in China would be willing to pay for an inactivated COVID-19 vaccine booster dose. An online survey estimating participants' willingness to pay (WTP) for a booster dose of COVID-19 vaccine was conducted in Taizhou, China. The participants received ane-mail or e-poster on WeChat. A total of 1576 subjects participated the survey. A total of 66.4% (1046/1576) of the respondents were willing to pay for a booster dose of COVID-19 vaccine for themselves. Using binary logistic regression analysis, the following factors were significantly related to a WTP for a booster dose of COVID-19 vaccine: 1) confidence in the safety of the COVID-19 vaccines (high vs. low, OR: 4.30, 95%CI: 1.61-11.43), 2) confidence in the preventive effectiveness of the COVID-19 vaccines against SARS-CoV-2 virus (moderate vs. little, OR: 1.76, 95%CI: 1.30-2.38; great vs. little, OR: 2.244, 95%CI: 1.62-3.12), and 3) COVID-19 vaccine hesitancy (unhesitant vs. very unhesitant, OR: 0.67, 95%CI: 0.45-1.02; hesitant vs. very unhesitant, OR: 0.29, 95%CI: 0.19-0.44; very hesitant vs. very unhesitant, OR: 0.09, 95%CI: 0.03-0.27). This study revealed that a moderate proportion of participants responded that they would be willing to pay for a booster dose of COVID-19 vaccine. These findings suggest the importance of a detailed assessment and a health education plan that better understands the population's risk perception as well as the potential health risks in China.

Studies have identified teacher effects on students' attitudes. This study explored the differences in and associations between teachers' and students' COVID-19 vaccine hesitancy, and the factors that affect it. A population-based self-administered online survey was conducted to evaluate the COVID-19 vaccine hesitancy of teachers and students in a college in Taizhou, China. A total of 835 valid questionnaires were obtained. All data were analyzed using IBM SPSS statistics 26.0 software. The proportions of COVID-19 vaccine hesitancy for teachers and students were 31.7%, and 23.8%, respectively. In the binary logistic regression analysis, teachers who perceived the safety of the COVID-19 vaccine as low (OR = 6.794 , 95%CI: 1.701-27.143), did not pay continuous attention to the vaccine news (OR = 3.498, 95%CI: 1.150-10.640), and suffered chronic diseases (OR = 2.659, 95%CI: 1.135-6.227) were more likely to hesitate to get vaccinated against COVID-19. The group of students who perceived the COVID-19 vaccine safety as being low (OR = 1.805, 95%CI: 1.094-2.979) were more hesitant to get the COVID-19 vaccine. While both teachers and students were hesitant about the COVID-19 vaccine, teachers were found to be more so. Perceptions regarding the safety of COVID-19 vaccines, attention to and awareness of vaccine news, and chronic medical conditions were the main factors that influenced the hesitation regarding COVID-19 vaccines. Therefore, students' vaccine hesitancy may depend largely on the perceptions of the vaccine's safety rather than teachers' vaccine hesitancy.

Biomarker research in head and neck squamous cell carcinoma (HNSCC) is constantly revealing promising findings. An enhancer of polycomb homolog 1 (The Kaplan-Meier plotter was used to evaluate the prognostic significance ofAccording to the clinical data, highHigh

Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation.We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice.Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC).Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.

Accumulating evidence demonstrates that the cerebellum is involved in a variety of cognitive functions. Recently, impaired auditory-motor integration for vocal control has been identified in patients with cerebellar degeneration, characterized by abnormally enhanced vocal compensations for pitch perturbations. However, the causal relationship between the cerebellum and auditory feedback during vocal production remains unclear. By applying anodal transcranial direct current stimulation (a-tDCS) over right cerebellum, the present study investigated cerebellar contributions to auditory-motor processing of feedback errors during vocal pitch regulation. Twenty young adults participated in a frequency-altered-feedback (FAF) task, in which they vocalized vowel sounds and heard their voice unexpectedly pitch-shifted by ± 50 or ± 200 cents. Active or sham cerebellar a-tDCS was applied either prior to or during the FAF task. Compensatory vocal responses to pitch perturbations were measured and compared across the conditions. Active cerebellar a-tDCS led to significantly larger and slower vocal compensations for pitch perturbations than sham stimulation. Moreover, this modulatory effect was observed regardless of the timing of cerebellar a-tDCS as well as the size and direction of the pitch perturbation. These findings provide the first causal evidence that the cerebellum is essentially involved in auditory feedback control of vocal production. Enhanced and slowed vocal compensations caused by cerebellar a-tDCS may be related to its inhibition on the prefrontal cortex that exerts inhibitory control over vocal compensation behavior, suggesting the importance of the cerebrocerebellar connections in this feedback control process.

Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in 'cell morphogenesis involved in differentiation', 'haematopoietic cell lineage', 'platelet activation, signalling and aggregation' and 'mitochondrial RNA metabolic process' signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.

Aims: Using Single-cell RNA sequencing (scRNA-seq), we explored the spatiotemporal heterogeneity of pancreatic neuroendocrine tumors (pNETs) and the underlying mechanism for malignant progression. Methods: scRNA-seq was conducted on three tumor tissues (two primary tissues from different sites, one liver metastatic lesion), one normal liver tissue, and peripheral blood mononuclear cells from one patient with a metastatic G2 pNET, followed by bioinformatics analysis and validation in a pNETs cohort. Results: The transcriptome data of 24.544 cells were obtained. We identified subpopulations of functional heterogeneity within malignant cells, immune cells, and fibroblasts. There were intra- and inter-heterogeneities of cell subpopulations for malignant cells, macrophages, T cells, and fibroblasts among all tumor sites. Cell trajectory analysis revealed several hallmarks of carcinogenesis, including the hypoxia pathway, metabolism reprogramming, and aggressive proliferation, which were activated at different stages of tumor progression. Evolutionary analysis based on mitochondrial mutations defined two dominant clones with metastatic capacity. Finally, we developed a gene signature (PCSK1 and SMOC1) defining the metastatic potential of the tumor and its prognostic value was validated in a cohort of thirty G1/G2 patients underwent surgical resection. Conclusions: Our scRNA-seq analysis revealed intra- and intertumor heterogeneities in cell populations, transcriptional states, and intercellular communications among primary and metastatic lesions of pNETs. The single-cell level characterization of the spatiotemporal dynamics of malignant cell progression provided new insights into the search for potential novel prognostic biomarkers of pNETs.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

Pancreatic carcinoma elevates quickly and thus has a high mortality rate. Therefore, early treatment is essential for treating pancreatic carcinoma. KRAS is the most frequently identified and one of the earliest mutations in pancreatic tumorigenesis. Thus, the KRAS-mutant cell is an ideal target for the treatment of pancreatic carcinoma, especially at the early stage. KRAS mutation increases macropinocytosis in pancreatic cancer cells, enhancing the internalization of exosomes. Because acquiring natural exosomes could be laborious and their encapsulation efficiency is often unsatisfactory, we aimed to develop a delivery system that mimics the Kras-mutant cell targeting capability of exosomes but is easier to generate and has better loading efficiency. For this purpose, we constructed a hybrid nanoplatform by fusing CLT (Celastrol)-Loaded PEGylated lipids with the DC2.4 cell membrane (M-LIP-CLT) to achieve targeted treatment of Kras-mutant pancreatic cancer. This hybrid nanoplatform improved CLT tumor accumulation and showed excellent anti-cancer efficiency both in vitro and in vivo with increased safety. These results suggest that M-LIP-CLT is an effective drug delivery system for targeted therapy against pancreatic carcinoma, and the fusion strategy showed attractive potential for further development.

Endogenous miRNA expression patterns are extremely cell-type-specific, thereby offering high prediction accuracy for different cell identities. Here, a DNA-tetrahedron-based "AND" logic gate is utilized as a molecular device that recognizes dual-miRNA inputs through strand hybridization to activate a computation cascade that produces controlled singlet oxygen in live cells, resulting in the death of the target cell.

