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Due to the decentralized, tamper-proof, and auditable properties of blockchain, more and more scholars and researchers are studying the application of blockchain technology in IoT data sharing. Federated learning is an effective way to enable data sharing, but can be compromised by dishonest data owners who may provide malicious models. In addition, dishonest data requesters may also infer private information from model parameters. To solve the above problems, a secure data sharing mechanism based on mutual-supervised federated learning and blockchain, BPCV-FL, is proposed. This mechanism ensures data privacy by adopting gradient descent algorithm with differential privacy protection in local model training and ensures the reliability of shared data through mutual supervision on the blockchain. Experimental results show that the proposed BPCV-FL has high accuracy and security in IoT data sharing.

A symmetric grating is proposed to obtain higher output power in spectral beam combination by increasing the number of lasers and spectral utilization. The grating allows laser beams to be incident from both sides of the grating normal to achieve coaxial beam combining, so the number of beams and the combined output power are doubled compared with the traditional grating under the same spectral line-width. The grating is designed with the central wavelength of 4.65 μm, and the calculation results show that this grating is very advantageous for spectral beam combining, especially for the light waves in the range 4.55–4.71 μm, where their diffraction efficiencies are high (over 80%) and correspond to a wide and linear range of incidence angles. Meanwhile, based on the symmetric gratings we further propose a circular grating to achieve the same frequency spectral beam combining. This beam combining design will not increase the laser spectral line width while enhancing the laser power, reducing the requirements for the unit laser spectral line width, which is very meaningful in some application fields and will further enrich the research of spectral beam combining.

Antimonide semiconductor laser is a new type of laser with unique advantages in the 2 μm band. However, employing FP cavities causes multiple transverse modes to degrade beam quality despite achieving higher power output. In this paper, an antimonide semiconductor laser operating in 2 μm band is realized by utilizing fiber coupling and combining. Fiber combining results in higher output power, while the uniform patterns in both near-field and far-field are obtained, and the beam quality is improved. The experimental results illustrate that the output power reaches 1.2 W after 7-channel beam combination, and the near-field distribution is approximately Gaussian, while the far-field distribution is a flat-top.

Circular RNAs (circRNAs) have been reported to play essential roles in tumorigenesis and progression. This study aimed to identify dysregulated circRNAs in gastric cancer (GC) and investigate the functions and underlying mechanism of these circRNAs in GC development. Here, we identify circ_CEA, a circRNA derived from the back-splicing of CEA cell adhesion molecule 5 (CEA) gene, as a novel oncogenic driver of GC. Circ_CEA is significantly upregulated in GC tissues and cell lines. Circ_CEA knockdown suppresses GC progression, and enhances stress-induced apoptosis in vitro and in vivo. Mechanistically, circ_CEA interacts with p53 and cyclin-dependent kinases 1 (CDK1) proteins. It serves as a scaffold to enhance the association between p53 and CDK1. As a result, circ_CEA promotes CDK1-mediated p53 phosphorylation at Ser315, then decreases p53 nuclear retention and suppresses its activity, leading to the downregulation of p53 target genes associated with apoptosis. These findings suggest that circ_CEA protects GC cells from stress-induced apoptosis, via acting as a protein scaffold and interacting with p53 and CDK1 proteins. Combinational therapy of targeting circ_CEA and chemo-drug caused more cell apoptosis, decreased tumor volume and alleviated side effect induced by chemo-drug. Therefore, targeting circ_CEA might present a novel treatment strategy for GC.

Circular RNA (circRNA) is characterized by a specific covalently closed ring structure. The back-splicing of precursor mRNA is the main way of circRNA generation, and various cis/trans-acting elements are involved in regulating the process. circRNAs exhibit multiple biological functions, including serving as sponges of microRNAs, interacting with proteins to regulate their stabilities and abilities, and acting as templates for protein translation. Autophagy participates in many physiological and pathological processes, especially it plays a vital role in tumorigenesis and carcinoma progression. Increasing numbers of evidences have revealed that circRNAs are implicated in regulating autophagy during tumor development. Until now, the roles of autophagy-associated circRNAs in carcinoma progression and their molecular mechanisms remain unclear. Here, the emerging regulatory roles and mechanisms of circRNAs in autophagy were summarized. Furtherly, the effects of autophagy-associated circRNAs on cancer development were described. We also prospected the potential of autophagy-associated circRNAs as novel therapeutic targets of tumors and as biomarkers for cancer diagnosis and prognosis.

Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial–mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration in vitro. We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic β-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions in vivo, suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression.

