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To solve the problem that there are many kinds of municipal solid waste and urban residents do not have a clear classification standard for garbage, an intelligent voice garbage classification system based on a deep residual neural network is designed. For the four kinds of common garbage in life, the voice commands of four kinds of typical garbage are collected. Through the speech endpoint detection algorithm, the silence and noise in the speech are removed, and the acoustic model based on the deep residual network is built to realize garbage classification. The experimental results show that after the model training is completed, the accuracy of the verification set reaches 98%, the accuracy of the test set reaches 96%, and the generalization ability is strong, which has a high application value.

Family with sequence similarity 83 (FAM83) members were shown recently to have oncogenic effect in a variety of cancer types, but the biological roles and prognostic value of FAM83 family in pancreatic ductal adenocarcinoma remain unknown. In the current study, the clinical significance and molecular function of the FAM83 family were assessed by multiple bioinformatics analysis. Besides, potential associations between differentially expressed genes (DEGs) of FAM83 family and antitumor immunity were evaluated using TIMER and TISIDB analyses. As the results show, FAM83A, FAM83D, FAM83E, and FAM83H were significantly upregulated in PDAC and were identified as DEGs. Higher expression of FAM83A, FAM83B, FAM83D, FAM83E, and FAM83H were associated with advanced tumor stage or worse patient prognosis. Importantly, the overexpression of DEGs was found to be significantly correlated with activated KRAS and loss of SMAD4, which are important drivers for PDAC. Further, FAM83A, FAM83D, and FAM83H were associated with CD8+ T cell, Gamma Delta T cell, and CD4+ T cell infiltration in PDAC and FAM83H was found closely correlated with some immunomodulators including immunoinhibitors, immunostimulators, and MHC molecules. In conclusion, FAM83A, FAM83D, FAM83E, and FAM83H have significant prognostic value in PDAC and they may play important roles in regulating tumor progression and the immune cell infiltration.

S100 calcium‐binding protein A (S100A) family members regulate multiple biological functions related to pancreatic cancer (PC) progression and metastasis. However, the prognostic and oncologic values of S100A family have not been systematically investigated in PC. In the present study, the mRNA expression and potential functions of S100A family were investigated by bioinformatic analysis. Our results demonstrated that overexpression of S100A2, S100A6, S100A10, S100A11, S100A14 and S100A16 was significantly associated with higher T stage, advanced histologic grade and worse prognosis in PC. Besides, one CpG of S100A2, three CpG of S100A6, four CpG of S100A10, four CpG of S100A11, two CpG of S100A14 and five CpG of S100A16 were negatively associated with corresponding S100A family members expression and positively associated with overall survival (OS). The signature based on four CpGs showed good prediction ability of OS. Besides, S100A2 overexpression took part in the regulation of mitotic cell cycle, ECM‐receptor interaction and HIF‐1α transcription factor network. Overexpression of S100A6, S100A10, S100A11, S100A14 and S100A16 may impair the infiltration and cytolytic activity of CD8+ T cells through focal adhesion‐Ras‐stimulating signalling pathway in PC. Overall, this study explores the multiple prognostic values and oncologic functions of the S100A family in PC.

Background: Recent evidence has shown that CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) promoted carcinogenesis and tumor progression in a variety of cancer types. The goal of our study is to investigate the association between CMTM3 and pancreatic cancer (PC). Materials and Methods: In current study, data from public databases was used to analyze CMTM3 expression in PC. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to investigate CMTM3 expression and determine its clinical significance in PC. Then CMTM3 promoting PC aggressiveness was demonstrated in vitro experiments by cell proliferation and migration assay. Functional and pathway enrichment analyses were performed to evaluate the potential role of CMTM3 in PC. Results: Results of qRT-PCR and IHC revealed that CMTM3 was significantly overexpressed in PC tissues. High CMTM3 expression was an independent risk factor for poor prognosis of PC patients. Overexpression of CMTM3 was associated with poor overall survival (P-value =0.031) and disease-free survival (P-value =0.0047) in the TCGA cohort. Functional and pathway enrichment analyses showed that CMTM3 were enriched in “Regulation of cell proliferation and regulation of cell differentiation, cell morphogenesis, regulation of cell differentiation, Hedgehog signaling pathway, Wnt signaling pathway, ECM-receptor interaction and pathways in cancer”. In PC cell lines, CCK8, clone formation and transwell assays showed that CMTM3 knockdown inhibited cells proliferation and migration. Conclusion: CMTM3 was overexpressed and promotes tumor aggressiveness in PC. Our findings provided a novel therapeutic target for PC.

