Novel advanced materials and magnetic solid phase extraction as approaches in sample preparation to enhance the analysis of ochratoxin A in peanuts.

Ochratoxin A (OTA) is a mycotoxin that can contaminate a variety of agricultural commodities, including fruit juices and wines. The capability of a magnetic solid-phase extraction (MSPE) method with a magnetic metal-organic framework (MOF) material having a three-layer core-shell structure to improve the detection of OTA in food matrices using high performance liquid chromatography is described. Analysis of the material through X-ray diffraction (XRD) indicated the successful synthesis of the magnetic nanomaterial Fe3O4@SiO2@UiO66-NH2. Scanning electron microscopy (SEM) and Zetasizer lab indicated its nano-sized morphological features. The conditions affecting the magnetic solid-phase extraction procedure, such as material dosage, pH, composition and amount of eluent, desorption solution and desorption time were investigated to obtain the optimal extraction conditions. Under optimized conditions, the recoveries of spiked analytes at three different concentrations ranged from 95.83 to 101.5%, and the relative standard deviations were below 5%. Coupling with HPLC allowed the limit of detection to be 0.3 µg kg-1. This method is simple and specific, and can effectively avoid the influence of coexisting elements and improve the sensitivity of determination through fast MSPE of OTA. It has broad development prospects in OTA detection pre-treatment.

A promising natural killer cell-based model and a nomogram for the prognostic prediction of clear-cell renal cell carcinoma.

BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is one of prevalent kidney malignancies with an unfavorable prognosis. There is a need for a robust model to predict ccRCC patient survival and guide treatment decisions. METHODS: RNA-seq data and clinical information of ccRCC were obtained from the TCGA and ICGC databases. Expression profiles of genes related to natural killer (NK) cells were collected from the Immunology Database and Analysis Portal database. Key NK cell-related genes were identified using consensus clustering algorithms to classify patients into distinct clusters. A NK cell-related risk model was then developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to predict ccRCC patient prognosis. The relationship between the NK cell-related risk score and overall survival, clinical features, tumor immune characteristics, as well as response to commonly used immunotherapies and chemotherapy, was explored. Finally, the NK cell-related risk score was validated using decision tree and nomogram analyses. RESULTS: ccRCC patients were stratified into 3 molecular clusters based on expression of NK cell-related genes. Significant differences were observed among the clusters in terms of prognosis, clinical characteristics, immune infiltration, and therapeutic response. Furthermore, six NK cell-related genes (DPYSL3, SLPI, SLC44A4, ZNF521, LIMCH1, and AHR) were identified to construct a prognostic model for ccRCC prediction. The high-risk group exhibited poor survival outcomes, lower immune cell infiltration, and decreased sensitivity to conventional chemotherapies and immunotherapies. Importantly, the quantitative real-time polymerase chain reaction (qRT-PCR) confirmed significantly high DPYSL3 expression and low SLC44A4 expression in ACHN cells. Finally, the decision tree and nomogram consistently show the dramatic prediction performance of the risk score on the survival outcome of the ccRCC patients. CONCLUSIONS: The six-gene model based on NK cell-related gene expression was validated and found to accurately mirror immune microenvironment and predict clinical outcomes, contributing to enhanced risk stratification and therapy response for ccRCC patients.