Circular RNAs (circRNAs) are covalently closed, endogenous molecules that are widespread in eukaryotes. Recent evidence indicates that circRNAs play important roles in carcinogenesis. Several circRNAs have been reported to comprise translatable RNA; however, whether circRNAs encode functional proteins remains unknown. In our study, circRNA sequencing was carried out using five pathologically diagnosed gastric carcinoma (GC) samples and their paired adjacent normal tissues, we characterized the circRNA GSPT1 (circGSPT1), which is expressed at low levels in GC. Antibody detections, and mass spectrometry were used to validate active circRNA translation. The spanning junction open reading frame in circGSPT1, driven by an internal ribosome entry site (IRES), encodes a functional peptide, termed GSPT1-238aa. Interestingly, GSPT1-238aa tends to select the start codon used to initiate translation. This is the first finding of selective translation driven by IRES. CircGSPT1 and GSPT1-238aa halted the proliferation, migration, and invasion in GC cells in vitro. We also confirmed that the vimentin/Beclin1/14-3-3 complex interacts with GSPT1-238aa and modulates autophagy via the PI3K/AKT/mTOR signaling pathway in GC cells. Our study reveals that GSPT1-238aa, a novel protein encoded by circGSPT1, halts GC tumorigenesis. We also provide insights into the function and underlying molecular mechanisms of GSPT1-238aa in GC and suggest that this protein represents a novel target for GC treatment.

Although great progress has been made in surgical techniques, traditional radiotherapy, and chemotherapy, gastric cancer (GC) is still the most common malignant tumor and has a high mortality, which highlights the importance of novel diagnostic markers. Emerging studies suggest that different microRNAs (miRNAs) are involved in tumorigenesis of GC. In this study, we found that miRNA-192 and -215 are significantly upregulated in GC and promote cell proliferation and migration. Adenomatous polyposis coli (APC), a well-known negative regulator in Wnt signaling, has been proved to be a target of miRNA-192 and -215. Inhibition of miRNA-192 or -215 reduced the Topflash activities and repressed the expression of Wnt signaling pathway proteins, while APC small interfering RNAs reversed the inhibitory effects, suggesting that miRNA-192 and -215 activate Wnt signaling via APC. In addition, APC mediates the cell proliferation and migration regulated by miRNA-192 and -215. Furthermore, APC is downregulated in GC tissues and negatively correlated with the expression of miRNA-192 and -215. In summary, miRNA-192 and -215 target APC and function as oncogenic miRNAs by activating Wnt signaling in GC, revealing to be potential therapeutic targets.

The majority of glucose in tumor cells is converted to lactate despite the presence of sufficient oxygen and functional mitochondria, a phenomenon known as the “Warburg effect” or “aerobic glycolysis”. Aerobic glycolysis supplies large amounts of ATP, raw material for macromolecule synthesis, and also lactate, thereby contributing to cancer progression and immunosuppression. Increased aerobic glycolysis has been identified as a key hallmark of cancer. Circular RNAs (circRNAs) are a type of endogenous single-stranded RNAs characterized by covalently circular structures. Accumulating evidence suggests that circRNAs influence the glycolytic phenotype of various cancers. In gastrointestinal (GI) cancers, circRNAs are related to glucose metabolism by regulating specific glycolysis-associated enzymes and transporters as well as some pivotal signaling pathways. Here, we provide a comprehensive review of glucose-metabolism-associated circRNAs in GI cancers. Furthermore, we also discuss the potential clinical prospects of glycolysis-associated circRNAs as diagnostic and prognostic biomarkers and therapeutic targets in GI cancers.

17β-hydroxysteroid dehydrogenase-13 is a hepatocyte-specific, lipid droplet-associated protein. A common loss-of-function variant ofHSD17B13(rs72613567: TA) protects patients against non-alcoholic fatty liver disease with underlying mechanism incompletely understood. In the present study, we identify the serine 33 of 17β-HSD13 as an evolutionally conserved PKA target site and its phosphorylation facilitates lipolysis by promoting its interaction with ATGL on lipid droplets. Targeted mutation of Ser33 to Ala (S33A) decreases ATGL-dependent lipolysis in cultured hepatocytes by reducing CGI-58-mediated ATGL activation. Importantly, a transgenic knock-in mouse strain carrying theHSD17B13S33A mutation (HSD17B1333A/A) spontaneously develops hepatic steatosis with reduced lipolysis and increased inflammation. Moreover,Hsd17B1333A/Amice are more susceptible to high-fat diet-induced nonalcoholic steatohepatitis. Finally, we find reproterol, a potential 17β-HSD13 modulator and FDA-approved drug, confers a protection against nonalcoholic steatohepatitis via PKA-mediated Ser33 phosphorylation of 17β-HSD13. Therefore, targeting the Ser33 phosphorylation site could represent a potential approach to treat NASH.