As nanoscale membranous vesicles, human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hucMSC-sEVs) have attracted extensive attention in the field of tissue regeneration. Under the premise that the mechanisms of hucMSC-sEVs on the treatment of diabetic kidney disease (DKD) have not been revealed clearly, we constructed DKD rat model with success. After tail vein injection, hucMSC-sEVs effectively reduced blood glucose, maintained body weight and improved renal function in DKD rats. Notably, we found that hucMSC-sEVs suppressed YAP expression in renal cortical regions. Further in vitro experiments, we confirmed that the expression of YAP in the nucleus of renal podocytes was increased, and the level of autophagy was inhibited in the high-glucose environment, which could be reversed by intervention with hucMSC-sEVs. We screened out the key protein 14-3-3

There were few data about the long-term outcomes of bio-compatible patches for pelvic organ prolapse (POP). The efficacy of poly (L-lactide-co-caprolactone) blended with fibrinogen [P(LLA-CL)/Fg] bio-patches were investigated for anterior vaginal wall prolapse treatment in a 6-year follow-up.The P(LLA-CL)/Fg bio-patch was fabricated through electrospinning. Nineteen patients with symptomatic anterior prolapse (Pelvic Organ Prolapse Quantification [POP-Q] stage ≥ 2) were treated with anterior pelvic reconstruction surgery using a P(LLA-CL)/Fg bio-patch and were followed up at 1, 2, 3, 6 months, and 6 years. The primary outcome was objective anatomical cure (anterior POP-Q stage ≤ 1). Secondary outcomes included complications, MRI evaluation, and scores of the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and the Pelvic Floor Distress Inventory-20 (PFDI-20).The micro-morphology of the bio-patch resembled the extracellular matrix, which was suitable for the growth of fibroblasts. Sixteen (84.2%) patients were finally assessed, with a mean follow-up of 6.08 ± 0.18 years. The cure rate without anterior prolapse recurrence was 93.8% at 6 years. Compared with baseline, the POP-Q measurements of Aa, Ba, and C points and scores of PFIQ-7 and PFDI-20 manifested significant differences at all times (all p0.05). One (5.26%) case of bio-patch-related infection, 1 (5.26%) case of urinary retention, and no exposures and erosion occurred. MRI evaluation showed that the bio-patch gradually degraded to fragments at 1 month and was completely absorbed at 3 months.Among long-term follow-ups, anterior pelvic reconstruction surgery with a P(LLA-CL)/Fg bio-patch demonstrated significant improvements in anatomical correction of anterior pelvic prolapse and pelvic function without severe morbidity.

The application of polypropylene mesh (PPM) in pelvic organ prolapse (POP) treatment was severely limited by the complications associated with PPM, such as mesh exposure, chronic inflammatory reactions and postoperative hematoma. This study applied a method of fabricating a hydrogel-mesh complex (PPM + TA@GelMA) to cross-link tannic acid (TA) directly with Methacrylate Gelatin (GelMA) hydrogel and thus to form a coating for PPM. This one-step coating modification improved the hydrophilicity and cyto-compatibility of PPM. The hemostatic effect of PPM+TA@GelMA was confirmed through tail amputation test. Through the defect tissue repair experiments in vivo, it was proved that PPM+TA@GelMA had effects of anti-inflammation and promoting tissue repair and regulated the M2 subtype macrophages polarization for tissue repair. The TA-loaded hydrogel coating endued PPM with multiple functions. It is believed that the novel hydrogel-mesh complex and its fabrication method will have great significance in basic research and clinical application.

Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) has been associated with tumor progression in several solid tumors, and inhibits CD8+ T cell-mediated anti-tumor immunity in breast cancer. However, little is known about the potential functions of B3GNT3 in immunosuppression in pancreatic cancer (PC). This study on B3GNT3 aims to provide novel insights into the mechanisms of immune suppression or evasion in PC. To this end, the clinical significance and oncologic roles of B3GNT3 were investigated through bioinformatic analysis and in vitro studies. Potential associations between the expression of B3GNT3 and tumor immunity were mainly analyzed by single-sample gene set enrichment analysis (ssGSEA) and immunofluorescence in tissue microarray (TMA). B3GNT3 overexpression was observed in PC tissue and was associated with larger tumor sizes, higher histologic grades, and poorer overall survival (OS). B3GNT3 overexpression was associated with the mutation status and expression of driver genes, especially for KRAS and SMAD4. B3GNT3 knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of PC cells. B3GNT3 overexpression significantly correlated with decreased infiltration of tumor infiltrating lymphocytes (TILs), especially CD8+ T cells. Overall, our results indicates that B3GTN3 plays a novel role in tumor progression and immunosuppression, thus serving as a potential therapeutic target in PC.

Background Pancreatic cancer (PC) is one of the most common cancers and the leading cause of cancer-related death worldwide. Exploring novel predictive biomarkers for PC patients’ prognosis is in urgent need. Methods In the present study, we conducted Cox proportional hazards regression to identify critical prognosis-associated lncRNAs (PALncs) in TCGA PC dataset. Based on the results of multivariate analysis, a PALnc-based risk score system was established, and validated in GSE62452 dataset. The validity and reliability of the risk score system for prognosis of PC were evaluated through ROC analysis. And function enrichment analyses for the PALncs were also performed. Result In the multivariate analysis, four PALncs (LINC00476, C9orf163, LINC00346 and DSCR9) were screened out to develop a risk score system, which showed a high AUC at 3 and 5 years overall survival (0.785 at 3 year OS, 0.863 at 5 year OS) in TCGA datasets. And the ROC analysis of the risk score system for RFS in TCGA dataset revealed that AUC for RFS was 0.799 at 3 years and 0.909 at 5 years. Further, the AUC for OS in the validation cohort was 0.705 at 3 years and 0.959 at 5 years. Furthermore, the functional enrichment analysis revealed that these PALncs may be involved in various pathways related to cancer, including Ras family activation, autophagy in cancer, MAPK signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, etc. And correlation analysis of these tumor infiltrating immune cells and risk score system revealed that the infiltration level of B cell naïve, plasma cells, and CD8+ T cells are negatively correlated to the risk score system, while macrophages M2 positively correlated to the risk score system. Conclusion Our study established a four PALncs based risk score system, which reflects immune cell infiltration and predicts patient survival for PC.

