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Abstract Exosomes are nanosized extracellular vesicles that can be released by almost all types of cells. Initially considered as the garbage bins acting to discard unwanted products of cells, exosomes are now recognized as an important way for cellular communication by transmitting bioactive molecules including proteins, DNA, mRNAs, and non-coding RNAs. The recent studies have shown that exosomes are critically involved in human health and diseases including cancer. Exosomes have been suggested to participate in the promotion of tumorigenesis, tumor growth and metastasis, tumor angiogenesis, tumor immune escape, and tumor therapy resistance. Increasing evidence indicate that exosomes play important roles in gastric cancer development and progression. In this review, we summarized the current understanding of exosomes in gastric cancer with an emphasis on the biological roles of exosomes in gastric cancer and their potential as biomarkers for gastric cancer diagnosis as well as potential targets for gastric cancer therapy.

Purine nucleotides are indispensable compounds for many organisms and participate in basic vital activities such as heredity, development, and growth. Blocking of purine nucleotide biosynthesis may inhibit proliferation and development and is commonly used in cancer therapy. However, the function of the purine nucleotide biosynthesis pathway in the pathogenic fungus Magnaporthe oryzae is not clear. In this study, we focused on the de novo purine biosynthesis (DNPB) pathway and characterized MoAde8, a phosphoribosylglycinamide formyltransferase, catalyzing the third step of the DNPB pathway in M. oryzae. MoAde8 was knocked out, and the mutant (∆Moade8) exhibited purine auxotroph, defects in aerial hyphal growth, conidiation, and pathogenicity, and was more sensitive to hyperosmotic stress and oxidative stress. Moreover, ∆Moade8 caused decreased activity of MoTor kinase due to blocked purine nucleotide synthesis. The autophagy level was also impaired in ∆Moade8. Additionally, MoAde5, 7, 6, and 12, which are involved in de novo purine nucleotide biosynthesis, were also analyzed, and the mutants showed defects similar to the defects of ∆Moade8. In summary, de novo purine nucleotide biosynthesis is essential for conidiation, development, and pathogenicity in M. oryzae.

Groundwater is an important water resource in arid and semi-arid regions. The impact of human activities on groundwater is increasing. After 60 years running, the groundwater quality and its formation mechanism are imperative questions needed to be answered in Jiaokou Irrigation District, Guanzhong Basin, China. In this study, the quality of groundwater in Jiaokou Irrigation District was assessed by a new integrated-weight water quality index (IWQI), and the groundwater chemistry is studied through integrated statistical, geostatistical and hydrogeochemical approaches. The patterns for the average anion and cation concentrations were HCO3− > SO42− > Cl− > NO3− > CO32− > NO2−, and Na+ > Mg2+ > Ca2+ > K+ > NH4+, respectively. Statistics showed that the major water chemistry types were HCO3-Na, SO4·Cl-Na, and Cl·SO4-Na. A new integrated-weight water quality index (IWQI) was proposed based on the entropy-weighted method and CRITIC method and showed excellent performance for explaining and evaluating the groundwater quality. The IWQI results show 65.33% of groundwater, mainly distributed in the central and western parts of this study area, was unsuitable for drinking. Furthermore, SO42－, HCO3－, Cl－, NO3－, and Na+ had more important effects on groundwater quality. The weathering process affecting groundwater quality in the study area is carbonate dissolution, followed by silicate weathering and evaporite dissolution, whereas the major geochemical processes include the dissolution and precipitation of calcite, as well as the dissolution of dolomite and gypsum (anhydrite). Cation exchange also plays an important role in the hydrogeochemical evolution of groundwater with a long residence time. Anthropogenic activities affecting groundwater quality included long-term irrigation infiltration and excessive use of fertilizers. The findings and the results of the study can improve understanding of the processes driving groundwater chemistry in Jiaokou Irrigation District, and can be used for reference to other similar regions in the world.

