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Diabetic ischemic wound treatment remains a critical clinical challenge. Neovascularization plays a significant role in wound healing during all stages of the tissue repair process. Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds, particularly diabetic wounds in highly ischemic conditions. We previously identified a cyclic peptide LXW7 that specifically binds to integrin αvβ3 on endothelial progenitor cells (EPCs) and endothelial cells (ECs), activates vascular endothelial growth factor (VEGF) receptors, and promotes EC growth and maturation. In this study, we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY, and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix (ECM) scaffolds. We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment. When applied in an established Zucker Diabetic Fatty (ZDF) rat ischemic skin flap model, LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing, enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment. Altogether, this study provides a promising novel treatment to accelerate diabetic ischemic wound healing, thereby reducing limb amputation and mortality of diabetic patients., Graphical abstract Schematics for the fabrication of ligand modified scaffolds.Image 1, Highlights • Diabetic foot ulcers represent a significant healthcare burden. • Neovascularization plays a significant role in all stages of the wound healing process. • Endothelial progenitor cells (EPCs) have the potential to facilitate neovascularization. • LXW7-DS-SILY promoted EPC attachment and growth on ECM scaffolds in vitro. • LXW7-DS-SILY improved neovascularization and wound healing in ZDF rat ischemic model.

Herein, we reported a novel photoelectrochemical immunoassay method based on a target-triggered on/off signal of the ultra-structured Bi2O2S (BOS) photoanode system for the sensitive testing of carcinoembryonic antigen (CEA) in serum samples.

Wi-Fi device authentication is crucial for defending against impersonation attacks and information forgery attacks. Most of the existing authentication technologies rely on complex cryptographic algorithms. However, they cannot be supported well on the devices with limited hardware resources. A fine-grained device authentication technology based on channel state information (CSI) provides a noncryptographic method, which uses the CSI fingerprints for authentication since CSI can uniquely identify the devices. But long-term authentication based on CSI fingerprints is a challenging work. First, the CSI fingerprints are environment-sensitive, which means that the local authenticator should be updated to adapt to the changing channel state. Second, the local authenticator trained with old CSI fingerprints is outdated when users reconnect to the network after being offline for a long time, thus, it needs to be retrained in the access phase with new fingerprints. To tackle these challenges, we propose a CSI-based enhancing Wi-Fi device authentication protocol and an authentication framework. The protocol helps to collect new CSI fingerprints for authenticator’s training in access phase and performs the fingerprints’ dispersion analysis for authentication. In the association phase, it provides packet-level authentication and updates the authenticator with valid CSI fingerprints. The authenticator consists of an ensemble of small-scale autoencoders, which has high enough time efficiency for packet-level authentication and authenticator’s update. Experiments show that the accuracy of the framework is up to 98.7%, and the authenticator updating method can help the framework maintains high accuracy.

Herein, we reported a novel photoelectrochemical immunoassay method based on a target-triggered on/off signal of the ultra-structured Bi

Lab-based testing systems utilizing photoelectrochemical (PEC) biosensing methodologies for the ultrasensitive carcinoembryonic antigen (CEA) have been developed, although the majority have shown complicated operating procedures and dependence on precise apparatus. Herein, a portable photoelectrochemical split diagnostic platform based on a hollow CdS/CdMoO

MET exon 14 skipping (METex14) is a validated oncogenic driver in lung cancer and MET tyrosine kinase inhibitors are now available as effective clinical treatments. The majority of known METex14 alterations are typical donor/acceptor splicing or ubiquitination site mutations. Herein, two new METex14 variants were detected in two patients with lung adenocarcinoma by targeted next generation sequencing (NGS). Reverse transcription (RT)-based analysis confirmed that these mutations led to MET exon 14 skipping. Our analysis provided evidence for possible targeted therapy options for patients carrying these MET mutations or similar METex14 analogs.

Background The influence of positive microscopic margin (R1) resection on the prognosis of gastrointestinal stromal tumors (GISTs) is controversial. Tumor rupture is significantly associated with the occurrence of R1 resection and may be a confounder of R1 resection in GISTs. The present meta-analysis evaluated the real influence of R1 resection on the prognosis of GISTs by excluding the confounding effect of tumor rupture. Methods The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were searched. Studies that compared R1 with negative microscopic margin (R0) resection in GIST patients and reported the time-to-event data of recurrence-free survival (RFS) or disease-free survival (DFS) were eligible for inclusion. The quality of the observational studies was assessed using the Newcastle–Ottawa scale. Results Of the 4896 records screened, 23 retrospective studies with 6248 participants were selected. In the overall analysis, R1 resection resulted in a significantly shorter RFS/DFS than R0 resection for GISTs (HR = 1.80, 95% CI = 1.54–2.10, P Conclusions This meta-analysis shows that R1 resection did not influence the survival outcome of GISTs. Reresection may not be necessary when positive microscopic margins exist. This analysis could provide high-quality evidence for the development of guidelines.

SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is a rare primary lung malignancy. These diseases are not listed separately in the 2021 World Health Organization (WHO) classification of lung neoplasms, but they have special morphological, immunophenotypic and molecular genetic characteristics. This study aims to improve understanding of SMARCA4-dNSCLC by discussing the clinicopathological features, diagonosis and differential diagnosis of the disease.The clinical and imaging data of 9 cases of SMARCA4-dNSCLC diagnosed in Shanghai Changhai Hospital from January 2020 to March 2022 were collected. The clinicopathological features were analyzed by histological and immunohistochemical staining, and the literature was reviewed.The median age of 9 patients was 65 years old. Six men were smokers. The average maximum diameter of tumor was 3.3 cm. Six cases had been metastasized. The imaging showed that it was an infiltrating mass with unclear boundary and 3 cases invaded the pleura. Nine cases were diagnosed as SMARCA4-dNSCLC, which mainly showed three pathological forms including classic lung adenocarcinoma, mucinous adenocarcinoma and poorly differentiated carcinoma. Poorly differentiated tumor cells are epithelioid, syncytial or rhabdomyoid, the cytoplasm was rich, the cytoplasm could be completely transparent to eosinophilic, eosinophilic globules or small abscesses could be seen, showing solid flakes, with more inflammatory cells and flake necrosis in the stroma. Immunohistochemistry showed that SMARCA4 was negative in all cases and eight cases demonstrated cytokeratin 5.2 (CAM5.2) and cytokeratin 7 (CK7) was diffusely strongly positive, p40 was negative, thyroid transcription factor-1 (TTF-1) was negative in 6 cases, partially positive in 2 cases and diffusely positive in 1 case.SMARCA4-dNSCLC is a rare subtype of lung cancer with complex and diverse pathological morphology. The characteristic of immunohistochemical phenotype can assist in the diagnosis.【中文题目：伴有SMARCA4缺失的非小细胞肺癌 9例临床病理分析】 【中文摘要：背景与目的 SMARCA4缺失的非小细胞肺癌（SMARCA4-deficient non-small cell lung cancer, SMARCA4-dNSCLC）是一种罕见的原发于肺的恶性肿瘤。虽然2021版世界卫生组织（World Health Organization, WHO）肺肿瘤分类中并未将其单独列出，但这类肿瘤具有独特的形态学、免疫表型及分子遗传学特征。本研究通过探讨SMARCA4-dNSCLC的临床病理特征、免疫组化、诊断及鉴别诊断，以加深对该类肿瘤的认识。方法 收集2020年1月-2022年3月上海长海医院诊断的9例SMARCA4-dNSCLC的临床与影像学资料，通过组织学、免疫组化染色分析其临床病理特征并进行文献复习。结果 9例患者中位发病年龄65岁。6例男性均有吸烟史。肿瘤平均直径3.3 cm。6例转移。影像学提示为边界不清的浸润性肿块，3例伴胸膜侵犯。9例诊断为SMARCA4-dNSCLC，主要表现为3种病理形态，包括经典的肺腺癌、肺黏液腺癌及低分化癌。低分化肿瘤细胞上皮样、合体样或横纹肌样，胞质丰富，胞质可完全透明至嗜酸性，可见嗜酸性小球或小脓肿，呈实性片状，间质较多炎细胞及片状坏死。免疫组化显示SMARCA4均为阴性，8例细胞角蛋白（cytokeratin 5.2, CAM5.2）、细胞角蛋白7（cytokeratin 7, CK7）弥漫强阳性，P40均阴性，6例甲状腺转录因子1（thyroid transcription factor-1, TTF-1）阴性，2例部分阳性，1例阳性。结论 SMARCA4-dNSCLC是一类罕见的肺癌亚型，病理形态复杂多样，特征性的免疫组化表型可协助诊断。 】 【中文关键词：SMARCA4；肺肿瘤；病理学特征；诊断】.

BackgroundColorectal surgery is associated with a high risk of surgical site infection (SSI). In March 2017, we developed an intervention, called “PRESS”, with the aim of reducing colorectal superficial SSI. This study assessed the effect of the new intervention in reducing the rates of superficial SSI in colorectal surgery.MethodsThis study was a retrospective review of 312 PRESS+ patients compared to 171 historical control PRESS− patients who were 18 years of age or older and underwent elective colorectal surgery with clean-contaminated wounds from January 2015 to June 2020. In the PRESS+ groups, we pressed the incision downward hard with clean gauze after the interrupted suturing of the skin. Propensity score matching with 15 variables was performed in a 1:1 ratio to reduce selection bias. Univariate analysis and multivariate analysis were performed to identify risk factors associated with SSI.ResultsThe characteristics of the PRESS+ (n = 160) and PRESS− (n = 160) groups were well balanced after propensity score matching. The PRESS+ group had a lower superficial SSI rate (1.9% vs. 6.9%, P = 0.029) and a lower overall SSI rate (2.5% vs. 10.0%, P = 0.006) than the PRESS− group. Furthermore, multivariate analysis showed that the incisional press was an effective protective factor for superficial SSI (adjusted odds ratio = 0.215, 95% confidence interval = 0.057–0.818, P = 0.024). In addition, female sex (P = 0.048) and blood transfusion (P = 0.011) were demonstrated to be independent risk factors for superficial SSI.ConclusionThe incisional press after suturing is a simple, costless, and effective intervention in reducing superficial incisional SSI.

Background: Both INPP5D and INPP5F are members of INPP5 family. INPP5F rs117896735 variant was associated with Parkinson’s disease (PD) risk, and INPP5D was an Alzheimer’s disease (AD) risk gene. However, it remains unclear about the roles of INPP5F rs117896735 variant in AD. Objective: We aim to investigate the roles of rs117896735 in AD. Methods: First, we conducted a candidate variant study to evaluate the association of rs117896735 variant with AD risk using the large-scale AD GWAS dataset. Second, we conducted a gene expression analysis of INPP5F to investigate the expression difference of INPP5F in different human tissues using two large-scale gene expression datasets. Third, we conducted an expression quantitative trait loci analysis to evaluate whether rs117896735 variant regulate the expression of INPP5F. Fourth, we explore the potentially differential expression of INPP5F in AD and control using multiple AD-control gene expression datasets in human brain tissues and whole blood. Results: We found that 1) rs117896735 A allele was associated with the increased risk of AD with OR = 1.15, 95% CI 1.005–1.315, p = 0.042; 2) rs117896735 A allele could increase INPP5F expression in multiple human tissues; 3) INPP5F showed different expression in different human tissues, especially in brain tissues; 4) INPP5F showed significant expression dysregulation in AD compared with controls in human brain tissues. Conclusion: Conclusion: We demonstrate that PD rs117896735 variant could regulate INPP5F expression in brain tissues and increase the risk of AD. These finding may provide important information about the role of rs117896735 in AD.