Background Circular RNA (circRNA), a subclass of non-coding RNA, plays a critical role in cancer tumorigenesis and metastasis. It has been suggested that circRNA acts as a microRNA sponge or a scaffold to interact with protein complexes; however, its full range of functions remains elusive. Recently, some circRNAs have been found to have coding potential. Methods To investigate the role of circRNAs in gastric cancer (GC), parallel sequencing was performed using five paired GC samples. Differentially expressed circAXIN1 was proposed to encode a novel protein. FLAG-tagged circRNA overexpression plasmid construction, immunoblotting, mass spectrometry, and luciferase reporter analyses were applied to confirm the coding potential of circAXIN1. Gain- and loss-of-function studies were conducted to study the oncogenic role of circAXIN1 and AXIN1-295aa on the proliferation, migration, invasion, and metastasis of GC cells in vitro and in vivo. The competitive interaction between AXIN1-295aa and adenomatous polyposis coli (APC) was investigated by immunoprecipitation analyses. Wnt signaling activity was observed using a Top/Fopflash assay, real-time quantitative RT-PCR, immunoblotting, immunofluorescence staining, and chromatin immunoprecipitation. Results CircAXIN1 is highly expressed in GC tissues compared with its expression in paired adjacent normal gastric tissues. CircAXIN1 encodes a 295 amino acid (aa) novel protein, which was named AXIN1-295aa. CircAXIN1 overexpression enhances the cell proliferation, migration, and invasion of GC cells, while the knockdown of circAXIN1 inhibits the malignant behaviors of GC cells in vitro and in vivo. Mechanistically, AXIN1-295aa competitively interacts with APC, leading to dysfunction of the “destruction complex” of the Wnt pathway. Released β-catenin translocates to the nucleus and binds to the TCF consensus site on the promoter, inducing downstream gene expression. Conclusion CircAXIN1 encodes a novel protein, AXIN1-295aa. AXIN1-295aa functions as an oncogenic protein, activating the Wnt signaling pathway to promote GC tumorigenesis and progression, suggesting a potential therapeutic target for GC.

Peptidylarginine deiminase 4 (PAD4), a Ca

Gastric cancer (GC) is the most common cancer throughout the world. Despite advances of the treatments, detailed oncogenic mechanisms are largely unknown. In our previous study, we investigated microRNA (miR) expression profiles in human GC using miR microarrays. We found miR-192/215 were upregulated in GC tissues. Then gene microarray was implemented to discover the targets of miR-192/215. We compared the expression profile of BGC823 cells transfected with miR-192/215 inhibitors, and HFE145 cells transfected with miR-192/-215 mimics, respectively. SET8 was identified as a proposed target based on the expression change of more than twofold. SET8 belongs to the SET domain-containing methyltransferase family and specifically catalyzes monomethylation of H4K20me. It is involved in diverse functions in tumorigenesis and metastasis. Therefore, we focused on the contributions of miR-192/215/SET8 axis to the development of GC. In this study, we observe that functionally, SET8 regulated by miR-192/215 is involved in GC-related biological activities. SET8 is also found to trigger oncogene-induced senescence (OIS) in GC in vivo and in vitro, which is dependent on the DDR (DNA damage response) and p53. Our findings reveal that SET8 functions as a negative regulator of metastasis via the OIS-signaling pathway. Taken together, we investigated the functional significance, molecular mechanisms, and clinical impact of miR-192/215/SET8/p53 in GC.

Cathodic plasma electrolytic deposition (CPED) was applied to efficiently produce a thick ceramic coating with superior wear and corrosion resistance on aluminium alloy. Ceramic composite coatings were synthesized in a glycerin-carbamide-based electrolyte with and without zirconium nitrate, and their phase components, morphologies and compositions were characterized by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and energy disperse spectroscopy (EDS). The tribological behaviour and electrochemical corrosion resistance were also evaluated. The results show that Al3C4-Al2O3 and Al3C4-Al2O3-ZrO2 coatings with thicknesses of 65 μm and 50 μm, respectively, were produced by DC-powered CPED in only 7 min. Relative to the uncoated alloy, both coated samples exhibited a much lower friction coefficient and wear rate. The ZrO2 incorporated in the coating enhanced the hardness of the coating and dramatically decreased the friction coefficient to 22% of that of the uncoated alloy. The incorporation of ZrO2 also increased the brittleness, resulting in a slightly higher wear rate than that of the ZrO2-free coating. The wear mechanisms of the Al3C4-Al2O3-ZrO2 and ZrO2-free coatings were concluded to be fatigue failure and abrasive wear, respectively. Both coated samples exhibited improved corrosion resistance. The ZrO2 introduced in the coating also decreased the corrosion current density to only 2.7% of that of the Al3C4-Al2O3 coating and enhanced the capacitive loop and impedance.

With the aim to modify the tribological properties of Ti6Al4V for engineering application, cathodic plasma electrolytic deposition (CPED) was performed to explore its feasibility of the preparation of MoS2 containing Ti(C, N) based coating in MoS2 particles-dispersed formamide based electrolyte. The phase constituents, morphologies, element composition and microstructure of the samples were analysed by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and optical microscopy (OM) respectively. The hardness distribution on the cross-section was tested. The ball-on-disk reciprocating sliding test was adopted to evaluate the tribological performance of samples, after which the wear tracks were measured by the step profiler to calculate the wear rate. SEM and EDX were also used to study the wear mechanism. Results show that MoS2-Ti(C, N)-TiO2 coating is synthesized by CPED on Ti6Al4V, with its thickness of ~23 μm. The addition of cationic surfactant, Dodecyl trimethyl ammonium chloride, in electrolyte promotes the deposition of MoS2 particles into the coating. The hardness of the coating reaches 1024 ± 58HV0.025, higher than that of the coating free of MoS2. Hardened regions in both samples with the depth of ~170 μm beneath the coatings, are attributed to the quenching effect of the substrate, make the hardness drop eventually from the coating to the substrate. Both coated samples show higher tribological properties. MoS2 incorporated in the coating, playing the role of lubricant and alleviating the wear damage, creates the extra promotion in tribological properties of the sample, significantly reducing the wear rate and friction coefficient to only 11% and 25% that of the bared Ti6Al4V respectively.

