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Background: Subcutaneous gastrointestinal stromal tumors (scGISTs) are extremely rare tumors, and the analysis of their long-term prognosis remains unreported. Therefore, our objective is to analyze the long-term prognosis of patients with scGISTs using the Surveillance, Epidemiology, and End Results database., Methods: Patients diagnosed with GISTs between 2000 and 2019 were included in the study. To handle missing data, multiple imputation techniques were employed. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate overall survival (OS) and cancer-specific survival (CSS), and subgroup analyses were conducted for various variables., Results: A total of 12,882 patients were enrolled, with 12,636 diagnosed with GISTs and 246 with scGISTs. In comparison to GISTs patients, scGISTs patients exhibited inferior OS [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.45-1.98, P < 0.001] and CSS (HR 2.16, 95% CI 1.78-2.61, P < 0.001). Across various subgroups, including age, sex, surgical intervention, marital status, and chemotherapy, scGISTs patients consistently demonstrated significantly poorer OS and CSS outcomes compared to GISTs patients (P < 0.05). The 1-, 3-, and 5-year OS rates for scGISTs patients were 78.4%, 60.3%, and 49.3%, respectively, with corresponding CSS rates of 83.3%, 67.8%, and 57.4%. Notably, scGISTs patients who received surgical treatment had significantly higher 5-year OS rates (62.1% vs 30.9%, P < 0.001) and CSS rates (67.8% vs 40.0%, P < 0.001) compared to those who did not undergo surgery. Multivariate Cox regression analysis identified age, surgical status, and mitotic rate as risk factors influencing OS in scGISTs patients, while surgical status and mitotic rate were identified as risk factors affecting CSS., Conclusions: Compared to GISTs patients, scGIST patients exhibit a less favorable prognosis; nonetheless, surgical intervention has been demonstrated to enhance their prognosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Research on ferroptosis in myocardial ischemia/reperfusion injury (MIRI) using mitochondrial viscosity as a nexus holds great promise for MIRI therapy. However, high-precision visualisation of mitochondrial viscosity remains a formidable task owing to the debilitating electrostatic interactions caused by damaged mitochondrial membrane potential. Herein, we propose a dual-locking mitochondria-targeting strategy that incorporates electrostatic forces and probe-protein molecular docking. Even in damaged mitochondria, stable and precise visualisation of mitochondrial viscosity in triggered and medicated MIRI was achieved owing to the sustained driving forces (e.g., pi-cation, pi-alkyl interactions, etc.) between the developed probe, CBS, and the mitochondrial membrane protein. Moreover, complemented by a western blot, we confirmed that ferrostatin-1 exerts its therapeutic effect on MIRI by improving the system xc - /GSH/GPX4 antioxidant system, confirming the therapeutic value of ferroptosis in MIRI. This study presents a novel strategy for developing robust mitochondrial probes, thereby advancing MIRI treatment., (© 2024 Wiley-VCH GmbH.)

This study aimed to assess the impact of Lactobacillaceae (L or H represents a low or high dose), inulin (I), and polydextrose (P) combined with aerobic exercise (A) on the composition of the gut microbiota and metabolic profiles in db/db mice. After a 12-week intervention, LIP, LIPA, and HIPA groups exhibited significant improvements in hyperglycemia, glucose tolerance, insulin resistance, inflammatory response, and short-chain fatty acid (SCFA) and blood lipid levels compared to type 2 diabetes mice (MC). After treatment, the gut microbiota composition shifted favorably in the treatment groups which significantly increased the abundance of beneficial bacteria, such as Bacteroides , Blautia , Akkermansia , and Faecalibaculum , and significantly decreased the abundance of Proteus . Metabolomics analysis showed that compared to the MC group, the contents of 5-hydroxyindoleacetic acid, 3-hydroxysebacic acid, adenosine monophosphate (AMP), xanthine and hypoxanthine were significantly decreased, while 3-ketosphinganine, sphinganine, and sphingosine were significantly increased in the LIP and LIPA groups, respectively. Additionally, LIP and LIPA not only improved sphingolipid metabolism and purine metabolism pathways but also activated AMP-activated protein kinase to promote β-oxidation by increasing the levels of SCFAs. Faecalibaculum , Blautia , Bacteroides , and Akkermansia exhibited positive correlations with sphingosine, 3-ketosphinganine, and sphinganine, and exhibited negative correlations with hypoxanthine, xanthine and AMP. Faecalibaculum , Blautia , Bacteroides , and Akkermansia may have the potential to improve sphingolipid metabolism and purine metabolism pathways. These findings suggest that the synergism of Lactobacillaceae , inulin, polydextrose, and aerobic exercise provides a promising strategy for the prevention and management of type 2 diabetes.

The 2000 series aluminium alloys are qualified for widespread use in lightweight structures, but solidification cracking during fusion welding has been a long-standing issue. Here, we create a zirconium (Zr)-core-aluminium (Al)-shell wire (ZCASW) and employ the oscillating laser-arc hybrid welding technique to control solidification during welding, and ultimately achieve reliable and crack-free welding of 2024 aluminium alloy. We select Zr wires with an ideal lattice match to Al based on crystallographic information and wind them by the Al wires with similar chemical components to the parent material. Crack-free, equiaxed (where the length, width and height of the grains are roughly equal), fine-grained microstructures are acquired, thereby considerably increasing the tensile strength over that of conventional fusion welding joints, and even comparable to that of friction stir welding joints. This work has important engineering application value in welding of high-strength aluminum alloys., (© 2024. The Author(s).)

Fresh milk should undergo sterilization before consumption to eliminate bacteria that can cause foodborne illnesses. Additional antimicrobial measures are beneficial to extend its shelf life. The nanoprobe developed herein can not only inspect the activity of alkaline phosphatase (ALP) for evaluating the degree of pasteurization, but also detect the activity of glucose oxidase (GOD), which is added as a chemical preservative. The facile preparation of the nanoprobe involved introducing gallic acid-Fe complex (GA-Fe) into lanthanide doped upconversion nanomaterials (UCNPs). Based on the alteration of iron's valence state in the complex through a straightforward redox reaction, both enzyme activities could be determined through colorimetric and luminometric dual-signal readouts. With detection limits of 1.669 × 10 -5 for GOD and 9.81 × 10 -6 U/mL for ALP respectively, this nanoprobe shows merits of easy operation and high sensitivity. Successful application in milk samples demonstrates its potential as an innovative and cost-effective approach to food safety inspection., 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 Ltd. All rights reserved.)

