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Silver carp (Hypophthalmichthys molitrix) can filter the carbon in the food taken up by phytoplankton and plays an important role in carbon fixation. In this study, the faeces of silver carp, the dominant fish species in Qiandao Lake, China, were collected and subjected to a closed incubation and transformation experiment for three months. The physical and chemical indices of water and sediment mixture, carbon metabolic enzyme activity, and microbial sequences were analyzed to identify the key microbial strains that affect carbon transformation as well as the main factors influencing carbon transformation. The results showed maximum CO 2 and CH 4 emission fluxes on day 15 of fish faeces and sediment interaction. In the faeces addition group, the contents of soluble organic carbon, soluble inorganic carbon, SO 4 2- , and PO 4 3- were significantly increased, while the dissolved oxygen content was significantly decreased. Furthermore, the pH, total carbon content, volatile suspended solids content, and activities of four carbon-metabolizing enzymes were significantly increased in the faeces addition group. The 16sRNA analysis of methanogenic and methane-oxidizing bacteria showed that Euryarchaea and Pseudomonas accounted for the highest proportion respectively. The most significant differences expression were found for Methylbacterium in the methanogenic bacteria and Methylobacter in the methane oxidizing bacteria. Structural variance model showed that interaction of fish faeces and sediments mainly caused changes in sulfate content, leading to variations in methanogens and methanotrophs and promotion of CH 4 emission. The results of this study can provide a theoretical reference for the mechanism of carbon reduction and emission reduction of lake filter-feeding fish., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Effects of filter-feeding fish feces on microbial driving mechanism of lake sediment carbon transformation”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Myxoid liposarcoma (MLPS) of the parotid gland is very rare, and only a few cases have been reported worldwide. It can be difficult to diagnose this disease when there is only a single lesion in the patient's body. A 56-year-old man was diagnosed with an MLPS in the left calf and was treated with wide resection. Two months after the surgery, a painless mass appeared in the man's left parotid gland area. Both fine-needle aspiration biopsy before surgery and intraoperative frozen sections suggested that the tumor was likely to be a pleomorphic adenoma. Both parotid ultrasound and CT indicated the same result. However, this mass was confirmed to be metastasis of MLPS through immunohistochemistry and multicolor fluorescence in situ hybridization. The authors report a case in which an MLPS metastasized to the parotid gland; this type of lesion is extremely rare and highly worthy of consideration because the authors misdiagnosed it., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

Background: Triple-negative breast cancer (TNBC) is a malignant tumor without specific therapeutic targets and a poor prognosis. Chemotherapy is currently the first-line therapeutic option for TNBC. However, due to the heterogeneity of TNBC, not all of TNBC patients are responsive to chemotherapeutic agents. Therefore, the demand for new targeted agents is critical. β-tubulin isotype III (Tubb3) is a prognostic factor associated with cancer progression, including breast cancer, and targeting Tubb3 may lead to improve TNBC disease control. Shikonin, the active compound in the roots of Lithospermun erythrorhizon suppresses the growth of various types of tumors, and its efficacy can be improved by altering its chemical structure., Purpose: In this work, the anti-TNBC effect of a shikonin derivative (PMMB276) was investigated, and its mechanism was also investigated., Study Design/methods: This study combines flow cytometry, immunofluorescence staining, immunoblotting, immunoprecipitation, siRNA silencing, and the iTRAQ proteomics assay to analyze the inhibition potential of PMMB276 on TNBC. In vivo study was performed, Balb/c female murine models with or without the small molecule treatments., Results: Herein, we screened 300 in-house synthesized analogs of shikonin against TNBC and identified a novel small molecule, PMMB276; it suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase, suggesting that it could have a tumor suppressive role in TNBC. Tubb3 was identified as the target of PMMB276 using proteomic and biological activity analyses. Meanwhile, PMMB276 regulated microtubule dynamics in vitro by inducing microtubule depolymerization and it could act as a tubulin stabilizer by a different process than that of paclitaxel. Moreover, suppressing or inhibiting Tubb3 with PMMB276 reduced the growth of breast cancer in an experimental mouse model, indicating that Tubb3 plays a significant role in TNBC progression., Conclusion: The findings support the therapeutic potential of PMMB276, a Tubb3 inhibitor, as a treatment for TNBC. Our findings might serve as a foundation for the utilization of shikonin and its derivatives in the development of anti-TNBC., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Pyrolysis technology is considered one of the most promising processes for the environmentally friendly disposal of sewage sludge (SS), as it can neutralize pathogens, reduce hazardous substances, and promote the immobilization of heavy metals. However, nitrogen-containing gases produced in SS pyrolysis can be converted to nitrogen oxides, causing serious environmental pollution. In this study, we investigated the evolution of the nitrogen (N) element in rapid pyrolysis of SS and explored the effect of clay minerals (attapulgite, montmorillonite, and kaolin) in regulating N conversion. The results showed that the higher temperature (800 °C) could promote the conversion of pyrroles/pyridines and NO x precursors in char to N 2 (the conversion rate was 32.76 %), and clay minerals catalyzed the cleavage of N-containing macromolecules in the bio-oil, reducing the N content in bio-oil from 28.70 % to 6.23 %, and was conducted to realize the denitrification of bio-oil. Notably, the attapulgite (ATP) on N migration was more effective and could reduce the yield of NO x precursors from 23.80 % to 10.55 % by capturing NH 4 * and inhibiting the secondary reaction, while catalyzing the removal of N 2 from pyridine/pyrrole (N 2 production increased to 34.38 %). MgO and CaO in the clays played a major role in facilitating the conversion of char-N to N 2 , and clay structures loading on the biochar surface promoted the catalysis of N-containing volatiles to N 2 by metal oxides. This study provides a viable and harmless approach to SS minimization., 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 © 2024 Elsevier B.V. All rights reserved.)