Comprehensive analysis of a tryptophan metabolism-related model in the prognostic prediction and immune status for clear cell renal carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized as one of the most common types of urological cancer with high degrees of malignancy and mortality. Due to the limited effectiveness of existing traditional therapeutic methods and poor prognosis, the treatment and therapy of advanced ccRCC patients remain challenging. Tryptophan metabolism has been widely investigated because it significantly participates in the malignant traits of multiple cancers. The functions and prognostic values of tryptophan metabolism-related genes (TMR) in ccRCC remain virtually obscure. METHODS: We employed the expression levels of 40 TMR genes to identify the subtypes of ccRCC and explored the clinical characteristics, prognosis, immune features, and immunotherapy response in the subtypes. Then, a model was constructed for the prediction of prognosis based on the differentially expressed genes (DEGs) in the subtypes from the TCGA database and verified using the ICGC database. The prediction performance of this model was confirmed by the receiver operating characteristic (ROC) curves. The relationship of Risk Score with the infiltration of distinct tumor microenvironment cells, the expression profiles of immune checkpoint genes, and the treatment benefits of immunotherapy and chemotherapy drugs were also investigated. RESULTS: The two subtypes revealed dramatic differences in terms of clinical characteristics, prognosis, immune features, and immunotherapy response. The constructed 6-gene-based model showed that the high Risk Score was significantly connected to poor overall survival (OS) and advanced tumor stages. Furthermore, increased expression of CYP1B1, KMO, and TDO2 was observed in ccRCC tissues at the translation levels, and an unfavorable prognosis for these patients was also found. CONCLUSION: We identified 2 molecular subtypes of ccRCC based on the expression of TMR genes and constructed a prognosis-related model that may be used as a powerful tool to guide the prediction of ccRCC prognosis and personalized therapy. In addition, CYP1B1, KMO, and TDO2 can be regarded as the risk prognostic genes for ccRCC.

Prevalence and a correlation analysis of discoid meniscus and femoral trochlear dysplasia.

BACKGROUND: Discoid meniscus (DM) and femoral trochlear dysplasia (FTD) are common knee disorders. Both as congenital malformation, whether there is a connection between them is unclear and the research on their prevalence in the general population is inadequate. This study aimed to investigate the prevalence of FTD and DM in the general population through a large sample size, and to explore the relationship between them. STUDY DESIGN: Retrospective study. METHODS: Patients undergoing knee magnetic resonance imaging (MRI) examinations at our outpatient clinic were screened and 1003 patients were enrolled in DM group with 989 patients in non-DM (NDM) group. The type of DM and FTD was classified with Watanabe classification and Dejour's classification, respectively. The prevalence of FTD and DM in the general population and the relationship between them were evaluated. RESULTS: The prevalence of DM and FTD was 10.0% and 14.5%, respectively. The overall percentage of FTD was higher in DM group (P < 0.001). The DM group has a higher percentage of all types of FTD except type D (P < 0.05), and a higher percentage of both low- and high-grade FTD (P < 0.001). There were 633 cases of type I DM and 370 cases of type II DM. The overall percentage of FTD was not significantly different between the two types (P = 0.106). No significant difference was detected for all types of FTD except type B (P < 0.05). The Type I DM group has a significant higher percentage of high-grade FTD than Type II group (P < 0.05). CONCLUSION: Patients with a DM are more likely to have FTD regardless of the type of DM, while those with a type I DM are more prone to have a high grade FTD.

Identification of molecular pattern and prognostic risk model based on ligand-receptor pairs in liver cancer.

Introduction: The tumor microenvironment of hepatocellular carcinoma is composed of multiple cells, and the interactive communication between cells drives tumor progression and characterizes the tumor. Communication between cells is mainly achieved through signal transduction between receptor ligands, and the rise of single-cell technology has made it possible to analyze the communication network between cells. Methods: We applied a train of bioinformatic techniques and in vitro experiments. We analyzed the composition of the microenvironment of liver cancer by combining single-cell sequencing data and transcriptome sequencing data from liver cancer to construct molecular typing and risk models for LRs. Then, we analyzed association of it with prognosis, mutation, KEGG, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB) and drug sensitivity in liver cancer. qPCR and was used to identify SLC1A5 expression in LIHC cell lines and CCK8, transwell and cell colony formation were performed to validate the function of SLC1A5. Meanwhile, we also performed polarization of macrophages. Results: In this experiment, we found that liver cancer tissues are rich in immune and mesenchymal cells, and there is extensive signaling between individual cells, so we constructed molecular typing and risk models for LRs. Combining clinical data revealed significant differences in clinical characteristics, prognosis and mutated genes between the molecular typing of receptor-ligand pairs, as well as in sensitivity to drugs; similarly, there were significant prognostic differences between the risk models. There were also notable differences in activated signaling pathways, infiltrating immune cells and immune subtypes. Subsequently, we used siRNA to knock down SLC1A5 in hepatocellular carcinoma cells and found that cell proliferation, migration and invasion were diminished. Conclusions: In conclusion, our LRs model may become a marker to guide clinical treatment and prognosis.