Ferroptosis has been confirmed as a potential mediator and an indicator of the severity of liver injury. Despite the fruitful results, there are still two deficiencies in the research on the association between ferroptosis and liver injury. First, iron ions are usually selected as the target bioanalyte, but its detection based on a fluorescent probe is interfered with by specific chemical reaction mechanisms, leading to low sensitivity and poor physiological stability. Second, more efforts were focused on the harmful effects of ferroptosis on liver injury and less involved in the therapeutic value of ferroptosis for liver injury. Hence, in this work, we proposed a new nonreactive analyte (mitochondrial viscosity) as an analysis marker, which can circumvent the challenges caused by specific reaction mechanisms of iron ions. Meanwhile, we constructed a novel label-detection integrated visual probe ( VPF ) to explore the feasibility of ferroptosis in the treatment of liver injury. As expected, we not only successfully traced the dynamic changes in mitochondrial viscosity but also visualized the changes in cell morphology during induced and inhibited ferroptosis. Conspicuously, this work revealed that liver injury can be alleviated by regulating ferroptosis, confirming the therapeutic value of ferroptosis in liver injury. In addition, a complex biological communication network between ferroptosis and liver injury was constructed by western blotting, providing an important theoretical mechanism for revealing their double-edged sword relationship. This study not only provides a new strategy for studying the complex relationship between ferroptosis and liver injury but also facilitates the future treatment of liver injury.

Microenvironment regeneration in wound tissue is crucial for wound healing. However, achieving desirable wound microenvironment regeneration involves multiple stages, including hemostasis, inflammation, proliferation, and remodeling. Traditional wound dressings face challenges in fully manipulating all these stages to achieve quick and complete wound healing. Herein, we present a VEGF-loaded, versatile wound dressing hydrogel based on gelatin methacryloyl (GelMA) and carboxymethyl chitosan (CMCS), which could be easily fabricated using UV irradiation. The newly designed GelMA-CMCS@VEGF hydrogel not only exhibited strong tissue adhesion capacity due to the interactions between CMCS active groups and biological tissues, but also possessed desirable extensible properties for frequently moving skins and joints. Furthermore, the hydrogel demonstrates exceptional abilities in blood cell coagulation, hemostasis and cell recruitment, leading to the promotion of endothelial cells proliferation, adhesion, migration and angiogenesis. Additionally, in vivo studies demonstrated that the hydrogel drastically shortened hemostatic time, and achieved satisfactory therapeutic efficacy by suppressing inflammation, modulating M1/M2 polarization of macrophages, significantly promoting collagen deposition, stimulating angiogenesis, epithelialization and tissue remodeling. This work contributes to the design of versatile hydrogel dressings for rapid and complete wound healing therapy., 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 B.V. All rights reserved.)

Increased glucocorticoid (GC) levels act as a master contributor to central obesity in estrogen-depleted females; however, what factors cause their increased GC production is unclear. Given (1) liver fibroblast growth factor 21 (FGF21) and GCs regulate each other's production in a feed-forward loop, and (2) circulating FGF21 and GCs are parallelly increased in menopausal women and ovariectomized mice, we thus hypothesized that elevation of hepatic FGF21 secretion causes increased GGs production in estrogen-depleted females. Using the ovariectomized mice as a model for menopausal women, we found that ovariectomy (OVX) increased circulating corticosterone levels, which in turn increased visceral adipose Hsd11b1 expression, thus causing visceral obesity in females. In contrast, liver-specific FGF21 knockout (FGF21 LKO) completely reversed OVX-induced high GCs and high visceral adipose Hsd11b1 expression, thus abrogating OVX-induced obesity in females. Even though FGF21 LKO failed to rescue OVX-induced dyslipidemia, hepatic steatosis, and insulin resistance. What's worse, FGF21 LKO even further exacerbated whole-body glucose metabolic dysfunction as evidenced by more impaired glucose and pyruvate tolerance and worsened insulin resistance. Mechanically, we found that FGF21 LKO reduced circulating insulin levels, thus causing the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes in OVX mice. Collectively, our results suggest that liver FGF21 plays an essential role in mediating OVX-induced central obesity by promoting GC production. However, lack of liver FGF21 signaling reduces insulin production and in turn causes the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes, highlighting a detrimental role for hepatic FGF21 signals in mediating the development of central obesity but a beneficial role in preventing metabolic abnormality from further exacerbation in estrogen-depleted females.

Background: Dietary fat intake is associated with an increased risk of colitis associated cancer (CAC). A high-fat diet (HFD) leads to systemic low-grade inflammation. The colon is believed to be the first organ suffering from inflammation caused by the infiltration of pro-inflammatory macrophages, and promotes CAC progression. We explored the role of HFD in driving CAC by altering gut microbial butyrate metabolism. Methods: Changes in the gut microbiota caused by HFD were investigated via HFD treatment or fecal microbiota transplantation (FMT). The underlying mechanisms were further explored by analyzing the role of gut microbiota, microbial butyrate metabolism, and NLRP3 inflammasome in colon tissues in a CAC mouse model. Results: HFD accelerated CAC progression in mice, and it could be reversed by broad-spectrum antibiotics (ABX). 16S-rRNA sequencing revealed that HFD inhibited the abundance of butyrate-producing bacteria in the gut. The level of short-chain fatty acids (SCFAs), especially butyrate, in the gut of mice treated with HFD was significantly reduced. In addition, treatment with exogenous butyrate reversed the M1 polarization of proinflammatory macrophages, aggravation of intestinal inflammation, and accelerated tumor growth induced by HFD; the NLRP3/Caspase-1 pathway activated by HFD in the colon was also significantly inhibited. In vitro , macrophages were treated with lipopolysaccharide combined with butyrate to detect the M1 polarization level and NLRP3/Caspase-1 pathway expression, and the results were consistent with those of the in vivo experiments. Conclusion: HFD drives colitis-associated tumorigenesis by inducing gut microbial dysbiosis and inhibiting butyrate metabolism to skew macrophage polarization. Exogenous butyrate is a feasible new treatment strategy for CAC, and has good prospect for clinical application., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Gastric cancer (GC) is among of the leading causes of cancer mortality worldwide. This is because many patients are diagnosed with advanced GC and postoperative radiotherapy and chemotherapy have also exhibited limited effects on GC. TYRO3 has been considered carcinogenic and a potential therapeutic target for GC. However, TYRO3 function and mechanism in GC remains elusive. The study results indicated that TYRO3 was aberrantly elevated in GC tissues and predicted poor prognosis. TYRO3 is closely associated with clinicopathological indicators in GC tissues such as lymph node metastasis, venous invasion, neural invasion, and the tumor-node-metastasis stage. In addition, TYRO3 expression levels are closely related to the AKT-mTOR pathway in GC tissues. Moreover, the oncogenic role of TYRO3 was determined through in vitro and in vivo functional assays, and knockdown of the TYRO3 expression level in GC cell lines can effectively suppress the AKT-mTOR pathway and inhibit tumor cell proliferation and migration. In conclusion, this study provides a theoretical basis for establishing the potential association and regulatory mechanism between TYRO3 and AKT-mTOR and offers a new strategy for GC-targeted therapy., (© 2023 Wiley Periodicals LLC.)

