Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia.

BACKGROUND: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. METHODS: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. RESULTS: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. CONCLUSIONS: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

[Assessment and Source Analysis of Heavy Metal Pollution in Farmland Soil Around Tin Mine].

Studying the status and source analysis of heavy metal pollution in farmland in typical mining and processing areas is an important prerequisite for promoting farmland soil ecological restoration and farmland protection in concentrated mining areas. In this study, the heavy metal content of farmland soil around a mining area in southwest China was detected, and the pollution status, distribution law, health risks, and sources of heavy metals were studied by using the land accumulation index method, comprehensive pollution index method, kriging interpolation method, health risk assessment method, and PMF receptor model on the sampling data. The results showed that the mean values of eight heavy metals in farmland soil except Ni exceeded the local soil background values, and the results of the ground accumulation index evaluation showed that Cd and Hg were extremely polluted； Pb and As showed medium pollution-heavy pollution； and Cr, Zn, Ni, and Cu were lightly polluted. In the health risk assessment, oral ingestion was the main exposure route posing a health risk to the human body； the main element that constituted non-carcinogenic health risks was As, and the carcinogenic risks were from As and Cd. PMF model analysis showed that the contribution rate of weathering natural sources of iron-bearing ore was 28.02%, and the main factors were Ca and Fe. The contribution rate of agricultural sources was 3.02%, and the main factors were Pb and As. The contribution rate of industrial and atmospheric deposition composite sources was 33.09%, and the main factor was Hg. The contribution rate of the parent material source was 17.27%, and the main factor was Ca. The contribution rate of mining activities such as mining and smelting was 18.60%, and the main factors were Zn and Cd.

Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.

BACKGROUND: Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. METHODOLOGYS/PRINCIPAL FINDINGS: In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms. CONCLUSIONS: Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.

Ghrelin Improves Glucolipotoxicity-Induced Pancreatic ß-Cellular Dysfunction and Apoptosis by Inhibiting Endoplasmic Reticulum Stress-Induced IRE1/JNK Pathway.

BACKGROUND: Glucose and fatty acid overload-induced glucolipid toxicity of pancreatic ß-cells is associated with the development of diabetes. Endoplasmic reticulum stress (ERS) plays an essential role in this process. Ghrelin, a peptide secreted by the pancreas, negatively correlates with oxidative stress. The study aimed to investigate ghrelin's role in glycolipid-induced ß-cell dysfunction and its possible mechanism. METHODS: Mouse insulinoma ß-cell, NIT-1 cells, were stimulated with high fat and high glucose to induce glucolipid toxicity. High fat and high glucose-induced NIT-1 cells were treated with acylated ghrelin (AG) or [d-Lys3]-growth hormone releasing peptide (GHRP)-6. Flow cytometry and Cell Counting Kit-8 (CCK-8) assay were performed to assess apoptosis and cell viability. The protein expression related to apoptosis, inositol-requiring kinase 1 (IRE1)/c-Jun N-terminal kinase (JNK) signaling, and ERS were investigated using western blot. Enzyme-linked immunosorbent assay (ELISA) was adopted to examine insulin's synthesis and secretion levels. RESULTS: Ghrelin treatment improved cell viability while inhibiting cell glucolipotoxicity-induced NIT-1 cell apoptosis. Ghrelin can promote the synthesis and secretion of insulin in NIT-1 cells. Mechanistically, ghrelin attenuates ERS and inhibits the IRE1/JNK signaling pathway in NIT-1 cells induced by glucolipotoxicity. CONCLUSION: Ghrelin improves ß-cellular dysfunction induced by glucolipotoxicity by inhibiting the IRE1/JNK pathway induced by ERS. It could be an effective treatment for ß-cellular dysfunction.

Brief research report: ETS-1 blockade increases ICAM-1 expression in activated human retinal endothelial cells.