Effect of Lower Extremity Torsion on Clinical Outcomes After Medial Patellofemoral Ligament Reconstruction and Tibial Tubercle Transfer for Recurrent Patellofemoral Instability.

BACKGROUND: Increased femoral torsion (FT) or tibial torsion (TT) has been suggested to be a potential risk factor for recurrent patellofemoral instability. However, the influence of increased FT or TT on the postoperative clinical outcomes of recurrent patellofemoral instability has rarely been investigated. PURPOSE: To assess the effect of increased FT or TT on postoperative results in patients with recurrent patellofemoral instability after combined medial patellofemoral ligament reconstruction (MPFLR) and tibial tubercle transfer, along with the influence of other risk factors. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Out of 91 patients, the study's analyses included 86 patients with recurrent patellofemoral instability who were treated with MPFLR and tibial tubercle transfer and enrolled between April 2020 and January 2021. FT and TT were assessed using preoperative computed tomography images. According to the torsion value of FT or TT, patients were categorized into 3 groups for each of FT and TT: group A (<20°), group B (20°-30°), and group C (>30°). Patellar height, femoral trochlear dysplasia, and the tibial tuberosity-trochlear groove (TT-TG) distance were also assessed. Patient-reported outcome scores (Tegner, Kujala, International Knee Documentation Committee [IKDC], Lysholm, and Knee injury and Osteoarthritis Outcome Score [KOOS]) were evaluated pre- and postoperatively. Clinical failure of MPFLR was recorded. Subgroup analysis was conducted to evaluate the effect of increased FT or TT on the postoperative outcomes. RESULTS: A total of 86 patients were enrolled with a median follow-up time of 25 months. At the final follow-up, all functional scores improved significantly. Patella alta, high-grade trochlear dysplasia, and increased TT-TG distance did not have any significant effect on the postoperative functional scores. Regarding FT, subgroup analysis indicated that all functional scores of group C were lower than those of groups A and B except the KOOS knee-related Quality of Life score. For TT, group C had lower scores than group A for all functional outcomes except Tegner and KOOS Quality of Life and lower scores than group B for Kujala, IKDC, KOOS (Symptoms and Sport and Recreation subscales), Tegner, and Lysholm scores. The comparison between group A and group B, whether for FT or TT, revealed no significant differences. CONCLUSION: For patients with recurrent patellofemoral instability, increased lower extremity torsion (FT or TT >30°) was associated with inferior postoperative clinical outcomes after combined MPFLR and tibial tubercle transfer.

Prognostic prediction and immunotherapy response analysis of the fatty acid metabolism-related genes in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a common urinary cancer. Although diagnostic and therapeutic approaches for ccRCC have been improved, the survival outcomes of patients with advanced ccRCC remain unsatisfactory. Fatty acid metabolism (FAM) has been increasingly recognized as a critical modulator of cancer development. However, the significance of the FAM in ccRCC remains unclear. Herein, we explored the function of a FAM-related risk score in the stratification and prediction of treatment responses in patients with ccRCC. Methods: First, we applied an unsupervised clustering method to categorize patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets into subtypes and retrieved FAM-related genes from the MSigDB database. We discern differentially expressed genes (DEGs) among different subtypes. Then, we applied univariate Cox regression analysis followed by least absolute shrinkage and selection operator (LASSO) linear regression based on DEGs expression to establish a FAM-related risk score for ccRCC. Results: We stratified the three ccRCC subtypes based on FAM-related genes with distinct overall survival (OS), clinical features, immune infiltration patterns, and treatment sensitivities. We screened nine genes from the FAM-related DEGs in the three subtypes to establish a risk prediction model for ccRCC. Nine FAM-related genes were differentially expressed in the ccRCC cell line ACHN compared to the normal kidney cell line HK2. High-risk patients had worse OS, higher genomic heterogeneity, a more complex tumor microenvironment (TME), and elevated expression of immune checkpoints. This phenomenon was validated in the ICGC cohort. Conclusion: We constructed a FAM-related risk score that predicts the prognosis and therapeutic response of ccRCC. The close association between FAM and ccRCC progression lays a foundation for further exploring FAM-related functions in ccRCC.

