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China's high-quality development cannot be achieved without high-quality research. As the university is an indispensable source of advanced research, analyzing the impact of university-industry collaboration (UIC) on firm performance helps us understand the significance of universities for China's economic development and innovation activities. As existing research does not pay attention to the impact of UIC on the productivity of Chinese firms, we examine the impact of such collaboration on firm productivity using natural language processing and by matching China's intellectual property and listed firms' operations databases. The empirical results show that UIC can promote firm productivity by improving the quality of their innovations, strengthening internalization efficiency, and broadening their research horizons. Moreover, the UIC process has a pronounced effect on promoting firm productivity in technology- and intellectual property-intensive industries. From the UIC perspective, we interpret China's economic development and provide new insights for developing countries regarding using universities to alleviate the insufficiency of private R&D investments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Due to the high heterogeneity of ovarian cancer (OC), it occupies the main cause of cancer-related death among women. As the most aggressive and frequent subtype of OC, high-grade serous cancer (HGSC) represents around 70 % of all patients. With the booming progress of single-cell RNA sequencing (scRNA-seq), unique and subtle changes among different cell states have been identified including novel risk genes and pathways. Here, our present study aims to identify differentially correlated core genes between normal and tumor status through HGSC scRNA-seq data analysis. R package high-dimension Weighted Gene Co-expression Network Analysis (hdWGCNA) was implemented for building gene interaction networks based on HGSC scRNA-seq data. DiffCorr was integrated for identifying differentially correlated genes between tumor and their adjacent normal counterparts. Software Cytoscape was implemented for constructing and visualizing biological networks. Real-time qPCR (RT-qPCR) was utilized to confirm expression pattern of new genes. We introduced ScHGSC-IGDC (Identifying Genes with Differential Correlations of HGSC based on scRNA-seq analysis), an in silico framework for identifying core genes in the development of HGSC. We detected thirty-four modules in the network. Scores of new genes with opposite correlations with others such as NDUFS5, TMSB4X, SERPINE2 and ITPR2 were identified. Further survival and literature validation emphasized their great values in the HGSC management. Meanwhile, RT-qPCR verified expression pattern of NDUFS5, TMSB4X, SERPINE2 and ITPR2 in human OC cell lines and tissues. Our research offered novel perspectives on the gene modulatory mechanisms from single cell resolution, guiding network based algorithms in cancer etiology field., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Hepatocellular carcinoma (HCC) represents a substantial global health burden. Tumorinfiltrating B lymphocytes (TIL-Bs) contribute to tumor progression and significantly impact the efficacy of tumor therapy. However, the characteristics of TIL-Bs in HCC and their effect on HCC therapy remain elusive. Single-cell RNA sequencing (scRNAseq) was applied to investigate the heterogeneity, cellular differentiation and cell-cell communication of TIL-Bs in HCC. Further, the Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC) and liver cancer institutes (LCI) cohorts were applied to construct and validate the plasma cell marker-based prognostic risk model. The relationship between the prognostic risk model and the responsiveness of immunotherapy and chemotherapy in patients with HCC were estimated by OncoPredict and tumor immune dysfunction and exclusion (TIDE) algorithm. Finally, we established nomogram and calibration curves to evaluate the precision of the risk score in predicating survival probability. Our data identified five subtypes of TIL-Bs in HCC, each exhibiting varying levels of infiltration in tumor tissues. The interactions between TIL-Bs and other cell types contributed to shaping distinct tumor microenvironments (TME). Moreover, we found that TIL-Bs subtypes had disparate prognostic values in HCC patients. The prognostic risk model demonstrated exceptional predictive accuracy for overall survival and exhibited varying sensitivities to immunotherapy and chemotherapy among patients with HCC. Our data demonstrated that the risk score stood as an independent prognostic predictor and the nomogram results further affirmed its strong prognostic capability. This study reveals the heterogeneity of TIL-Bs and provides a prognostic risk model based on plasma cell markers in HCC, which could prove valuable in predicting prognosis and guiding the choice of suitable therapies for patients with HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Huang, Wang, Zheng, Zhou, Kong, Huang, Zhang and Zhou.)