Intercellular adhesion molecule 1 (ICAM-1) is a central cell adhesion molecule for retinal transendothelial migration of the leukocytes in non-infectious posterior uveitis. Inhibiting ICAM1 gene transcription reduces induction of ICAM-1 in inflamed retinal endothelium. Based on published literature implicating transcription factor ETS-1 as an activator of ICAM1 gene transcription, we investigated the effect of ETS-1 blockade on ICAM-1 levels in cytokine-stimulated human retinal endothelial cells. We first examined ICAM1 and ETS1 transcript expression in human retinal endothelial cells exposed to tumor necrosis factor-alpha (TNF-α) or interleukin-1beta (IL-1ß). ICAM1 and ETS1 transcripts were increased in parallel in primary human retinal endothelial cell isolates (n = 5) after a 4-hour stimulation with TNF-α or IL-1ß (p ≤ 0.012 and ≤ 0.032, respectively). We then assessed the effect of ETS-1 blockade by small interfering (si)RNA on cellular ICAM1 transcript and membrane-bound ICAM-1 protein. ETS1 transcript was reduced by greater than 90% in cytokine-stimulated and non-stimulated human retinal endothelial cell monolayers following a 48-hour treatment with two ETS-1-targeted siRNA, in comparison to negative control non-targeted siRNA (p ≤ 0.0002). The ETS-1 blockade did not reduce ICAM1 transcript expression nor levels of membrane-bound ICAM-1 protein, rather it increased both for a majority of siRNA-treatment and cytokine-stimulation conditions (p ≤ 0.018 and ≤ 0.004, respectively). These unexpected findings indicate that ETS-1 blockade increases ICAM-1 transcript and protein levels in human retinal endothelial cells. Thus ETS-1-targeting would be expected to promote rather than inhibit retinal transendothelial migration of leukocytes in non-infectious posterior uveitis.

Metabolomics reveals that ferroptosis participates in bisphenol A-induced testicular injury.

Objective: Bisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model. Methods: The mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis. Results: BPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered. Conclusion: BPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.

Selective detection of paraquat by a cucurbit[7]uril-based fluorescent probe.

A simple fluorescent "on-off" system that can be utilized for the selective identification and determination of paraquat (PQ) is presented herein. 1H NMR spectroscopic data indicated that in aqueous solution the alkaloid palmatine can be partially encapsulated within the cucurbit[7]uril (Q[7]) cavity, whereby a stable 1 : 1 host-guest inclusion complex is formed. Other characterization techniques including mass spectrometry, UV-Vis and fluorescence spectroscopy also provided further evidence, and the host-guest inclusion complex was found to exhibit reasonable fluorescence intensity. It is noteworthy that the addition of PQ resulted in quenching the fluorescence of the host-guest inclusion complex, whereas the presence of 12 other pesticides did not significantly affect the fluorescence intensity. Given the linear relationship between the intensity of the fluorescence and the PQ concentration, the PQ concentration in aqueous solution was easily detected. Thus, a new method for identifying and determining the fluorescence quenching of PQ has been developed in this work.

Gastric Section Correlation Network for Gastric Precancerous Lesion Diagnosis.

Goal: Diagnosing the corpus-predominant gastritis index (CGI) which is an early precancerous lesion in the stomach has been shown its effectiveness in identifying high gastric cancer risk patients for preventive healthcare. However, invasive biopsies and time-consuming pathological analysis are required for the CGI diagnosis. Methods: We propose a novel gastric section correlation network (GSCNet) for the CGI diagnosis from endoscopic images of three dominant gastric sections, the antrum, body and cardia. The proposed network consists of two dominant modules including the scaling feature fusion module and section correlation module. The front one aims to extract scaling fusion features which can effectively represent the mucosa under variant viewing angles and scale changes for each gastric section. The latter one aims to apply the medical prior knowledge with three section correlation losses to model the correlations of different gastric sections for the CGI diagnosis. Results: The proposed method outperforms competing deep learning methods and achieves high testing accuracy, sensitivity, and specificity of 0.957, 0.938 and 0.962, respectively. Conclusions: The proposed method is the first method to identify high gastric cancer risk patients with CGI from endoscopic images without invasive biopsies and time-consuming pathological analysis.

Advanced cervix cancer patient with chemotherapy-induced grade IV myelosuppression achieved complete remission with cadonilimab: A case report.

BACKGROUND: The prognosis for patients with advanced metastatic cervix cancer (MCC) is poor, and this disease continues to pose a considerable therapeutic challenge. Despite the administration of first-line regimens consisting of cisplatin, paclitaxel, and bevacizumab, survival rates for patients with metastasis remain poor. The emergence of bispecific antibodies (BsAbs) offers a novel treatment option for patients diagnosed with MCC. CASE SUMMARY: In this report, we present a patient with MCC who was treated with cadonilimab monotherapy at a dose of 6 mg/kg every two weeks after chemotherapy was proven to be intolerable. The patient exhibited a sustained complete response for a duration of 6 months, demonstrating an optimistic outlook. CONCLUSION: This case illustrates the considerable efficacy of cadonilimab for treating advanced MCC. Therefore, BsAb therapy is a promising strategy for effectively treating patients with advanced MCC and should be considered as an option when patients are intolerant to standard chemotherapy.

Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Predictive value of serum albumin levels on cancer survival: a prospective cohort study.

Background: Serum albumin levels and cancer mortality are closely related, yet large-sample studies encompassing a broad spectrum of cancer types are lacking. Methods: This study encompassed patients diagnosed with cancer across the continuous 10 cycles of NHANES surveys from 1999 to 2018. The study population was stratified into two groups based on median albumin levels (≤ 4.2g/dL and > 4.2 g/dL) or cancer aggressiveness (well-survived cancers and poorly-survived cancers). Survival rates were estimated using the Kaplan-Meier method. The Cox proportional hazards model was employed to evaluate the association between serum albumin levels and cancer mortality. Restricted cubic spline (RCS) analysis was conducted to assess the nonlinear relationship between serum albumin levels and the risk of cancer mortality. Results: Kaplan-Meier curves demonstrated that patients with albumin levels ≤ 4.2 g/dL exhibited lower survival rates compared to those with levels > 4.2 g/dL, irrespective of cancer aggressiveness. Following adjustment for confounders, decreased albumin levels were associated with an elevated risk of cancer mortality across all groups [all cancers, HR (95%CI) = 2.03(1.73, 2.37); well survived cancers, HR (95%CI) = 1.78(1.38, 2.32); and poorly survived cancers, HR (95%CI) = 1.99(1.64, 2.42)]. RCS analyses revealed a stable nonlinear negative association between albumin levels and cancer mortality in all groups, regardless of confounder adjustment. Conclusion: Low serum albumin levels predict higher cancer mortality. Furthermore, a nonlinear negative association was observed between serum albumin levels and the risk of cancer mortality.

Disulfidptosis and ferroptosis related genes predict prognosis and personalize treatment for hepatocellular carcinoma.

Background: Understanding the interplay between disulfidptosis, ferroptosis, and hepatocellular carcinoma (HCC) could provide valuable insights into the pathogenesis of HCC and potentially identify novel therapeutic targets for the treatment of this deadly disease. This study aimed to identify a prognostic signature for HCC by examining the differential expression of genes related to disulfidptosis and ferroptosis (DRG-FRG), and to assess its clinical applicability. Methods: By integrating 23 disulfidptosis and 259 ferroptosis related genes with HCC messenger RNA (mRNA) expression data from The Cancer Genome Atlas (TCGA), differentially expressed DRG-FRG genes were identified. From these, 11 DRG-FRG genes were selected to construct a risk signature model using least absolute shrinkage and selection operator regression analyses. The prognostic performance of this model was evaluated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) analysis. Subsequently, a nomogram was built by combining the signature with clinical variables. To further delve into the underlying mechanisms, we performed bioinformatics analysis using a variety of databases. Results: A prognostic signature based on 11 DRG-FRG genes effectively categorized HCC patients into high- and low-risk groups, showing a significant survival difference. Even after considering clinical variables, this signature remained an independent prognostic factor. Furthermore, the signature played a role in various critical biological processes and pathways that drive HCC progression. Potential therapeutic benefits could be derived from small molecule drugs targeting NQO1 and SLC7A11. Interestingly, the high-risk group exhibited resistance to several chemotherapeutic drugs, yet showed sensitivity to others when contrasted with the low-risk group. Lastly, the DRG-FRG genes signature had a strong correlation with the tumor immune microenvironment, marked by an elevated expression of immune checkpoint molecules in the high-risk group. Conclusions: The signature based on 11 DRG-FRG genes stands out as a promising prognostic biomarker for HCC. Beyond its predictive value, it sheds light on the intricate crosstalk between DRG-FRG genes and HCC. Importantly, these findings could pave the way for enhanced prognostic prediction, informed treatment decisions, and the advancement of immunotherapy for HCC patients.

Exploration of neuron heterogeneity in human heart failure with dilated cardiomyopathy through single-cell RNA sequencing analysis.

OBJECTIVE: We aimed to explore the heterogeneity of neurons in heart failure with dilated cardiomyopathy (DCM). METHODS: Single-cell RNA sequencing (scRNA-seq) data of patients with DCM and chronic heart failure and healthy samples from GSE183852 dataset were downloaded from NCBI Gene Expression Omnibus, in which neuron data were extracted for investigation. Cell clustering analysis, differential expression analysis, trajectory analysis, and cell communication analysis were performed, and highly expressed genes in neurons from patients were used to construct a protein-protein interaction (PPI) network and validated by GSE120895 dataset. RESULTS: Neurons were divided into six subclusters involved in various biological processes and each subcluster owned its specific cell communication pathways. Neurons were differentiated into two branches along the pseudotime, one of which was differentiated into mature neurons, whereas another tended to be involved in the immune and inflammation response. Genes exhibited branch-specific differential expression patterns. FLNA, ITGA6, ITGA1, and MDK interacted more with other gene-product proteins in the PPI network. The differential expression of FLNA between DCM and control was validated. CONCLUSION: Neurons have significant heterogeneity in heart failure with DCM, and may be involved in the immune and inflammation response to heart failure.