Lilii Bulbus is a folk medicine for both culinary and medicinal purpose. In traditional medicine theory, Lilii Bulbus is usually used as an complementary therapy for nourishing the heart and lung, clearing heat in the treatment of mental instability and depression. In this study, NLPS-1a (Mw = 2610 Da, DP = 16), a water-soluble non-starch Lilii Bulbus polysaccharides, was isolated and purified. Structural analysis showed that NLPS-1a mainly contained Man and Glc with a molar ratio of 11.137 and 9.427. The glycosidic linkages of NLPS-1a were 1,3-Manp (59.93%), 1,2-Glcp (37.93%), T-Glcp (1.21%) and T-Manp (0.93%), indicating the highly-linear structures. In addition, NLPS-1a could significantly repair the injury of PC12 cells induced by corticosterone (CORT), reduce Lactate dehydrogenase (LDH) leakage and decrease the cell apoptosis in a dose-dependent manner. Above all, the results indicated that NLPS-1a had protective effects against CORT-induced neurotoxicity in PC12 cells, and might be a natural antidepressant, which enriched the study of the metabolic mechanism between herbal polysaccharides and antidepressant., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Prokaryotic Argonautes (pAgos) have been recently used in many nucleic acid biosensing applications but have rarely been used for regulating the isothermal amplification system. Herein, we reported Thermus thermophilus Argonaute (TtAgo)-mediated background-suppressed exponential isothermal amplification (EXPAR) as the first example to explore the binding activity of pAgos toward regulation of the amplification template. It was demonstrated that thermophilic pAgos efficiently eliminated nonspecific hybridization between templates by their binding affinity with the template, resulting in greatly enhancing the specificity of EXPAR. TtAgo-mediated, background-suppressed EXPAR was employed to detect miRNA with a detection limit of 10 -15 M, which was 1000 times and 100 times more sensitive than that of traditional RT-PCR and EXPAR, respectively. This method further showed good performance in discriminating cancer patients from healthy individuals, indicating its potential for practical clinical applications.