Adjuvants that contain pathogen-associated molecular patterns (PAMPs) can enhance vaccination efficacy by binding to pattern recognition receptors (PRRs), thereby stimulating immune responses. Particularly effective may be the combination of multiple PAMPs that activate different PRRs, which occurs with natural pathogens. Here we hypothesized the enhanced effects would occur in two adjuvants that stimulate different PRRs: CpG oligodeoxynucleotide (CpG-ODN), which is Toll-like receptor 9 agonist; and 5′-triphosphate, short, double-stranded RNA (3pRNA), which activates retinoic acid-inducible gene I (RIG-I). The model antigen ovalbumin (OVA) was loaded and adjuvants were surface-adsorbed to aluminum hydroxide nanoparticles (hereafter NP-3pRNA-CpG) by electrostatic interaction with an average size of 120 nm and a negative surface charge for targeting lymph nodes. These nanoparticles were efficiently internalized by antigen-presenting cells (APCs) in the lymph nodes, and the resulting APC activation and antigen cross-presentation generated strong humoral immunity and cytotoxic T lymphocyte responses and IFN-γ secretion. NP-3pRNA-CpG significantly suppressed B16-OVA tumor growth and prolonged survival of tumor-bearing mice in therapeutic and prophylactic models, illustrating the enhanced effects of CpG-ODN and 3pRNA. Our study highlights the potential of combining multiple adjuvants for effective vaccine design.

Carbon dioxide (CO2) hydrogenation to liquid fuels including gasoline, jet fuel, diesel, methanol, ethanol, and other higher alcohols via heterogeneous catalysis, using renewable energy, not only effectively alleviates environmental problems caused by massive CO2 emissions, but also reduces our excessive dependence on fossil fuels. In this Outlook, we review the latest development in the design of novel and very promising heterogeneous catalysts for direct CO2 hydrogenation to methanol, liquid hydrocarbons, and higher alcohols. Compared with methanol production, the synthesis of products with two or more carbons (C2+) faces greater challenges. Highly efficient synthesis of C2+ products from CO2 hydrogenation can be achieved by a reaction coupling strategy that first converts CO2 to carbon monoxide or methanol and then conducts a C-C coupling reaction over a bifunctional/multifunctional catalyst. Apart from the catalytic performance, unique catalyst design ideas, and structure-performance relationship, we also discuss current challenges in catalyst development and perspectives for industrial applications.

Syntaxin17, a key autophagosomal N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) protein, can associate with ATG8 family proteins SNAP29 and VAMP8 to facilitate the membrane fusion process between the double-membraned autophagosome and single-membraned lysosome in mammalian macroautophagy. However, the inherent properties of Syntaxin17 and the mechanistic basis underlying the interactions of Syntaxin17 with its binding proteins remain largely unknown. Here, using biochemical, NMR, and structural approaches, we systemically characterized Syntaxin17 as well as its interactions with ATG8 family proteins, SNAP29 and VAMP8. We discovered that Syntaxin17 alone adopts an autoinhibited conformation mediated by a direct interaction between its Habc domain and the Qa-SNARE motif. In addition, we revealed that the Qa-SNARE region of Syntaxin17 contains one LC3-interacting region (LIR) motif, which preferentially binds to GABARAP subfamily members. Importantly, the GABARAP binding of Syntaxin17 can release its autoinhibited state. The determined crystal structure of the Syntaxin17 LIR–GABARAP complex not only provides mechanistic insights into the interaction between Syntaxin17 and GABARAP but also reveals an unconventional LIR motif with a C-terminally extended 3(10) helix for selectively binding to ATG8 family proteins. Finally, we also elucidated structural arrangements of the autophagic Syntaxin17–SNAP29–VAMP8 SNARE core complex, and uncovered its conserved biochemical and structural characteristics common to all other SNAREs. In all, our findings reveal three distinct states of Syntaxin17, and provide mechanistic insights into the Syntaxin17-mediated autophagosome–lysosome fusion process.