Gastric cancer is a malignant tumor characterized by high morbidity and invasion. Surgery combined with chemo-radiotherapy is the most common treatment for gastric cancer, while multiple drug resistance always results in treatment failure. Once the anti-tumor drugs enter the tumor foci, tumor cells as well as those found in the microenvironment are affected. However, the effects of drugs on tumor microenvironment (TME) are easily overlooked. In this study, we investigated the effects of the anti-cancer drug 3,3’-diindolylmethane (DIM) on gastric cancer-derived mesenchymal stem cells (GC-MSCs) and their subsequent impact on cancer progression. Surprisingly, we found that the therapeutic concentration of DIM upregulated the expression level of tumor-related factors such as CCL-2, IL-6, and IL-8 in GC-MSCs. The conditioned medium of DIM-treated GC-MSCs promoted the proliferation, invasion, and migration of gastric cancer cells in vitro and tumor growth in vivo. Mechanistically, DIM enhanced the expression of β-TrCP, an E3 ubiquitin ligase leading to IκBα degradation and NF-κB activation in GC-MSCs. The β-TrCP knockdown partially eliminated positive results caused by DIM. Our results showed that the therapeutic dosage of DIM induced cell death in cancer cells, while enhancing MSC paracrine functions in the stroma to offset the original DIM effect on cancer cells. These findings provide a new mechanism of anti-cancer drug resistance and remind us to adjust the chemotherapeutic scheme by combining the anti-cancer drug with an appropriate signaling pathway inhibitor to block the side effects of drug on targeted TME cells.

A feature of arbuscular mycorrhiza is enhanced drought tolerance of host plants, although it is unclear whether host H+-ATPase activity and gene expression are involved in the physiological process. The present study aimed to investigate the effects of an arbuscular mycorrhizal fungus (AMF), Funneliformis mosseae, on H+-ATPase activity, and gene expression of trifoliate orange (Poncirus trifoliata) seedlings subjected to well-watered (WW) and drought stress (DS), together with the changes in leaf gas exchange, root morphology, soil pH value, and ammonium content. Soil drought treatment dramatically increased H+-ATPase activity of leaf and root, and AMF inoculation further strengthened the increased effect. A plasma membrane (PM) H+-ATPase gene of trifoliate orange, PtAHA2 (MW239123), was cloned. The PtAHA2 expression was induced by mycorrhization in leaves and roots and also up-regulated by drought treatment in leaves of AMF-inoculated seedlings and in roots of AMF- and non-AMF-inoculated seedlings. And, the induced expression of PtAHA2 under mycorrhization was more prominent under DS than under WW. Mycorrhizal plants also showed greater photosynthetic rate, stomatal conductance, intercellular CO2 concentration, and transpiration rate and better root volume and diameter than non-mycorrhizal plants under DS. AMF inoculation significantly increased leaf and root ammonium content, especially under DS, whereas it dramatically reduced soil pH value. In addition, H+-ATPase activity was significantly positively correlated with ammonium contents in leaves and roots, and root H+-ATPase activity was significantly negatively correlated with soil pH value. Our results concluded that AMF stimulated H+-ATPase activity and PtAHA2 gene expression in response to DS, which resulted in great nutrient (e.g., ammonium) uptake and root growth, as well as low soil pH microenvironment.

Circular RNAs (circRNAs) are newly discovered intriguing RNAs due to the covalently closed loop structure, high stability, tissue specificity, and functional diversity. In recent years, a large number of circRNAs have been identified through high-throughput sequencing technology and bioinformatics methods, the abnormal expression of circRNAs are closely related to many diseases including bladder cancer (BC). CircRNAs have been proven to have several functions, such as acting as a regulator of parental gene transcription, miRNA sponge and interacting with proteins to regulate its expression. In addition, some circRNAs have been identified to encode proteins. CircRNAs have the characteristics of high abundance, high stability, wide distribution in body fluids, tissue specificity, and developmental stage specificity, which determine that circRNAs has great potential to be utilized as biomarkers for BC. Herein, we briefly summarize the biogenesis, functions and roles, and the current research progress of circRNAs in BC with a focus on the potential application for BC diagnosis, treatment, and prognosis.