Introduction Polygoni Multiflori Caulis (PMC) has been used as a traditional Chinese medicine for a long time in China. However, hepatotoxic events of PMC have been reported in recent years, but the potential toxic compounds have remained unclear. Dianthrones as the secondary plant metabolites were revealed to potential hepatotoxicity in a previous study. However, no reports focused on dianthrones in PMC. Objective In the quest for exploring potential hepatotoxic compounds in PMC, the aim of this work was to undertake a comprehensive characterisation of dianthrones in PMC. Methods A simple and effective macroporous absorbent resin column chromatography method was established in this study to enrich the minor dianthrones from PMC extracts. Exploration and characterisation of dianthrones in PMC was conducted by an ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) method and information dependent acquisition (IDA) mode. The aglycones of dianthrone glycosides were further verified by acid hydrolysis method. Results Seventy-two dianthrone glycosides and their five aglycones were discovered and tentatively characterised in PMC for the first time, of which 29 dianthrones were identified as potential new compounds. Dianthrone glycosides could be classified into three types according to their aglycone structures, and their fragmentation pathway rules and diagnosed ions were also summarised comprehensively. Conclusion This was the first comprehensive investigation on dianthrones in PMC. The result would help to fully understand the phytochemical constituents and toxic components in PMC, and highlight the need for further toxicological investigations of the dianthrones in PMC due to their potential hepatotoxicity correlation.

The development and supporting technologies of high-strain line pipe steel and pipes used for oil and gas pipeline projects in special geological environments (such as earthquake zone, landslide zone, mine goaf and subsidence zone) is one of the international research hotspots, and it is also a major problem that China's major oil and gas pipeline projects have to solve. Focusing on a series of key technical difficulties in the research & development and application of high-strain line pipe steel and pipes, a number of theoretical and technological innovations have been achieved after more than ten years of joint researches. And the main achievements are as follows. First, the method of applying many different parameters (e.g. stress ratio, yield to tensile ratio and uniform elongation (UEL)) to comprehensively characterize and evaluate the deformation behavior of steel pipes is proposed, and a technical index system and standard for the new products of X70HD/X80HD high-strain line pipe steel and pipes are established. Second, a complete set of X70HD/X80HD steel plate manufacturing technology is researched and developed, and the high-strain steel plate with the properties of low yield to tensile ratio, high uniform elongation, high stress ratio and high strength and toughness is worked out. Third, the X70HD/X80HD JCOE and UOE high-strain longitudinal submerged arc welded pipe manufacturing technology is researched and developed, reasonable performance matching between a steel pipe and a welding seam is realized, and the performance deterioration in the process of forming, welding, diameter-expending and thermal coating is solved. Fourth, a full-scale test device of steel pipe internal pressure + bending large deformation is independently developed, and the physical simulation based steel pipe deformation test technology is formed. X70HD/X80HD high-strain line pipe steel and pipes have been applied in the West to East Gas Pipeline, the China–Myanmar Pipeline and other major gas pipeline projects in the large scale, and their application effects are remarkable. To satisfy the new needs of pipeline construction and long-term safe operation under complex geological conditions, some suggestions were put forwarded, such as developing new methods of strain-based pipeline design, and researching and developing or improving the supporting technologies suitable for the higher matching requirements of girth weld, such as welding methods, welding materials, welding processes, and girth weld performance quality and defect control requirements.

Background The purpose of the study was to evaluate the association between microfibrillar collagen hemostat and anastomotic leakage after anterior resection. Method Between March 2015 and December 2019, a total of 203 consecutive rectal cancer patients who underwent elective anterior resection were included. Patient parameters were analyzed. The relevant risk factors were identified by univariate and multivariate analysis. Propensity score matching was performed to reduce the selection bias. Results In total, 26 (12.8%) of the 203 study patients developed clinical anastomotic leakage. The length of hospital stay was significantly prolonged by anastomotic leakage. In univariate analysis and multivariate analysis, male sex, low tumor location, and intraoperative application of microfibrillar collagen hemostat significantly increased the risk of anastomotic leakage. Furthermore, analysis after propensity score matching confirmed the independent role of microfibrillar collagen hemostat in anastomotic leakage. In addition, the median time of anastomotic leakage occurrence from the initial operation in patients with microfibrillar collagen hemostat was 9.00 days, which was significantly later than that in patients without microfibrillar collagen hemostat. Conclusion In addition to male sex and low tumor location, intraoperative application of microfibrillar collagen hemostat was demonstrated to be a significant risk factor for anastomotic leakage. This finding suggested that surgeons should be fully aware of this potential risk in anterior resection. Because of the limitation of retrospective study, however, randomized controlled trials are needed to confirm this association in the future.