The endocrine system's interference caused by environmental estrogens (EEs) residue in food is a topic of public concern. Here, we construct an aptasensor for the sensitive detection of EEs based on luminescence resonance energy transfer (LRET). With MoS 2 nanosheets acting as the energy acceptor and upconversion luminescence nanoparticles@gold nanoparticles (UCNPs@Au) as the luminescence donor, autofluorescence from food is prevented from interfering. The in-situ deposition of AuNPs not only induces local field enhancement to significantly increase the luminescence intensity of UCNPs, but also conduces to the modification of aptamer through Au-S bond. This aptasensor can respond to multiple estrogens thanks to the choice of a universal aptamer that recognizes phenolic hydroxyl group, and it offers the probability to screen unidentified phenolic estrogens. This method has a high sensitivity and a low limit of detection (LOD), and the satisfactory recovery rates acquired from water and milk samples confirmed its considerable application value., 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 Ltd. All rights reserved.)

Gastric cancer (GC) is the most common gastrointestinal cancer and the leading cause of worldwide cancer-associated mortality. Several GC patients are diagnosed at the advanced stage with an unsatisfactory 5-year survival rate. Rab1A was significantly associated with IL4Rα expression in non-small cell lung cancer. However, their potential correlation in expression and prognosis remains largely unknown in GC. In this study, Rab1A/IL-4Rα was significantly increased in GC than in para-cancerous tissues, and Rab1A/IL-4Rα overexpression caused poor prognosis among GC patients. Rab1A expression was significantly correlated with IL-4Rα expression in GC tissues, as determined by IHC analysis. In addition, the mRNA expression of Rab1A was closely linked with the IL-4Rα mRNA expression in GC tissue expressed by qPCR. Furthermore, the Kaplan-Meier analysis demonstrated that the group with negative Rab1A and IL-4Rα expression had longer 5-year survival rates than the other group. Besides, the group with positive Rab1A and IL-4Rα expression had a worse prognosis than the other group. Finally, nomograms revealed the overall 3 and 5-year survival determined crucial roles of Rab1A/IL-4Rα expression in predicting the prognosis of GC patients. Therefore, Rab1A/IL-4Rα is vital in GC, providing a novel perspective on targeted GC therapy., (© 2023. The Author(s).)

Thioredoxin-interacting protein (TXNIP) was first isolated from Vitamin D3-exposed HL60 cells. TXNIP is the main redox-regulating factor in various organs and tissues. We begin with an overview of the TXNIP gene and protein information, followed by a summary of studies that have shown its expression in human kidneys. Then, we highlight our current understanding of the effect of TXNIP on diabetic kidney disease (DKD) to improve our understanding of the biological roles and signal transduction of TXNIP in DKD. Based on the recent review, the modulation of TXNIP may be considered as a new target in the management of DKD., 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 © 2023 Sun, Sun, Hua, Lu and Shao.)

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although considerable advances in CRC treatment have been achieved, effective treatment improvement has hit a bottleneck. This study demonstrated that TYRO3 expression was aberrantly increased in CRC tissues with prognosis association. The prediction model of prognosis for CRC patients was constructed based on TYRO3 expression. The model suggested that the TYRO3 level is crucial to the final prediction results. We observed that knockdown TYRO3 expression could inhibit the proliferation and migration ability and reverse the drug resistance by constructing drug-resistant CRC cell lines. In vivo experiments also confirmed this conclusion. Thus, targeting TYRO3 combined with 5-Fu treatment could provide a better therapeutic effect. Additionally, TYRO3 could inhibit the EMT process by down-regulating ENO1, which may be achieved by interfering with energy metabolism in cancer cells. Therefore, the current study provides a theoretical basis for TYRO3 in drug-resistance of CRC cells and highlights a new strategy for CRC-targeted therapy.

Remaining useful life (RUL) prediction of aircraft engine (AE) is of great importance to improve its reliability and availability, and reduce its maintenance costs. This article proposes a novel deep bidirectional recurrent neural networks (DBRNNs) ensemble method for the RUL prediction of the AEs. In this method, several kinds of DBRNNs with different neuron structures are built to extract hidden features from sensory data. A new customized loss function is designed to evaluate the performance of the DBRNNs, and a series of the RUL values is obtained. Then, these RUL values are reencapsulated into a predicted RUL domain. By updating the weights of elements in the domain, multiple regression decision tree (RDT) models are trained iteratively. These models integrate the predicted results of different DBRNNs to realize the final RUL prognostics with high accuracy. The proposed method is validated by using C-MAPSS datasets from NASA. The experimental results show that the proposed method has achieved more superior performance compared with other existing methods.

Disinfection eliminates pathogenic microorganisms and ensures a biosafe environment for human beings. The rapid spread of COVID-19 is challenging traditional disinfection methods in terms of reducing harmful side effects and conducting faster processes. Spraying large-scale chemical disinfectants is harmful to individuals and the environment, while UV lamp and light-emitting diode (LED) disinfection still requires a long exposure time due to the low irradiance and highly divergent beam characteristics. Given that a laser maintains a high irradiance over a long distance, we studied the effectiveness of lasers as a new disinfection method, and the results show the capability for ultrafast inactivation of SARS-CoV-2 virus with a 266 nm laser. This work confirms UV lasers as a good candidate for disinfection., (© 2022. The Author(s).)