Current Progress on Predictive Biomarkers for Response to Immune Checkpoint Inhibitors in Gastric Cancer: How to Maximize the Immunotherapeutic Benefit?

Gastric cancer is the fifth most prevalent cancer and the fourth leading cause of cancer death globally. Delayed diagnosis and pronounced histological and molecular variations increase the complexity and challenge of treatment. Pharmacotherapy, which for a long time was systemic chemotherapy based on 5-fluorouracil, is the mainstay of management for advanced gastric cancer. Trastuzumab and programmed cell death 1 (PD-1) inhibitors have altered the therapeutic landscape, contributing to noticeably prolonged survivorship in patients with metastatic gastric cancer. However, research has revealed that immunotherapy is only beneficial to some individuals. Biomarkers, such as programmed cell death ligand 1 (PD-L1), microsatellite instability (MSI), and tumor mutational load (TMB), have been shown to correlate with immune efficacy in numerous studies and are increasingly employed for the selection of patients most likely to respond to immunotherapy. Gut microorganisms, genetic mutations like POLE/POLD1 and NOTCH4, tumor lymphoid infiltrating cells (TILs), and other novel biomarkers have the potential to develop into new predictors. Prospective immunotherapy for gastric cancer should be guided by a biomarker-driven precision management paradigm, and multidimensional or dynamic marker testing could be the way to go.

Development and validation of a contrast-enhanced CT-based radiomics nomogram for preoperative diagnosis in neuroendocrine carcinoma of digestive system.

Objectives: To develop and validate a contrast-enhanced CT-based radiomics nomogram for the diagnosis of neuroendocrine carcinoma of the digestive system. Methods: The clinical data and contrast-enhanced CT images of 60 patients with pathologically confirmed neuroendocrine carcinoma of the digestive system and 60 patients with non-neuroendocrine carcinoma of the digestive system were retrospectively collected from August 2015 to December 2021 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and randomly divided into a training cohort (n=84) and a validation cohort (n=36). Clinical characteristics were analyzed by logistic regression and a clinical diagnosis model was developed. Radiomics signature were established by extracting radiomic features from contrast-enhanced CT images. Based on the radiomic signature and clinical characteristics, radiomic nomogram was developed. ROC curves and Delong's test were used to evaluate the diagnostic efficacy of the three models, calibration curves and application decision curves were used to analyze the accuracy and clinical application value of nomogram. Results: Logistic regression results showed that TNM stage (stage IV) (OR 6.8, 95% CI 1.320-43.164, p=0. 028) was an independent factor affecting the diagnosis for NECs of the digestive system, and a clinical model was constructed based on TNM stage (stage IV). The AUCs of the clinical model, radiomics signature, and radiomics nomogram for the diagnosis of NECs of the digestive system in the training, validation cohorts and pooled patients were 0.643, 0.893, 0.913; 0.722, 0.867, 0.932 and 0.667, 0.887, 0.917 respectively. The AUCs of radiomics signature and radiomics nomogram were higher than clinical model, with statistically significant difference (Z=4.46, 6.85, both p < 0.001); the AUC difference between radiomics signature and radiomics nomogram was not statistically significant (Z=1.63, p = 0.104). The results of the calibration curve showed favorable agreement between the predicted values of the nomogram and the pathological results, and the decision curve analysis indicated that the nomogram had favorable application in clinical practice. Conclusions: The nomogram constructed based on contrast-enhanced CT radiomics and clinical characteristics was able to effectively diagnose neuroendocrine carcinoma of the digestive system.

The Modified Assessment Tool Based on Scapular Y-View for Global Fatty Infiltration in the Supraspinatus Muscle: Correlation, Predictive Performance, and Reliability Analyses.