In recent years, an elevated concentration of nitrate in groundwater has been a growing problem on a global scale. It directly shows the adverse effects on human health via various intake pathways. Herein, the aim of the present study was to evaluate the nitrate concentration in groundwater and its associated human health risk in various age groups (females, males and children) in the investigated region. For this purposes, thirty groundwater samples were collected and analyzed physico-chemical parameters including nitrate concentration. The results showed that, the concentration of nitrate ranges from 14 to 82 mg/L and about 43.3% of these groundwater samples beyond the safe level of 45 mg/L according to Indian guidelines. The higher nitrate contamination is observed in the vicinity of Sarvepalli and Timmapur villages where groundwater chemistry is majorly influenced by anthropogenic sources. Health risks were assessed through oral/ingestion and dermal contact exposure routes for females, males and children population in the study region. Oral exposure was much higher than dermal contacts. For the non-carcinogenic risk, the HITotal values of groundwater in the investigated region varied from 0.313 to 1.976 (mean of 0.941) for males, 0.370 to 2.336 (mean of 1.112) for females and 0.443 to 2.694 (mean of 1.314) for children. The health risk assessment for nitrate divulged that 60%, 57% and 50% of groundwater samples pose a non-carcinogenic health risk for children, females and males, respectively.

Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure. Sexual dysfunction has been reported in patients with seizure, which mostly manifests as erectile dysfunction and premature ejaculation in men. In this study, we report the case of a 65-year-old Chinese man with frequent spermatorrhea. Electroencephalography suggested local epilepsy in the left temporal lobe. After treatment with anti-epilepsy drugs, the symptoms disappeared and did not recur. To the best of our knowledge, this is the first reported case of epilepsy-induced spermatorrhea. The symptoms of spermatorrhea are probably a rare manifestation of seizure. When repetitive stereotyped symptoms occur, seizure should be considered, and tentative anti-epileptic treatment may be a good option.

Exosomes are small extracellular vesicles (EVs) secreted by almost all cells, which have been recognized as a novel platform for intercellular communication in the central nervous system (CNS). Exosomes are capable of transferring proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, contributing to CNS development and maintenance of homeostasis. Evidence shows that exosomes originating from CNS cells act as suppressors or promoters in the initiation and progression of neurological disorders. Moreover, these exosomes have been shown to transfer molecules associated with diseases through the blood-brain barrier (BBB) and thus can be detected in blood. This unique feature enables exosomes to act as potential diagnostic biomarkers for neurological disorders. In addition, a substantial number of researches have indicated that exosomes derived from mesenchymal stem cells (MSCs) have repair effects on neurological disorders. Herein, we briefly introduce the roles of exosomes under physiological and pathological conditions. In particular, novel roles of exosomes as potential diagnostic biomarkers and therapeutic tools for neurological disorders are highlighted.

Circular RNA CDR1as has been demonstrated to participate in various cancer progressions as miRNA sponges. The exact underlying mechanisms of CDR1as on gastric cancer (GC) metastasis remain unknown. Here, we found that CDR1as knockdown facilitated GC cell migration and invasion while its overexpression inhibited the migration and invasion abilities of GC cells in vitro and in vivo. Moreover, epithelial-mesenchymal transition- (EMT-) associated proteins and MMP2 and MMP9 were downregulated by CDR1as. Bioinformatics analysis combined with dual-luciferase reporter gene assays, western blot, RT-qPCR analysis, and functional rescue experiments demonstrated that CDR1as served as a miR-876-5p sponge and upregulated the target gene GNG7 expression to suppress GC metastasis. In summary, our findings indicate that CDR1as suppresses GC metastasis through the CDR1as/miR-876-5p/GNG7 axis.