Introduction: The increasing number of studies have shown that Lycium barbarum polysaccharides possess anti-tumor effects. However, the determination of the active ingredients and their mechanism against melanoma inhibition are still unknown., Methods: In this study, we aimed to investigate the mechanisms of action of Lycium barbarum active glycopeptide (LBAG) on melanoma. LBAG was extracted and isolated from the fruit of Lycium barbarum using aqueous alcoholic precipitation and identified using ultra-performance liquid chromatography-quadrupole-time of flightmass spectrometry. Various assays including cell apoptosis, cell cycle analysis, colony formation assay, cell scratch test, flow cytometry, and Western blot were performed to evaluate the effects of LBAG on melanoma., Results: The results showed that LBAG has a molecular weight of 10-15 kDa and contains Man, Rha, GlcA, Glc, Gal, and Ara18 amino acids. Treatment with LBAG significantly decreased B16 cell proliferation and induced cell cycle arrest at the G0/G phase, accompanied by the accumulation of reactive oxygen species. Western blot analysis revealed that the phosphorylation of P38-MAPK and AKT, as well as the expression of N-acetyl-Lcysteine, were related to cell apoptosis and cell cycle regulation. In mouse xenografts, LBAG inhibited tumor growth through the P38-MAPK and AKT signaling pathways., Conclusion: In conclusion, the anti-melanoma activity of LBAG may induce apoptosis in cancer cells through ROSmediated activation of the P38-MAPK and AKT signaling pathways. These findings provide a foundation for further research on the anti-melanoma potential of LBAG., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Accumulating studies demonstrated that resistance of colon cancer (CC) to 5-fluorouracil (5-FU) contributes to adverse prognosis. We investigated how Kruppel-like factor 4 (KLF4) affected 5-FU resistance and autophagy in CC cells., Methods: KLF4 expression and its downstream target gene RAB26 in CC tissues was analyzed by bioinformatics analysis, and the effect of abnormal KLF4 expression on prognoses of CC patients was predicted. Luciferase reporter assay detected the targeted relationship between KLF4 and RAB26. The viability and apoptosis of CC cells were analyzed by CCK-8 and flow cytometry. The formation of intracellular autophagosomes was detected by confocal laser scanning microscopy and immunofluorescence staining. The mRNA and protein levels were assayed by qRT-PCR and western blot. A xenograft animal model was constructed to verify the function of KLF4. Rescue assay was employed to verify whether KLF4/RAB26 could affect 5-FU resistance in CC cells through autophagy., Results: KLF4 and RAB26 were lowly expressed in CC. KLF4 correlated with patients' survival. KLF4 was down-regulated in 5-FU resistant CC cells. KLF4 overexpression suppressed the proliferation and 5-FU resistance of CC cells, and inhibited LC3 II/I expression and autophagosome formation. Autophagy activator Rapamycin or sh-RAB26 treatment reversed the impact of KLF4 overexpression on 5-FU resistance. In vivo assay verified that KLF4 inhibited 5-FU resistance in CC cells. Rescue experiments revealed that KLF4 targeted RAB26 to inhibit CC cell autophagy, resulting in decreasing the resistance to 5-FU., Conclusion: KLF4 strengthened the sensitivity of CC cells to 5-FU by targeting RAB26 to restrain autophagy pathway.

Background: Astragali Radix (also known as Astragulus) is a traditional medicinal and edible homologous plant for tonifying Qi. Honey-processed Astragalus is a dosage form of Astragali Radix processed with honey, which exhibited better efficacy of tonifying Qi than the raw product. Polysaccharides are their main active components., Results: APS2a and HAPS2a were initially isolated from Astragulus and honey-processed Astragulus. Both of them are highly branched acidic heteropolysaccharides containing ɑ-configuration and β-configuration glycosidic bonds. The molecular weight and the molecular dimension of HAPS2a decreased and the GalA contained in APS2a was converted to Gal in HAPS2a. The α-configuration galactose residue 1,3,4-α-Galp in the backbone of APS2a was converted to the corresponding β-configuration galactose residue 1,3,4-β-Galp in the backbone of HAPS2a and the uronic acid residue T-α-GalpA in the sidechain of APS2a was converted to the corresponding neutral residue T-α-Galp in the side chain of HAPS2a. Bioactivity results showed that HAPS2a had better probiotic effects on Bacteroides ovatus, Bacteroides thetaiotaomicron, Bifidobacterium longum and Lactobacillus rhamnosus strains than APS2a. After degradation, the molecular weights of HAPS2a and APS2a decreased with the changes in their monosaccharide composition. The contents of total short-chain fatty acids (SCFAs) and other organic acids in HAPS2a group were higher than APS2a group., Conclusions: Two novel high-molecular-weight polysaccharides named APS2a and HAPS2a had different probiotic activities in vitro, which might be due to their structural differences before and after honey processing. Both of them might be possibly used as an immunopotentiator in healthy foods or dietary supplement. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Objectives: To detect the contents of Tangwei capsule main components with high performance liquid chromatography-quantitative analysis of multicomponents by single marker (HPLC-QAMS) method and to evaluate the quality with chemometrics and entropy weight-technique for order preference by similarity to an ideal solution (EW-TOPSIS)., Methods: A symmetry C 18 column and 0.1% formic acid-acetonitrile as mobile phase were used for HPLC of Tangwei capsule. The contents of 3'-hydroxypuerarin, puerarin, 3'-methoxypuerarin, methylnissolin-3-O-glucoside, calycosin, formononetin, rosmarinic acid, salvianolic acid B, dihydrotanshinone Ⅰ, cryptotanshinone, tanshinone Ⅰ, tanshinone ⅡA and cucurbitacin B in 15 batches of Tangwei capsule were determined simultaneously. The quality differences of 15 batches of samples were analyzed by chemometrics and EW-TOPSIS., Results: The HPLC-UV showed that 13 components had good linear relationships in corresponding concentration ranges ( r ≥0.9991). The relative standard deviations (RSD) of precision, repeatability and stability were all less than 2.00%. The average recovery rates were between 96.86% and 100.13%, and RSD were all less than 2.00%. Cluster analysis showed that 15 batches of samples were clustered into 3 groups. Partial least squares-discriminant analysis showed that salvianolic acid B, formononetin, puerarin, 3'-methoxypuerarin and rosmarinic acid were the main potential markers affecting the quality of Tangwei capsule. EW-TOPSIS analysis showed that the quality of S12-S15 was superior., Conclusions: The analytical method established in this study can be used for the comprehensive evaluation of the quality of Tangwei capsule to provide laboratory support for its quality control and overall evaluation.