BACKGROUND: The accurate evaluation of rotator cuff (RC) fatty degeneration after tears is critical for appropriate surgical decision making and prognosis. However, there is currently no reliable and practical tool to reflect the global fatty infiltration (Global-FI) throughout the 3-dimensional (3D) volumetric RC muscles. PURPOSE: (1) To determine the correlations between 2 modified assessment tools and the Global-FI and their predictive performances and reliabilities for Global-FI prediction, and (2) to compare these predictive parameters with those of the conventional tool using a single scapular Y-view slice. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: A total of 49 patients with full-thickness RC tears scheduled to undergo arthroscopic repairs were included, and their surgical shoulders underwent 6-point Dixon magnetic resonance imaging preoperatively. The Global-FI was measured by calculating the 3D-volumetric fat fraction (FF) of the whole supraspinatus muscle through all acquired oblique sagittal slices. As a commonly used radiological landmark, the scapular Y-view was used to evaluate single-plane fatty infiltration (Y-FI) by calculating the FF in 1 slice, defined as the conventional assessment tool. Two modified assessment tools expand the analytic imaging by integrating the FFs from the scapular Y-view slice and its neighboring slices, which were calculated by averaging the FFs of these 3 slices (meanY3-FI) and accumulating local 3D-volumetric FFs from 3 slices (volY3-FI), respectively. The correlations between 3 assessment tools and the Global-FI were analyzed, and the predictive performance for Global-FI prediction using these tools was determined by goodness of fit and agreement. Moreover, the inter- and intraobserver reliabilities of these assessment tools were evaluated. Similar analyses were performed in the small-medium, large, or massive tear subgroups. RESULTS: The Y-FI was significantly higher than the Global-FI in all cases and tear size subgroups, while the 2 modified assessment tools (meanY3-FI and volY3-FI) did not significantly differ from the Global-FI. All assessment tools were significantly correlated with the Global-FI, but the meanY3-FI and volY3-FI showed stronger correlations than the Y-FI, which was also determined in different tear sizes. Moreover, the regression models of the meanY3-FI and volY3-FI showed superior goodness of fit to Y-FI in Global-FI prediction in all cases and subgroups, with larger coefficients of determination (R2) and smaller root mean square errors. The predicted Global-FI using the regression model of volY3-FI had the best agreement with the measured Global-FI, followed by the meanY3-FI, both showing smaller biases and standard deviation of the percentage difference between predicted- and measured Global-FI than the conventional Y-FI. In addition, the 2 modified assessment tools achieved better interobserver and intraobserver reliabilities than the conventional tool in all cases and subgroups. CONCLUSION: Two modified assessment tools (meanY3-FI and volY3-FI) were comparable with the Global-FI of the whole supraspinatus muscle, showing stronger correlations with the Global-FI and better predictive performances and reliabilities than the conventional tool (Y-FI). Moreover, the volY3-FI was slightly superior to meanY3-FI in the predictive performance and reliability.

FGFR2 upregulates PAI-1 via JAK2/STAT3 signaling to induce M2 polarization of macrophages in colorectal cancer.

Fibroblast growth factor receptor 2 (FGFR2) is frequently activated by overexpression or mutation, and an abnormal fibroblast growth factor (FGF)/FGFR signaling pathway is associated with the occurrence, development, and poor prognosis of colorectal cancer (CRC). Our preliminary analysis found that plasminogen activator inhibitor-1 (PAI-1) expression may be related to FGF/FGFR signaling, however, their role in the tumor immune microenvironment remains unclear. In this study, we observed markedly higher PAI-1 expression in CRC patients with poor survival rates. PAI-1 is regulated by FGF/FGFR2 in colon cancer cells and is involved in M2 macrophage polarization. Mechanistically, inhibiting the JAK2/STAT3 signaling pathway could cause PAI-1 downregulation. Furthermore, the activation of phosphorylated STAT3 upregulated PAI-1. In vivo, FGFR2 overexpression in tumor-bearing mouse models suggested that a PAI-1 inhibitor could rescue FGFR2/PAI-1 axis-induced M2 macrophage polarization, which leads to effective immune activity and tumor suppression. Moreover, the combination of a PAI-1 inhibitor and anti-PD-1 therapy exhibited superior antitumor activity in mice. These findings offer novel insights into the molecular mechanisms underlying tumor deterioration and provide potential therapeutic targets for CRC treatment.