The realistic simulation of the dynamic responses of a moving articulated vehicle has attracted considerable attention in various disciplines, with the identification of the vehicle model being the prerequisite. To this end, a double-sensor hump calibration method (DHCM) was developed to identify both unladen and laden vehicle models, consisting of a sensor layout optimization step and a system identification step. The first step was to optimize the number and position of sensors via parameter sensitivity analysis; the second was to inversely identify the vehicle system based on sensor responses. For comparison, the DHCM and the existing single-sensor hump calibration method (SHCM) were used to calibrate a small-sized vehicle model and a multi-axle articulated vehicle model. Vertical accelerations of the vehicle models were then simulated and characterized by power spectral densities (PSDs). Validation against experimental measurements indicated that the PSDs of the models identified with the DHCM matched the measured PSDs better than those of the SHCM, i.e., the DHCM-identified model accurately simulated the dynamic response of an articulated vehicle with relative errors below 16% in the low-frequency range. Therefore, the DHCM could identify models of small-sized vehicles and multi-axle articulated vehicles, while the SHCM was only suitable for the former.

Barley is a diagnostic plant that often used in the research of soil pollution by heavy metals, our research explored the detoxification and tolerance mechanism of cadmium(Cd) in barley through pot experiment. We investigated subcellular distribution, chemical forms and oxidative damage of Cd in barley leaves, combing with the transmission electron microscopy and Fourier-transform infrared spectroscopy(FT-IR) to further understand the translocation, transformation characteristics and toxic effect of Cd in cells. The results showed that, the bioaccumulation factors in roots and shoots of barley were ranged of 4.03-7.48 and 0.51-1.30, respectively. Barley reduces the toxic effects by storing Cd in the roots and reducing its transport to the shoots. Compared to the control treatment (0 mg/kg), the percentage of Cd in the cell wall fractions of leaves in 300 mg/kg Cd treatment increased from 34.74 % to 38.41 %; the percentage of the organelle fractions increased from 24.47 % to 56.02 %; and the percentage of soluble fraction decreased from 40.80 % to 5.57 %. We found that 69.13 % of the highly toxic inorganic Cd and water-soluble Cd were converted to less toxic pectates and protein-integrated Cd (50.20 %) and undissolved Cd phosphates (18.93 %). This conversion of Cd was mainly due to its combination with -OH, -NH, -CN, -C-O-C, and -C-O-P groups. Excessive Cd induced a significant (P < 0.05) increase in the levels of peroxidase, malondialdehyde, and cell membrane permeability, which damaged the cell membrane and allowed Cd to enter the organelles. The chloroplasts and mitochondria were destroyed, and eventually the metabolism of intracellular substances was affected, resulting in symptoms of toxicity. Our research provides cellular-scale insight into the mechanisms of Cd tolerance in barley., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

As one of the main characteristics of neoplasia, metabolic reprogramming provides nutrition and energy to enhance cell proliferation and maintain environment homeostasis. Glycolysis is one of the most important components of cancer metabolism and the Warburg effect contributes to the competitive advantages of cancer cells in the threatened microenvironment. Studies show strong links between N 6 -methyladenosine (m 6 A) modification and metabolic recombination of cancer cells. As the most abundant modification in eukaryotic RNA, m 6 A methylation plays important roles in regulating RNA processing, including splicing, stability, transportation, translation and degradation. The aberration of m 6 A modification can be observed in a variety of diseases such as diabetes, neurological diseases and cancers. This review describes the mechanisms of m 6 A on cancer glycolysis and their applications in cancer therapy and prognosis evaluation, aiming to emphasize the importance of targeting m 6 A in modulating cancer metabolism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

EZY-1 is an antifibrosis peptide purified from Eucheuma. In this study, we explored the acute toxicology of EZY-1 and the signaling pathways involved in its antifibrotic role. The mouse model of pulmonary fibrosis was induced by bleomycin. Pathological changes in lung tissue could be effectively inhibited by EZY-1. Acute toxicity and cell proliferation tests indicated that EZY-1 had no apparent toxicity to mice and cells. We identified proteins that could bind directly to EZY-1 in vitro on the basis of liquid chromatography-tandem mass spectrometry and bioinformatics analysis. EZY-1 inhibited pulmonary fibrosis via Wnt/β-catenin, transforming growth factor (TGF)-β/Smad, phosphoinositide 3-kinase/protein kinase B/ mammalian target of rapamycin, and activator of transcription 3 and Janus kinase 2/signal transducer pathways. A transwell micropore experiment showed that EZY-1 could inhibit cell migration and invasion. Western blotting analysis on transforming growth factor-β1 (TGF-β1)-induced A549 pulmonary fibrosis cell model suggested that EZY-1 could downregulate p-Smad3 (Ser423/Ser425), Smad4, β-catenin, vimentin, and N-cadherin expression. ELISA showed that EZY-1 could inhibit collagen-I secretion. EZY-1 alleviated idiopathic pulmonary fibrosis (IPF) through regulating TGF-β/Smad pathways, epithelial-mesenchymal transition processes, and collagen secretion, which provides a potential foundation for theoretical development of EZY-1 as a potential drug against IPF. PRACTICAL APPLICATIONS: We isolated a new 16-amino-acid peptide derived from the polypeptide extract of Eucheuma, named EZY-1. In vitro and in vivo assays show peptide EZY-1 is safe. The EZY-1 peptide alleviates IPF at lower doses than pirfenidone. EZY-1 alleviated idiopathic pulmonary fibrosis (IPF) through regulating TGF-β/Smad pathways, epithelial-mesenchymal transition (EMT) processes, and collagen secretion, which provides a theoretical basis for the development of EZY-1 as a potential drug against IPF., (© 2022 Wiley Periodicals LLC.)