Exosomes are small membrane vesicles secreted by most cell types, and widely exist in cell supernatants and various body fluids. They can transmit numerous bioactive elements, such as proteins, nucleic acids, and lipids, to affect the gene expression and function of recipient cells. Mesenchymal stem cells (MSCs) have been confirmed to be a potentially promising therapy for tissue repair and regeneration. Accumulating studies demonstrated that the predominant regenerative paradigm of MSCs transplantation was the paracrine effect but not the differentiation effect. Exosomes secreted by MSCs also showed similar therapeutic effects as their parent cells and were considered to be used for cell-free regenerative medicine. However, the inefficient and limited production has hampered their development for clinical translation. In this review, we summarize potential methods to efficiently promote the yield of exosomes. We mainly focus on engineering the process of exosome biogenesis and secretion, altering the cell culture conditions, cell expansion through 3D dynamic culture and the isolation of exosomes. In addition, we also discuss the application of MSCs-derived exosomes as therapeutics in disease treatment., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

Pyruvate kinase 2 (PKM2) and pyruvate dehydrogenase kinase 1 (PDK1) are two key enzymes in tumor glucose metabolism pathway that not only promote tumor growth and proliferation through accelerating aerobic glycolysis, but also contribute to drug resistance of non-small cell lung cancer (NSCLC). Considering that targeting PKM2 or PDK1 alone seems insufficient to remodel abnormal glucose metabolism to achieve significant antitumor activity, we proposed a "two-step approach" that regulates PKM2 and PDK1 synchronously. Firstly, we found that the combination of ML265 (PKM2 activator) and AZD7545 (PDK1 inhibitor) could synergistically inhibit proliferation and induce apoptosis in H1299 cells. Base on this, we designed a series of novel shikonin (SK) thioether derivatives as PKM2/PDK1 dual-target agents, among which the most potent compound E5 featuring a 2-methyl substitution on the benzene ring exerted significantly increased inhibitory activity toward EGFR mutant NSCLC cell H1975 (IC 50  = 1.51 μmol/L), which was 3 and 17-fold more active than the lead compound SK (IC 50  = 4.56 μmol/L) and the positive control gefitinib (IC 50  = 25.56 μmol/L), respectively. Additionally, E5 also showed good anti-tumor activity in xenografted mouse models, with significantly lower toxicity side effects than SK. Moreover, E5 also inhibited the entry of PKM2 into nucleus to regulate the transcriptional activation of oncogenes, thus restoring the sensitivity of H1975 cell to gefitinib. Collectively, these data demonstrate that E5, a dual inhibitor of PKM2/PDK1, may be a promising adjunct to gefitinib in the treatment of EGFR-TKIs resistant NSCLC, deserving further investigation., 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 © 2023 Elsevier Masson SAS. All rights reserved.)

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 4 (h-CdS@CdMoO 4 ) shell-shell structured photoanode system was developed for ultrasensitive detection of CEA. Using a small LED flashlight as the excitation light source and a digital multimeter (DMM) as the signal readout device, real-time CEA on a paper-based printed screen electrode developed in-house was quickly detected. The composite h-CdS@CdMoO 4 featured a special hollow shell-shell heterojunction structure that optimizes photon usage in the bulk phase on the one hand, and facilitates directed separation of the electrons and holes therein on the other. A split-sandwich immunoassay and detection antibodies for modified glucose oxidase were introduced into the paper-based photoanode test system, and the signals were displayed with a DMM to realize a point-of-care test for CEA. Under optimized conditions, the constructed portable PEC sensing system was sensitive to the target CEA from 0.02 to 50.0 ng mL -1 with a detection limit of 11.3 pg mL -1 . Interferent experiments and stability test evaluations demonstrate the specificity and robustness of the constructed paper-based portable PEC sensor. The portable, paper-based PEC immunoassay system developed offers a fresh way of exploring affordable, approachable sensors to satisfy both the relevant community medical testing demands and hospital objectives for quick testing., 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 Elsevier B.V. All rights reserved.)

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 K 2 O and K 2 CO 3 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.