Qinling liquid ameliorates renal immune inflammatory damage via activating autophagy through AMPK/Stat3 pathway in uric acid nephropathy.

BACKGROUND: Excessive deposition of uric acid (UA) is one of the risk factors for kidney damage. Qinling liquid (QL) has a certain therapeutic effect on uric acid nephropathy (UAN), but its regulation mechanism is still unclear. METHODS: UAN rat models and UA induced rat renal tubular epithelial cells (NRK-52E) were constructed to evaluate the functional roles of QL. We firstly evaluated the kidney function and the degree of kidney damage in rats after QL treatment. Then, effects of QL on autophagy and NLRP3 inflammasome activation were assessed. Moreover, the regulation of QL in AMPK and Stat3 phosphorylation levels and the relationship among autophagy, AMPK/Stat3 pathway and NLRP3 inflammasomes were determined. RESULTS: QL could alleviate the inflammatory damage in UAN rats and promote the activation of autophagy. In addition, QL suppressed UA-induced activation of NLRP3 inflammasomes in rat renal tubular epithelial cells, which was partially reversed by autophagy inhibitor. Further, AMPK/Stat3 axis-mediated autophagy participated in the regulation of UA-induced NLRP3 inflammasome activation in NRK-52E cells. Finally, we confirmed that inhibiting AMPK/Stat3 pathway partly deteriorated the ameliorating effect of QL on renal immune inflammatory injury in UAN rats. CONCLUSION: Through in vivo and in vitro experiments, we found that QL promotes autophagy by activating the AMPK/Stat3 pathway, thereby improving renal immune inflammatory injury in UAN.

Satellite observed reversal in trends of spring phenology in the middle-high latitudes of the Northern Hemisphere during the global warming hiatus.

The start of the growing season (SOS) is essential to track the responses of vegetation to climate change. However, recent findings on whether the SOS in the middle-high latitudes of the Northern Hemisphere (NH) continued to advance or reversed during the global warming hiatus were not consistent. It is necessary to investigate the causes of this controversy and to examine the relationship between the SOS and preseason temperature trends. To this end, we first applied four widely used phenology extraction methods to derive the SOS from the GIMMS NDVI3g dataset and then used the ensemble empirical modal decomposition (EEMD) method to extract the nonlinear trends of the SOS and preseason temperature. Our results clarify, for the first time, that the limitations of the linear assumption-based trend analysis methods are an important but overlooked cause of the discrepancies among existing studies on whether the SOS was advanced or delayed in the NH (>30° N) during the global warming hiatus. We further revealed the range of the mismatches between the SOS and preseason temperature trends at the latitude, altitude and biome levels. Specifically, we discovered that the SOS in the NH (>30° N) obtained by the four phenology extraction methods showed a significant reversal from advance to delay during the global warming hiatus, and the corresponding average rate of change was very small. The area showing increasing preseason temperatures decreased during the global warming hiatus, but it always occupied most of the NH (>30° N). However, delayed SOS trends were dominant in the NH from 50° N to 60° N, above 3000 m and in biomes other than TBMF and BF. Accordingly, using an EEMD-like approach to evaluate the changes in the SOS and preseason temperature is necessary for improving our understanding of the changes in the SOS and their association with climate.

The genetic alterations of rectal neuroendocrine tumor and indications for therapy and prognosis: a systematic review.