Considering the low indoor positioning accuracy and poor positioning stability of traditional machine-learning algorithms, an indoor-fingerprint-positioning algorithm based on weighted k-nearest neighbors (WKNN) and extreme gradient boosting (XGBoost) was proposed in this study. Firstly, the outliers in the dataset of established fingerprints were removed by Gaussian filtering to enhance the data reliability. Secondly, the sample set was divided into a training set and a test set, followed by modeling using the XGBoost algorithm with the received signal strength data at each access point (AP) in the training set as the feature, and the coordinates as the label. Meanwhile, such parameters as the learning rate in the XGBoost algorithm were dynamically adjusted via the genetic algorithm (GA), and the optimal value was searched based on a fitness function. Then, the nearest neighbor set searched by the WKNN algorithm was introduced into the XGBoost model, and the final predicted coordinates were acquired after weighted fusion. As indicated in the experimental results, the average positioning error of the proposed algorithm is 1.22 m, which is 20.26–45.58% lower than that of traditional indoor positioning algorithms. In addition, the cumulative distribution function (CDF) curve can converge faster, reflecting better positioning performance.

LncRNA Cyclin‐dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) plays a role in the progression of multiple cancers like cholangiocarcinoma, osteosarcoma and several gastrointestinal tumors. Few studies have linked its function and mechanism to the development of colorectal cancer (CRC). The expression of CDKN2B-AS1, microRNA (miR)-378b, and cytoplasmic activation/proliferation-associated protein 2 (CAPRIN2) was analyzed in CRC patients and cell lines. The proliferation and migration of CRC cells were evaluated after gain and loss-of function mutations. Interactions between CDKN2B-AS1 and miR-378b, miR-378b and CAPRIN2 were validated by luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. The role of CDKN2B-AS1 was further confirmed in a xenograft mouse model. We found that the expression of CDKN2B-AS1 and CAPRIN2 was upregulated in CRC and they were linked to the poor differentiation and distant metastasis in CRC patients. CDKN2B-AS1 knockdown attenuated while CDKN2B-AS1 overexpression promoted CRC cell proliferation and migration. Notably, the results of Starbase 2.0 database analysis and in vitro experiments demonstrated that CDKN2B-AS1 could interact with miR-378b and regulate its expression. Furthermore, CAPRIN2 acted as a downstream target of CDKN2B-AS1/miR-378b that involved in modulating β-catenin expression in CRC cells. Upregulation of CDKN2B-AS1 contributed to CRC progression via regulating CAPRIN2 expression by binding to miR-378b. Downregulation of CDKN2B-AS1 suppressed tumor growth and Ki-67 staining in vivo that was related to the miR-378b/CAPRIN2 pathway. This study indicated that lncRNA CDKN2B-AS1 promoted the development of CRC through the miR-378b/CAPRIN2/β-catenin axis. CDKN2B-AS1 might serve as a potential and useful target in CRC diagnosis and treatment.

As the most widely consumed beverage in the world, tea has various nutritional, economic, and global cultural values. With the development of the third-generation sequencing technology, several genome sequences of tea plants have been published. These genomic data have pivotal information that is of benefit to tea plant breeders and biologists in advancing tea plant improvement and the final quality of tea products. We hereby present the integrative online database, Tea Plant Genome Database (TeaPGDB; http://eplant.njau.edu.cn/tea ), which incorporates the published genome sequences of tea plants. The current release of TeaPGDB hosts published tea plant genome data with various online tools, including JBrowse, gene search, SSR search, BLAST. TeaPGDB also contains a download server, which provides access for the download of genome-related data and rich annotation files. TeaPGDB is committed to collecting, integrating, and annotating published tea plant genome data, providing data support for research on tea plant heredity, evolution, breeding for resistance, plant improvement, and facilitating the characterization of important traits or flavor related genes in the community. Compared with other tea plant databases, this database not only contains more complete genome data and gene annotation information, but also has a user-friendly interface for researchers in the field.

Nymphanthus calcicola, a new species from Pengshui county of Chongqing, China, is described. The new species is similar to N. bodinieri (Lévl.) R.W. Bouman in morphology, but differs from the latter by its cylindrical and twisting branchlets, elliptic or lanceolate leaves that are acuminate or acute at apex and broadly cuneate to slightly round at base, inconspicuous midrib of leaf blades adaxially, triangular-subulate stipules, larger flowers (female flowers 6.5–8.0 mm in diameter and male flowers 5.5–6.5 mm in diameter), longer pedicels of male flowers (10–20 mm long), depressed globose ovary, deeply bifid stigmas and obscurely grooved fruits.

High-quality stanene films have been actively pursued for realizing not only quantum spin Hall edge states without backscattering, but also intrinsic superconductivity, two central ingredients that may further endow the systems to host topological superconductivity. Yet to date, convincing evidence of topological edge states in stanene remains to be seen, let alone the coexistence of these two ingredients, owing to the bottleneck of growing high-quality stanene films. Here we fabricate one- to five-layer stanene films on the Bi(111) substrate and observe the robust edge states using scanning tunneling microscopy/spectroscopy. We also measure distinct superconducting gaps on different-layered stanene films. Our first-principles calculations further show that hydrogen passivation plays a decisive role as a surfactant in improving the quality of the stanene films, while the Bi substrate endows the films with nontrivial topology. The coexistence of nontrivial topology and intrinsic superconductivity renders the system a promising candidate to become the simplest topological superconductor based on a single-element system.