N6-methyladenosine (m6A) RNA methylation contributes to the cancer stem cell (CSC) phenotype through regulating gene expression. YTHDF2, an m6A reader, was shown to be associated with hepatocellular carcinoma (HCC) patient prognosis. However, the effect of YTHDF2 on liver CSC and cancer metastasis and the molecular mechanism of this effect have not been documented. Here, we show that YTHDF2 expression is negatively correlated with HCC patient survival in both data from the Cancer Genome Atlas (TCGA) database and clinical data from our center. By detecting CD133+ cells and carrying out sphere culture assays, we found that knockdown of YTHDF2 led to impaired stemness in Hep3B and Huh7 cells. In contrast, overexpression of YTHDF2 increased the CSC phenotype. Mechanistically, the knockdown and overexpression of YTHDF2 in liver cancer cells resulted in decreased and increased m6A levels in the 5'-untranslated region (UTR) of OCT4 mRNA, respectively, leading to decreased and increased OCT4 protein expression, respectively. A luciferase activity assay showed that mutation of the corresponding m6A methylation sequence in the 5'-UTR of OCT4 mRNA caused significantly decreased gene expression, suggesting a role for YTHDF2-dependent m6A methylation in protein translation. Polysome profiling results also indicated the knockdown and overexpression of YTHDF2 could decrease and increase OCT4 translation, respectively. In particular, overexpression of OCT4 rescued the impaired stemness caused by YTHDF2 depletion, which confirmed the effect of YTHDF2 on CSC phenotype is dependent on OCT4. In vivo, the loss of YTHDF2 reduced tumor burden and inhibited lung metastasis following orthotopic transplantation in nude mice. Last, we demonstrated that YTHDF2 expression is positively correlated with OCT4 expression and m6A levels in the 5'-UTR of OCT4 mRNA in clinical HCC specimens. In conclusion, YTHDF2 promotes the CSC liver phenotype and cancer metastasis by modulating the m6A methylation of OCT4 mRNA.

Background Obg-like ATPase 1 (OLA1) has been found to have a dual role in cancers. However, the relationship between OLA1 and hepatocellular carcinoma (HCC) remains unclear. Results High expression of OLA1 in HCC was detected in public datasets and clinical samples, and correlated with poor prognosis. Downregulation of OLA1 significantly inhibited the proliferation, migration, invasion and tumorigenicity of HCC cells. Mechanistically, GSEA showed that OLA1 might promote tumor progression by regulating the cell cycle and apoptosis. In addition, OLA1 knockdown resulted in G0/G1 phase arrest and high levels of apoptosis. OLA1 could bind with P21 and upregulate CDK2 expression to promote HCC progression. Conclusions Overall, these findings uncover a role for OLA1 in regulating the proliferation and apoptosis of HCC cells. Materials and methods The Cancer Genome Atlas and Gene Expression Omnibus datasets were analyzed to identify gene expression. Immunohistochemistry staining, western blot and real-time polymerase chain reaction were performed to evaluate OLA1 expression in samples. Cell count Kit-8, wound-healing, transwell and flow cytometry assays were used to analyze HCC cell progression. Subcutaneous xenotransplantation models were used to investigate the role of OLA1 in vivo. Coimmunoprecipitation was used to analyze protein interactions.

Limited research on the role of membrane-bound O-acyltransferase domain-containing 2 (In the current study, the potential biological and clinical significances ofThe level ofOur findings suggest that

Exosomes (30–100 nm in diameter) are a group of cell-derived membrane vesicles, packaged as valuable cargo with lipid, proteins, and genetic materials from their parent cells. With the increasing interest in exosomes for diagnostic and therapeutic applications, the rapid isolation of pure exosome populations has become a hot topic. In this paper, we propose modified microchannels with aptamer in a microfluidics system for rapid and efficient isolation of exosomes by targeting exosome-carrying CD63 and PTK 7. The capture efficiency in surface-modified channels reaches around 107–108 particles/mL in 20 min, and purified exosomes with reliable size can be achieved.

A constrained variation modeling method for free vibration analysis of rotating double tapered functionally graded beams with different shear deformation beam theories is proposed in this paper. The material properties of the beam are supposed to continuously vary in the width direction with power-law exponent for different indexes. The mathematical formulation is developed based on the geometrically exact beam theory for each beam segment, the admissible functions denoting motion quantities are then expressed by a series of Chebyshev orthogonal polynomials. The governing equations are eventually derived using the constrained variational method to involve the continuity conditions of adjacent segments. Different shear deformation beam theories have been incorporated in the formulations, and the nonlinear effect of bending–stretching coupling vibration together with the Coriolis effect is taken into account. Comparison of dimensionless natural frequencies is performed with the existing literature to ensure the accuracy and reliability of the proposed method. Comparative discussions are performed on the vibration behaviors of the double tapered rotating functionally graded beam with first-order shear deformation beam theory and other higher-order shear deformation beam theories. The effect of material property graduation, power-law index, rotation speed, hub radius, slenderness ratio, and taper ratios is scrutinized via parametric studies, respectively.