Exosomes are nanometer-sized small EVs coated with bilayer structure, which are released by prokaryotic and eukaryotic cells. Exosomes are rich in a variety of biologically active substances, such as proteins, nucleotides, and lipids. Exosomes are widely present in various body fluids and cell culture supernatants, and it mediates the physiological and pathological processes of the body through the shuttle of these active ingredients to target cells. In recent years, studies have shown that exosomes from a variety of cell sources can play a beneficial role in acute and chronic kidney disease. In particular, exosomes derived from mesenchymal stem cells have significant curative effects on the prevention and treatment of kidney disease in preclinical trials. Besides, some encapsulated substances are demonstrated to exert beneficial effects on various diseases, so they have attracted much attention. In addition, exosomes have extensive sources, stable biological activity, and good biocompatibility and are easy to store and transport; these advantages endow exosomes with superior diagnostic value. With the rapid development of liquid biopsy technology related to exosomes, the application of exosomes in the rapid diagnosis of kidney disease has become more prominent. In this review, the latest development of exosomes, including the biosynthesis process, the isolation and identification methods of exosomes are systematically summarized. The utilization of exosomes in diagnosis and their positive effects in the repair of kidney dysfunction are discussed, along with the specific mechanisms. This review is expected to be helpful for relevant studies and to provide insight into future applications in clinical practice.

Exosomes have emerged as a new drug delivery system. In particular, exosomes derived from mesenchymal stem cells (MSCs) have been extensively studied because of their tumor-homing ability and yield advantages. Considering that MSC-derived exosomes are a double-edged sword in the development, metastasis, and invasion of tumors, engineered exosomes have broad potential use. In this review, we focused on the latest development in the treatment of tumors using engineered and nonengineered MSC-derived exosomes (MSC-EXs). Nonengineered MSC-EXs exert an antitumor effect on several well-studied tumors by affecting tumor growth, angiogenesis, metastasis, and invasion. Furthermore, engineered exosomes have promising research prospects as drug-carrying tools for the transport of miRNAs, small-molecule drugs, and proteins. Although exosomes lack uniform standards in terms of definition, separation, and purification, they still have great research value because of their unique advantages, such as high biocompatibility and low toxicity. Future studies on MSC-EXs should elucidate the mechanisms underlying their anticancer effect and the safety of their application.

Existing dynamic load factors (DLF) for crowd jumping loads are modeled by identifying the peaks and energies from the corresponding Fourier amplitude spectrum, which may underestimate and overestimate structural responses, respectively. Based on the principle of equal structural responses, this study herein develops an equivalent DLF, using the frequency response function to weight and integrate the power spectral density (PSD) matrix of crowd jumping loads. Firstly, massive PSD matrices of different crowd sizes and different metronome frequencies are simulated using a random field model of crowd jumping loads. Thereafter, the equivalent DLF of different structural damping ratios, crowd sizes, metronome frequencies, and non-exceedance probabilities are investigated, and a model of the equivalent DLF is established accordingly. It is believed that this model could provide an efficient and accurate way to conduct reliability design for structures subjected to crowd jumping loads.

In response to tumor signals, mesenchymal stem cells (MSCs) are recruited to tumor sites and activated to promote tumor progression. Emerging evidences suggest that in addition to tumor cells, non-tumor cells in tumor microenvironment could also interact with MSCs to regulate their phenotype and function. However, the mechanism for MSCs regulation in gastric cancer has not been fully understood. In this study, we reported that tumor-educated neutrophils (TENs) induced the transformation of MSCs into cancer-associated fibroblasts (CAFs) which in turn remarkably facilitated gastric cancer growth and metastasis. Mechanistic study showed that TENs exerted their effects by secreting inflammatory factors including IL-17, IL-23 and TNF-α, which triggered the activation of AKT and p38 pathways in MSCs. Pre-treatment with neutralizing antibodies to these inflammatory factors or pathway inhibitors reversed TENs-induced transformation of MSCs to CAFs. Taken together, these data suggest that TENs promote gastric cancer progression through the regulation of MSCs/CAFs transformation.