microRNA (miR) and Wnt/β-catenin signaling pathway are two major modules in the field of tumor research. The dysregulation of miR expression and Wnt/β-catenin signaling activation are closely related to the tumorigenesis, metastasis and drug resistance. On one hand, miR activates or inhibits classical Wnt signaling pathway through various pathways. On the other hand, Wnt binds to its promoter to activate transcription, which in turn promotes miR expression in tumors. In this review, we describe the relationship between miR and classical Wnt signaling pathway and the regulatory mechanism by which they affect tumor cell proliferation, migration, metastasis and drug reaction in a variety of tumors. This will provide more comprehensive understanding for the mechanistic studies of miR and Wnt signaling in tumor pathology, and bring new insights into tumor diagnosis, molecular typing, drug screening, and prognostic judgment.

SMG‐1,a member of the phosphoinositide kinase‐like kinase family, functioned as a tumor suppressor gene. However, the role of SMG‐1 in GC remain uncharacterized. In this study, regulation of SMG‐1 by miR‐192 and‐215, along with the biological effects of this modulation, were studied in GC. We used gene microarrays to screening and luciferase reporter assays were to verify the potential targets of miR‐192 and‐215. Tissue microarrays analyses were applied to measure the levels of SMG‐1 in GC tissues. Western blot assays were used to assess the signaling pathway of SMG‐1 regulated by miR‐192 and‐215 in GC. SMG‐1 was significantly downregulated in GC tissues.The proliferative and invasive properties of GC cells were decreased by inhibition of miR‐192 and‐215, whereas an SMG‐1siRNA rescued the inhibitory effects. Finally, SMG‐1 inhibition by miR‐192 and‐215 primed Wnt signaling and induced EMT. Wnt signaling pathway proteins were decreased markedly by inhibitors of miR‐192 and‐215, while SMG‐1 siRNA reversed the inhibition apparently. Meanwhile, miR‐192 and‐215 inhitibtors increased E‐cadherin expression and decreased N‐cadherin and cotransfection of SMG‐1 siRNA reversed these effects. In summary, these findings illustrate that SMG‐1 is suppressed by miR‐192 and‐215 and functions as a tumor suppressor in GC by inactivating Wnt signaling and suppressing EMT.

Besides oxides ceramic coating, cathodic plasma electrolytic saturation (PES) could produce more other types ceramic coatings, including nitrides, carbonitrides, borides, etc., on nearly all kinds of metal substrate. Owing to the accompanying electrochemical deposition (ED) effect of PES, special functional compounds could be deposited in mentioned ceramic coatings by PES simultaneously in special designed electrolyte. In this study, the target Hydroxyapatite (HA)-Ti(C,N)-TiO2 composite coatings were synthesized in one step by PES and accompanying ED in calcium nitrate and sodium dihydrogen phosphate containing formamide based electrolyte. The phase structures, functional groups of molecules, chemical compositions of the surfaces and binding energies of atoms in coatings were characterized by X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) respectively. The surfaces morphologies, cross sections morphologies, and element maps of the surface were analyzed by Scanning electron microscopy (SEM) and energy dispersive spectrum (EDS). The coatings exhibit porous structure with island like bulges or spheroids around the pores. The phases formed in coatings are verified to be constituted of HA, Ti(C,N) and anatase. The suggested formation mechanism of anatase in coatings differs to that obtained on anodic titanium surface in PEO process. The phase of HA distributes homogenously on surfaces and displays as clusters congressed by nano-scale needles or rods with their transverse length about ~ 10 nm. The size of the pores and bulges, the crystalline amount of HA phase, and the thickness of the coatings all increase with increasing duration time. The thickness reaches about 56 ± 7 μm when the duration time grew to 30 min, 26% higher than that of the HA-free coating produced in formamide electrolyte with the same process parameters.

Emerging evidence has shown that miRNA-194 is aberrantly upregulated in gastric cancer (GC); however, the biological mechanisms underlying its involvement are largely unknown. Wnt/β-catenin signaling has been implicated in gastric tumorigenesis; we therefore hypothesized that miRNA-194 promotes gastric carcinogenesis by activating Wnt/β-catenin signaling. MiRNA-194 was found to be overexpressed in GC cell lines and 43 paired GC tissues. Overexpression of miRNA-194 promoted cell proliferation and migration, while inhibition of miRNA-194 blocked these processes. Inhibition of miRNA-194 decreased tumor volumes in nude mice. Furthermore, miRNA-194 inhibitors promoted cytoplasmic localization of β-catenin, leading to repression of Wnt signaling. We also discovered that SUFU, a known negative regulator of Hedgehog and Wnt signaling, was a target of miRNA-194. Anti-SUFU siRNAs rescued the inhibitory effects of miRNA-194 antagonists on cell proliferation and migration and on colony formation. We also found that SUFU expression was downregulated in GC tissues and cell lines and negatively correlated with miRNA-194 expression in primary GC tissues. Moreover, SUFU expression was negatively correlated with tumor stage, supporting its potential as a diagnostic or prognostic marker in GC. Taken together, these findings suggest that miRNA-194 is oncogenic and promotes GC cell proliferation and migration by activating Wnt signaling, at least in part, via suppression of SUFU.