MicroRNA-141 (miR-141-3p) is upregulated in preeclampsia. This study investigated the effect of methylation of the miR-141-3p promoter on cell viability, invasion capability, and inflammasomes in vitro. The expression of miR-141-3p and methylation status of the miR-141-3p promoter were examined by RT-qPCR and pyrosequencing in villus tissues of women with spontaneous delivery (VTsd), villus tissues of women with preeclampsia (VTpe), and also in HTR-8/SVneo cells treated with a miR-141-3p inhibitor and 20 μmol/L 5-aza-2′-deoxycytidine (5-Aza), a DNA methyltransferase inhibitor. Cell viability and invasion were evaluated by CCK-8 and transwell assays. In addition, the levels of CXCL12, CXCR4, CXCR2, MMPs, NLRP3, and ASC expression were assessed by western blotting, and IL-1β and IL-18 concentrations were assayed by ELISA. miR-141-3p expression was upregulated, and the levels of miR-141-3p promoter methylation and CXCL12, CXCR4, and CXCR2 expression were decreased in VTpe relative to VTsd. In HTR-8/SVneo cells, hypomethylation caused by 5-Aza treatment increased miR-141-3p expression, while DNA methyltransferase 3 (DNMT3) transfection decreased miR-141-3p expression. miRNA-141-3p induced NLRP3, IL-1β, and IL-18 production, decreased CXCR4, MMP, and MMP2 production, and suppressed cell growth and invasion. Furthermore, we observed that NLRP3 plays an important mediatory role in the effects of miR-141-3p described above. Decreased methylation of the miR-141-3p promoter increases miR-141-3p expression, which in turn increases NLRP3 expression, resulting in higher IL-1β and IL-18 levels and lower levels of MMP2/9 and CXCR4. We conclude that modification of the miR-141-3p promoter might be a curial mediator in preeclampsia.

Objective. Soluble CD206 (sCD206) is considered a macrophage activation marker, and a previous study proved it as a potential biomarker to predict the severity of anti-melanoma differentiation-associated gene 5- (anti-MDA-5-) positive dermatomyositis- (DM-) associated interstitial lung disease (ILD). To investigate the role of sCD206 in various subtypes of DM, we evaluated the serum level of sCD206 in patients with different myositis-specific autoantibodies besides anti-MDA-5 and clarified its clinical significance. Methods. Commercial enzyme-linked immunosorbent assay kits were used to detect serum concentrations of sCD206 in 150 patients with DM and 52 healthy controls (HCs). Correlations between sCD206 levels and clinical features, laboratory examinations, and pulmonary function test parameters were analysed. Results. The median concentrations of serum sCD206 in DM patients were significantly higher than those in HCs ( p < 0.0001 ). Furthermore, median sCD206 levels were elevated in patients with ILD ( p = 0.001 ), especially in those with rapidly progressive ILD (RP-ILD) ( p < 0.0001 ). In addition, sCD206 levels were negatively correlated with the pulmonary function test results, including the percent predicted forced vital capacity ( r = − 0.234 , p = 0.023 ), percent predicted forced expiratory volume in one second ( r = − 0.225 , p = 0.030 ), and percent predicted carbon monoxide diffusion capacity ( r = − 0.261 , p = 0.014 ). Age- and gender-adjusted multivariable analysis showed that sCD206 was an independent prognostic factor for RP-ILD in patients with DM. A longitudinal study showed that sCD206 levels were positively correlated with the physician global assessment visual analog scale scores ( β = 54.201 , p = 0.001 ). Conclusion. Serum sCD206 levels were significantly increased in patients with DM and significantly associated with RP-ILD, suggesting that sCD206 is an important biological predictor of RP-ILD in patients with DM.

The family of resistin-like molecules (RELMs) consists of four members in rodents (RELMα/FIZZ1/HIMF, RELMβ/FIZZ2, Resistin/FIZZ3, and RELMγ/FIZZ4) and two members in humans (Resistin and RELMβ), all of which exhibit inflammation-regulating, chemokine, and growth factor properties. The importance of these cytokines in many aspects of physiology and pathophysiology, especially in cardiothoracic diseases, is rapidly evolving in the literature. In this review article, we attempt to summarize the contribution of RELM signaling to the initiation and progression of lung diseases, such as pulmonary hypertension, asthma/allergic airway inflammation, chronic obstructive pulmonary disease, fibrosis, cancers, infection, and other acute lung injuries. The potential of RELMs to be used as biomarkers or risk predictors of these diseases also will be discussed. Better understanding of RELM signaling in the pathogenesis of pulmonary diseases may offer novel targets or approaches for the development of therapeutics to treat or prevent a variety of inflammation, tissue remodeling, and fibrosis-related disorders in respiratory, cardiovascular, and other systems.