Abstract Background Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammation that is a risk factor for many gastrointestinal cancers. Exosomes are gradually gaining attention as an emerging treatment method for IBD due to their important biological characteristics. NF‐κB is an important pro‐inflammatory transcription factor kept inactive by IκB protein in the cytoplasm by masking the nuclear localization signal of NF‐κB. The deterioration of IκB is mainly ubiquitination, and this depends on neddylation. Methods In this study, we established a dextran sulfate sodium (DSS)‐induced IBD model in BABL/C mice to evaluate the effect of human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes, hucMSC‐Ex) on the repair of IBD. At the same time, human colorectal mucosa cells (FHC) were stimulated by LPS (lipopolysaccharide) in vitro to activate the inflammatory environment to study the mechanism of hucMSC‐Ex regulating neddylation. The microRNA (miRNA) obtained by sequencing and transfection with hucMSC‐Ex was used to verify the role of miR‐326/neddylation/IκB/NF‐κB signaling pathway in IBD repair. Results HucMSC‐Ex inhibited the process of neddylation in relieving DSS‐induced IBD in mice. The binding of NEDD8 (neural precursor cell‐expressed, developmentally downregulated gene 8) to cullin 1 and the activation of NF‐κB signaling pathway were suppressed along with reduced expression levels of neddylation‐related enzyme molecules. The same phenomenon was observed in FHC cells. The miRNA comparison results showed that miR‐326 was highly expressed in hucMSC‐Ex and played an important role in inhibiting the neddylation process. The therapeutic effect of hucMSC‐Ex with high expression of miR‐326 on IBD mice was significantly stronger than that of ordinary hucMSC‐Ex. Conclusions HucMSC‐Ex relieves DSS‐induced IBD in a mouse model by inhibiting neddylation through miR‐326.

The extracellular polymeric substances (EPS) construct the three-dimensional (3-D) structure of biofilms, but their respective roles are still not clear. Therefore, this study aimed to illuminate the role of key chemical components [extracellular DNA (eDNA), extracellular proteins, and carbohydrates] of EPS in biofilm formation of Vibrio parahaemolyticus. The correlations between each key chemical component and biofilm formation were first determined, showing that the biofilm formation of V. parahaemolyticus was strongly positively correlated with both eDNA and protein content (P < 0.01), but not with carbohydrates. Subsequently, individual DNase I or protease K treatment markedly reduced the initial adhesion and structural stability of the formed biofilms by hydrolyzing the eDNA or extracellular proteins, but did not induce significant dispersion of mature biofilms. However, the combination of DNase I and protease K treatment induced the obvious dispersion of the mature biofilms through the concurrent destruction of eDNA and extracellular proteins. The analysis at a structural level showed that the collapse of biofilms was mainly attributed to the great damage of the loop configuration of eDNA and the secondary structure of proteins caused by the enzyme treatment. Therefore, this study provides a deep understanding of the role of key chemical components of EPS in biofilm development of V. parahaemolyticus, which may give a new strategy to develop environmentally friendly methods to eradicate the biofilms in food industry.

Neutrophils are prominent components of solid tumors and exhibit distinct phenotypes in different tumor milieu. We have previously shown that tumor extracellular vesicles (EVs) could induce pro-tumor activation of neutrophils; however, the role of tumor EV-elicited neutrophils in tumor immunity remains unclear. Herein, we reported that gastric cancer cell-derived EVs (GC-EVs) induced the expression of programmed death-ligand 1 (PD-L1) on neutrophils. GC-EVs transported high-mobility group box-1 (HMGB1) to activate signal transducer and activator of transcription 3 (STAT3) and upregulate PD-L1 gene expression in neutrophils. Blocking STAT3 pathway and silencing HMGB1 reversed GC-EV-induced PD-L1 expression on neutrophils. GC-EV-elicited neutrophils suppressed T cell proliferation, activation, and function in vitro, which could be antagonized by a specific PD-L1 antibody. Furthermore, GC tissue-derived EVs also showed similar effects. Taken together, our results indicate that EVs from the GC microenvironment induce PD-L1 expression on neutrophils to suppress T-cell immunity, which provides a new insight into the pro-tumor roles of neutrophils in GC and sheds light on the multifaceted roles of EVs in orchestrating an immunosuppressive microenvironment.