Since 1910, omentectomy has been an essential component of radical gastrectomy for advanced gastric cancer. However, researchers have recently questioned the benefit of omentectomy in radical gastrectomy. The aim of this meta-analysis was to compare omentectomy and omentum preservation in gastrectomy for advanced gastric cancer in terms of survival outcomes and short-term outcomes.The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched. Studies that compared omentum preservation with omentectomy were included. Overall survival (OS) and relapse-free survival (RFS) were analyzed as primary outcomes.Of 3509 records screened, one randomized clinical trial and five propensity-score matched retrospective studies with 1661 patients were selected. Omentum preservation was associated with improved OS (hazard ratio [HR] = 0.757, 95% confidence interval [CI] = 0.603-0.950, P = 0.016, IBasing on the current literature, gastrectomy with omentum preservation was associated with improved OS and short-term outcomes compared with omentectomy for advanced gastric cancer. Further randomized trials are required to confirm the survival benefit of omentum-preserving gastrectomy.

AIM Surgeons have concerns whether high ligation (HL) of the inferior mesenteric artery (IMA) increases the incidence of anastomotic leakage (AL). This meta-analysis aimed to evaluate the influence of HL of the IMA on AL compared with low ligation (LL). METHODS PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases were searched. Randomized controlled trial studies that compared HL with LL of the IMA in anterior resection for rectal cancer and reported AL outcomes were eligible for inclusion. The odds ratios and mean differences were analysed by a random-effects model. Trial sequential analysis was performed to minimize the risk of random errors. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence for outcomes. RESULTS Of the 531 records screened, five randomized controlled trials with 779 patients were selected for analysis. The pooled incidence of AL was 12.1% (95% Cl 7.77-18.26) in the HL group and 9.7% (95% Cl 5.79-15.82) in the LL group (OR 1.20, 95% CI 0.77-1.87, P = 0.42). In trial sequential analysis, the cumulative Z-score curve exceeded the futility boundary, although the required information size of 1060 had not been reached. The quality of evidence was judged to be high according to the GRADE approach. CONCLUSIONS This meta-analysis shows that HL of the IMA does not increase the incidence of AL in anterior resection for rectal cancer.

Excavators are widely used at various construction sites, and they can significantly reduce difficulties during construction and improve construction efficiency. However, conventional excavators still exhibit many shortcomings. In certain construction environments that require precision, the construction accuracy cannot be guaranteed because excavators usually operate in harsh environments. Hence, they can cause potential life hazards to the drivers in certain situations. To address these issues, an excavator automatic control system is developed via retrofitting, modelling, and designing a control program for an excavator. This system can realise three working modes: manual operation, remote control operation, and automatic operation. A test prototype based on the aforementioned concept is developed and relevant experiments are performed. The results under automatic operation mode show that the automatic control system can move the excavator smoothly along the expected trajectory. The fluctuation in the operation velocity is low, and the positioning error to the target position is within 7 cm. Thus, the system can realise the desired control accuracy and satisfy other task design requirements.

Proper regulation of innate immune response is important for individual health. The NF-κB signaling pathway plays crucial roles in innate immunity and inflammation, and its aberrant activation is implicated in diverse diseases and disorders. In this study, we report that calmodulin-like 6 (CALML6), a member of the EF-hand protein family, is a negative regulator of the NF-κB signaling pathway. CALML6 attenuated TNF-stimulated phosphorylation of proteins downstream of TGF-β–activated kinase 1 (TAK1) and inhibited TAK1-induced NF-κB activation. Further studies showed that CALML6 interacted with TAK1 and recruited the deubiquitylating enzyme cylindromatosis to repress the K63-linked polyubiquitination of TAK1. CALML6 transgenic mice had higher tolerances to lethal LPS treatment in vivo. These findings suggest that CALML6 is a negative regulator of the NF-κB signaling pathway, which is important for maintaining the balance of the innate immune response.

Honey-processed Astragalus is a widely used traditional Chinese medicine that has a better effect on reinforcing "Qi" (vital energy) than the raw one. A comparative study of metabolites analysis between them in rat serum for finding the bioactive ingredients was carried out using serum pharmacochemistry and multivariate statistical analysis. The blood collection methods and time were optimized first. Then the prototypes and metabolites in serum samples after oral administration were investigated by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry integrated with principal component analysis and orthogonal partial least squares discriminant analysis. The contents of metabolites were also analyzed to evaluate the metabolic profile differences. As a result, nine prototypes and 36 metabolites were identified. Only two prototypes and 15 metabolites were different between raw and honey-processed Astragalus. Their biotransformation reactions contained the process of oxidation, demethylation, and hydrolysis in phase I and glucuronide conjugation or sulfate conjugation in phase II. Most of the detected metabolites were transformed from isoflavones and isoflavanes. Our results expand the knowledge about the influence of honey-processing on Astragalus and suggest the different curative effects between raw and honey-processed Astragalus might due to their therapeutic material discrepancy.

Paclitaxel is a powerful and effective anti-tumor drug with wide clinical application. However, there are still some limitations, including poor water solubility, low specificity, and susceptibility to drug resistance. The peptide-drug conjugates (PDCs) represent a rising class of therapeutic drugs, which combines small-molecule chemotherapeutic drugs with highly flexible peptides through a cleavable or non-cleavable linker. When this strategy is applied, the therapeutic effects of paclitaxel can be improved.In this review, we discuss the application of the PDCs strategy in paclitaxel, including two parts: the tumor targeting peptide-paclitaxel conjugates and the cell penetrating peptide-paclitaxel conjugates.Combining drugs with multifunctional peptides covalently is an effective strategy for delivering paclitaxel to tumors. Depending on different functional peptides, conjugates can increase the water solubility of paclitaxel, tumor permeability of paclitaxel, the accumulation of paclitaxel in tumor tissues, and enhance the antitumor effect of paclitaxel. In addition, due to the change of cell entry mechanism, partial conjugates can restore the therapeutic activity of paclitaxel against resistant tumors. Notably, in order to better translate into the clinical field in the future, more research should be conducted to ensure the safety and effectiveness of peptide-paclitaxel conjugates.