We previously screened 6 differentially expressed miRNAs in ovarian tissues of 4-vinylcyclohexene diepoxide (VCD)-treated premature ovarian failure (POF) model in SD rats, including miRNA-190a-5p, miRNA-98-5p, miRNA-29a-3p, miRNA-144-5p, miRNA-27b-3p, miRNA-151-5p. In this study, to investigate the mechanisms causing the onset of POF, we first identified miRNAs with earlier differential expression at consecutive time points in the VCD-treated rat POF model and explored the mechanisms by which the target miRNAs promote POF. The SD rats were injected with VCD for 15 days to induce POF. Additionally, we collected rat blood and ovaries at the same time every day for 15 consecutive days, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), Anti-Mullerian hormone (AMH), and estradiol (E 2 ) serum levels were detected by ELISA. Six miRNAs expression were measured in rat ovaries by qRT-PCR. Dual-luciferase reporter gene assays were employed to predict and verify the target gene (PHLPP1) of target miRNAs (miRNA-190a-5p). Western blot was examined to detect the expression levels of PHLPP1, AKT, p-AKT, FOXO3a, p-FOXO3a, and LHR proteins on the target gene PHLPP1 and its participation in the primordial follicular hyperactivation-related pathways (AKT-FOXO3a and AKT-LH/LHR). During the VCD modeling POF rat ovaries, miRNA-190a-5p was the first to show significant differential expression, i.e., 6th of VCD treating, and PHLPP1 was verified to be a direct downstream target of it. Starting from the 6th of VCD treatment, the more significant the up-regulation trend of miRNA-190a-5p expression, the more obvious the down-regulation trend of PHLPP1 and LHR mRNA and protein expression, accompanied by the more severe phosphorylation of AKT and FOXO3a proteins, thus continuously over-activating the rat primordial follicle to promote the development of POF. In conclusion, miRNA-190a-5p may become a potential biomarker for early screening of POF, and it can continuously activate primordial follicles in rats by targeting the expression of PHLPP1 and key proteins in the AKT-FOXO3a and AKT-LH/LHR pathways., 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 © 2022 Zhang, Han, Yu, Shao, Zong, Zhang, Wang, Liang and Ge.)

Bovine uterine infection is commonly caused by Escherichia coli (E. coli). Elevated concentrations of plasma cortisol have been reported in postpartum cows. However, the direct role of cortisol in the inflammatory response of bovine endometrial stromal cells (BESCs) remains unclear. Therefore, the aim of the study was to explore the regulatory effect of cortisol on lipopolysaccharide (LPS)-induced inflammatory response in BESCs. Both the primary and immortalized BESCs were used in this study. BESCs were treated with cortisol (5, 15, and 30 ng/mL) in the presence of LPS. The mRNA expression of inflammatory cytokines and chemokines was detected using RT-qPCR. Western blot and immunofluorescence were used to analyze the activation of the NF-κB and MAPK signaling pathways. The results revealed that cortisol downregulated the LPS-induced overexpression of interleukin(IL)-1β, IL-6, IL-8, TNF-α, COX-2, iNOS in BESCs. Moreover, cortisol inhibited LPS-induced phosphorylation levels of IκB, p65, ERK1/2, JNK and p38, and p65 nuclear translocation in BESCs. These results indicated that cortisol inhibited LPS-induced inflammatory response in BESCs, which may be mediated by suppressing the NF-κB and MAPK signaling pathways., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Inflammatory bowel disease (IBD) is a global disease that is in increasing incidence. The gut, which contains the largest amount of lymphoid tissue in the human body, as well as a wide range of nervous system components, is integral in ensuring intestinal homeostasis and function. By interacting with gut microbiota, immune cells, and the enteric nervous system, the intestinal barrier, which is a solid barrier, protects the intestinal tract from the external environment, thereby maintaining homeostasis throughout the body. Destruction of the intestinal barrier is referred to as developing a "leaky gut," which causes a series of changes relating to the occurrence of IBD. Changes in the interactions between the intestinal barrier and gut microbiota are particularly crucial in the development of IBD. Exploring the leaky gut and its interaction with the gut microbiota, immune cells, and the neuroimmune system may help further explain the pathogenesis of IBD and provide potential therapeutic methods for future use.

Enzyme-linked immunosorbent assay (ELISA) is one of the most common methods in biological studies, and enzyme-linked immunospot (ELISpot) is a method to measure specific cell numbers by detecting protein secretion at a single-cell level. However, these two current methods can only detect one signal at one time and the sensitivity is not high enough to test low-concentration samples, which are major shortcomings in systematically analyzing the samples of interest. Herein, we demonstrated fluorescence-based oligo-linked immunosorbent assay (FOLISA) and fluorescence-based oligo-linked immunospot (FOLISPOT), which utilized DNA-barcoded antibodies to provide a highly multiplexed method with signal amplification. Signal amplification and simultaneous multiple-target detection were achieved by DNA complementary pairing and modular orthogonal DNA concatemers. By comparing FOLISA with traditional ELISA and comparing FOLISPOT with traditional ELISPOT, we found that the detection sensitivities of FOLISA and FOLISPOT are much higher than those of traditional ELISA and ELISPOT. The detection limit of ELISA is around 3 pg/mL, and the detection limit of FOLISA is below 0.06 pg/mL. FOLISPOT can detect more spots than ELISPOT and can detect targets that are undetectable for ELISPOT. Furthermore, FOLISA and FOLISPOT allowed sequential detection of multiple targets by using a single dye or multiple dyes in one round and sequential detection in multiple rounds. Thus, FOLISA and FOLISPOT enabled simultaneous detection of a large number of targets, significantly improved the detection sensitivity, and overcame the shortcomings of ELISA and ELISPOT. Overall, FOLISA and FOLISPOT presented effective and general platforms for rapid and multiplexed detection of antigens or antibodies with high sensitivity, either in laboratory tests or potentially in clinic tests.

Postpartum uterine infection in dairy cows is commonly caused by pathogenic bacteria such as Escherichia coli (E. coli). Progesterone elicits immunosuppressive function within bovine endometrium, and has been suggested to be related to postpartum uterine infection. Endometrial stroma is exposed to bacteria due to the disruption of epithelium during parturition, but the effect and mechanism of progesterone on innate immune response of stromal cells has not been reported. This study evaluated the impact of progesterone on inflammatory response of primary endometrial stromal cells stimulated by lipopolysaccharide or heat-killed E. coli. Quantitative PCR analysis revealed that progesterone repressed mRNA induction of IL1B, IL6, TNF, CXCL8, NOS2, and PTGS2 in stromal cells in response to lipopolysaccharide or E. coli challenge. Consistently, Western blot and immunofluorescence staining results showed that progesterone suppressed lipopolysaccharide- or E. coli-induced MAPK and NF-κB activations characterized with decreased phosphorylations of ERK1/2, JNK, P38, IκBα, and P65, and inhibition of P65 nuclear translocation. In unstimulated stromal cells, progesterone alone did not affect the mRNA transcription for IL6, TNF, CXCL8, NOS2, and PTGS2, and the signaling cascade of MAPK and NF-κB, but decreased IL1B mRNA expression. These results revealed that the anti-inflammatory effect of progesterone in lipopolysaccharide- or E. coli-challenged endometrial stromal cells was probably mediated through MAPK and NF-κB pathways., Competing Interests: The authors have declared that no competing interests exist.