Enhanced Recovery after Surgery has been proven effective for patients with gastrointestinal cancer. But radical enhanced recovery could also lead to adverse clinical outcomes. Compared with reports on the estimation of successful implementation of enhanced recovery, studies on risk factors of enhanced recovery failure are still lacking. A retrospective analysis was carried out on 102 patients in ERAS who underwent elective colon cancer surgery. This study included 102 patients with colon cancer between 2015 and 2019, defining enhanced recovery failure as postoperative length of stay over 10 days, stay in ICU over 24 h after surgery, reoperation, death, or unplanned readmission within 30 days after surgery. Univariate and multivariate analyses were performed to explore potential risk factors of failure. Aged ≥ 75, open operation, number of drainage tube over 1, re-urethral catheterization, and Clavien-Dindo grade over 2 were associated with ERAS failure, according to univariate analysis. Multivariate analysis showed that age ≥ 75 [OR 7.231; P = 0.009]; open operation (OR 3.599; P = 0.021); and number of drainage tube over 1 (OR 3.202; P = 0.020) were independent risk factors for ERAS failure. We found age ≥ 75, open operation, and number of drainage tube over 1 are independent risk factors associated with ERAS failure after colon cancer surgery.

The increasing and simultaneous pollution of plastic debris and antibiotic resistance in aquatic environments makes plastisphere a great health concern. However, the development process of antibiotic resistome in the plastisphere is largely unknown, impeding risk assessment associated with plastics. Here, we profiled the temporal dynamics of antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and microbial composition in the plastisphere from initial microbial colonization to biofilm formation in urban water. A total of 82 ARGs, 12 MGEs, and 63 bacterial pathogens were detected in the plastisphere and categorized as the pioneering, intermediate, and persistent ones. The high number of five MGEs and six ARGs persistently detected in the whole microbial colonization process was regarded as a major concern because of their potential role in disseminating antibiotic resistance. In addition to genomic analysis, D2O-labeled single-cell Raman spectroscopy was employed to interrogate the ecophysiology of plastisphere in a culture-independent way and demonstrated that the plastisphere was inherently more tolerant to antibiotics than bacterioplankton. Finally, by combining persistent MGEs, intensified colonization of pathogenic bacteria, increased tolerance to antibiotic, and potential trophic transfer into a holistic risk analysis, the plastisphere was indicated to constitute a hot spot to acquire and spread antibiotic resistance and impose a long-term risk to ecosystems and human health. These findings provide important insights into the antibiotic resistome and ecological risk of the plastisphere and highlight the necessity for comprehensive surveillance of plastisphere.

To evaluate the accuracy of compressed sensing (CS) cardiovascular magnetic resonance imaging (CMR) in the classifications of heart failure (HF). One hundred and fifty-four patients underwent 3 T CMR using CS single-breath-hold cine (SBH-cine) after a standard multiple-breath-hold cine (MBH-cine). The image quality of the two methods was compared. Cardiac function parameters were quantitatively analyzed. The patients were divided into different HF types based on diagnostic criteria using two sequences. The scan time for CS SBH-cine was reduced by 88% compared with that of standard MBH-cine. In the non-atrial-fibrillation (NAF) group (n = 121), the image quality score of CS SBH-cine was slightly decreased compared with standard MBH-cine (4.5 ± 0.6 for the CS SBH-cine vs. 4.7 ± 0.5 for the standard MBH-cine, T = 5.038, p

Medical students' perceptions of the medical school learning environment (MSLE) have an important impact on their professional development, and physical and mental health. Few studies reported potential factors that influenced medical students' perceptions of MSLE. Thus, the main goal of this study was to identify influencing factors for medical students' perception levels of MSLE. The perception levels of MSLE were assessed by the Johns Hopkins Learning Environment Scale. The univariate and multivariate logistic regression analyses were performed to identify significant predictors for the perceptions of MSLE. The nomograms were established to predict medical students' perception levels of MSLE. In the multivariate logistic regression model, gender, university category, grade, mother education level, learning environment of schools, interests in medicine, and Kolb learning experience were significantly associated with medical students' perceptions of MSLE. Correspondently, the nomograms were built based on significant variables identified by the univariate logistic regression analysis. The validation of the nomograms showed that the model had promising predictive accuracy, discrimination, and accordance (area under the curve (AUC) = 0.751). This study identified influencing factors of medical students' perceptions of MSLE. It is essential to implement corresponding interventions to improve medical students' perceptions.