Ideal single-cell viscometer has remained unachieved, leaving a gap in current palette of single-cell nanotools. Information of single-cell viscosity could contribute to our knowledge of fundamental biological processes, e.g., mass diffusion, biochemical interaction, and cellular responses to many diseases and pathologies. Although advances have been made to this end, existing methods generally suffer from limitations, e.g., low spatiotemporal resolution. Here, we describe a high spatiotemporal iontronic single-cell viscometer that operates upon a patch clamp integrated with double-barreled nanopores separated by a septum of ca. 32 nm. The system enables reversible electroosmotic manipulation of the adjacent small fluid bridging two nanopores, the viscous alternation of which could be sensitively monitored by the ionic responses. In practical cellular studies, significantly, our findings reveal not only the less deviated medium viscosities than those of lysosomes and mitochondria but also the highest viscosities in the near-nuclear region than those of mitochondrion-dense and lysosome-dense regions. This work has provided an accessible single-cell viscometer and enriched the armory of single-cell nanotools.

Durian shell, a biomass waste, was simply burned and then could serve as a heterogeneous catalyst for the transesterification reaction of palm oil with methanol at room temperature. The chemical composition, structure, and morphology of the catalyst were well-characterized by XRD, BET, SEM, TEM, EDS, TGA, FT-IR, and XPS measurement. With the preparation temperature rising to 350 °C, the maximum yield of the biodiesel could reach 94.1% at room temperature, and the optimum reaction conditions were 8 wt.% catalyst, 8:1 methanol/oil molar ratio, ad 2.5 h reaction time. The characterizations results indicated that K2O and K2CO3 existed on the surface of catalyst, and a moderate amount of carbon, which acts as a carrier, attributed to the activity of the catalyst. After repeating five times, the catalyst prepared at 350 °C showed better stability than other catalysts. This might be because the incomplete combustion of the remaining carbon slowed down the loss of K to some extent.

Background: The efficacy of a traditional anticancer drug is challenged by adverse effects of the drug, including its nonspecific bio-distribution, short half-life, and side effects. Dendrimer-based targeted drug delivery system has been considered a promising strategy to increase targeting ability and reduce adverse effects of anti-cancer drugs. Objective: This study analyzed the feasibility of whether the anticancer drug 5-fluorouracil (5-FU) could be delivered by functionalized fifth-poly(amidoamine) (PAMAM) with the peptide WP05 and the acetic anhydride to the liver cancer cells, reducing the toxicity of the PAMAM and improving the targeting property of 5-FU during delivery. Methods: The functionalized PAMAM-based nanoformulation (WP05-G5.0NHAC-FUA) was fabricated through an amide condensation reaction to improve the therapeutic efficacy of 5-Fluorouracil (5-FU) in hepatocellular carcinoma (HCC). The physicochemical structure, particle size, zeta potential, stability, and in vitro release characteristics of WP05-G5.0NHAC-FUA were evaluated. In addition, the targeting, biocompatibility, anti-proliferation, and anti-migration of WP05-G5.0NHAC-FUA were investigated. The anti-tumor effect of WP05-G5.0NHAC-FUA in vivo was evaluated by constructing xenograft tumor models of human hepatoma cells (Bel-7402) implanted in nude mice. Results: The resultant WP05-G5.0NHAC-FUA displayed spherical-like nanoparticles with a size of 174.20 ± 3.59 nm. Zeta potential and the drug loading of WP05-G5.0NHAC-FUA were 5.62 ± 0.41mV and 28.67 ± 1.25%, respectively. Notably, the optimized 5-FU-loaded formulation showed greater cytotoxicity with an IC50 of 30.80 ± 4.04 μg/mL than free 5-FU (114.93 ± 1.43 μg/mL) in Bel-7402 cancer liver cells, but a significantly reduced side effect relative to free 5-FU in L02 normal liver cells. In vivo animal study further confirmed efficient tumor accumulation and enhanced therapeutic efficiency. Conclusion: The developed nanoformulation is a promising platform for the targeting delivery of 5-FU and provides a promising solution for improving the efficacy of hepatocellular carcinoma chemotherapy.

As an important component of strain-based design, the tensile strain capacity (TSC) concept has been extensively used for pipelines that experience expectable plastic strain for both installation and service. However, some stress-based designed pipelines have experienced unforeseen plastic strain in the past decade that resulted in failure. It seems that the tensile strain capacity has gradually become an important requirement for geohazard risk management and pipeline maintenance of stress-based design pipelines. The tensile strain capacity of an X80 pipeline is investigated. The assessment in this work was based on the fracture initiation–control-based limit state. This limit state corresponds to the onset of stable tearing and generally provides a reasonably conservative estimate. Besides that, factors such as wall thickness, material’s strain hardening capacity, toughness, weld strength mismatch, HAZ (heat-affected zone) softening, pipe wall thickness, high–low misalignment, and internal pressure were also investigated to construct a prediction model of the X80 vintage pipeline.