We propose a new video vectorization approach for converting videos in the raster format to vector representation with the benefits of resolution independence and compact storage. Through classifying extracted curves in each video frame into salient ones and non-salient ones, we introduce a novel bipartite diffusion curves (BDCs) representation in order to preserve both important image features such as sharp boundaries and regions with smooth color variation. This bipartite representation allows us to propagate non-salient curves across frames such that the propagation, in conjunction with geometry optimization and color optimization of salient curves, ensures the preservation of fine details within each frame and across different frames, and meanwhile, achieves good spatial-temporal coherence. Thorough experiments on a variety of videos show that our method is capable of converting videos to the vector representation with low reconstruction errors, low computational cost, and fine details, demonstrating our superior performance over the state of the art. We also show that, when used for video upsampling, our method produces results comparable to video super-resolution.

Background: The mechanism through which death-associated protein kinase 1 (DAPK1) causes hepatocellular carcinoma (HCC) progression remains unclear. In this study, we aimed to identify key proteins that were altered after DAPK1 knockout., Methods: Stable DAPK1 knockout HCC cell lines were established, then the differentially expressed genes (DEGs) of HCC were screened using the NetworkAnalyst database and enriched using the Metascape software. Protein-protein interaction networks (PPIs) were analyzed and visualized using the STRING database expansion., Results: In total, 732 differentially expressed genes were identified, including 415 upregulated genes and 317 downregulated genes. Through Cytoscape software scoring, 10 pivotal genes were found to be closely related to changes in DAPK1 expression; Kininogen-1 (KNG1), Complement C3 (C3), Metalloproteinase inhibitor 1 (TIMP1), and Alpha-2-HS-glycoprotein (AHSG) were the most strongly associated with DAPK1 expression changes. Moreover, western blot analysis results revealed that changes in the levels of proteins encoded by the four key genes after DAPK1 knockout were consistent with those seen in the database screening., Conclusions: These results provide a direction for further studies on the DAPK1 gene and on the mechanism through which DAPK1 leads to hepatocellular carcinoma development., Competing Interests: The authors declare there are no competing interests., (©2022 Li et al.)

Background: The use of standard cytotoxic chemotherapy seems to have reached a "treatment plateau". The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC., Methods: According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted., Results: The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001)., Conclusion: Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Activation of Adenosine 5'-monophosphate-activated protein kinase/Sirtuin1 (AMPK/SIRT1) exerts an effect in alleviating obesity and gut damage. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, has been reported to activate AMPK. This study was to investigate the effect of SNP on HFD induced gut dysfunction and the mechanism., Methods: SNP was applied on lipopolysaccharide (LPS) stimulated Caco-2 cell monolayers which mimicked intestinal epithelial barrier dysfunction and HFD-fed mice which were complicated by gut dysfunction. Then AMPKα/SIRT1 pathway and gut barrier indicators were investigated., Results: SNP rescued the loss of tight junction proteins ZO-1 and occludin, the inhibition of AMPKα/SIRT1 in LPS stimulated Caco-2 cell monolayers, and the effects were not shown when AMPKa1 was knocked-down by siRNA. SNP also alleviated HFD induced obesity and gut dysfunction in mice, as indicated by the decreasing of intestinal permeability, the increasing expression of ZO-1 and occludin, the decreasing levels of pro-inflammatory cytokine IL-6, and the repairing of gut microbiota dysbiosis. These effects were complicated by the increased colonic NO content and the activated AMPKα/SIRT1 signaling., Conclusions: The results may imply that SNP, as a NO donor, alleviates HFD induced gut dysfunction probably by activating the AMPKα/SIRT1 signaling pathway., (© 2021. The Author(s).)