To solve the problem of rapid degradation for magnesium-based implants, surface modification especially coating method is widely studied and showed the great potential for clinical application. However, as concerned to the further application and medical translation for biodegradable magnesium alloys, there are still lack of data and comparisons among different coatings on their degradation and biological properties. This work studied three commonly used coatings on Mg-Sr alloy, including micro-arc oxidation coating, electrodeposition coating and chemical conversion coating, and compared these coatings for requirements of favorable degradation and biological performances, how each of these coating systems has performed. Finally the mechanism for the discrepancy between these coatings is proposed. The results indicate that the micro-arc oxidation coating on Mg-Sr alloy exhibited the best corrosion resistance and cell response among these coatings, and is proved to be more suitable for the orthopedic application.

In this work, the effects of aging time on intergranular and pitting corrosion behavior of Cu-bearing 304L and 304L stainless steels were investigated by using the double loop electrochemical potentiokinetic reactivation (DL-EPR) and the potentiostatic polarization electrochemical methods. The results showed that the Cu-bearing 304L stainless steel possessed a higher intergranular corrosion tendency and a higher pitting corrosion rate for extended aging time. The TEM observation and 3D APT analysis confirmed that above behavior could mainly attribute to the precipitation of the Cu-rich phase in the Cu-bearing 304L stainless steel.

Magnesium-based metals are considered as promising biodegradable orthopedic implant materials due to their potentials of enhancing bone healing and reconstruction, and in vivo absorbable characteristic without second operation for removal. However, the rapid corrosion has limited their clinical applications. Ca-P coating by electrodeposition has been supposed to be effective to control the degradation rate and enhance the bioactivity. In this work, a brushite coating was fabricated on the Mg-Sr alloy by pulse electrodeposition (PED) to evaluate its efficacy for orthopedic application. Interestingly, an inner corrosion layer was observed between the PED coating and the alloy substrate. Meanwhile the results of in vitro immersion and electrochemical tests showed that the corrosion resistance of the coated alloy was undermined in comparison with the uncoated alloy. It was deduced that the existence of this corrosion layer was attributed to the worse corrosion performance of the alloy. The mechanism on formation of the inner corrosion layer and its influence on consequent degradation were analyzed. It can be concluded that the electrodeposition coating should be not suitable for those magnesium alloys with poor corrosion resistance such as the Mg-Sr alloy. More importantly, it should be noted that the process of coating formation combined with the nature of substrate alloy is important to evaluate the efficacy of coating for biodegradable Mg-based implants application.

Considering the compatibility between degradation and bioactivity of magnesium-based implants for bone repair, micro-arc oxidation is used to modify the magnesium alloy surface in aqueous electrolytes, allowing strontium, calcium, and phosphorus to be incorporated into the coating. The thickness, composition, morphology and phase of this Sr–Ca–P containing coating are characterized by scanning electron microscopy equipped with energy dispersive X-ray spectrometer and X-ray diffraction. The in vitro and in vivo degradation of the coating is evaluated by immersion test, electrochemical test and implantation test. Moreover, the cytocompatibility is tested with osteoblast cell according to ISO 10993. The results show that Sr, Ca and P elements are incorporated into the oxide coating, and a refined structure with tiny discharging micro-pores is observed on the surface of the coating. The Sr–Ca–P coating possesses a better corrosion resistance in vitro and retards the degradation in vivo. Such coating is expected to have significant medical applications on orthopedic implants and bone repair materials.

Recently, traditionally non-encoding circRNA has been shown to encode a new protein to play an important role in oncogenesis. Based on the sequencing data and bioinformatics analysis, circAX was screened as an oncogenic circRNA encoding AX-295aa in gastric cancer. CircAX is highly expressed in gastric cancer and associated with lymph node metastasis. We found that circAX promotes GC cell proliferation and migration and it encodes a novel protein AX-295aa. AX-295aa interacts with APC and competitively inhibits AXIN1 binding to APC. It enhances β-catenin nuclear translocation and activates Wnt signaling pathway to promote the carcinogenesis and development of gastric cancer. The study reveals a new regulatory mechanism of circAX and clarify the mechanism by which circAX promotes gastric carcinogenesis. It will ultimately provide novel circRNA molecular markers for early diagnosis and targets for more effective treatment of gastric cancer. Citation Format: Yin Peng, Xiaojing Zhang, Shiqi Deng, Jieqiong He, Wangchun Chen, Xiaohui Zhu, Yuan Yuan, Xianling Feng, Xinmin Fan, Zhe Jin. Novel protein AX-295aa encoded by circAX promotes gastric carcinogenesis by activating Wnt pathway [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4820.