In this study, an adaptive modified reaching law-based switch controller design was developed for robotic manipulator systems using the disturbance observer (DO) approach. Firstly, a standard DO is employed to estimate the unknown disturbances of the plant, from which the control signal could be compensated. Then, an adaptive modified reaching law is established to dynamically adapt the switching gain of the sliding mode robust term and further guarantee the finite-time arrival of the established sliding surface. Additionally, the convergence of the error system is analyzed via the Lyapunov method. At last, the feasibility and effectiveness of the proposed control scheme are verified by using a two-joint robotic manipulator model. The simulation results show that the developed controller can achieve rapid tracking, reduce system chattering and improve the robustness of the plant. The main innovations of the work are as follows. 1) A new adaptive reaching law is proposed; it can reduce chattering effectively, and it has a fast convergence speed. 2) Regarding the nonlinear robotic manipulator model, a novel adaptive sliding-mode controller was synthesized based on the DO to estimate the unknown disturbance and ensure effective tracking of the desired trajectory.

Patients with persistent ulcerative colitis (UC) are at a higher risk of developing colitis-associated cancer (CAC). Previous studies have reported that intestinal microbiota disturbance plays an important role in the process of CAC development in patients with UC, indicating that targeted intervention of intestinal microbiota and its metabolites may be a potential therapeutic strategy. Gut microbiota in the process of colorectal cancer development in UC patients was analyzed using the gutMEGA database and verified in fecal samples. The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development. Broad-spectrum antibiotics (BSAB) intervene with the intestinal microbiota of mice and accelerate the process of colon cancer development. However, gavage transplantation with B. fragilis can effectively reverse the effects of BSAB. In the intestinal tract, B. fragilis promotes the secretion of short-chain fatty acids (SCFAs). Subsequently, SCFAs, especially butyrate, negatively regulate the inflammatory signaling pathway mediated by NLRP3 to inhibit the activation of macrophages and the secretion of proinflammatory mediators such as IL-18 and IL-1β, reducing the level of intestinal inflammation and restricting CAC development. In conclusion, colonization with B. fragilis has been shown to be effective in ameliorating intestinal epithelial damage caused by chronic inflammation and preventing the development of colonic tumors. Thus, it can be a therapeutic intervention strategy with good clinical application prospects., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Nanozyme-mediated 3,3',5,5'-tetramethylbenzidine (TMB) - H 2 O 2 systems have spawned the establishment of multiple colorimetric sensing platforms that are effective but sometimes subject to low sensitivity. Taking temperature as the output signal, photothermal effects lead to new strategies for sensitive detection. In this paper, a colorimetric and photothermal dual-mode immunoassay for diethylstilbestrol (DES) was constructed. It is based on the oxidation reaction of TMB catalyzed by black phosphorus-gold nanoparticle (BP/Au) nanohybrids, and the kinetics as well as catalytic mechanism of the nanohybrids were investigated in detail for the first time. Herein, the nanohybrids playcatalytic and photothermal dual roles. Moreover, the one-electron oxidation product of TMB (oxidized TMB) not only acts as chromogenic agent but also an excellent NIR laser-driven photothermal agent. The temperature (ΔT/°C) was gauged by a portable digital thermometer. Through an indirect competition strategy, a simple, sensitive, and economic immunosensor was proposed. Higher DES content in the sample correlated with less BP/Au nanohybrids conjugated to the surface of ELISA microplate, a weaker color change, and a lower temperature variation when exposed to laser irradiation. This method was applied for DES determination in real samples with gratifying recovery rates, showing great promise in food safety inspection applications., Competing Interests: Declaration of competing interest We declare no conflict of benefit., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the past two decades, several methylated DNA targets, including gene promoters and other intronic markers have been explored in tumors and benign lesions. Therefore, it can be expected that a panel of stool-based biomarkers will become a screening method for colorectal cancer (CRC) and adenoma with better sensitivity and specificity, aiming to decrease the incidence and mortality of CRC. In this study, the methylation of secreted frizzled-related protein 1 (SFRP1), hyperplastic polyposis protein 1 (HPP1), α-internexin (INA), Wnt inhibitory factor 1 (WIF1), tissue factor pathway inhibitor 2 (TFPI2), ikaros family zinc finger protein 1 (IKZF1), and spastic paraplegia 20 (SPG20) were detected in stool samples from patients with CRC, adenoma, polyps, and healthy controls, respectively, and these biomarkers were used to establish a logistic regression model for classification. Receiver operating characteristic (ROC) curves were drawn to assess the importance of each biomarker. Subsequently, a biomarker or combination of biomarkers was analyzed for early screening of high-risk neoplasm. The data showed that when a single biomarker was used for CRC screening, the sensitivity ranged from 63.9% to 76.8%, the area under the curve (AUC) ranged from 0.821 to 0.875, and the accuracy ranged from 77.0% to 84.5%. Finally, the methylation of SFRP1, HPP1, TFPI2, and IKZF1 was selected using a backward stepwise method in the multivariate logistic analysis according to the Akaike Information Criterion. These findings indicate that stool DNA biomarkers have good diagnostic power in discriminating high-risk level of neoplasm from healthy population., Competing Interests: None., (AJTR Copyright © 2021.)

Colorectal cancer (CRC) is now the third most common malignancy and the second leading cause of cancer death globally. Bile acid has bidirectional regulatory effects on CRC and influences its progression by interacting with gut microbiota. In this review, we provide evidence for bidirectional regulation of bile acid on CRC at multi-level and discuss the communication of gene, immune, metabolism and diet in the context of CRC with bile acid-gut microbiota interaction. The study on bidirectional regulation of bile acid is helpful to provide a more comprehensive and in-depth understanding of CRC pathogenesis and expect to be a new option for the treatment of CRC., Competing Interests: None., (AJTR Copyright © 2021.)

Gastric cancer (GC) is a common malignancy around the world with a poor prognosis. Aldo-keto reductase family 1 member B10 (AKR1B10) is indispensable to cancer development and progression, which has served as a diagnostic biomarker for tumors. In our study, we demonstrated that the expression of AKR1B10 in GC tissues was significantly lower compared with normal gastric tissues. Subgroup analysis showed that, according to the clinic-pathological factors, the effect of the AKR1B10 expression level on the prognosis of GC patients was significantly different. Moreover, reduced expression of AKR1B10 promoted the ability of GC cells in proliferation and migration. Furthermore, increased AKR1B10 levels resulted in the opposite trend in vitro . Moreover, AKR1B10 was correlated with epithelial-mesenchymal transition (EMT) in a significant way. In vivo experiment, knockdown of AKR1B10 promoted the growth of tumor, increased Vimentin, and E-cadherin significantly. In summary, AKR1B10 is considered as a tumor suppressor in GC and is a promising therapeutic target.