In this study, a waste walnut shell-derived biochar enriched with nitrogen (N-biochar) is mixed with nitrogen-doped TiO 2 (N-TiO 2 ) to fulfill an affordable composite material for the degradation of methyl orange (MO). Results showed that porous structure and oxygen-containing functional groups of biochar facilitate contact with MO during the reaction process. Meanwhile, doped nitrogen has a positive effect on improving the reaction activity due to the existence of a substituted state and a gap state in the catalyst. It was revealed that the N-TiO 2 /N-biochar (NCNT0.2/1) exhibited better photocatalytic degradation efficiency (97.6%) and mineralization rate (85.4%) of MO than that of TiO 2 , N-TiO 2 , and TiO 2 /N-biochar due to its stronger synergistic effect of N, TiO 2 , and biochar, in accordance with its high charge separation by photoluminescence (PL) analysis. Trapping experiments showed that ·OH is the predominant active species during the decolorization and mineralization process of MO. After five repeated use, the loss of activity of the catalyst was negligible. In addition, the catalytic degradation process was consistent with the pseudo-first-order kinetic model with the rate constant of 4.02 × 10 -2 min -1 ., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Herein, we reported a novel photoelectrochemical immunoassay method based on a target-triggered on/off signal of the ultra-structured Bi 2 O 2 S (BOS) photoanode system for the sensitive testing of carcinoembryonic antigens (CEAs) in serum samples. Well-defined three-dimensional sheet-like self-assembled flower-like Bi 2 O 2 S superstructures were obtained using a time-controlled hydrothermal method. Such well-shaped multifaceted surfaces were considered to be good laser cavity mirror surfaces for multifaceted reflection and refraction of excitation light in the material. An elegant enzyme biocatalytic strategy was introduced into the constructed detection model to sensitively detect CEAs. The substrate 4-chloro-1-naphthol (4-CN) was oxidized to 4-chloro-hexadienone (4-CD) under the formation of target-triggered immune complexes against mAb 1 and peroxidase-modified mAb 2 . Subsequently, 4-CD produced by the biocatalytic precipitation reaction was transferred to the photoanodes of Bi 2 O 2 S nanoflowers (BOS NFs) to burst their photoelectric signals, thus achieving the quantification of CEAs. Through optimization of the conditions of the immunization protocol, a good negative photocurrent response to the target CEA was found in the wide range of 0.02-50 ng mL -1 with a detection limit of 11.2 pg mL -1 . Impressively, the reported biocatalytic PEC sensing strategy on superstructures is comparable, or superior, to the gold standard ELISA kit in terms of sensitivity and the target response range. This study presents a target-mediated PEC immunoassay for biocatalytic precipitation based on a self-assembled superstructure of Bi 2 O 2 S, providing a fresh scheme for the analysis of disease-related markers.

Background: Anastomotic leakage (AL) is one of the most severe and frequent complications occurring after laparoscopic low anterior resection (LAR) for rectal cancer. This study aimed to examine the association between circular stapler size and AL after laparoscopic LAR., Methods: This retrospective single-institution study involved 181 patients with rectal cancer who underwent laparoscopic LAR performed by a single surgical team between July 2016 and June 2021. The characteristics of the patients were analyzed. Risk factors for AL were identified via univariate and multivariate analyses. Additionally, a further propensity score matching (PSM) analysis was performed to reduce the selection bias., Results: Among the 181 patients who underwent laparoscopic LAR for rectal cancer, 17 (9.4%) developed clinical AL. In the univariate and multivariate analyses, male sex, incomplete intestinal obstruction, and the usage of a 32-mm stapler during the surgery were independent risk factors for the occurrence of AL. Furthermore, the PSM analysis confirmed that the incidence of AL with a 32-mm stapler was higher than that with a 29-mm stapler after laparoscopic low anterior resection. However, there was no difference in the incidence of anastomotic bleeding and stenosis., Conclusion: Choosing a smaller-diameter circular stapler may reduce the incidence of AL after laparoscopic LARfor rectal cancer without increasing the incidence of anastomotic stenosis., Competing Interests: None

The hot deformation behavior of high-grade pipeline steels was studied in the strain rate range of 0.001~0.1 s -1 and the temperature range of 1050~1200 °C by using hot compression tests on a Gleeble 3500 thermomechanical simulator. The flow stress increases with the increase in strain rate and the decrease in deformation temperature, and the deformation activation energy is about 358 kJ/mol. The flows stress-strain behavior of the work-hardening and dynamic recovery (DRV) was calculated using the Estrin-Mecking equation, and the kinetics model of the dynamic recrystallization (DRX) was established based on the Avrami equation through characteristic strains. Furthermore, the flow stress-strain behavior of high-grade pipeline steels was predicted by the established model based on the coupling effects of DRV and DRX. The corresponding predicted results are in good agreement with the experimental results according to standard statistical parameters analysis. Finally, the economic strain ( ε 3 ) is proposed by the third derivative of the given kinetic model. Based on these calculation results, when the economic strain ( ε 3 ) is reached, uniform and refined DRX grains can be obtained, the energy consumption reduced, and the production costs controlled, which is of great significance to actual factory production.