Long and automatic control of blood glucose levels in diabetic patients could solve the problems caused by frequent insulin injections. Herein, we exploited the protection potential of erythrocytes by a "hitchhiking" strategy to significantly prolong the blood circulation time of a specifically-designed smart hitchhiking insulin delivery system (SHIDS). In the SHIDS, insulin, glucose oxidase, and catalase were co-loaded into nanoparticles formed by modified chitosan. The free glucosamines in chitosan anchor glucose transporters on the surface of erythrocytes, allowing erythrocyte-hitchhiking in the blood flow. A high glucose level triggers quick insulin release from the SHIDS to reduce the glucose level, which then slows the insulin release. This closed-loop glucose regulation by the SHIDS effectively controlled blood glucose within the normal range for at least 24 h and under 250 mg dL

The obesity paradox has been observed in short-term outcomes from critical illness. However, little is known regarding the impact of obesity on long-term outcomes for survivors of critically ill patients. We aimed to evaluate the influence of obesity on long-term mortality outcomes after discharge alive from ICU. The adult patients who were discharged alive from the last ICU admission were extracted. After exclusion, a total of 7619 adult patients discharged alive from ICU were included, with 4-year mortality of 32%. The median body mass index (BMI) was 27.2 (IQR 24–31.4) kg/m2, and 2490 (31.5%) patients were classified as obese or morbidly obese. The morbidly obese patients had the highest ICU and hospital length of stay. However, higher BMI was associated with lower hazard ratio for 4-year mortality. The results showed the obesity paradox may be also suitable for survivors of critically ill patients.

4 páginas.- 2 figuras.- 19 referencias.- Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41396-022-01225-8, Soils harbor the most diverse naturally evolved antibiotic resistance genes (ARGs) on Earth, with implications for human health and ecosystem functioning. How ARGs evolve as soils develop over centuries, to millennia (i.e., pedogenesis), remains poorly understood, which introduces uncertainty in predictions of the dynamics of ARGs under changing environmental conditions. Here we investigated changes in the soil resistome by analyzing 16 globally distributed soil chronosequences, from centuries to millennia, spanning a wide range of ecosystem types and substrate age ranges. We show that ARG abundance and diversity decline only after millions of years of soil development as observed in very old chronosequences. Moreover, our data show increases in soil organic carbon content and microbial biomass as soil develops that were negatively correlated with the abundance and diversity of soil ARGs. This work reveals natural dynamics of soil ARGs during pedogenesis and suggests that such ecological patterns are predictable, which together advances our understanding of the environmental drivers of ARGs in terrestrial environments., This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 702057. MD-B is supported by a project from the Spanish Ministry of Science and Innovation (PID2020-115813RA-I00), and a project PAIDI 2020 from the Junta de Andalucía (P20_00879).

Natural killer (NK) cells, a subgroup of innate lymphoid cells, act as the first line of defense against cancer. Although some evidence shows that NK cells can develop in secondary lymphoid tissues, NK cells develop mainly in the bone marrow (BM) and egress into the blood circulation when they mature. They then migrate to and settle down in peripheral tissues, though some special subsets home back into the BM or secondary lymphoid organs. Owing to its success in allogeneic adoptive transfer for cancer treatment and its “off-the-shelf” potential, NK cell-based immunotherapy is attracting increasing attention in the treatment of various cancers. However, insufficient infiltration of adoptively transferred NK cells limits clinical utility, especially for solid tumors. Expansion of NK cells or engineered chimeric antigen receptor (CAR) NK cells ex vivo prior to adoptive transfer by using various cytokines alters the profiles of chemokine receptors, which affects the infiltration of transferred NK cells into tumor tissue. Several factors control NK cell trafficking and homing, including cell-intrinsic factors (e.g., transcriptional factors), cell-extrinsic factors (e.g., integrins, selectins, chemokines and their corresponding receptors, signals induced by cytokines, sphingosine-1-phosphate (S1P), etc.), and the cellular microenvironment. Here, we summarize the profiles and mechanisms of NK cell homing and trafficking at steady state and during tumor development, aiming to improve NK cell-based cancer immunotherapy.