Colorectal cancer (CRC) is one of the most frequent malignant neoplasms worldwide, and the effect of treatments is limited. Fibroblast growth factor 1 (FGF1) has been involved in a wide variety of several malignant diseases and takes part in the tumorigenesis of CRC. However, the function and mechanism of FGF1 in CRC remains elusive. In this study, the results indicated that FGF1 is elevated in CRC tissues and linked with poor prognosis ( P < 0.001). In subgroup analysis of FGF1 in CRC, regardless of any clinic-factors except gender, high level FGF1 expression was associated with markedly shorter survival ( P < 0.05). In addition, the expression of p-S6K1 and FGF1 was not associated in normal tissue ( P = 0.781), but their expression was closely related in tumor tissue ( P = 0.010). The oncogenic role of FGF1 was determined using in vitro and in vivo functional assays. FGF1 depletion inhibited the proliferation and migration of CRC cells in vitro and vivo . FGF1 was also significantly correlated with mTOR-S6K1 pathway on the gene and protein levels ( P < 0.05). In conclusion, FGF1 acts as a tumor activator in CRC, and against FGF1 may provide a new visual field on treating CRC, especially for mTORC1-targeted resistant patients., 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 Duan, Zhou, Yao and Shao.)

Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. Our recent study indicated that Rab1A expression was closely related to GLI1 expression. A previous study shows that aberrant overexpression of GLI1 promotes colorectal cancer metastasis via FoxM1 overexpression. However, the potential correlation between Rab1A and FoxM1 in CRC remains elusive. Immunohistochemistry was performed to investigate the association of the expression of Rab1A and FoxM1 and to determine the prognosis in 135 CRC tissue and adjacent normal tissues. Using Oncomine datasets, we found that Rab1A and FoxM1 mRNA were obviously upregulated in CRC tissues compared to normal tissues. Additionally, the expression of Rab1A and FoxM1 was significantly higher in CRC tissues than that in normal tissues. Rab1A expression was positively correlated with FoxM1 expression in CRC, especially in TNM stage III. In addition, Rab1A and FoxM1 overexpression was found to be significantly correlated with poor prognosis in CRC patients. Besides, both high expression of Rab1A and FoxM1 led to a worse prognosis than anyone low group, and both low expression of Rab1A and FoxM1 had a better prognosis than the anyone low group. Therefore, Rab1A and FoxM1 play crucial roles and could be used as clinical biomarkers in CRC.

Inflammatory bowel disease (IBD) is a chronic intestinal disease of unknown etiology. However, recent studies have established a pathological role of disordered intestinal microbiota and immune dysregulation. Clinical studies have suggested that the reconstruction of the normal intestinal flora in patients with IBD can reverse the dysbiosis caused by genetic, environmental, dietary, or antibiotic factors to ameliorate the symptoms of IBD. Lactobacillus reuteri is widely present in the intestines of healthy individuals and regulates the intestinal immune system, reducing inflammation through multiple mechanisms. This review summarizes the current knowledge of the role of L. reuteri in maintaining intestinal homeostasis and considers its possible value as a new therapeutic agent for patients with IBD., Competing Interests: None., (AJTR Copyright © 2020.)

Remaining useful life (RUL) prediction is very important for improving the availability of a system and reducing its life cycle cost. This paper proposes a deep long short-term memory (DLSTM) network-based RUL prediction method using multiple sensor time series signals. The DLSTM model fuses multi-sensor monitoring signals for accurate RUL prediction, which is able to discover the hidden long-term dependencies among sensor time series signals through deep learning structure. By grid search strategy, the network structure and parameters of the DLSTM are efficiently tuned using an adaptive moment estimation algorithm so as to realize an accurate and robust prediction. Two various turbofan engine datasets are adopted to verify the performance of the DLSTM model. The experimental results demonstrate that the DLSTM model has a competitive performance in comparison with state-of-the-arts reported in literatures and other neural network models., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2019 ISA. Published by Elsevier Ltd. All rights reserved.)

Background: Nucleotide-binding domain Leucine-rich Repeat Protein 3 (NLRP3) plays a regulatory role in the immune and inflammatory responses, and has been implicated in Colorectal Cancer (CRC) progression and metastasis. However, the underlying molecular mechanisms have not been fully elucidated., Methods: In this study, we analyzed the expression levels of NLRP3 in human CRC tissues, and performed functional assays in CRC cell lines and a subcutaneous tumor model to elucidate its role in the development and progression of CRC., Results: In this study, we found that NLRP3 was significantly upregulated in human CRC tissues and was associated with tumor size and invasion, lymph node metastasis, venous invasion, neural invasion and TNM staging. Furthermore, knockdown of NLRP3 in CRC cells inhibited their migration and growth in vitro and in vivo, and reversed Epithelial-Mesenchymal Transition (EMT) in vitro., Conclusion: Our findings indicate that NLRP3 likely regulates CRC metastasis by activating the EMT program, and is a potential therapeutic target., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

As the heat load within the central core of chirally-coupled-core (CCC) fibers will change the pre-designed refractive index profile through the thermo-optic effect, its impact on the laser performance of CCC fibers is investigated. Analysis and simulation results on two typical CCC fibers show that the effects of the heat load include the modal loss reduction and the transmission spectrum drift. The former comes from the thermal lensing effect in the central core, and the latter is caused by the change in the refractive index difference between the central core and the side core. Considering the non-uniform axial heat distribution in the actual laser operation, the overall laser performance of CCC fibers with different pump power is simulated. It is found that, because of the high pre-designed high-order mode loss, the single-mode operation of CCC fibers will be maintained but the slope efficiency may reduce dramatically if the fundamental mode loss is strongly dependent on the heat load.

Background: This study aims to assess the relationship between Rab1A expression and clinicopathological parameters and prognosis of patients with human solid cancer by summarizing the studies included., Methods: PubMed, EMBASE, The Cochrane Library, and other sources were searched for relative studies. The risk ratios (RRs) and confidence interval (CI) were used to assess association between Rab1A expression and clinical parameters and prognosis in solid cancer patients., Results: Eight studies were included in the final analysis with 800 patients. The results revealed that expression of Rab1A was significantly related with differentiation (RR = 0.883, 95%CI = 0.782-0.997, P = .044), lymph node metastasis (RR = 0.835, 95%CI = 0.753-0.926, P = .001), tumor-lymph node-metastasis (TNM) stage (RR = 1.190, 95%CI = 1.071-1.322, P < .001) and tumor size (RR = 0.818, 95%CI = 0.730-0.915, P < .001). What is more, no significant difference was seen in 1-year survival between high and low expression of Rab1A in multiple malignancies (RR = 0.855, 95%CI = 0.697-1.050, P = .136). However, increased Rab1A revealed poorer prognosis with 2-year survival (RR = 0.760, 95%CI = 0.701-0.824, P < .001), 3-year survival (RR = 0.669, 95%CI = 0.604-0.742, P < .001), 4-year survival (RR = 0.622, 95%CI = 0.554-0.698, P < .001) and 5-year survival (RR = 0.525, 95%CI = 0.458-0.698, P < .001). Expression of Rab1A was increased obviously in solid cancer tissues compared with the adjacent normal tissue (RR = 4.78, 95%CI 4.05-5.63, P = .015)., Conclusion: This study revealed Rab1A expression links closely with tumor size, differentiation, lymph node metastasis, TNM stage and poor prognosis of human solid cancer patients. It may act as a biomarker of prognosis and a novel therapeutic target in solid cancer.