Introduction: Polycystic ovary syndrome (PCOS) is caused by the hormonal environment in utero, abnormal metabolism, and genetics, and it is common in women of childbearing age. A large number of studies have reported that lncRNA is important to the biological process of cancer and can be used as a potential prognostic biomarker. Thus, we studied lncRNAs' roles in PCOS in this article., Methods: We obtained mRNAs', miRNAs', and lncRNAs' expression profiles in PCOS specimens and normal specimens from the National Biotechnology Information Gene Expression Comprehensive Center database. The EdgeR software package is used to distinguish the differentially expressed lncRNAs, miRNAs, and mRNAs. Functional enrichment analysis was carried out by the clusterProfiler R Package, and the lncRNA-miRNA-mRNA interaction ceRNA network was built in Cytoscape plug-in BiNGO and Database for Annotation, Visualization, and Integration Discovery (DAVID), respectively., Results: We distinguished differentially expressed RNAs, including 1087 lncRNAs, 14 miRNAs, and 566 mRNAs in PCOS. Among them, 410 lncRNAs, 11 miRNAs, and 185 mRNAs were contained in the ceRNA regulatory network. The outcomes from Gene Ontology (GO) analysis showed that the differentially expressed mRNAs (DEMs) were mainly enriched in response to the maternal process involved in female pregnancy, morphogenesis of embryonic epithelium, and the intracellular steroid hormone receptor signaling pathway. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis data showed that DEMs were primarily enriched in pathways related to the TGF- β signaling pathway, Type I diabetes mellitus, and glycolysis/gluconeogenesis. In addition, we chose NONHSAT123397, ENST00000564619, and NONHSAT077997 as key lncRNAs due to their high bearing on PCOS., Conclusion: ceRNA networks play an important role in PCOS. The research indicated that specific lncRNAs were related to PCOS development. NONHSAT123397, ENST00000564619, and NONHSAT077997 could be regarded as potential diagnostic mechanisms and biomarkers for PCOS. This discovery might provide more effective and more novel insights into the mechanisms of PCOS worthy of further exploration., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yuanqi Li and Yong Tan.)

Background: There are no effective preoperative diagnostic measures to predict the probability of left and right recurrent laryngeal nerve (RLN) lymph node (LN) metastasis using preoperative clinical data in patients undergoing thoracolaparoscopic esophagectomy with cervical anastomosis., Methods: We retrospectively reviewed the clinical data of 1,660 consecutive patients with thoracic esophageal cancer who underwent esophagectomy with cervical anastomosis at the Department of Thoracic Surgery at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2020., Results: A total of 299 and 343 patients who underwent left (Cohort 1) and right (Cohort 2) RLN LN dissection were included in the final analyses. The analyses were conducted within each cohort. Among the 299 patients in Cohort 1, left RLN LN involvement was found in 41 patients (13.7%). A multivariable analysis showed that age, tumor location, and short axis were significantly associated with RLN LN metastasis (all P<0.05). Among the 343 patients in Cohort 2, right RLN LN involvement was found in 65 patients (19.0%). A multivariable analysis showed that computed tomography (CT) appearance, tumor location, long axis, and short axis were significantly associated with RLN LN metastasis (all P<0.05). Based on the results of the multivariable analyses, we constructed nomograms that could estimate the probability of RLN LN metastasis. Finally, we stratified the 2 cohorts into risk subgroups using a recursive partitioning analysis (RPA). The risk of left and right RLN LN metastasis was found to be 9.3% and 7.5%, 27.3% and 21.4%, and 52.4% and 47.3% for the low-risk, intermediate-risk, and high-risk groups, respectively., Conclusions: Our nomograms and RPAs appear to be suitable for the risk stratification of left and right RLN LN metastasis in patients undergoing thoracolaparoscopic esophagectomy with cervical anastomosis. This tool could be used to help clinicians to select more effective locoregional treatments, such as surgical protocols and radiation area selection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2374). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Previous studies have demonstrated the ubiquitin-proteasome inhibitor bortezomib (BTZ) can effectively alleviate hypoxia-induced pulmonary hypertension (HPH) by suppressing the intracellular calcium homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Further evaluation showed that the antiproliferation roles of BTZ are mainly mediated by inhibition of the intracellular calcium homeostasis. Caveolin-1 belongs to one of the key regulators of the intracellular calcium homeostasis in PASMCs, which can regulate the store-operated calcium entry (SOCE). However, the effects of BTZ on Caveolin-1 remain unclear., Methods: Primarily cultured human PASMCs were used as the cell model. CCK-8 assay was performed to assess the PASMCs proliferation. Western blotting and real-time qPCR were used to detect the mRNA and protein expressions. Fura-2-based fluorescence imaging experiments were used to determine the intracellular calcium concentration ([Ca 2+ ] i ). The protein synthesis inhibitor cycloheximide (CHX) was utilized to determine the protein degradation process., Results: Firstly, in cultured human PASMCs, treatment of BTZ for 24 or 60 hours significantly downregulates Caveolin-1 at both mRNA and protein levels. Secondly, in the presence CHX, BTZ treatment also leads to downregulated protein expression and fastened protein degradation of Caveolin-1, indicating that BTZ can promote the Caveolin-1 protein degradation, other than the BTZ on Caveolin-1 mRNA transcription. Then, BTZ significantly attenuates the hypoxia-elevated baseline [Ca 2+ ] i , SOCE, and cell proliferation., Conclusion: We firstly observed that the ubiquitin-proteasome inhibitor BTZ can inhibit the Caveolin-1 expression at both mRNA transcription and protein degradation processes, providing new mechanistic basis of BTZ on PASMC proliferation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Chao Wang et al.)