Bone immunity regulates osteoclast differentiation and bone resorption and is a potential target for the treatment of postmenopausal osteoporosis (PMOP). The molecular network between bone metabolism and the immune system is complex. However, the molecular mechanism underlying the involvement of the major histocompatibility complex class II (MHC-II) molecule protein presentation pathway in PMOP remains to be elucidated. The MHC-II molecule is a core molecule of the protein presentation pathway. It is combined with the processed short peptide and presented to T lymphocytes, thereby activating them to become effector T cells. T-cell-derived inflammatory factors promote bone remodeling in PMOP. Moreover, the MHC-II molecule is highly expressed in osteoclast precursors. MHC-II transactivator (CIITA) is the main regulator of MHC-II gene expression and the switch for protein presentation. CIITA is also a major regulator of osteoclast differentiation and bone homeostasis. Therefore, we hypothesized that the MHC-II promotes osteoclast differentiation, providing a novel pathogenic mechanism and a potential target for the treatment of PMOP.

Microglia are the earliest activated and the longest lasting immune cells after stroke, and they participate in almost all the pathological reactions after stroke. However, their regulatory mechanism has not been fully elucidated. Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor that is mainly expressed in microglia of the central nervous system. The receptor plays an important role in regulating microglia energy metabolism and phenotypic transformation. At present, TREM2 has been developed as a potential target for AD, coronary atherosclerosis and other diseases. However, TREM2 does not provide a systematic summary of the functional transformation and intrinsic molecular mechanisms of microglia after stroke. In this paper, we have summarized the functional changes of TREM2 in microglia after stroke in recent years, and found that TREM2 has important effects on energy metabolism, phagocytosis and anti-inflammatory function of microglia after stroke, suggesting that TREM2 is a potential therapeutic target for the treatment of stroke.

This population-based cross-sectional study was conducted to explore whether parents are willing to pay to vaccinate their children against COVID-19 in China.With a self-administered online questionnaire, we investigated parents' willingness to pay for their children to be vaccinated against COVID-19 in Taizhou, China. Of the 1,845 parents who answered the structured questionnaire when they received an e-mail or e-poster invitation, 1788 samples with valid data underwent data analysis.A total of 66.1% of parents reported being willing to pay to inoculate their children with the COVID-19 vaccine. After adjustment for confounding factors, lower education level, one-child family (yes vs. no, OR = 1.35, 95%CI: 1.04-1.74), knowledge score of vaccination against COVID-19 (high vs. low, OR = 1.31, 95%CI: 1.01-1.69), awareness of the permitted use of the vaccine (yes vs. no, OR = 1.51, 95%CI: 1.16-1.97), and willingness to pay for a COVID-19 vaccine for themselves (yes vs. no, OR = 16.31, 95%CI: 12.59-21.14) were significantly associated with parents' willingness to pay for their children.We found that a moderate proportion of parents reported unwillingness to pay for their child to be vaccinated against COVID-19. The results indicate that further detailed assessment and more health education planning are required to increasing parents' WTP for the vaccination of children in China.

This meta-analysis aimed to analyze retinal microvasculature features in eyes with Behçet’s disease (BD) using optical coherence tomography angiography (OCTA). Electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched for published studies comparing retinal microvasculature characteristics between eyes with BD and controls. Continuous variables were calculated using the mean difference (MD) with 95% confidence interval (CI). Review Manager software (version 5.30) was used to conduct statistical analysis. A total of 13 eligible studies involving 599 eyes with BD and 622 control eyes were included in the meta-analysis. The pooled results showed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in eyes with BD than in control eyes (superficial VD: MD = − 3.05, P P = 0.0004). The foveal superficial and deep VD values were also significantly lower in the BD group than in the control group (superficial VD: MD = − 1.50, P = 0.009; deep VD: MD = − 4.25, − = 0.03). Similarly, the analysis revealed a significant reduction in the parafoveal superficial and deep VD in eyes with BD than in control eyes (superficial VD: MD = − 3.68, P P = 0.0007). In addition, the superficial and deep foveal avascular zones (FAZs) were significantly larger in patients with BD than in controls (superficial FAZ: MD = 0.06, P = 0.02; deep FAZ: MD = 0.12, P = 0.03). The present meta-analysis found that macular whole enface VD, foveal VD, and parafoveal VD were lower in eyes with BD, and the FAZ was larger in patients with BD. The findings suggest that OCTA can assist clinicians in diagnosing and monitoring the status of patients with BD.