BackgroundPancreatic adenocarcinoma (PAAD) is a highly malignant cancer with a poor prognosis. The tumor microenvironment (TME) is closely related to tumorigenesis, progression, and treatment. However, the relationship between TME immune cell genes and prognosis in PAAD is currently unclear.Methodsn this study, we identified three prognostic subtypes based on the TME by using data from The Cancer Genome Atlas (TCGA) database, The International Cancer Genome Consortium (ICGC) database and University of California Santa Cruz (UCSC) database. The Silhouette plot analysis was used to evaluate 758 immune genes expression in PAAD from each database, then to divide all samples into three subtypes (Clusters A, B, C) by Lasso’s binomial logistic regression. We analyzed the relationship between subtypes and prognosis by the survival R package. CIBERSORT was used for evaluating the expression changes of immune cells. We detect the copy number variation areas between two groups through GISTIC 2.0 algorithm. The TIDE network tool was used to predict the response of immune therapy.ResultsWe defined three clusters (Clusters A, B, and C) based on the analysis of immune gene expression. Cluster B got a worse prognosis than the other two clusters. The Cluster B group had the highest level of Macrophages M0 and Macrophage M2. NK cell resting was much higher in Cluster B than other groups in TME. Gene KRAS was mutated in 77% of all samples. Cluster C had a better immune therapy effect than others.ConclusionsWe found a news model to predicted patients’ prognosis who with pancreatic adenocarcinoma. Cluster B had the significant worse prognosis than other groups. Patients in Cluster C could get batter treatment effect by using immunotherapy.

The CRISPR-Cas system has achieved breakthrough applications in the field of molecular diagnostics. CRISPR/Cas12a can accurately identify subtle changes in a target nucleic acid sequence and has a wide range of applications such as in highly sensitive detection methods. In this study, an upconversion-magnetic probe-DNA-Fe

Background: Although some improvements in the management of pancreatic cancer (PC) have been made, no major breakthroughs in terms of biomarker discovery or effective treatment have emerged. Here, we applied artificial intelligence (AI)-based methods to develop a model to diagnose PC and predict survival outcome.Methods: Multiple bioinformatics methods, including RankProd, were performed to identify differentially expressed genes (DEGs) in PC. A Back Propagation (BP) model was constructed, followed by Genetic Algorithm (GA) filtering and verification of its prognosis capacity in the TCGA cohort. Furthermore, we validated the protein expression of the selected DEGs in 92 clinical PC tissues using immunohistochemistry.Results: Four candidate genes (LCN2, SLC6A14, SPOCK1, and VCAN) were selected to establish a four-gene signature for PC. The gene signature was validated in the TCGA PC cohort, and found to show satisfactory discrimination and prognostic power. Areas under the curve (AUC) values of overall survival were both greater than 0.60 in the TCGA training cohort, test cohort, and the entire cohort. Kaplan-Meier analyses showed that high-risk group had a significantly shorter overall survival and disease-free survival than the low-risk group. Further, the elevated expression of SLC6A14 and SPOCK1 in PC tissues was validated in the TCGA+GETx datasets and 92 clinical PC tissues, and was significantly associated with poor survival in PC.Conclusions: Using RankProd and GA-ANN, we developed and validated a diagnostic and prognostic gene signature that yielded excellent predictive capacity for PC patients’ survival.

A functionalized nanofiber membrane with high oil/water separation efficiency and methylene blue adsorption has been successfully fabricated by electrospinning and a surface modification approach. The substrate poly(lactic acid) (PLA) nanofiber film was firstly coated with titanium dioxide (TiO2) nanoparticles (NPs) by the sol–gel method. Then, polysiloxane formed by the hydrolysis and polycondensation of methyltrichlorosilane (MTS) was deposited on the modified nanofiber surface to increase the surface roughness and reduce the surface energy. The PLA nanofibrous membrane functionalized with TiO2 NPs and MTS exhibited excellent superhydrophobicity (water contact angle = 157.4 ± 0.9°), high permeation flux (2297.6 ± 51.6 L m−2 h−1) and ideal filtration efficiency (98.4 ± 1.0%). Moreover, the functionalized nanofibrous membrane could also achieve rapid and recyclable adsorption of toxic dyes such as methylene blue in aqueous solution. It provides a new prospect to facilely fabricate nanofibrous membrane materials to achieve the dual functions of oil/water separation and removal of toxic dyes with high efficiency.

Aiming at the problem that fault feature extraction is susceptible to background noises and burrs, we proposed a new feature extraction method based on a new decomposition method and an effective intrinsic mode function (IMF) selection method. Firstly, pairs of white noises with opposite signs were introduced to neutralize the residual noises in ensemble empirical mode decomposition (EEMD) and suppress mode mixing. Both the reconstruction error (1.8445 × 10−17) and decomposition time (0.01 s) were greatly reduced through fast, complementary ensemble empirical mode decomposition (FCEEMD). Secondly, we integrated the energy and kurtosis of the IMF and proposed an effective IMF selection method based on energy kurtosis mean filtering, and the background noise of the signal was greatly suppressed. Finally, the periodic impacts were extracted from the IMF reconstruction signal by multipoint optimal minimum entropy deconvolution adjusted (MOMEDA). The fault frequencies were extracted from the periodic impacts through Hilbert demodulation, and the relative errors between the measured values and the theoretical values were all less than 0.05. The experimental results show that the proposed method can extract fault features more efficiently and provide a novel method for the fault diagnosis of rotating machinery.