Cisplatin has strong broad-spectrum anticancer activity and is one of the most effective anticancer drugs currently used. The clinical application of cisplatin has led to the resistance of cancer cells to cisplatin. Tachyplesin is an active, natural marine peptide with antitumour activity. In the present study, we investigated whether tachyplesin can be used in non-small cell lung cancer (NSCLC) A549 and H460 cells as well as the cisplatin-resistant human A549/DDP NSCLC cell line. The results revealed that tachyplesin treatment significantly inhibited proliferation and induced apoptosis in A549 and H460 cells and the combination of tachyplesin and cisplatin significantly suppressed migration and improved sensitivity to cisplatin in A549/DDP cells. Further mechanistic examination revealed that tachyplesin induced apoptosis in A549/DDP cells by increasing Fas, FasL and p-RIPK1 levels. These results indicated that tachyplesin induces lung cancer death by activating the Fas, mitochondrial and necroptosis pathways. Tachyplesin could be developed as a candidate drug for cisplatin-resistant NSCLC., (© 2020 John Wiley & Sons A/S.)

Background and Aims: Heller myotomy (HM) is considered the standard surgical treatment for patients with achalasia. However, approximately 10% to 20% of patients with achalasia have persistent or recurrent symptoms after HM that require further therapy. Several studies have reported the outcomes of peroral endoscopic myotomy (POEM) in these patients. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of POEM in patients with achalasia with previous HM., Methods: An electronic literature search of PubMed, Embase, and the Cochrane Library was conducted up to January 31, 2020. Studies evaluating the outcomes of POEM in patients with achalasia with previous HM were eligible for inclusion. The primary outcomes were the pooled rates of clinical success (defined as post-POEM Eckardt score ≤3), mean change in Eckardt score, lower esophageal sphincter pressure, and integrated relaxation pressure (IRP). The secondary outcomes were procedure-related adverse events (AEs) and incidence of postoperative GERD., Results: A total of 9 studies involving 272 patients with achalasia were recruited in this review. POEM was successfully performed in 270 (99.3%) patients after previous HM. Clinical success was achieved in 90.0% (95% confidence interval [CI], 83.1%-96.8%) of patients. Eckardt score, lower esophageal sphincter pressure, and IRP were significantly lowered by 5.14 (95% CI, 4.19-6.09), 12.01 mm Hg (95% CI, 6.74-17.27), and 10.02 mm Hg (95% CI, 4.95-15.09), respectively. The pooled rates of postoperative symptomatic reflux, esophagitis, and abnormal pH monitoring were 36.9% (95% CI, 20.7%-53.1%), 33.0% (95% CI, 9.6%-56.4%), and 47.8% (95% CI, 33.4%-62.2%), respectively. Substantial heterogeneity was detected across all outcome measurements. Most of the AEs were self-limiting or managed conservatively., Conclusions: POEM is a safe and effective treatment for patients with achalasia with previous HM. Further data from prospective, controlled studies with long-term follow-up are needed to confirm these findings., (Copyright © 2021. Published by Elsevier Inc.)