Development and Validation of a 3D Resnet Model for Prediction of Lymph Node Metastasis in Head and Neck Cancer Patients.

The accurate diagnosis and staging of lymph node metastasis (LNM) are crucial for determining the optimal treatment strategy for head and neck cancer patients. We aimed to develop a 3D Resnet model and investigate its prediction value in detecting LNM. This study enrolled 156 head and neck cancer patients and analyzed 342 lymph nodes segmented from surgical pathologic reports. The patients' clinical and pathological data related to the primary tumor site and clinical and pathology T and N stages were collected. To predict LNM, we developed a dual-pathway 3D Resnet model incorporating two Resnet models with different depths to extract features from the input data. To assess the model's performance, we compared its predictions with those of radiologists in a test dataset comprising 38 patients. The study found that the dimensions and volume of LNM + were significantly larger than those of LNM-. Specifically, the Y and Z dimensions showed the highest sensitivity of 84.6% and specificity of 72.2%, respectively, in predicting LNM + . The analysis of various variations of the proposed 3D Resnet model demonstrated that Dual-3D-Resnet models with a depth of 34 achieved the highest AUC values of 0.9294. In the validation test of 38 patients and 86 lymph nodes dataset, the 3D Resnet model outperformed both physical examination and radiologists in terms of sensitivity (80.8% compared to 50.0% and 91.7%, respectively), specificity(90.0% compared to 88.5% and 65.4%, respectively), and positive predictive value (77.8% compared to 66.7% and 55.0%, respectively) in detecting individual LNM + . These results suggest that the 3D Resnet model can be valuable for accurately identifying LNM + in head and neck cancer patients. A prospective trial is needed to evaluate further the role of the 3D Resnet model in determining LNM + in head and neck cancer patients and its impact on treatment strategies and patient outcomes.

Wearable sensor supports in-situ and continuous monitoring of plant health in precision agriculture era.

Plant health is intricately linked to crop quality, food security and agricultural productivity. Obtaining accurate plant health information is of paramount importance in the realm of precision agriculture. Wearable sensors offer an exceptional avenue for investigating plant health status and fundamental plant science, as they enable real-time and continuous in-situ monitoring of physiological biomarkers. However, a comprehensive overview that integrates and critically assesses wearable plant sensors across various facets, including their fundamental elements, classification, design, sensing mechanism, fabrication, characterization and application, remains elusive. In this study, we provide a meticulous description and systematic synthesis of recent research progress in wearable sensor properties, technology and their application in monitoring plant health information. This work endeavours to serve as a guiding resource for the utilization of wearable plant sensors, empowering the advancement of plant health within the precision agriculture paradigm.

Clinical analysis of contrast-enhanced ultrasound combined with serum SMURF1 detection in the diagnosis of thyroid cancer / 局解手术学杂志

Objective To investigate the diagnostic value of contrast-enhanced ultrasound(CEUS)combined with serum Smad ubiquitin regulatory factor 1(SMURF1)detection for thyroid cancer.Methods A total of 144 suspected thyroid cancer patients admitted to Lishui branch of Zhongda Hospital Affiliated to Southeast University from February 2019 to February 2020 were selected as the study subjects.Based on the histopathological results,they were divided into the thyroid cancer group(76 cases)and the benign group(68 cases).All patients underwent contrast-enhanced ultrasound examination and serum SMURF1 level detection;the diagnostic value of contrast-enhanced ultrasound parameters,serum SMURF1 detection alone,and the combination of the two methods for thyroid cancer were analyzed.Results Contrast-enhanced ultrasound parameters peak intensity(PI),mean perfusion intensity(SImean)and maximum perfusion intensity(SImax)in the thyroid cancer group were lower than those in the benign group,and the level of SMURF1 mRNA was higher than that in the benign group(P<0.05).The sensitivity of contrast-enhanced ultrasound parameter SImax in the diagnosis of thyroid cancer was 82.89%,the specificity was 72.06%,the accuracy was 77.78%,and the Kappa value was 0.552.The sensitivity of serum SMURF1 in the diagnosis of thyroid cancer was 65.79%,the specificity was 94.12%,the accuracy was 79.17%,and the Kappa value was 0.589.The sensitivity,specificity,accuracy and Kappa value of SImax combined with serum SMURF1 in the diagnosis of thyroid cancer were 97.37%,85.29%,91.67%and 0.832,respectively,which were higher than those of SImax and SMURF1 alone(P<0.05),the AUC of the combination of the two methods was 0.927,which was significantly higher than that of the two methods alone(Zcombined vs.SImax=3.999,P<0.001;Zcombined vs.SMURF1=3.270,P=0.001).Conclusion Contrast-enhanced ultrasound combined with serum SMURF1 detection can improve the diagnostic efficiency of thyroid cancer,which may avoid the over-diagnosis on the premise of ensuring the effective diagnosis of thyroid cancer patients.