Less than a century ago, gastric cancer (GC) was the most common cancer throughout the world. Despite advances in surgical, chemotherapeutic, and radiotherapeutic treatment, GC remains the number 3 cancer killer worldwide. This fact highlights the need for better diagnostic biomarkers and more effective therapeutic targets. RAB11-FIP2, a member of the Rab11 family of interacting proteins, exhibits potential tumor suppressor function. However, involvement of RAB11-FIP2 in gastric carcinogenesis is yet to be elucidated. In this study, we demonstrated that RAB11-FIP2 was downregulated in GC tissues and constituted a target of the known onco-miRs, miR-192/215. We also showed that functionally, Rab11-FIP2 regulation by miR-192/215 is involved in GC-related biological activities. Finally, RAB11-FIP2 inhibition by miR-192/215 affected the establishment of cell polarity and tight junction formation in GC cells. In summary, this miR-192/215–Rab11-FIP2 axis appears to represent a new molecular mechanism underlying GC progression, while supplying a promising avenue of further research into diagnosis and therapy of GC.

A new phenylethanoid glycoside (2) and a new secoiridoid glycoside (16) were isolated from the leaves of Ligustrum purpurascens together with fourteen known compounds (1 and 3–15). The structures of the new compounds were determined by spectroscopic analyses (UV, IR, HR-ESI-MS, 1D, and 2D NMR). The absolute configuration of 16 was further determined by CD analysis. All phenylethanoid glycosides were prepared and their up-regulation of IFN-γ production in mouse splenic lymphocytes was evaluated. Compounds 1, 5, 6, 10, 11, 13 and 15 exhibited potent stimulatory effect on IFN-γ secretion.

Controlling the corrosion rate of magnesium alloys in vivo to match the bone repair is crucially important for application as biodegradable orthopedic implants. To solve this challenge, a Si-doped Ca-P coating with a novel dual-layer structure was deposited on AZ31 alloy substrate by pulse electrodeposition. The morphology, composition and formation of dual-layer coating were believed to be determined by pulse electrodeposition parameters, thus the deposition time, temperature, duty cycle, pH value of the electrolyte and the standing duration of mixed electrolyte were regulated to seek possible influences and mechanism on the coating formation. Weight gain and pH monitoring tests were also used to evaluate the performance of coating under the varied parameters. The results indicated that deposition temperature and time remarkably influenced the morphology, homogeneity and crystallinity of Ca-P coating. A uniform and compact coating with better degradation performance was obtained at 60 degrees C with deposition time of 40 min. The shorter standing duration of the electrolyte lead to an incomplete coating and uneven distribution of Si contents. The two coupled deposition models contributed to this dual-layer structure of Si-doped Ca-P coating and possible formation mechanism was proposed. (C) 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Current automation-assisted technologies for screening cervical cancer mainly rely on automated liquid-based cytology slides with proprietary stain. This is not a cost-efficient approach to be utilized in developing countries. In this article, we propose the first automation-assisted system to screen cervical cancer in manual liquid-based cytology (MLBC) slides with hematoxylin and eosin (H&E) stain, which is inexpensive and more applicable in developing countries. This system consists of three main modules: image acquisition, cell segmentation, and cell classification. First, an autofocusing scheme is proposed to find the global maximum of the focus curve by iteratively comparing image qualities of specific locations. On the autofocused images, the multiway graph cut (GC) is performed globally on the a* channel enhanced image to obtain cytoplasm segmentation. The nuclei, especially abnormal nuclei, are robustly segmented by using GC adaptively and locally. Two concave-based approaches are integrated to split the touching nuclei. To classify the segmented cells, features are selected and preprocessed to improve the sensitivity, and contextual and cytoplasm information are introduced to improve the specificity. Experiments on 26 consecutive image stacks demonstrated that the dynamic autofocusing accuracy was 2.06 μm. On 21 cervical cell images with nonideal imaging condition and pathology, our segmentation method achieved a 93% accuracy for cytoplasm, and a 87.3% F-measure for nuclei, both outperformed state of the art works in terms of accuracy. Additional clinical trials showed that both the sensitivity (88.1%) and the specificity (100%) of our system are satisfyingly high. These results proved the feasibility of automation-assisted cervical cancer screening in MLBC slides with H&E stain, which is highly desirable in community health centers and small hospitals.