Native tissues such as nerve bundles, blood vessels and tendons have extracellular matrices with a characteristic linear orientation, which cannot be fully achieved with the current technology for the development of regenerative biomaterials. In this study, bioactive and oriented collagen filaments have been fabricated using a combination of wet-spinning and carbodiimide-based crosslinking. The wet-spinning techniques, including extrusion and collection rates, and their influences on collagen filaments were studied and optimized. The diameter of the attained collagen filaments can be adjusted ranging from 30 μm to 650 μm. Further characterizations, such as circular dichroism, scanning electron microscopy, small-angle X-ray scattering and Fourier transform infrared spectra analysis, showed that the native structure of the collagen was greatly preserved after the filament preparation process. The measurements of weight swelling ratio and degradation rate indicate that the crosslinking method can efficiently regulate the physico-chemical properties of collagen filaments, including water absorption and degradation behaviors. In particular, the mechanical strength of collagen filaments can be greatly improved via crosslinking. In addition, cells can adhere and spread on collagen filaments in well-aligned patterns, showing appropriate biological features. It can be concluded that the bioactive collagen filaments with tunable properties are preferable for developing tissue engineering scaffolds with characteristic orientation features. With further study of the interactions between collagen filaments and cells, this work may shed light on the development of collagen based biomaterials that would be beneficial in the field of tissue engineering.

Laser speckle contrast imaging (LSCI) is a high-resolution full-field optical technique for measuring blood flow, which has been widely used in clinical and biomedical research. However, most of the current LSCI instruments are bulky, limiting their application settings. In this work, we proposed a prototype system of portable laser speckle imager. Different from the desktop laser speckle systems that utilize personal computer (PC), our system was designed with embedded GPU system (Jetson TX2, NVIDIA, USA) and a LCD touch screen (16.5 × 12.4 cm in size, 380 g in weight). In-vivo experiments showed that the portable GPU-based system had comparable performance with our laboratory LSCI system. Such a portable LSCI imager could be potentially used in a situation that requires for easy operation and installation, such as intraoperative monitoring or bedside diagnosis.

Hydrogels, which provide three-dimensional (3D) niches for encapsulating bone marrow mesenchymal stem cells (BMSCs), are becoming a promising tissue engineering solution for chondrogenic differentiation of BMSCs. However, it remains a challenge to design a hydrogel material for effective chondrogenesis of BMSCs because of the complexity of cartilage ECM and cell-matrix interactions. Thus far, various studies have shown the physical-chemical cues of hydrogel materials to impact BMSCs chondrogenesis, but the design of the 3D network microstructure of the hydrogel to induce BMSCs chondrogenesis is still far from optimized. In this study, we successfully prepared two types of collagen hydrogels, namely, the fibrous network and porous network, with the same chemical composition and similar mechanical strength but with two distinct network microstructures. The two different network microstructures significantly influenced mass transfer, protein adsorption, degradability, and contraction of the collagen hydrogels. Moreover, the cells presented distinct proliferation and morphology in the two hydrogels, which consequently modulated chondrogenic differentiation of BMSCs derived from rat. Collagen hydrogels with a fibrous network promoted more chondrogenic differentiation of BMSCs without additional growth factors in vitro and subcutaneous implantation in vivo than those with a porous network. Moreover, fibrous network resulted in less ECM calcification than porous network. However, the fibrous network could not prevent hypertrophy of the chondrogenic cells induced by BMSCs. Overall, these results revealed that the 3D network microstructure of a hydrogel was a key design parameter for the chondrogenic differentiation of BMSCs. STATEMENT OF SIGNIFICANCE: Hydrogels had been used to induce the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in cartilage tissue engineering, but the key design parameters remain unoptimized. This was mainly due to the different material properties including composition, strength, and microstructure, which would interplay with each other and result in difficulties to investigate the effects for one factor. In this study, we fabricated two collagen hydrogels with the same chemical composition and mechanical strength, but two distinct network microstructures. The effects of the two network microstructures on the chondrogenic differentiation of BMSCs were investigated by in vitro and in vivo assays. The results highlight the effects of network microstructures and provide important information about optimizing the design of future hydrogels in cartilage tissue engineering., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