The sessile biofilms of Vibrio parahaemolyticus and Listeria monocytogenes have increasingly become a critical threat in seafood safety. This study aimed to evaluate the effects of modified atmospheres on the formation ability of V. parahaemolyticus and L. monocytogenes biofilms. The stress responses of bacterial biofilm formation to modified atmospheres including anaerobiosis (20% carbon dioxide, 80% nitrogen), micro-aerobiosis (20% oxygen, 80% nitrogen), and aerobiosis (60% oxygen, 40% nitrogen) were illuminated by determining the live cells, chemical composition analysis, textural parameter changes, expression of regulatory genes, etc. Results showed that the biofilm formation ability of V. parahaemolyticus was efficiently decreased, supported by the fact that the modified atmospheres significantly reduced the key chemical composition [extracellular DNA (eDNA) and extracellular proteins] of the extracellular polymeric substance (EPS) and negatively altered the textural parameters (biovolume, thickness, and bio-roughness) of biofilms during the physiological conversion from anaerobiosis to aerobiosis, while the modified atmosphere treatment increased the key chemical composition of EPS and the textural parameters of L. monocytogenes biofilms from anaerobiosis to aerobiosis. Meanwhile, the expression of biofilm formation genes (luxS, aphA, mshA, oxyR, and opaR), EPS production genes (cpsA, cpsC, and cpsR), and virulence genes (vopS, vopD1, vcrD1, vopP2β, and vcrD2β) of V. parahaemolyticus was downregulated. For the L. monocytogenes cells, the expression of biofilm formation genes (flgA, flgU, and degU), EPS production genes (Imo2554, Imo2504, inlA, rmlB), and virulence genes (vopS, vopD1, vcrD1, vopP2β, and vcrD2β) was upregulated during the physiological conversion. All these results indicated that the modified atmospheres possessed significantly different regulation on the biofilm formation of Gram-negative V. parahaemolyticus and Gram-positive L. monocytogenes, which will provide a novel insight to unlock the efficient control of Gram-negative and Gram-positive bacteria in modified-atmosphere packaged food.

Approximately 18.1×106 new cases of cancer were recorded globally in 2018, out of which 9.6 million died. It is known that people who have Inflammatory Bowel Disease (IBD) turn to be prone to increased risks of developing colorectal cancer (CRC), which has global incident and mortality rates of 10.2% and 9.2%, respectively. Over the years, conventional treatments of IBD and its associated CRC have been noted to provide scarce desired results and often with severe complications. The introduction of biological agents as a better therapeutic approach has witnessed a great deal of success in both experimental and clinical models. With regard to mesenchymal stem cell (MSC) therapy, the ability of these cells to actively proliferate, undergo plastic differentiation, trigger strong immune regulation, exhibit low immunogenicity, and express abundant trophic factors has ensured their success in regenerative medicine and immune intervention therapies. Notwithstanding, MSC-based therapy is still confronted with some challenges including the likelihood of promoting tumor growth and metastasis, and possible overestimated therapeutic potentials. We review the success story of MSC-based therapy in IBD and its associated CRC as documented in experimental models and clinical trials, examining some of the challenges encountered and possible ways forward to producing an optimum MSC therapeutic imparts.

Magnaporthe oryzae is the causal agent of rice blast outbreaks. L-ascorbic acid (ASC) is a famous antioxidant found in nature. However, while ASC is rare or absent in fungi, a five-carbon analog, D-erythroascorbic acid (EASC), seems to appear to be a substitute for ASC. Although the antioxidant function of ASC has been widely described, the specific properties and physiological functions of EASC remain poorly understood. In this study, we identified a D-arabinono-1,4-lactone oxidase (ALO) domain-containing protein, MoAlo1, and found that MoAlo1 was localized to mitochondria. Disruption of MoALO1 (ΔMoalo1) exhibited defects in vegetative growth as well as conidiogenesis. The ΔMoalo1 mutant was found to be more sensitive to exogenous H2O2. Additionally, the pathogenicity of conidia in the ΔMoalo1 null mutant was reduced deeply in rice, and defective penetration of appressorium-like structures (ALS) formed by the hyphal tips was also observed in the ΔMoalo1 null mutant. When exogenous EASC was added to the conidial suspension, the defective pathogenicity of the ΔMoalo1 mutant was restored. Collectively, MoAlo1 is essential for growth, conidiogenesis, and pathogenicity in M. oryzae.