Pre-procedure liver dysfunction was associated with acute kidney injury after percutaneous coronary intervention (PCI). The aim of this study is to assess and compare the predictive value of different liver function scoring systems for contrast-associated acute kidney injury (CA-AKI) in patients undergoing elective PCI.Methods and Results:A total of 5,569 patients were retrospectively enrolled. The model for end-stage liver disease (MELD) including albumin (MELD-Albumin) score (AUC=0.661) had the strongest predictive value in comparison to the MELD score (AUC=0.627), the MELD excluding the international normalized ratio (MELD-XI) score (AUC=0.560), and the MELD including sodium (MELD-Na) score (AUC=0.652). In the fully adjusted logistic regression model, the MELD-Albumin score and the MELD-Na score were independently associated with CA-AKI regardless of whether they were treated as continuous or categorical variables; however, this was not the case for the MELD score and the MELD-XI score. Furthermore, the addition of the MELD-Albumin score significantly improved the reclassification beyond the fully adjusted logistic regression model. The study further explored the association between different versions of the MELD score and CA-AKI using restricted cubic splines and found a linear relationship between the MELD-Albumin score and the risk of CA-AKI.The MELD-Albumin score had the highest predictive value for CA-AKI in patients undergoing elective PCI. The addition of the MELD-Albumin score to the existing risk prediction model significantly improved the reclassification for CA-AKI.

This population-based study aimed to determine the willingness to receive a booster dose of vaccine against coronavirus disease (COVID-19) in Taizhou, China.An online questionnaire investigation addressing participants' willingness to receive a booster dose of the COVID-19 vaccine was organized in Taizhou, China. Of the 2318 interviewees who received the invitation, 1576 finished a qualifying questionnaire, corresponding to a response rate of 68.0%.The majority of respondents (A moderate proportion of the participants who responded were willing to receive a booster dose of the COVID-19 vaccine. These results are valuable for starting health education and interventions to accelerate vaccine uptake and improve public health outcomes during the COVID-19 pandemic in China.

Background Negative fluid balance (NFB) is associated with reduced extubation failure. However, whether achieving more NFB can further improve extubation outcome has not been investigated. This study aimed to investigate whether more NFB and restricted fluid intake were associated with extubation success. Methods We performed a retrospective study of adult patients with mechanical ventilation (MV) admitted to Medical Information Mart for Intensive Care (MIMIC-III) from 2001 to 2012. Patients with duration of MV over 24 hours and NFB within 24 hours before extubation were included for analysis. The primary outcome was extubation failure, defined as reintubation within 72 hours after extubation. Association between fluid balance or fluid intake and extubation outcome were investigated with multivariable logistic models. Results A total of 3433 extubation events were recorded. 1803 with NFB were included for the final analysis, of which 201(11.1%) were extubation failure. Compared with slight NFB (− 20 to 0 ml/kg), more NFB were not associated improved extubation outcome. Compared with moderate fluid intake (30 to 60 ml/kg), lower (p = 0.088) or higher (> 60 ml/kg, OR 1.63, 95% CI [0.73, 3.35], p = 0.206) fluid intake was not associated with extubation outcome. Duration of MV, chronic obstructive pulmonary disease (COPD), hypercapnia, use of diuretics, and SAPSIIscore were associated with extubation failure. Conclusions More NFB or restricted fluid intake were not associated with reduced extubation failure in patients with NFB. However, for COPD patients, restricted fluid intake was associated with extubation success.

To observe the effects of penetrating technique of scalp acupuncture on emotion, sleep and function development in children of autism spectrum disorder (ASD).A total of 60 SAD children aged 3 to 6 years were randomized in a control group (music education rehabilitation,Compared with the scores before treatment, CARS score, the score of each subscale of CSHQ, e.g. bedtime resistance, sleep onset delay, irregular sleep duration, sleep anxiety, parasomnias and daytime sleepiness as well as the total score of CSHQ were all reduced in children of two groups (Penetrating technique of scalp acupuncture improves the emotion and sleep disorder and promotes the function development in ASD children.