This paper explores the mass transfer mechanism of microvias electroforming under ultrasonic agitation by numerical simulations and electrochemical experiments. Firstly, the velocity distribution of electroforming solution inside the microvias under ultrasound treatment is simulated by COMSOL Multiphysics software. The ultrasonic frequency is that of 120 kHz. The ultrasonic powers are 100 W, 200 W, 300 W and 400 W, respectively. The simulation results indicate that the mean liquid velocity inside the microvias increases with the increasing of acoustic power. In addition, under a certain ultrasonic power, the mean liquid velocity will decrease with increasing the distance between microvias and transducer, the aspect ratio of microvias and the distance between cathode and central position. Secondly, electrochemical experiments are presented to investigate the effect of ultrasonic agitation on the electrode kinetics of microvias electroforming. It is found that ultrasonic treatment decreases the thickness of diffusion layer, increases the limiting diffusion current densities and further enhances the mass transfer of microvias electroforming. Compared with the silent condition, the diffusion layer thicknesses with the acoustic power of 100 W, 200 W, 300 W, 400 W are decreased by 50.0%, 64.1%, 69.3% and 74.5%, respectively. Finally, according to the results above, the 200 × 200 metal micro-column array structures are fabricated by ultrasonic electroforming under the condition of 120 kHz and 200 W. The metal micro-column is 250 μm high and has a diameter of 80 μm. The results show that ultrasonic electroforming can enhance the mass transfer of microvias electroforming, and further solve the problem of porous structure in electroforming layer. This work contributes to expanding the application of ultrasonic agitation in the microvias electroforming., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Tumor is the most serious threat to human beings. Although war against cancer has been launched over forty years, cancer treatment is still far away from being satisfactory. Immunotherapy, especially checkpoint blockade immunotherapy, is a rising star that shows a promising future. To fulfill the requirement of depleting primary tumor and inhibiting tumor metastasis and recurrence, many researchers combined checkpoint blockade immunotherapy with other treatment strategies to extend the treatment outcome. Photodynamic therapy could induce immunogenic cell death, and checkpoint blockade could further accelerate the immunity; therefore, combining these two strategies publishes many papers. Additionally, photothermal therapy and immunotherapy were also utilized for combining with checkpoint blockade, which were also reviewed in this paper. Furthermore, antibodies, siRNA, and small molecule inhibitors are developed to block the checkpoint; therefore, we categorized the papers into three sections, combination nanoparticles with checkpoint blockade antibody, combination nanoparticles with checkpoint blockade siRNA, and combination nanoparticles with small molecule checkpoint inhibitors, and related researches were summarized. In conclusion, the combination nanoparticle with checkpoint blockade cancer immunity is a promising direction that may fulfill the requirement of cancer treatment.

Brain plasticity after amputation is related to the short-term unmasking of latent synapses as well as the long-term reorganization due to the sprouting new synaptic connections. The cortical functional reorganization has been reported along the intact somatosensory pathway after unilateral deafferentation. Cerebral blood flow (CBF) change serves as an important biomarker of the functional reorganization of brain. Using laser speckle contrast imaging (LSCI) technology, we performed a longitudinal study to unveil the cortical functional reorganization after forelimb amputation in rodent model, particularly along the intact somatosensory pathway. Our results showed that the CBF response to electrical stimulation of the intact forepaw increased significantly at 9 hours after amputation in acute stage. While in chronic stage (>14 days), the CBF response showed a pattern similar to the control group. The results showed the dynamic brain functional response along the intact somatosensory pathway at different stages after amputation and indicated that cortical functional reorganization occurred within the acute stage. Our work provided additional insights in understanding the inter-hemispheric functional changes from acute to chronic stages of amputation.

Lung cancer is the leading cause of cancer-related death and cigarette smoking is the main risk factor for lung cancer. Circulating microRNAs (miRNAs) are considered potential biomarkers of various cancers, including lung cancer. However, it is unclear whether changes in circulating miRNAs are associated with smoking and smoking-related lung cancer. In this study, we determined the serum miRNA profiles of 10 nonsmokers, 10 smokers, and 10 lung-cancer patients with miRCURY LNA microRNA arrays. The differentially expressed miRNAs were then confirmed in a larger sample. We found that let-7i-3p and miR-154-5p were significantly downregulated in the sera of smokers and lung-cancer patients, so the serum levels of let-7i-3p and miR-154-5p are associated with smoking and smoking-related lung cancer. The areas under receiver operating characteristic curves for let-7i-3p and miR-154-5p were approximately 0.892 and 0.957, respectively. In conclusion, our results indicate that changes in serum miRNAs are associated with cigarette smoking and lung cancer and that let-7i-3p and miR-154-5p are potential biomarkers of smoking-related lung cancer.

MicroRNAs (miRNAs) are small RNA molecules that regulate posttranscriptional gene expression. Previous research has suggested that aberrant miRNA expression often plays a critical role in many types of cancer, including lung cancer. However, the exact miRNAs that are involved in pulmonary carcinogenesis remain unclear. We investigated the miRNA-based molecular changes that occur in urethane-induced carcinogenicity and identified specific miRNA deregulation in pulmonary carcinogenesis induced by urethane. In this study, we used a lung cancer model in which Balb/c mice were exposed to urethane via ip injection once a week for four consecutive weeks. The mice were then killed in weeks 6, 12, or 24. Two small RNA libraries were constructed with the total RNA from the lung tumor and normal adjacent lung tissues of the urethane-injected mice collected in week 24. Using Solexa sequencing, we identified a plethora of differentially expressed miRNAs and predicted nine novel miRNAs. Further analysis demonstrated the sustainable downregulation of miR-1a in the lung tissues in lung carcinogenesis induced by urethane. The levels of miR-1a were also reduced in the serum. Our findings indicate that urethane exposure alters the expression of a cluster of miRNAs. The simultaneous downregulation of miR-1a in lung tissues and serum in urethane-induced pulmonary carcinogenesis suggests that miR-1a is associated with tumorigenesis.