Abstract Background Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. Methods We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. Results GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. Conclusion We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.

Abstract Background Lipoxygenase (LOX) from Anabaena sp. PCC 7120 (Ana-rLOX) offers important applications in the food industry, especially for improving aroma and dough rheological properties. However, industrial applications of LOXs have been limited by their poor thermostability. Herein, we report a bioinformatics-based consensus concept approach for the engineering of thermostable Ana-rLOX. Results A series of mutations (N130D, G260A, S437T, N130D/G260Q, N130D/S437Y) showed higher thermostability and activity than the wild-type enzyme. Thus, N130D/G260Q exhibited a 6.6-fold increase in half-life and 2.45 °C increase in unfolding temperature; N130D/S437Y showed a 10 °C increase in optimal temperature. The secondary structure did not change much that contributed to improved thermostability were investigated in detail using circular dichroism. Homology modeling suggested that enhanced thermostability and specific activity may result from favorable hydrophobic interactions. Conclusions A series of mutations were achieved, showing higher thermostability and activity than the wild-type enzyme by semi-rational mutagenesis with limited structure information. Our findings provide important new insights into molecular modifications aimed at improving Ana-rLOX thermostability and activity.

Abstract Background Long non-coding RNAs (lncRNAs) have emerged as important regulators of human cancers. However, the functional roles of lncRNAs and the mechanisms responsible for their aberrant expression in gastric cancer (GC) have not been well characterized. Methods In this study, we examined the expression of lncRNA UFC1 in GC by qRT-PCR and explored its correlation with clinicopathological parameters. In vitro cell functional assays and in vivo animal studies were performed to determine the roles of UFC1 in GC progression. Results UFC1 was elevated and predicted poorer prognosis in GC. UFC1 knockdown inhibited while UFC1 overexpression promoted GC cell proliferation, migration, and invasion. UFC1 bound to miR-498 to antagonize its tumor suppressive effect on Lin28b. Suppression of Lin28b by miR-498 could be rescued by UFC1 overexpression, whereas Lin28b overexpression partially rescued UFC1 knockdown-mediated inhibition of GC cell function. Lin28b expression was increased in GC and suggested a co-expression pattern with UFC1. Conclusions UFC1 has a promoting role in GC progression, at least in part, by acting as a miR-498 sponge and derepressing Lin28b expression, which would provide a novel biomarker for GC diagnosis and prognosis and offer a potential target for GC therapy.

Abstract Background Exosomes are critically involved in cancer development and progression. The exosomal contents have been suggested as ideal cancer biomarkers. In this study, we investigated the expression of exosomal proteins in the serum of gastric cancer patients and their roles in gastric cancer. Methods The proteomic profile of exosomes from the serum of gastric cancer patients was detected by using LC-MS/MS. The expression of TRIM3 in exosomes from the serum of gastric cancer patients and healthy controls was assessed by ELISA and western blot. Immunohistochemistry was used to detect TRIM3 expression in gastric cancer tissues and their matching adjacent tissues. The growth and migration abilities of gastric cancer cells with TRIM3 overexpression or knockdown in vitro were evaluated by colony formation assay and transwell migration assay. The effects of TRIM3 overexpression or knockdown on gastric cancer growth and metastasis in vivo were investigated by using subcutaneous xenograft tumor and peritoneal metastasis mouse model. The effects of TRIM3-overexpressing exosomes on gastric cancer growth and metastasis in vitro and in vivo were also evaluated. Results We found that the expression levels of TRIM3 mRNA and protein were decreased in gastric cancer tissues compared to the matched control tissues. In addition, the levels of TRIM3 protein in the serum exosomes of gastric cancer patients were lower than that in healthy controls. We demonstrated that TRIM3 overexpression reduced while TRIM3 knockdown promoted the growth and metastasis of gastric cancer in vitro and in vivo through the regulation of stem cell factors and EMT regulators. Moreover, exosomes-mediated delivery of TRIM3 protein could suppress gastric cancer growth and metastasis in vitro and in vivo. Conclusions Taken together, our findings suggest that exosomal TRIM3 may serve as a biomarker for gastric cancer diagnosis and the delivery of TRIM3 by exosomes may provide a new avenue for gastric cancer therapy.