BACKGROUND Endoglin (ENG) is a 180-kilodalton transmembrane glycoprotein that functions as a component of the transforming growth factor-β receptor complex. Recently, ENG promoter hypermethylation was reported in several human cancers. METHODS The authors examined ENG promoter hypermethylation using real-time, quantitative, methylation-specific polymerase chain reaction in 260 human esophageal tissues. RESULTS ENG hypermethylation demonstrated highly discriminative receiver operating characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (P

// Chunman Li 1 , Meiqi Zeng 1 , Huju Chi 1 , Jing Shen 2 , Tzi-Bun Ng 3 , Guangyi Jin 4 , Desheng Lu 4 , Xinmin Fan 4 , Bilian Xiong 1 , Zhangang Xiao 2 , Ou Sha 1 1 Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, Guangdong, China 2 Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China 3 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China 4 School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, Guangdong, China Correspondence to: Ou Sha, email: shaou@szu.edu.cn Zhangang Xiao, email: xzg555898@hotmail.com Keywords: trichosanthin, granzyme B (GrzB), cation-independent mannose-6-phosphate receptor, tumor cells, immunotherapy Received: December 23, 2016 Accepted: February 08, 2017 Published: February 19, 2017 ABSTRACT Trichosanthin is a plant toxin belonging to the family of ribosome-inactivating proteins. It has various biological and pharmacological activities, including anti-tumor and immunoregulatory effects. In this study, we explored the potential medicinal applications of trichosanthin in cancer immunotherapy. We found that trichosanthin and cation-independent mannose-6-phosphate receptor competitively bind to the Golgi-localized, γ-ear containing and Arf-binding proteins. It in turn promotes the translocation of cation-independent mannose-6-phosphate receptor from the cytosol to the plasma membrane, which is a receptor of Granzyme B. The upregulation of this receptor on the tumor cell surface increased the cell permeability to Granzyme B, and the latter is one of the major factors of cytotoxic T lymphocyte-mediated tumor cell apoptosis. These results suggest a novel potential application of trichosanthin and shed light on its anti-tumor immunotherapy.

Exploring novel anticancer agents that can trigger non-apoptotic or non-autophagic cell death is urgent for cancer treatment. In this study, we screened and identified an unexplored anticancer activity of gypenoside L (Gyp-L) isolated from Gynostemma pentaphyllum. We showed that treatment with Gyp-L induces non-apoptotic and non-autophagic cytoplasmic vacuolation death in human hepatocellular carcinoma (HCC) cells. Mechanically, Gyp-L initially increased the intracellular reactive oxygen species (ROS) levels, which, in turn, triggered protein ubiquitination and unfolded protein response (UPR), resulting in Ca(2+) release from endoplasm reticulum (ER) inositol trisphosphate receptor (IP3R)-operated stores and finally cytoplasmic vacuolation and cell death. Interruption of the ROS-ER-Ca(2+) signaling pathway by chemical inhibitors significantly prevented Gyp-L-induced vacuole formation and cell death. In addition, Gyp-L-induced ER stress and vacuolation death required new protein synthesis. Overall, our works provide strong evidence for the anti-HCC activity of Gyp-L and suggest a novel therapeutic option by Gyp-L through the induction of a unconventional ROS-ER-Ca(2+)-mediated cytoplasmic vacuolation death in human HCC.

Lipopolysaccharide (LPS) can exacerbate asthma; however, the mechanisms are not fully understood. This study investigated the effect of LPS on antigen-stimulated mast cell degranulation and the underlying mechanisms. We found that LPS enhanced degranulation in RBL-2H3 cells and mouse peritoneal mast cells upon FceRI activation, in a dose- and time-dependent manner. Parallel to the alteration of degranulation, LPS increased FceRI-activated Ca(2+) mobilization, as well as Ca(2+) entry through store-operated calcium channels (SOCs) evoked by thapsigargin. Blocking Ca(2+) entry through SOCs completely abolished LPS enhancement of mast cell degranulation. Consistent with functional alteration of SOCs, LPS increased mRNA and protein levels of Orai1 and STIM1, two major subunits of SOCs, in a time-dependent manner. In addition, LPS increased the mRNA level of Toll-like receptor 4 (TLR4) in a time-dependent manner. Blocking TLR4 with Cli-095 inhibited LPS, increasing transcription and expression of SOC subunits. Concomitantly, the effect of LPS enhancement of Ca(2+) mobilization and mast cell degranulation was largely reduced by Cli-095. Administration of LPS (1 μg) in vivo aggravated airway hyperreactivity and inflammatory reactions in allergic asthmatic mice. Histamine levels in serum and bronchoalveolar lavage fluid were increased by LPS treatment. In addition, Ca(2+) mobilization was enhanced in peritoneal mast cells isolated from LPS-treated asthmatic mice. Taken together, these results imply that LPS enhances mast cell degranulation, which potentially contributes to LPS exacerbating allergic asthma. Lipopolysaccharide increases Ca(2+) entry through SOCs by upregulating transcription and expression of SOC subunits, mainly through interacting with TLR4 in mast cells, resulting in enhancement of mast cell degranulation upon antigen stimulation.

In light-cut milling operations, specific correlations have been identified empirically between the maximum cutting force on a cutter and its associated cutting parameters, and a series of ball-end milling tests for P20 tool steel has been conducted to establish the nature of these correlations. The experimental results indicate that the maximum cutting force on a cutter can be expressed as a logarithmic function of the associated cutting parameters. This paper describes the structure and testing of a simplified cutting force model for planar milling based on these results.