Neuroendocrine tumors (NETs) are a type of rare tumor that can occur at multiple organs. Rectal NETs are the most common NETs in gastrointestinal tract. Due to the rarity of rectal NETs in rectal cancer, the molecular features and the correlation with patient therapeutic response and prognosis have not been investigated in detail. In this review, we focused on the molecular features, potential therapeutic targets and prognosis of rectal NETs. By summarizing the relevant studies, we established the mutational landscape of rectal NETs and identified a series of large fragment variations. Driver genes including TP53, APC, KRAS, BRAF, RB1, CDKN2A and PTEN were found as the top mutated genes. Large fragment alterations mainly involved known driver genes, including APC, TP53, CCNE1, MYC, TERT, RB1 and ATM. Germline mutations of APC, MUTYH, MSH6, MLH1 and MSH2 associated with Lynch syndrome or FAP were also found in rectal NETs. The BRAF-V600E mutation was reported as an actionable target in rectal NETs, and the combined BRAF/MEK inhibitors were found to be effective targeting BRAF-V600E in advanced or metastatic NETs. The known prognostic risk factors of rectal adenocarcinoma, including a series of demographic and clinicopathological factors were also prognostic factors for rectal NETs. Furthermore, three types of markers, including genetic alterations, protein expression levels and methylation, were also suggested as prognostic factors for rectal NETs. In summary, we established the landscape of mutations and large-fragment alterations of rectal NETs, and identified potential therapeutic targets and a series of prognostic factors. Future studies may focus on the optimization of therapeutic strategies based on potential actionable biomarkers.

Correlation of Tibial Torsion With Lower Limb Alignment and Femoral Anteversion in Patients With Patellar Instability.

Background: Alignment and rotation of the lower extremities have been suggested to be predisposing pathologic factors for patellar instability. Purpose: To elucidate the relationship between the lower limb alignment and lower extremity rotation in patients with patellar instability. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Included were 83 patients with patellar instability. Computed tomography scans and standing full-leg radiographs were used to measure the tibial tuberosity-trochlear groove (TT-TG) distance, mechanical femorotibial angle (mFTA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), femoral torsion, and tibial torsion of the different segments. The relationships between femoral torsion, tibial torsion of the different segments, and the mFTA, mLDFA, and mMPTA were evaluated. The levels of tibial torsion and femoral torsion in patients with varus, normal, or valgus alignment were compared with 1-way analysis of variance and chi-square test. Results: The total tibial torsion was significantly associated with total femoral anteversion (r = 0.329; P = .002) and mFTA (r = -0.304; P = .005). There were no significant correlations between mFTA and TT-TG distance or femoral anteversion. Compared with patients with valgus malalignment, patients with varus malalignment tended to have higher tibial torsion. Conclusion: Tibial torsion was associated with leg axis alignment and femoral anteversion in patients with patellar instability. Patients with patellar instability, especially those with concurrent leg axis deformities, should undergo further radiological imaging so that tibial torsion can be assessed and a diagnosis of torsion deformity made early in the treatment pathway and the proper surgical plan formulated.

The integrated comprehension of lncRNA HOXA-AS3 implication on human diseases

Long non-coding RNA (lncRNA) is a non-protein-coding RNA with a length of more than 200 nucleotides. Studies have shown that lncRNAs have vital impacts on various pathological processes and participate in the development of human diseases, usually through acting as competing endogenous RNAs to modulate miRNA expression and biological functions. lncRNA HOXA Cluster Antisense RNA 3 (HOXA-AS3) was a newly discovered lncRNA and has been demonstrated to be abnormally expressed in many diseases. Moreover, HOXA-AS3 expression was closely correlated with the clinicopathologic characteristics in cancer patients. In addition, HOXA-AS3 exhibited significant properties in regulating several biological processes, including cell proliferation, invasion, and migration. Furthermore, HOXA-AS3 has provided promising values in the diagnosis, prognosis, and therapeutic strategies of several diseases such as liver cancer, glioma, lung cancer, oral cancer, gastric cancer, and even atherosclerosis. In this review, we discuss the abnormal expression of HOXA-AS3 in several human disorders and some pathobiological processes and its clinical characteristics, followed by a summary of HOXA-AS3 functions, regulatory mechanisms, and clinical application potential (AU)

A highly sensitive bio-barcode immunoassay for multi-residue detection of organophosphate pesticides based on fluorescence anti-quenching.