A dual-polarized antenna with omnidirectional radiation and high isolation performance is proposed in this paper. The proposed antenna consists of courtyard-shaped metal frame, feeding network, and metal background. Working mechanism of the proposed antenna is analyzed by the theory of characteristic modes. Two orthogonal polarizations can be achieved by utilizing the orthogonal current distributions on the courtyard-shaped metal frame. In order to obtain the horizontal-polarized mode, eight slots etched on the walls of the courtyard-shaped metal frame are excited. A feeding network is placed at the inner part of courtyard-shaped metal frame for a compact design. Measured results show that the proposed antenna can cover the impedance bandwidth of 1.80–2.81 GHz for both polarizations with their corresponding isolations better than 35 dB. A peak gain of 7 dBi and a gain ripple less than 3 dB in the horizontal radiation plane are achieved. The proposed antenna can be applied in the indoor wireless communication.

Traditional modal testing has difficulty accurately identifying the ultralow-frequency modes of flexible structures. Ultralow-frequency excitation and vibration signal acquisition are two main obstacles. Aiming at ultralow-frequency modal identification of flexible structures, a modal testing method based on Digital Image Correlation method and Eigensystem Realization Algorithm is proposed. Considering impulse and shaker excitation are difficult to make generate ultralow-frequency vibration of structures, the initial displacement is applied to the structure for excitation. The ultralow-frequency accelerometer always has a large mass, which will change the dynamics performance of the flexible structure, so a structural vibration response was obtained through the Digital Image Correlation method. After collecting the free-decay vibration signal, the ultralow-frequency mode of the structure was identified by using the Eigensystem Realization Algorithm. Ground modal tests were conducted to verify the proposed method. Firstly, a solar wing structure was adopted, from which it was concluded that the signal acquisition using Digital Image Correlation method had high feasibility and accuracy. Secondly, an ultralow-frequency flexible cantilever beam structure which had the theoretical solution was employed to verify the proposed method and the theoretical fundamental frequency of the structure was 0.185 Hz. Results show that the Digital Image Correlation method can effectively measure the response signal of the ultralow-frequency flexible structure, and obtain the dynamics characteristics.

In order to realize the self-centering, high energy consumption, and high ductility of the existing building structure through strengthening and retrofit of structure, a method of reinforced concrete (RC) beam strengthened by using Shape Memory Alloy (SMA) and Engineered Cementitious Composites (ECC) was proposed. Four kinds of specimens were designed, including one beam strengthened with enlarging section area of steel reinforced concrete, one beam strengthened with enlarging section area of SMA reinforced concrete, beam strengthened with enlarging section area of SMA reinforced ECC, and beam strengthened with enlarging section area of steel reinforced ECC; these specimens were manufactured for the monotonic cycle loading tests study on its bending behavior. The influence on the bearing capacity, energy dissipation performance, and self-recovery capacity for each test specimens with different strengthening materials were investigated, especially the bending behavior of the beams strengthened by SMA reinforced ECC. The results show that, compared with the ordinary reinforced concrete beams, strengthening existing RC beam with enlarging section area of SMA reinforced ECC can improve the self-recovery capacity, ductility, and deformability of the specimens. Finally, a revised design formula for the bending capacity of RC beams, strengthened with enlarging sections of ECC, was proposed by considering the tensile capacity provided by ECC, and the calculated values are in good agreement with the experimental value, indicating that the revised formula can be well applied to the beam strengthening with enlarging section of SMA-ECC Materials.