This study investigated the feasibility and efficiency of neuron-targeting hybrid placental mesenchymal stromal cell-derived extracellular vesicles (PMSC-EVs), engineered by membrane fusion with Targeted Axonal Import (TAxI) peptide modified, TrkB agonist 7,8-DHF-loaded liposomes for treatment of myelomeningocele (MMC) via intra-amniotic cavity administration. The prepared TAxI modified liposomes with 7,8-DHF were used to fuse with PMSC-EVs. Different fusion approaches were investigated and freeze-thaw-extrude method was found to be the optimal. The engineered PMSC-EVs had a uniform particle size and efficiently loaded 7,8-DHF. It also had typical markers of native EVs. Freeze-thaw-extrude process did not change the release profile of 7,8-DHF from engineered EVs compared to TAxI modified, 7,8-DHF loaded liposomes. The engineered EVs could elicit TrkB phosphorylation depending on the incorporation of 7,8-DHF while native EVs did not. The engineered EVs increased neurite outgrowth of apoptotic cortical neurons induced by staurosporine, suggesting that they exhibited neuroprotective function. In a rodent model of MMC, neuron-targeting, engineered EVs became an active targeting delivery system to MMC defect sites. Pups treated with engineered EVs had the lowest density of apoptotic cells and displayed a therapeutic outcome. The study suggests the potential use of engineered hybrid, active neuron-targeting EVs for the in utero treatment of MMC.

Honey-processed Astragalus is a dosage form of Radix Astragalus mixed with honey by a traditional Chinese medicine processing method which improves immune activity. This pharmacological activity of honey-processed Astragalus polysaccharide (HP-APS) might be due to structural changes during the honey roasting process. Previously, we have prepared and characterized HP-APS and preliminarily found its anti-inflammatory effects. However, whether the pharmacodynamic activity of HP-APS induces tumor cell apoptosis and the mechanisms responsible for the immunogenic death (ICD) have not been elucidated. Here, A549, MC38 and B16 cells were used to evaluate the cells viability, apoptosis and cell cycles, respectively. Cellular immunogenic cell death-related molecules calreticulin (CRT), Heat Shock Proteins (HSP)70, major histocompatibility complex I (MHC-I), and co-stimulator molecules CD80/CD86 were determined by flow cytometry. The extracellular ATP release was also detected. B16-OVA and MC38-OVA cells were treated with HP-APS and co-cultivated with OT1 mouse of CD3+T cells for assessment of proliferation, in mice model, and the establishment of C57BL/B6 mouse model bearing B16 cells for assessment of HP-APS the regulation of immune activity in vivo. Our results showed that HP-APS has an inhibitory effect on tumor cell proliferation, which induces tumor cell apoptosis, preventing cells-transforming from G1 phase to S phase in cell cycles. Furthermore, HP-APS could effectively increase the expression of HSP70, CRT, MHC-I, CD86, CD80 and ATP release. T cell proliferation index is significantly improved. CD3 cell proliferation in OT1 mice was significantly increased from the 4th generation to the 5th generation. Moreover, the results have also shown that HP-APS could inhibit tumor growth by increasing immune cell infiltration in the tumor tissues. In the mouse melanoma model with HP-APS treatment, the tumor weight and volume were significantly reduced, and the growth of melanoma was inhibited. CD8+ T is significantly increased. The ratio of CD4+ T and CD8+ T cells numbers are also significantly increased in mouse spleen, but it is less than PD-1 alone treatment separately. Altogether, these findings suggest that HP-APS exerts anti-tumor effects, and that its underlying mechanisms might be associated with the expression of immunogenicity cell death related molecules and the immunomodulatory effects of immune cells.

The differential constituents in leaves, stems and roots of Polygonum multiflorum Thunb. were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) and by multivariate statistical analysis. The established extraction and analysis method showed relative standard deviations (RSDs) for intra-day precision of less than 3.40%, for repeatability of less than 4.06% and for stability of less than 5.10%. Principal component analysis and orthogonal projections to latent structures discriminant analysis of the UPLC/ESI-Q-TOF-MS data showed good ability to classify the leaves, stems and roots of P. multiflorum Thunb. The differential constituents, such as stilbenes, polygoacetophenoside, flavonoids and anthraquinones, accounting for variations between the leaves, stems and roots, were filtered through the variable importance in projection values and were further identified by elemental composition analysis, mass fragmentation data and retention times of available standards. Differences between the chemical compositions in the leaves, stems and roots of P. multiflorum Thunb. were closely related to their various therapeutic effects. This UPLC/ESI-Q-TOF-MS-based analytical strategy could be further utilized to evaluate the overall quality of traditional Chinese medicines and their differences of chemical constituents in different parts of the plant and/or in the plants of different geographical locations.

It is a challenge to ascertain the quality of polysaccharides due to their complex chemical structure; therefore, multi-fingerprint profiling was used to investigate the quality of Astragalus polysaccharides (APS) harvested from Inner Mongolia (NM) and Gansu (GS) with the help of chemometric analysis. Additionally, FT-IR and 1H NMR were applied to characterize the chemical structure of the harvested APS. The spectral fingerprinting results indicated that APS had reduced similarity when they were from different origins. Further, PCA showed that NM and GS could be distinguished and that the main differences from the loading plots were in the absorption intensity of carbonyls and H1 signals of Galp and β-glucose. Moreover, UPLC/Q-TOF-MS fingerprints were established based on the monosaccharide composition of the APS. The concentration of monosaccharides and results of cluster analysis indicated that GlcA might be an indicator that can be used to distinguish NM and GS. Overall, this multiple fingerprint method was stable, comprehensive and valid for monitoring APS quality.