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.

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.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Background: 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., Methods: 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., Results: 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, I 2 = 0%), but not with improved RFS (HR = 0.821, 95% CI = 0.668-1.009, P = 0.060, I 2 = 9%) compared with omentectomy for advanced gastric cancer. Furthermore, less blood loss and shorter operation time were found in the omentum preservation group than in the omentectomy group. Additionally, the rate of peritoneal recurrence, the number of harvested lymph nodes, and the incidences of postoperative complications and ileus were comparable in the two groups., Conclusions: Basing 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., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Colorectal 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., Methods: This 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., Results: The 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., Conclusion: The incisional press after suturing is a simple, costless, and effective intervention in reducing superficial incisional SSI., 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., (© 2022 Jiang, Chen, Liu, Liu, Kong and Sheng.)

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.

Importance: Two large randomized clinical trials (RCTs) found that laparoscopic surgery failed to yield noninferior pathologic outcomes compared with open surgery for patients with rectal cancer. The results raised concerns regarding the effectiveness of the laparoscopic approach for patients with rectal cancer., Objective: To compare the long-term oncologic outcomes of laparoscopic and open surgery for patients with rectal cancer., Data Sources: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched from database inception to August 13, 2021. Studies published in English were retrieved., Study Selection: The meta-analysis included RCTs that compared laparoscopic surgery with open surgery for patients with rectal cancer and reported the outcome of disease-free survival (DFS) or overall survival (OS). The following exclusion criteria were used: (1) non-RCTs, (2) studies without long-term survival outcomes of interest, and (3) studies that did not report Kaplan-Meier survival curves., Data Extraction and Synthesis: This meta-analysis was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline for individual participant data development groups. Individual participant data on DFS and OS were extracted from the published Kaplan-Meier survival curves. One-stage and 2-stage meta-analyses were performed., Main Outcomes and Measures: Meta-analyses were conducted for DFS and OS. Hazard ratios (HRs) were used as effective measures., Results: Of 8471 records screened, 10 articles with 12 RCTs and 3709 participants were selected. The reconstructed survival curves for the combined population showed that the 5-year estimated DFS rates were 72.2% (95% CI, 69.4%-74.8%) for the laparoscopic group and 70.1% (95% CI, 67.0%-73.0%) for the open surgery group, and the 5-year estimated OS rates were 76.2% (95% CI, 73.8%-78.5%) for the laparoscopic group and 72.7% (95% CI, 69.8%-75.3%) for open surgery group. In 1-stage meta-analyses, DFS had a nonsignificant HR of 0.92 (95% CI, 0.80-1.06; P = .26), which suggested that DFS in the laparoscopic and open surgery groups was comparable; however, OS was significantly better in the laparoscopic group (HR, 0.85; 95% CI, 0.74-0.97; P = .02). The results were confirmed by 2-stage meta-analyses and were validated by sensitivity analysis with large RCTs., Conclusions and Relevance: A similar DFS but significantly better OS were found for patients who have undergone laparoscopic surgery compared with open surgery for rectal cancer. These findings address concerns regarding the effectiveness of laparoscopic surgery and support the routine use of laparoscopic surgery for patients with rectal cancer.

Introduction: 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., Areas Covered: 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., Expert Opinion: 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.

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 IC 50 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Amphiphilic self-assembling peptides are widely used in tissue and cell engineering, antimicrobials, drug-delivery systems and other biomedical fields due to their good biocompatibility, functionality, flexibility of design and synthesis, and tremendous potential as delivery carriers for drugs. Currently, the design and study of amphipathic peptides by a bottom-up method to develop new biomedical materials have become a hot topic. However, defined rules have not been established for the design and development of self-assembled peptides. Therefore, the focus of this review is to summarize and provide several rational strategies for the design and study of amphiphilic self-assembly peptides. In addition, this paper also describes the types and general self-assembling mechanism of amphipathic peptides, and outlines their applications in the delivery of hydrophobic drugs, nucleic acid drugs, peptide drugs and vaccines. Amphiphilic self-assembled peptides are expected to exploit new functional materials for drug delivery and other applications., (Copyright © 2021. Published by Elsevier B.V.)