Quizalofop-p-ethyl is a widely used herbicide that poses a threat to human health and environmental safety. In this study, anti-quizalofop-p-ethyl monoclonal antibodies (mAbs) were prepared and used to develop a gold nanoparticle-based lateral flow immunoassay (AuNP-LFIA) for the detection of quizalofop-p-ethyl in agriproducts and environmental samples. Four hybridoma cell lines were obtained, among which 5B6D10E11 secreted mAb with the highest sensitivity, with a 50 % inhibition concentration of 4.57 ng/mL in the indirect competitive enzyme-linked immunosorbent assay. After optimization, the AuNP-LFIA strip based on the mAb (5B6D10E11) showed a visual detection limit of 10 ng/mL, and the results could be directly determined by the naked eye within 8 min. The cross-reactivity of the AuNP-LFIA for analogs of quizalofop-p-ethyl was negligible except for quizalofop-p-acid. The established AuNP-LFIA was proven to be accurate and precise based on the recovery test. Furthermore, the detection results of AuNP-LFIA were consistent with those of ultra-high-performance liquid chromatography tandem mass spectrometry.

A high salt diet (HSD) is often associated with a high risk for a variety of diseases, such as obesity and cardiovascular disease. Previous studies have demonstrated that an HSD enhances Th17 responses and increases the severity of autoimmune diseases. In this study, we investigated the effects of HSD (4% NaCl w/w) on colitis in IL-10

Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA NLiquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect mWe observed the abundance of mOur study revealed that METTL14 contributes to OS progression and ATRA resistance as an mThis work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864).

Myofiber necrosis is a significant pathologic characteristic of idiopathic inflammatory myopathies (IIMs), and its molecular mechanism is largely unknown. Necroptosis is a recently identified form of regulated necrotic cell death, and its activation might have crucial biologic consequences. The aim of the present study was to investigate the role of necroptosis in IIM muscle damage.Western blot and immunohistochemistry analyses were performed to examine the expression of receptor-interacting protein 3 (RIP-3) and mixed-lineage kinase domain-like (MLKL) proteins in 26 IIM patients and 4 healthy controls, as well as necroptosis-related damage-associated molecular pattern molecules. Tumor necrosis factor (TNF) was used to stimulate cultured C2C12 myoblasts, and the involvement of necroptosis in cell death of C2C12 cells was studied in vitro.The expression of RIP-3 and MLKL proteins and their phosphorylated forms was significantly increased in the muscle tissue of IIM patients compared to that of healthy controls. The expression levels of RIP-3 and MLKL proteins were associated with the severity of muscle damage in patients with IIM. Significant colocalization of MLKL with high mobility group box chromosomal protein 1 in necrotizing myofibers was observed in muscle biopsy tissue from patients with IIM. Stimulation of C2C12 myoblasts with TNF and a pan-caspase inhibitor, Z-VAD, resulted in the overactivation of necroptosis and significantly increased necrotic cell death. Strategies involving either inhibition of necroptosis with necrostatin-1 or knockdown of MLKL expression successfully prevented necroptosis-induced cell death of C2C12 cells.These findings demonstrate that overactivated necroptosis contributes to muscle damage in IIMs and suggest that necroptosis inhibitors could represent a new therapeutic target in the treatment of IIMs.

The pathogenesis of hypoxic-ischemic white matter injury (WMI) in premature infants is still unclear, and the imbalance of cerebral iron metabolism may play an important role. Our study set out to investigate the changes in iron distribution, iron content and malondialdehyde (MDA) in disparate brain regions (parietal cortex, corpus callosum, hippocampus) within 84 days after hypoxia-ischemia (HI) in neonatal rats and to clarify the role of iron metabolism in WMI.We adopted a rat model of hypoxic-ischemic WMI. Alterations in iron metabolism were detected by iron staining and iron assay kits, and the degree of brain injury was determined by MDA assays.Our results showed that different degrees of brain iron deposition occurred within 28 days after HI, and iron staining was the most obvious 3 days after HI. The iron content increased remarkably at 1-7 d after HI in the mixed tissues, especially at 3 d after HI. While the iron content in the parietal cortex and corpus callosum elevated obviously 14 days after HI. And the change trend of MDA was almost consistent with that of the iron content.Our findings revealed that brain iron metabolism changed dynamically in 3-day-old neonatal rats suffering from HI, which may cause lipid peroxidation damage to brain tissues. This process may be one of the pathogeneses of hypoxic-ischemic WMI.