Due to the wide application of flux-cored arc welds (FCAW) susceptible to significant scatter in weld and Heat Affected Zone (HAZ) fracture toughness, there is an interest in methods for evaluating the reliability of welds containing defects. The mechanical properties of the FCAW girth weld of an X80 pipeline are tested and then analyzed. By obtaining fracture toughness results from a statistically significant number of SENB specimens, with notches positioned in different HAZ locations, the effect of variation within the results can be evaluated. The results of the fracture toughness tests were analyzed using statistical methods, to compare both the difference in behavior between HAZ microstructures and the variation when a similar microstructure has been sampled. The range of different characteristic toughness values was analyzed using a postulated ECA case to illustrate the sensitivity of the results to how toughness is defined. The analyses supported recommendations to be made on the optimum approach to characterizing HAZ fracture toughness for reliable pipeline assessments in multi-pass girth welds with complex HAZ microstructure distributions.

In this paper, a strain capacity assessment on high-strain marine pipe was carried out by comparing the crack growth driving force and the crack growth resistance. The crack growth driving force was given by FEA, the stress-stain relationship was given by a DIC tensile test, and the crack growth resistance was given by a single-edge notched tensile (SENT) test using a single-specimen flexibility method. The proposed approach was compared with the failure assessment curve and validated against full-scale tests with a girth weld notch. The results of the full-scale tests showed that the assessment method using FEA was more accurate and the result of the failure assessment curve assessment was more conservative.

An important step of somatic variant calling algorithms for deep sequencing data is quantifying the errors. For targeted sequencing in which hotspot mutations are of interest, site-specific error estimation allows more accurate calling. The site-specific error rates are often estimated from a panel of normal samples, which has limited size and is subject to sampling bias and variance. We propose a novel statistical validation method for single-nucleotide variation (SNV) calling based on historical data. The validation method extracts the high-quality reads from the Binary Alignment/Map (BAM) files, finds the negative samples in the data, and builds a statistical model to call individual samples. It is particularly useful in detecting low-frequency variants that may be missed by traditional panel of normal-based SNV methods. The proposed method makes it possible to launch a simple and parallel validation pipeline for SNV calling and improve the detection limit.

More and more studies indicated that extracellular vesicles (EVs) carrying miRNAs have been potential biomarkers of various cancers including colorectal cancer (CRC). This study aims to explore the function of miR-224-5p carried by EVs derived from cancer-associated fibroblasts (CAFs) in CRC. Here, we found that miR-224-5p was highly expressed while SLC4A4 was lowly expressed in CRC cells. Moreover, dual-luciferase reporter gene assay testified that miR-224-5p targeted SLC4A4. The expression of miR-224-5p in CAFs-derived EVs was found to be elevated. It was also testified that CAFs-derived EVs could transfer miR-224-5p into CRC cells. miR-224-5p in CAFs-derived EVs facilitated the proliferation, migration, invasion and anti-apoptosis of CRC cells. Overexpressing miR-224-5p increased the proliferative, migratory and invasive abilities of CRC cells and inhibit CRC cell apoptosis, while overexpressing SLC4A4 caused the opposite result. Research in vitro and in vivo further indicated that miR-224-5p promoted CRC cell progression via binding to its downstream target gene SLC4A4. Rescue assay also demonstrated that overexpressing miR-224-5p reversed the inhibitory effect of overexpressed SLC4A4 on cancer cell growth. In addition, in vivo assay identified that high level of miR-224-5p promoted the growth of cancer cells in mice in vivo. In conclusion, we explored the effect of miR-224-5p in CRC, which helps for further exploration of new methods for CRC targeted therapy.

Background: Approximately one-quarter of patients with early-stage hepatocellular carcinoma (HCC) suffer from tumor recurrence within the first year after hepatectomy. Identification of patients at high risk of recurrence and new therapeutic approaches are crucial to improve clinical outcome. This study aimed to assess the prognostic significance of miR-203 and Zinc finger E-box binding homeobox 1 (ZEB1) in early-stage HCC and explore the association between the expression of ZEB1 and miR-203 in HCC. Methods: Tissue microarray-based immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to investigate ZEB1 and miR-203 expression in 73 patients with early-stage HCC and their correlation with clinicopathological features and prognosis of patients were analyzed. The prognostic value of the two factors was also measured by public KM plotter database. Quantitative reverse transcription PCR (qRT-PCR) assays were conducted to study the relationship between miR-203 and ZEB1. Transwell assays, Cell Counting Kit-8 (CCK-8) assays were performed to detect the roles of miR-203 in migration, invasion and proliferation of HCC cells. Results: We found low expression of miR-203 was associated significantly with tumor recurrence (P

Wi-Fi device authentication is crucial for defending against impersonation attacks and information forgery attacks. Most of the existing authentication technologies rely on complex cryptographic algorithms. However, they cannot be supported well on the devices with limited hardware resources. A fine-grained device authentication technology based on channel state information (CSI) provides a non-cryptographic method, which uses the fingerprint extracted from CSI for authentication since CSI can uniquely identify the device in a limited time. But maintaining a fingerprint database for fingerprint matching is a challenging work. Firstly, the fingerprints extracted from the CSI are time-sensitive, which means that the fingerprint database must be updated in real time; Secondly, the authentication device may collect false fingerprints under the attack of identity-based attackers, which means that the authenticity of the fingerprint used to update the database must be checked. In this paper, we propose an enhancing Wi-Fi device authentication protocol based on CSI to implement the fingerprint database update and the device authentication. We provide a viable method of database update and an authentication algorithm based on Local Outlier Factor (LOF). We also present a complete authentication process. In addition, we evaluate the performance of our CSI-based authentication algorithm and database updating method. The experiments showed that the accuracy of the authentication algorithm is up to 97.1% and our database updating method can help the system maintain high accuracy.