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.

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., (© 2021 John Wiley & Sons, Ltd.)

In this work, the Co-Ni basic carbonate nanowires were in-situ grown on carbon nanotube (CNT) network through a facile chemical bath deposition method, which could be further converted into active hydroxide via cyclic voltammetry strategy. A series of carbonate nanowire/nanotube with different Co/Ni ratio revealed the different growth status of the nanowires on CNT network. The nanostructures of the as-synthesized samples were examined via powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) techniques. The Co/Ni ratio of the carbonate largely affected the size of the nanowires, that the low Co/Ni ratio was beneficial for thin nanowire formation and the nanowires loading on CNT network. Subsequently, the electrochemical performance of the Co-Ni basic hydroxides was studied in a three-electrode test system. The nanowires with low Co/Ni ratio 1/2 can form nanowire array on individual CNTs, which exhibited better electrochemical capacitive performance than the composite network with high Co/Ni ratio nanowires after electrochemical activation. The addition of Co enhanced the rate performance of the hydroxide/CNT, especially improved the long cycle stability largely compared to the rate performance of pure Ni converted hydroxide/CNT composite film reported by our previous research. This result is valuable for the design of inorganic electrochemical active composites based on conductive networks for energy conversion/storage applications., 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 © 2021 Tan, Chen, Yuan, Zhang and Chen.)

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., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Single-molecule localization allows determining the underlying biological and biochemical processes and promotes the development of super-resolution imaging techniques. Here, we present an optical technique of tracking the motion of a single nanoparticle linked to a substrate via a biomolecule tether to reveal the localization of single biomolecules and the transient states of single nanoparticle switching between specific binding pairs. The affinities, steric hindrance, and conformational variation of a single-molecule binding pair uncover the dynamic details and intrinsic mechanism of binding processes with high specificity and accuracy (a few nanometers). The application of tracking motions of single soft liposomes on different modified surfaces was further demonstrated, which revealed the characteristic behavior related to surface chemistry. Our results show that the trajectory of nanoscale liposomes loaded with small-drug molecules is linked to the compositional inhomogeneity, which provides a route for thorough comprehension of the fundamental biotechnological process.

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KL, AP and AW are founders in VasoBio Inc, which has a license to the LXW7 peptide., (© 2021 The Authors.)

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., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Honey-processed Astragalus is a dosage form of Radix Astragali processed with honey, which exhibits better efficacy of tonifying Qi than the raw product. Polysaccharides are its main water-soluble active components. This work was designed to study the structural differences of homogeneous honey-processed Astragalus polysaccharides (HAPS3a) and Astragalus polysaccharides (APS3a) and their effects on colitis mice. The results showed that HAPS3a (Mw = 2463.5 kDa) and APS3a (Mw = 3373.2 kDa) differed in molecular weight, monosaccharide compositions, glycosidic bonds and degree of branching (DB). Notably, the molar ratios of galactose and galacturonic acid in HAPS3a were 22.66% and 33.24%, while those in APS3a were 11.87% and 49.55%, respectively. The uronic acid residues 1,4-β-GalpA and 1,6-α-GlcpA of the backbone in APS3a were converted into the corresponding neutral residues in HAPS3a after honey processing. The different DB of HAPS3a (15.35%) and APS3a (25.13%) suggested that the chain conformation became smoother. The anti-inflammatory effects on colitis mice revealed that HAPS3a exhibited better effects than APS3a by protecting intestinal mucosa, regulating the expression of cytokines and influencing microbiota diversity. Taken together, the differences in anti-inflammatory activity might be related to structural differences caused by honey processing. Our findings have laid a foundation for the processing mechanism of Astragalus., (Copyright © 2021. Published by Elsevier B.V.)