Background:The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) of pancreatic head remains poor, even after potentially curative R0 resection. The aim of this study was to develop an accurate model to predict patients’ prognosis for PDAC of pancreatic head following pancreaticoduodenectomy.Methods:We retrospectively reviewed 112 patients with PDAC of pancreatic head after pancreaticoduodenectomy in Guangdong Provincial People’s Hospital between 2014 and 2018.Results:Five prognostic factors were identified using univariate Cox regression analysis, including age, histologic grade, American Joint Committee on Cancer (AJCC) Stage 8th, total bilirubin (TBIL), CA19-9. Using all subset analysis and multivariate Cox regression analysis, we developed a nomogram consisted of age, AJCC Stage 8th, perineural invasion, TBIL, and CA19-9, which had higher C-indexes for OS (0.73) and RFS (0.69) compared with AJCC Stage 8th alone (OS: 0.66; RFS: 0.67). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the nomogram for OS and RFS were significantly higher than other single parameter, which are AJCC Stage 8th, age, perineural invasion, TBIL, and CA19-9. Importantly, our nomogram displayed higher C-index for OS than previous reported models, indicating a better predictive value of our model.Conclusions:A simple and practical nomogram for patient prognosis in PDAC of pancreatic head following pancreaticoduodenectomy was established, which shows satisfactory predictive efficacy and deserves further evaluation in the future.

In the context of the current pandemic caused by the novel coronavirus, molecular detection is not limited to the clinical laboratory, but also faces the challenge of the complex and variable real-time detection fields. A series of novel coronavirus events were detected in the process of food cold chain packaging and transportation, making the application of molecular diagnosis in food processing, packaging, transportation, and other links urgent. There is an urgent need for a rapid detection technology that can adapt to the diversity and complexity of food safety.This review introduces a new molecular diagnostic technology-biosensor analysis technology based on CRISPR-Cas12a. Systematic clarification of its development process and detection principles. It summarizes and systematically organizes its applications in viruses, food-borne pathogenic bacteria, small molecule detection, etc. In the past four years, which provides a brand-new and comprehensive solution for food detection. Finally, this article puts forward the challenges and the prospects for food safety.The novel coronavirus hazards infiltrated every step of the food industry, from processing to packaging to transportation. The biosensor analytical technology based on CRISPR-Cas12a has great potential in the qualitative and quantitative analysis of infectious pathogens. CRISPR-Cas12a can effectively identify the presence of the specific nucleic acid targets and the small changes in sequences, which is particularly important for nucleic acid identification and pathogen detection. In addition, the CRISPR-Cas12a method can be adjusted and reconfigured within days to detect other viruses, providing equipment for nucleic acid diagnostics in the field of food safety. The future work will focus on the development of portable microfluidic devices for multiple detection. Shao et al. employed physical separation methods to separate Cas proteins in different microfluidic channels to achieve multiple detection, and each channel simultaneously detected different targets by adding crRNA with different spacer sequences. Although CRISPR-Cas12a technology has outstanding advantages in detection, there are several technical barriers in the transformation from emerging technologies to practical applications. The newly developed CRISPR-Cas12a-based applications and methods promote the development of numerous diagnostic and detection solutions, and have great potential in medical diagnosis, environmental monitoring, and especially food detection.

Structural studies reveal a previously unknown molecular mechanism of selective autophagy processes mediated by autophagy receptor NDP52., The recruitment of Unc-51-like kinase and TANK-binding kinase 1 complexes is essential for Nuclear dot protein 52-mediated selective autophagy and relies on the specific association of NDP52, RB1-inducible coiled-coil protein 1, and Nak-associated protein 1 (5-azacytidine-induced protein 2, AZI2). However, the underlying molecular mechanism remains elusive. Here, we find that except for the NDP52 SKIP carboxyl homology (SKICH)/RB1CC1 coiled-coil interaction, the LC3-interacting region of NDP52 can directly interact with the RB1CC1 Claw domain, as that of NAP1 FIP200-binding region (FIR). The determined crystal structures of NDP52 SKICH/RB1CC1 complex, NAP1 FIR/RB1CC1 complex, and the related NAP1 FIR/Gamma-aminobutyric acid receptor-associated protein complex not only elucidate the molecular bases underpinning the interactions of RB1CC1 with NDP52 and NAP1 but also reveal that RB1CC1 Claw and Autophagy-related protein 8 family proteins are competitive in binding to NAP1 and NDP52. Overall, our findings provide mechanistic insights into the interactions of NDP52, NAP1 with RB1CC1 and ATG8 family proteins.