The alteration of microRNA (miRNA) expression plays an important role in chemical carcinogenesis. Presently, few reports have been published that concern the significance of circulating miRNAs in lung carcinogenesis induced by environmental carcinogens. The purpose of this study was to identify serum miRNAs that could be associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Male F344 rats were systemically administered with NNK. The rat serum differential expression profiles of miRNAs were analyzed by small RNA solexa sequencing. Using quantitative real-time PCR, the differentially expressed serum miRNAs were identified in each individual rat. Serum miR-206 and miR-133b were selected for further identification in rat serum at different stages of lung carcinogenesis; we detected the levels of serum miR-206 and miR-133b in lung cancer tissues induced by NNK. NNK causes significant alteration of serum miRNA expression. Compared to the control group, serum miR-206 and miR-133b were significantly up-regulated in the early stage of NNK-induced lung carcinogenesis. miR-206 and miR-133b exhibited low-expression in lung cancer tissues. Our results demonstrate that lung carcinogen NNK exposure changes the expression of serum miRNAs. Serum miR-206 and miR-133b could be associated with lung carcinogenesis induced by NNK., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aberrant expression of microRNA (miRNA) has been previously demonstrated to play an important role in a wide range of cancer types and further elucidation of its role in the mechanisms underlying tumorigenesis, anticarcinogenesis and potential chemotherapeutics is warranted. We chose the anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-transformed human bronchial epithelial cell line 16HBE-T to study miRNAs involved in anticarcinogenesis. In resveratrol-treated cells, we found that miR-622 was upregulated, whereas it was downregulated in 16HBE-T cells, suggesting that miR-622 potentially acts as a tumor suppressor. Increasing the level of miR-622 by transient transfection-induced inhibition of proliferation and G(0) arrest in 16HBE-T cells and the lung cancer cell line H460 as demonstrated by cell viability and cell cycle analysis. MiR-622 dramatically suppressed the ability of 16HBE-T cells to form colonies in vitro and to develop tumors in nude mice. According to bioinformatics analysis, K-Ras messenger RNA was predicted as a putative miR-622 target; this was confirmed by western blot and luciferase reporter assays. Cell growth retardation was inhibited upon knockdown of K-Ras and an increase in the level of miR-622 in 16HBE-T cells. Furthermore, miR-622 inhibitor partially impaired the growth of 16HBE-T cells as demonstrated by luciferase reporter activity and K-Ras protein expression in 16HBE-T cells. In summary, miR-622 functions as a tumor suppressor by targeting K-Ras and impacting the anticancer effect of resveratrol. Therefore, miR-622 is potentially useful as a clinical therapy. MiR-622 impacts the K-Ras signal pathway and the potentially anticarcinogenic or chemotherapeutic properties warrant further investigation.

Growing evidence indicates that the alteration of microRNA (miRNA) expression in tumors that is induced by chemical carcinogens plays an important role in tumor development and progression. However, the mechanism underlying miRNA involvement in lung carcinogenesis induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti-BPDE) remains unclear. In our study, we used the malignant transformation of human bronchial epithelial cells (16HBE-T) induced by anti-BPDE to explore the mechanisms of human lung carcinogenesis. We found that expression of miR-506 was reduced in 16HBE-T transformed malignant human bronchial epithelial cells compared with 16HBE normal human bronchial epithelial cells. Restoration of miR-506 in 16HBE-T cells led to a decrease in cell proliferation, G0/G1 phase cell cycle arrest, as well as significantly suppressed anchorage-dependent growth in vitro and tumor growth inhibition in a nude mouse xenograft model. In addition, we provided novel evidence regarding the role miR-506 potentially plays in negatively regulating the protein and mRNA expression level of N-Ras in cancer cells. Together, these findings revealed that miR-506 acts as an anti-oncogenic miRNA (anti-oncomir) in malignantly transformed cells. The identification of tumor suppressive miRNAs could provide new insight into the molecular mechanisms of chemical carcinogenesis., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)