Background: Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. The glycolytic enzyme α-enolase ( ENO1 ) is overexpressed in multiple cancers and is involved in tumor cell proliferation and metastasis. However, its clinical significance, biological role, and underlying molecular mechanisms in CRC are still unclear. The aim of the present study was to investigate the potential role of ENO1 in the initiation and development of CRC., Patients and Methods: The in situ expression of ENO1 in CRC and adjacent normal tissues was examined by immunohistochemistry. The effects of ENO1 on the in vitro proliferation and migration of CRC cell lines were investigated by MTT, colony formation, and Transwell assays. Finally, the in vivo tumorigenic capacity of ENO1 was assessed in a mouse model., Results: ENO1 was overexpressed in CRC tissues and significantly correlated with the clinicopathological parameters. Furthermore, Rab1A was also overexpressed in CRC tissues and was positively correlated to that of ENO1. The high expression levels of both ENO1 and Rab1A led to significantly worse prognosis of CRC patients compared to either alone. Furthermore, knockdown of ENO1 significantly inhibited CRC cells proliferation and migration in vitro and reduced xenograft growth in vivo via the concomitant downregulation of Rab1A., Conclusion: The ENO1/Rab1A signaling axis is involved in CRC progression and is a potential biomarker for the treatment of CRC., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Cheng et al.)

Mode instabilities (MI) threshold in the Yb:YAG crystalline fiber amplifier is simulated by a full numerical model. The propagation of signal fields is simulated by the finite-difference beam-propagation method combined with the rate equations, and the time-dependent heat equation is solved by the alternating-direction-implicit method. Considering the strong temperature-dependent laser performance of Yb:YAG, an iterative method is applied to reach the steady state of Yb:YAG, the crystalline fiber amplifier, before the simulation of MI behavior. The simulated MI thresholds in Yb:YAG crystalline fiber amplifiers are found to be at least 28 times of those in Yb-doped silica-glass fiber amplifiers, up to tens of kilowatts. Simulation results show that, in addition to the expected higher thermal conductivity and lower thermo-optic coefficient, strong gain saturation also plays an important role in the high MI threshold of the Yb:YAG crystalline fiber.

Gastrointestinal cancers have become increasingly prevalent worldwide. Previous studies have reported an oncogenic function of Rab1A in colorectal cancer and hepatocellular carcinomas via the mTOR pathway. However, the exact role of Rab1A in gastrointestinal cancers remains elusive. We detected significantly higher expression of Rab1A in the gastrointestinal tumor tissues compared to that in other cancer types following an in silico analysis of TGCA and GTEX databases. Furthermore, Rab1A was overexpressed in the gastrointestinal tumor tissues compared to the para-tumor tissues. Although Rab1A expression levels were not associated with the tumor-lymph node-metastasis (TNM) stage, Rab1A overexpression in the tumor tissues of a gastric cancer (GC) cohort was strongly correlated with poor prognosis in the patients. In addition, Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of GC cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. Taken together, Rab1A regulates the PI3K-AKT-mTORC1 pathway through the mTORC1 complex consisting of mTORC1, Rheb and Rab1A, and is a promising therapeutic target in GC.

Accurate and timely bearing fault diagnosis is crucial to decrease the probability of unexpected failures of rotating machinery and improve the efficiency of its scheduled maintenance. Since convolutional neural networks (CNN) have poor feature extraction capability for sensor data with 1D format, CNN combined with signal processing algorithm is often adopted for fault diagnosis. This increases manual conversion work and expertise dependence while reducing the feasibility and robustness of the corresponding fault diagnosis method. In this paper, a novel sensor data-driven fault diagnosis method is proposed by fusing S-transform (ST) algorithm and CNN, namely ST-CNN. First of all, a ST layer is designed based on S-transform algorithm. In the ST layer, sensor data is automatically converted into 2D time-frequency matrix without manual conversion work. Then, a new ST-CNN model is constructed, and the time-frequency coefficient matrixes are inputted into the constructed ST-CNN model. After the training process of the ST-CNN model is completed, the classification layer such as softmax performs the fault diagnosis. Finally, the diagnosis performance of the proposed method is evaluated by using two public available datasets of bearings. The experimental results show that the proposed method performs the higher and more robust diagnosis performance than other existing methods.

Colorectal carcinoma (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer‑related deaths in the US. Recently, Rab1A has been reported to be an activator of mTORC1 and p‑S6K1, which is downstream of mTORC1. However, the association between Rab1A and p‑S6K1 in CRC remains elusive. In the present study, we first demonstrated that Rab1A was overexpressed in CRC tissues and Rab1A overexpression was positively related to lymph node invasion, degree of differentiation, venous invasion and tumor‑node‑metastasis (TNM) stage. In both TNM stage I‑II and III‑IV patients, Rab1A‑positive patients had a shorter survival time than Rab1A‑negative patients. Furthermore, in univariate and multivariate analyses, only Rab1A expression was verified as an independent prognostic factor for survival in CRC patients. The level of p‑S6K1 was markedly high in CRC tissues and Rab1A expression level had a positive association with p‑S6K1 level. In addition, high levels of both Rab1A and p‑S6K1 were associated with a poorer prognosis compared with low expression of either Rab1A or p‑S6K1 level. Moreover, high levels of both Rab1A and p‑S6K1 were associated with a poorer prognosis than patients with high levels of either Rab1A or p‑S6K1 alone. Finally, knockdown of Rab1A expression inhibited migration and proliferation of SW480 and HCT116 cell lines by targeting regulation of p‑S6K1. Thus, our findings indicate that Rab1A plays an important role in CRC and may provide a therapeutic target for CRC, particularly for mTORC1‑targeted therapy‑resistant cancers.