The egg ribonuclease SjCP1412 accelerates liver fibrosis caused by Schistosoma japonicum infection involving damage-associated molecular patterns (DAMPs).

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

Magnetic chitin beads (MCB) coated with Vibrio cholerae reveals transcriptome dynamics in adult mice with a complex gut microbiota.

Vibrio cholerae adapts to the host environment by altering gene expression. Because of the complexity of the gut microbiome, current in vivo V. cholerae transcriptome studies have focused on microbiota-undeveloped conditions, neglecting the interaction between the host's commensal gut microbiota and V. cholerae. In this study, we analyzed the transcriptome of fully colonized adult mice in vivo using V. cholerae coated-magnetic chitin beads (vcMCB). This provides a simple yet powerful method for obtaining high-quality RNA from V. cholerae during colonization in mice. The transcriptome of V. cholerae recovered from adult mice infected with vcMCB shows differential expression of several genes when compared to V. cholerae recovered from the infant mouse and infant rabbit model. Some of these genes were also observed to be differentially expressed in previous studies of V. cholera recovered from human infection when compared to V. cholerae grown in vitro. In particular, we confirmed that V. cholerae resists the inhibitory effects of low pH and formic acid from gut microbiota, such as Anaerostipes caccae and Dorea formicigenerans, by downregulating vc1080. We propose that the vc1080 product may protect V. cholerae from formic acid stress through a novel acid tolerance response mechanism. Transcriptomic data obtained using the vcMCB system provide new perspectives on the interaction between V. cholerae and the gut microbiota, and this approach can also be applied to studies of other pathogenic bacteria.

Cross-Scale Fusion Transformer for Histopathological Image Classification.

Histopathological images provide the medical evidences to help the disease diagnosis. However, pathologists are not always available or are overloaded by work. Moreover, the variations of pathological images with respect to different organs, cell sizes and magnification factors lead to the difficulty of developing a general method to solve the histopathological image classification problems. To address these issues, we propose a novel cross-scale fusion (CSF) transformer which consists of the multiple field-of-view patch embedding module, the transformer encoders and the cross-fusion modules. Based on the proposed modules, the CSF transformer can effectively integrate patch embeddings of different field-of-views to learn cross-scale contextual correlations, which represent tissues and cells of different sizes and magnification factors, with less memory usage and computation compared with the state-of-the-art transformers. To verify the generalization ability of the CSF transformer, experiments are performed on four public datasets of different organs and magnification factors. The CSF transformer outperforms the state-of-the-art task specific methods, convolutional neural network-based methods and transformer-based methods. The source code will be available in our GitHub https://github.com/nchucvml/CSFT.

Facile Synthesis of Chromium-Doped Fe1.1Mn1.9O4 Nanoparticles and the Effect of Cr Content on Their Magnetic and Structural Properties.

In the present study, Fe1.1(CrxMn1-x)1.9O4 nanoparticles (0 ≤ x ≤ 0.5) were successfully synthesized by a combustion method, and the influence of Cr substitution on the structural and magnetic properties of the obtained nanoparticles was studied by various methods. The structural analysis revealed that the sample with x = 0 has a tetragonal structure, while all Cr-doped samples crystallize into a cubic structure. Additionally, the results of TEM show that doping with chromium leads to an increase in particle size. The magnetic hysteresis loops demonstrate the behavior typical for soft magnetic materials with low coercivity and remanence magnetization. The magnetic measurements revealed that the saturation magnetization of the obtained nanoparticles demonstrates a decreasing trend with increasing Cr content. The influence of chromium doping on the observation change in saturation magnetization is discussed. Based on the results of temperature-dependent magnetization measurements, it was found that the temperature of a magnetic transition in synthesized nanoparticles depends on Cr content.