The ULK complex initiates the autophagosome formation, and has recently been implicated in selective autophagy by interacting with autophagy receptors through its FIP200 subunit. However, the structural mechanism underlying the interactions of autophagy receptors with FIP200 and the relevant regulatory mechanism remain elusive. Here, we discover that the interactions of FIP200 Claw domain with autophagy receptors CCPG1 and Optineurin can be regulated by the phosphorylation in their respective FIP200-binding regions. We determine the crystal structures of FIP200 Claw in complex with the phosphorylated CCPG1 and Optineurin, and elucidate the detailed molecular mechanism governing the interactions of FIP200 Claw with CCPG1 and Optineurin as well as their potential regulations by kinase-mediated phosphorylation. In addition, we define the consensus FIP200 Claw-binding motif, and find other autophagy receptors that contain this motif within their conventional LC3-interacting regions. In all, our findings uncover a general and phosphoregulatable binding mode shared by many autophagy receptors to interact with FIP200 Claw for autophagosome biogenesis, and are valuable for further understanding the molecular mechanism of selective autophagy., Cooperation between the ULK complex and autophagy receptors mediates targeting cargoes to autophagosomes. Here, the authors show that interactions of ULK subunit FIP200 with autophagy receptors CCPG1 and Optineurin can be regulated by phosphorylation, suggesting a general binding mode shared by autophagy receptors.

Background. Gallbladder cancer (GBC), which accounts for more than 80% of biliary tract malignancies, has a poor prognosis with an overall 5-year survival less than 10%. The study aimed to identify risk factors and develop a predictive model for GBC following surgical resection. Methods. 98 GBC patients who underwent surgical resection from Guangdong Provincial People’s Hospital were enrolled in the study. Cox-regression analysis was performed to identify significant prognostic factors. A nomogram was constructed and Harrell’s concordance index, calibration plot, and decision cure analysis were used to evaluate the discrimination and calibration of the nomogram. Results. Liver resection, tumor size, perineural invasion, surgical margin, and liver invasion were identified as independent risk factors for overall survival (OS) in GBC patients who underwent surgical resection. Based on the selected risk factors, a novel nomogram was constructed. The C-index of the nomogram was 0.777, which was higher than the American Joint Committee on Cancer (AJCC) staging system (0.724) and Nevin staging system (0.659). Decision cure analysis revealed that the nomogram had a better net benefit and the calibration curves for the 1-, 3-, and 5-year survival probabilities were also well matched with the actual survival rates. Lastly, high-risk GBC were stratified based on the scores of the nomogram and we found high-risk GBC were associated with both worse OS and disease-free survival (DFS). Conclusion. We developed a nomogram showing a better predictive capacity for patients’ survival of resected GBC than the AJCC staging systems. The established model may help to stratify high-risk GBC and facilitate decision-making in the clinic.

Background. KRAS was reported to affect some metabolic genes and promote metabolic reprogramming in solid tumors. However, there was no comprehensive analysis to explore KRAS-associated metabolic signature or risk model for pancreatic cancer (PC). Methods. In the current study, multiple bioinformatics analyses were used to identify differentially expressed metabolic genes based on KRAS mutation status in PC. Then, we developed and validated a prognostic risk model based on the selected KRAS-associated metabolic genes. Besides, we explored the association between the risk model and the metabolic characteristics as well as gemcitabine-associated chemoresistance in PC. Results. 6 KRAS-associated metabolic genes (i.e., CYP2S1, GPX3, FTCD, ENPP2, UGT1A10, and XDH) were selected and enrolled to establish a prognostic risk model. The prognostic model had a high C-index of 0.733 for overall survival (OS) in TCGA pancreatic cancer database. The area under the curve (AUC) values of 1- and 3-year survival were both greater than 0.70. Then, the risk model was validated in two GEO datasets and also presented a satisfactory discrimination and calibration performance. Further, we found that the expression of some KRAS-driven glycolysis-associated genes (PKM, GLUT1, HK2, and LDHA) and gemcitabine-associated chemoresistance genes (i.e., CDA and RMM2) was significantly upregulated in high-risk PC patients evaluated by the risk model. Conclusions. We constructed a risk model based on 6 KRAS-associated metabolic genes, which predicted patients’ survival with high accuracy and reflected tumor metabolic characteristics and gemcitabine-associated chemoresistance in PC.

Background: KRAS was reported to affect some metabolic genes and promote metabolic reprogramming in solid tumors. However, there is no comprehensive analysis to explore KRAS associated metabolic signature or risk model for Pancreatic cancer (PC).Methods: In current study, multiple bioinformatics analyses were used to identify differentially expressed metabolic genes based on KRAS mutation status in PC. Then we developed and validated a prognostic risk model based on the selected KRAS-associated metabolic genes. Besides, we explored the association of the risk model and the metabolic characteristics as well as Gemcitabine associated chemoresistance in PC.Results: 6 KRAS-associated metabolic genes (i.e. CYP2S1, GPX3, FTCD, ENPP2, UGT1A10, and XDH) were selected and were enrolled to establish a prognostic risk model. The prognostic model had a high C-index of 0.733 for overall survival (OS) in the TCGA pancreatic cancer database. The area under the curve (AUC) values of 1- and 3-year survival were both greater than 0.70. Then the risk model was validated in two GEO datasets and also presented a satisfactory discrimination and calibration performance. Further, we found that the expression of some KRAS-driven glycolysis associated genes (PKM, GLUT1, HK2, and LDHA) and Gemcitabine associated chemoresistance genes (i.e. CDA and RMM2) were significantly up-regulated in high-risk PC patients evaluated by the risk model.Conclusions: We constructed a risk model based on 6 KRAS associated metabolic genes, which predicts patients' survival with high accuracy and reflects tumor metabolic characteristics and Gemcitabine associated chemoresistance in PC.