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 < 0.001, I 2  = 14%). However, the inferior RFS/DFS vanished when tumor rupture cases were excluded (HR = 1.34, 95% CI = 0.98-1.83, P = 0.07, I 2  = 33%). Sensitivity analysis by high-quality studies brought about a more robust HR of 1.15 (95% CI = 0.88-1.50, P = 0.29), with low heterogeneity (I 2  = 0%). The qualities of evidence for the outcomes were high., 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., 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 © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Cyclophilins (Cyps) is a kind of ubiquitous protein family in organisms, which has biological functions such as promoting intracellular protein folding and participating in the pathological processes of inflammation and tumor. Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are two common intestinal diseases, but the etiology and pathogenesis of these two diseases are still unclear. IBD and CRC are closely associated, IBD has always been considered as one of the main risks of CRC. However, the role of Cyps in these two related intestinal diseases is rarely studied and reported. In this review, the expression of CypA, CypB and CypD in IBD, especially ulcerative colitis (UC), and CRC, their relationship with the development of these two intestinal diseases, as well as the possible pathogenesis, were briefly summarized, so as to provide modest reference for clinical researches and treatments in future., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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 <0.001) and poor survival ( P =0.020) of patients with early-stage HCC. Multivariate analysis revealed that low miR-203 expression was a poor prognostic factor for both overall survival (OS) ( P =0.036) and recurrence free survival (RFS) ( P =0.017). ZEB1 did not show any prognostic significance in our cohort. Correlation analysis indicated that there was no significant correlation between miR-203 and ZEB1 on both mRNA and protein levels. Furthermore, functional studies indicated that miR-203 repressed migration, invasion and proliferation of HCC cells in vitro . Conclusion : Our study suggested that miR-203 could be a novel predictor in early-stage HCC and might also be a potential molecular target for HCC therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: This study aimed to design and screen a dual functional fusion peptide that could penetrate the blood-brain barrier and target neuropilin 1 (NRP1) overexpressed in vascular endothelial cells for the anti-angiogenesis of glioma treatment., Main Methods: At the cellular level, the in vitro anti-angiogenic activity of six NRP1 targeting peptides was screened by testing the ability to inhibit the proliferation and tube formation of HUVECs. Then, the in vitro anti-angiogenic activity of two fusion peptides containing different linkers was screened by testing the ability to inhibit HUVECs proliferation, tube formation and migration. The effect of fusion peptide on VEGFR2 related signal pathway was confirmed by Western-blotting. Surface plasmon resonance technology was used to detect the affinity of the fusion peptide to NRP1. The ability of FITC-labeled peptides to penetrate cells was confirmed by cell uptake assay. By establishing an orthotopic glioma model, we evaluated the ability of FITC-labeled peptides to penetrate the blood-brain barrier and their anti-glioma growth activity in vivo., Key Findings: We found that NRP1 targeting peptide RP7 and linker cysteine were the most suitable key components in the fusion peptide. We also found that the fusion peptide Tat-C-RP7 we constructed had the strongest ability to penetrate the blood-brain barrier and anti-angiogenic activity in vitro and in vivo., Significance: At present, NRP1 targeting peptide as a drug delivery tool and molecular probe seems to have received more attention. We constructed a fusion peptide Tat-C-RP7 with strong anti-angiogenic activity for the treatment of glioma., (Copyright © 2021. Published by Elsevier Inc.)

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., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Local tumour sites lead to pathological angiogenesis and lymphangiogenesis due to malignant conditions such as hypoxia. Although VEGF and VEGFR are considered to be the main anti-tumour treatment targets, the problems of limited efficacy and observable side effects of some drugs relevant to this target still remain to be solved. Therefore, it is necessary to identify new therapeutic targets for angiogenesis or lymphangiogenesis. The neuropilin family is a class of single transmembrane glycoprotein receptors, including neuropilin1 (NRP1) and neuropilin2 (NRP2), which could act as co-receptors of VEGFA-165 and VEGFC and play a key role in promoting tumour proliferation, invasion and metastasis. In this review, we introduced the schematic diagram to visually reveal the function of NRP1 and NRP2 in enhancing the binding affinity of VEGFR2 to VEGFA-165 and VEGFR3 to VEGFC, respectively. We also discussed the signalling pathways that depend on the co-receptors NRP1 and NRP2 and some existing targeted therapeutic strategies, such as monoclonal antibodies, targeted peptides, microRNAs and small molecule inhibitors. It will contribute a vital foundation for the future research and development of new drugs targeting NRPs. HIGHLIGHTS NRP1 acts as a co-receptor with VEGFR2 and the pro-angiogenic factor VEGFA-165 to up-regulate tumour angiogenesis by promoting endothelial cells proliferation, survival, migration, invasion and by preventing of apoptosis. NRP2 acts as a co-receptor with VEGFR3 and the pro-lymphogenic factor VEGFC to facilitate tumour metastasis by promoting lymphangiogenesis. Although NRP1 and NRP2 do not have enzymatic signalling activity, the affinity of VEGFR2 for VEGFA-165 and VEGFR3 for VEGFC can increase in a co-receptor manner, as detailed in the schematic. The exclusive roles of NRP1 and NRP2 in signalling pathways are specifically described to emphasise the molecular regulatory mechanisms involved in co-receptors. Various studies have shown that the co-receptors NRP1 and NRP2 can be directly or indirectly targeted by different methods to prevent tumour angiogenesis and lymphangiogenesis. Therapeutic strategies targeting NRPs look promising soon as evidenced by preclinical and clinical studies.