Balancing the risks and benefits of organophosphate pesticides (OPs) on human and environmental health relies partly on their accurate measurement. A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs (triazophos, parathion, and chlorpyrifos) in apples, turnips, cabbages, and rice. Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs. DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification. The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore. The resulting fluorescence signal enables multiplexed quantification of triazophos, parathion, and chlorpyrifos residues over the concentration range of 0.01-25, 0.01-50, and 0.1-50 ng/mL with limits of detection of 0.014, 0.011, and 0.126 ng/mL, respectively. The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%-17.6%, which correlate well with results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proposed bio-barcode immunoassay is stable, reproducible and reliable, and is able to detect low residual levels of multi-residue OPs in agricultural products.

The emerging potentials of lncRNA DRAIC in human cancers.

Long non-coding RNA (lncRNA) is a subtype of noncoding RNA that has more than 200 nucleotides. Numerous studies have confirmed that lncRNA is relevant during multiple biological processes through the regulation of various genes, thus affecting disease progression. The lncRNA DRAIC, a newly discovered lncRNA, has been found to be abnormally expressed in a variety of diseases, particularly cancer. Indeed, the dysregulation of DRAIC expression is closely related to clinicopathological features. It was also reported that DRAIC is key to biological functions such as cell proliferation, autophagy, migration, and invasion. Furthermore, DRAIC is of great clinical significance in human disease. In this review, we discuss the expression signature, clinical characteristics, biological functions, relevant mechanisms, and potential clinical applications of DRAIC in several human diseases.

Identification of molecular patterns and prognostic models of epithelial-mesenchymal transition- and immune-combined index in the gastric cancer.

Background: Epithelial-mesenchymal transition (EMT) and the immune microenvironment play important roles in the progression of gastric cancer (GC), but the joint role of both in GC is not clear. Methods: We identified EMT- and immune-related genes (EIRGs), and the molecular subtypes of EIRGs were identified by unsupervised cluster analysis. Then, we constructed an accurate EIRG_score model by using differential genes of molecular subtypes. The correlation of EIRG_score with prognosis, immune infiltration, gene mutation, chemotherapeutic drug sensitivity, and immunotherapy response was comprehensively analyzed. In addition, we investigated the biological function of EIRG_score via in vitro experiments. Results: A total of 808 GC patients were classified into two molecular subtypes, which were enriched in EMT and immune-related biological pathways and significantly correlated with prognosis and immune infiltration. The constructed EIRG_score had an important role in predicting prognosis and immunotherapeutic response. The higher EIRG_score was associated with worse prognosis, higher abundance of immunosuppressive cell infiltration, lower immune checkpoint genes expression, lower tumor mutation burden, microsatellite instability-high, lower chemotherapeutic drug sensitivity, and poorer immunotherapeutic response. Conclusion: EIRG_score may be used as a biomarker to assess prognosis and guide precise treatment.

The integrated comprehension of lncRNA HOXA-AS3 implication on human diseases.

Long non-coding RNA (lncRNA) is a non-protein-coding RNA with a length of more than 200 nucleotides. Studies have shown that lncRNAs have vital impacts on various pathological processes and participate in the development of human diseases, usually through acting as competing endogenous RNAs to modulate miRNA expression and biological functions. lncRNA HOXA Cluster Antisense RNA 3 (HOXA-AS3) was a newly discovered lncRNA and has been demonstrated to be abnormally expressed in many diseases. Moreover, HOXA-AS3 expression was closely correlated with the clinicopathologic characteristics in cancer patients. In addition, HOXA-AS3 exhibited significant properties in regulating several biological processes, including cell proliferation, invasion, and migration. Furthermore, HOXA-AS3 has provided promising values in the diagnosis, prognosis, and therapeutic strategies of several diseases such as liver cancer, glioma, lung cancer, oral cancer, gastric cancer, and even atherosclerosis. In this review, we discuss the abnormal expression of HOXA-AS3 in several human disorders and some pathobiological processes and its clinical characteristics, followed by a summary of HOXA-AS3 functions, regulatory mechanisms, and clinical application potential.