Integrin β (ITGB) superfamily members have been reported to play important roles in multiple biological functions in various cancers. However, the prognostic and oncologic values of ITGB superfamily members have not been systematically investigated in pancreatic cancer (PC). In this study, the mRNA expression and biological functions of ITGB superfamily members in PC were evaluated by bioinformatic analysis. Our results demonstrated that ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were significantly associated with advanced AJCC stage and histologic grade, and worse prognosis in PC. A prognostic signature based on ITGB1, ITGB4, ITGB5 and ITGB6 showed a reliable predictive performance. Furthermore, one CpGs (cg20545410) in promoter region of ITGB1, four (cg18709893, cg15700850, cg20667796 and cg18326022) of ITGB4, two (cg10977398 and cg03518058) of ITGB5 and one (cg23008083) of ITGB6 were negatively associated with their corresponding mRNA expression, and positively associated with prognosis in PC. We also identified TFAP2A as the potential transcription factor for ITGB4, SP1 for ITGB1 and ITGB6, and FHL2 for ITGB5 and ITGB6. ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were all significantly involved in focal adhesion signalling pathway. ITGB1 and ITGB5 overexpressions also associated with up‐regulation of TGF‐β and WNT signalling pathway, whereas ITGB4 and ITGB6 overexpressions associated with up‐regulation of Notch signalling pathway. Besides, ITGB1, ITGB5 and ITGB6 overexpressions significantly correlated with immunosuppression in PC. In summary, our study investigated the multilevel prognostic and biological values of ITGB superfamily members in PC.

Background: Acute kidney injury (AKI) was defined by rapid deterioration of renal function, as a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) were considered a promising therapeutic strategy for damaged tissues repair. Platelet rich plasma (PRP) regulates stromal cells to repair tissue damage through the release of growth factors. Here we proposed a possible therapeutic use of human umbilical cord mesenchymal stem cells stimulated by platelet-rich plasma (PRP-MSCs) in glycerin-induced acute kidney injury murine model.Methods: In vivo, we constructed glycerin-induced acute kidney injury rat models. On day 1 post injury, rat received a tail vein injection of 1×106 MSCs and 1×106 PRP-MSCs. All animals were sacrificed at Day 3 after glycerin injection. In vitro, NRK-52E cells were damaged by 20% glycerol for 12 hours, after that NRK-52E incubated with MSCs and PRP-MSCs for 24 hours in transwell co-culture system, DMEM as a negative control. NRK-52E cells were harvested for apoptosis assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Then the number of MSCs exosomes stimulated by PRP was detected by confocal microscopy and Nanosight tracking analysis (NTA), PRP-MSCs-Ex (10mg/kg) and MSCs-Ex (10mg/kg) were injected intravenously, saline as control. The therapeutic effect of PRP-MSCs was evaluated by analyzing renal function (serum BUN, Creatinine), histopathological structure changes and apoptosis and proliferation of renal tubular cells. Results: In vivo and vitro studies confirmed that the PRP induced YAP nucleus expression to promoting the proliferation and reinforces the stemness of MSCs, and PRP could promoted the paracrine secretion of exosomes by MSCs to repair AKI though AKT/Rab27 pathway.Conclusions: Our results revealed that PRP stimulated MSCs paracrine pathway could effectively alleviate glycerin-induced acute kidney injury. Therefore, RPP pretreatment may be a new method to improve the therapeutic effect of MSCs.

Objective This study developed a prognosis-associated miRNA (PAM)-based risk score system to predict overall survival for pancreatic cancer. Methods We screened potential PAMs using bioinformatics technology. A risk score system integrating the PAMs was established, and the predictive value was evaluated. The targets of these PAMs were identified and functional enrichment analysis was performed. Results Seven PAMs (hsa-mir-188, hsa-mir-1301, hsa-mir-424, hsa-mir-5010, hsa-mir-584, hsa-mir-5091, and hsa-mir-3613) were identified. We also developed a risk score system, which showed a high Harrell concordance index (C-index, 0.723) for overall survival in the Cancer Genome Atlas data sets. The areas under the curve of the receiver operating characteristic curve at the 1-, 2-, and 3-year survival points were 0.718, 0.832, and 0.903, respectively. In addition, both the C-index and the areas under the curve for recurrence-free survival showed a good outcome, indicating that the system had a satisfactory predictive power. Furthermore, 49 target genes of PAMs were identified. Functional enrichment analysis revealed that these targets may be involved in various biological pathways, including the transforming growth factor β signaling pathway, Notch signaling, and downregulation of SMAD2/3. Conclusions The findings of this study suggest that the 7-miRNA-based risk score system is a promising prognostic model for pancreatic cancer.

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.