Hedgehog (HH) pathway significantly affected the pathogenesis of Gastric cancer (GC), but the multiple uncanonical HH pathways that are mediated by Zinc Finger protein GLI1 (GLI1) are still unclear. In the present work, we evaluated GLI1 and p-AKT expression in GC using immunohistochemistry (IHC) analysis. GLI1 and AKT specific shRNA was transfected into GC cell lines to investigate the cross-regulation between HH pathway and AKT-mTOR pathway. The effect of GLI1 and p-AKT on proliferation, migration, and drug resistance were examined. Moreover, a mouse xenograft model of GC was established to verify the role of GLI1 and p-AKT in promoting drug sensitivity in vivo. Our results suggested the clinicopathological factors and prognosis by the differential expression of GLI1 and p-AKT in GC patients. GLI1 was activated by the AKT-mTOR pathway. Co-expression of GLI1 and p-AKT was associated with cell viability, migration, and drug resistance and indicated a poor prognosis in GC patients. Agents targeted against both GLI1 and p-AKT may reverse drug-resistance and achieve better inhibition than agents targeted against a single molecule. There was a significant correlation between the high expression of GLI1 and p-AKT in GC. Additionally, our study confirmed the activity of the AKT-mTOR-GLI1 axis, which provided a new viable field for GC treatment., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Since obesity is largely responsible for the growing incidence of renal tubulointerstitial inflammation, exploration into the mechanisms of obesity‑associated tubulointerstitial inflammation is essential. Studies have demonstrated that mammalian target of rapamycin (mTOR) is a crucial molecule in the pathogenesis of renal inflammation, including regulating the expression of inflammatory factors. The purpose of the present study was to further elucidate the role of mTOR in obesity‑associated tubulointerstitial inflammation. In the clinical study, obese and healthy subjects were recruited for physical examination, as well as the collection of blood and urine samples. Further study was performed on a high fat diet (HFD)‑induced obese rat model and a cultured human renal tubular epithelial cell line (HK‑2). The clinical study demonstrated that the participants with obesity had increased serum lipids, creatinine (Cr), urinary albumin to creatinine ratio (UACR) and urinary neutrophil gelatinase‑associated lipocalin (u‑NGAL). Moreover, the level of urinary monocyte chemoattractant protein‑1 (u‑MCP‑1) was increased in the participants with obesity, and it was positively correlated with free fatty acid (FFA), UACR and u‑NGAL. In the in vivo study, the results indicated that the levels of serum lipids, Cr and blood urea nitrogen (BUN), as well as 24 h urine protein and u‑NGAL, were significantly increased in the HFD‑fed obese rats. In addition, the infiltration of CD68+ cells into the renal interstitial area and the release of interleukin‑1β (IL‑1β) was observed in the kidneys of obese rats. Meanwhile, the supernatant from HK‑2 cells treated with palmitic acid stimulated THP‑1 monocyte migration. The upregulation of MCP‑1, phosphorylated forkhead boxO1 (p‑FOXO1), and phosphorylated mTOR (p‑mTOR) was observed in vivo and in vitro. However, inhibition of mTOR was able to alleviate the above effects. Overall, these results demonstrated that activated mTOR induced FOXO1 phosphorylation, which mediates renal MCP‑1 release, causes tubulointerstitial inflammation and ultimately leads to pathological renal changes and dysfunction. However, inhibition of mTOR may play a renoprotective role during the progression of obesity‑associated tubulointerstitial inflammation.

Background: Gastric Cancer (GC) is a frequently common malignancy. Recent studies have reported Rab1A as an activator of mTORC1, and the mTOR1 pathway is involved in regulating Gli1 expression in several cancers. Only a few studies have been performed to explore the relationship between Rab1A and p-S6K/Gli1in GC., Methods: Immunohistochemistry (IHC) was performed to explore the association of Rab1A/p-S6K/Gli1 expression and prognosis in 117 GC tissue samples and adjacent normal tissues., Results: Our results indicated that Rab1A/p-S6K/Gli1 was significantly overexpressed in GC tissues. High expression of Rab1A was closely related to the tumor size and the depth of tumor invasion. In addition, Rab1A expression was closely related with p-S6K/Gli1 expression in GC, and high level of Rab1A/p-S6K/Gli1 caused worse prognosis of GC patients. The univariate and multivariate analysis indicated that the expression of Rab1A was an independent prognostic factor. Moreover, both high Rab1A and p-S6K expression led to a worse prognosis when compared to a single positive expression as well as both high Rab1A/Gli1 expression also led to a worse prognosis than the single positive expression of Rab1A/Gli1. Strikingly, the overexpression of p-S6K also led to a worse prognosis in Rab1A positive patients, as did Gli1., Conclusion: Our results indicate that Rab1A/mTOR/S6K/Gli1 axis played a crucial role in GC, which may provide a novel field on targeted therapy of GC, especially for mTORC1-targeted therapy-resistant cancers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The study aims to assess the relationship between FoxM1 expression and clinicopathological parameters and prognosis of patients diagnosed with colorectal cancer (CRC) by summarizing the studies included., Methods: PubMed, EMBASE, The Cochrane Library and other sources were searched for relative studies. Odds ratio (OR) and confidence interval (CI) were used to assess association between FoxM1 expression and clinical parameters and prognosis of CRC patients., Results: Eight studies were included in the final analysis, with 1149 CRC patients. The outcome revealed that expression of FoxM1 was associated with lymph node metastasis (OR = 0.33, 95%CI = 0.19-0.62, P < .001), distant metastasis (OR = 0.35, 95%CI = 0.24-0.46, P < .001) and tumor node metastasis (TNM) stage (OR = 0.45, 95%CI = 0.29-0.72, P < .001). Meanwhile, reduced FoxM1 expression indicated higher 5-year survival rate (OR = 0.38, 95%CI = 0.18-0.78, P = .01). Expression of FoxM1 was also increased obviously in CRC tissues (OR = 13.04, 95%CI = 4.07-41.71, P < .001)., Conclusion: This pooled analysis indicated that FoxM1 expression related to lymph node metastasis, distant metastasis, TNM stage and poor prognosis of the CRC patients.

This publisher's note amends a figure caption in Appl. Opt.57, 8182 (2018)APOPAI0003-693510.1364/AO.57.008182.

An all-in-fiber method of generating orbital angular momentum (OAM) is proposed. A simple device composed with a section of helically symmetric fiber and another section of regular fiber is designed to convert input light to optical vortices. Finite element method calculation of first- and second-order OAM generation based on the coordinates transformation technique is taken to show that the eigenmodes of the helically symmetric fiber structures carry orbital and spin angular momentum. Simulation using the self-developed beam propagation method algorithm is also performed to verify the orbital angular momentum generation and evaluate the performance of the OAM generator.

A new three-dimensional finite-difference (FD)-based beam propagation method (BPM) is proposed for simulating optical propagation in weakly guiding waveguides with torsional birefringence, which cannot be simulated by existing FD-BPM algorithms. We also demonstrate that this new BPM algorithm is capable of obtaining eigenmode solutions in a helically-symmetric z-dependent waveguide structure with torsional birefringence.