Bone defects are very challenging in orthopedic practice. There are many practical and clinical shortcomings in the repair of the defect by using autografts, allografts or xenografts, which continue to motivate the search for better alternatives. The ideal bone grafts should provide mechanical support, fill osseous voids and enhance the bone healing. Biodegradable magnesium-strontium (Mg-Sr) alloys demonstrate good biocompatibility and osteoconductive properties, which are promising biomaterials for bone substitutes. The aim of this study was to evaluate and pair the degradation of Mg-Sr alloys for grafting with their clinical demands. The microstructure and performance of Mg-Sr alloys, in vitro degradation and biological properties including in vitro cytocompatibility and in vivo implantation were investigated. The results showed that the as-cast Mg-Sr alloy exhibited a rapid degradation rate compared with the as-extruded alloy due to the intergranular distribution of the second phase and micro-galvanic corrosion. However, the initial degradation could be tailored by the coating protection, which was proved to be cytocompatible and also suitable for bone repair observed by in vivo implantation. The integrated fracture calluses were formed and bridged the fracture gap without gas bubble accumulation, meanwhile the substitutes simultaneously degraded. In conclusion, the as-cast Mg-Sr alloy with coating is potential to be used for bone substitute alternative.

Background Interleukin-37 (IL-37) has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of ankylosing spondylitis (AS) has not been investigated. Here, we examined the serum levels of IL-37 and its clinical association in AS, and explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from AS patients. Methods The mRNA levels of IL-37, TNF-α, IL-6, IL-17, and IL-23 in PBMCs and their serum concentrations from 46 AS patients were examined by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunoassay (ELISA), respectively. The correlations between serum IL-37 levels with disease activity, laboratory values and pro-inflammatory cytokines in AS were analyzed by Spearman correlation test. PBMCs from 46 AS patients were stimulated with recombinant IL-37 protein, expressions of TNF-α, IL-6, IL-17 and IL-23 were determined by RT-PCR and ELISA. Results Compared to healthy controls (HC), AS patients and active AS patients showed higher levels of IL-37 in PBMCs and serum respectively. Strikingly, serum IL-37 levels were higher in AS patients with osteoporosis than those without. Serum levels of IL-37 were correlated with laboratory values as well as TNF-α, IL-6 and IL-17, but not IL-23 in patients with AS. The productions of pro-inflammatory cytokines such as TNF-α, IL-6, IL-17, IL-23 in PBMCs from AS patients were obviously attenuated after recombinant IL-37 stimulation, but not in the HC. Conclusion The higher levels of IL-37 were found in AS patients, which were correlated with disease activity and AS related pro-inflammatory cytokines. More importantly, IL-37 inhibits the expressions of the pro-inflammatory cytokines from PBMCs in AS patients, indicating the potential anti-inflammatory role of IL-37 in AS. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0394-3) contains supplementary material, which is available to authorized users.

Esophageal cancer ranks as the eighth most frequent and sixth most fatal cancer type worldwide. Progression of esophageal cancer is a multistep process that begins with the accumulation of genetic and epigenetic alterations, and leads to the inactivation of tumor suppressor genes (TSGs) and the activation of oncogenes. DNA hypermethylation and miRNA deregulation are recognized as common molecular alterations, and contribute to the neoplastic development and progression by different mechanisms in esophageal cancer. Hypermethylation of TSG promoter regions and deregulation of miRNA occur not only in advanced cancer but also in premalignant lesions. This chapter is mainly focused on these epigenetic changes in esophageal cancer and the value of early detection, risk stratification, prognosis, predicting response to treatment and potential targeting therapy, with special attention to DNA methylation and miRNA deregulation.

Ras-related associated with diabetes (RRAD), a member of the Ras-related GTPase superfamily, is frequently methylated in several human cancers, though its methylation profile remains unclear in esophageal cancer.We examined RRAD promoter hypermethylation using real-time quantitative methylation-specific PCR in 229 primary human esophageal tissues of contrasting histological types.RRAD hypermethylation showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) from esophageal adenocarcinoma (EAC) or normal esophagus (NE) (p0.01 and p0.01, respectively). RRAD normalized methylation values were significantly higher in ESCC (0.0242) than in NE (0.0057, p0.05) or EAC (0.0139, p0.01). RRAD hypermethylation frequency was also significantly higher in ESCC (23.1%) than in NE (0%, p0.05) or EAC (5.4%, p0.05).Promoter hypermethylation of RRAD is a frequent, tissue-specific event in ESCC, and is uncommon in EAC. The aberrant methylation of RRAD may be involved in the pathogenesis of a subset of ESCC, but not in EAC.

MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.

Current automation-assisted technologies for screening cervical cancer mainly rely on automated liquid-based cytology slides with proprietary stain. This is not a cost-efficient approach to be utilized in developing countries. In this article, we propose the first automation-assisted system to screen cervical cancer in manual liquid-based cytology (MLBC) slides with hematoxylin and eosin (HE) stain, which is inexpensive and more applicable in developing countries. This system consists of three main modules: image acquisition, cell segmentation, and cell classification. First, an autofocusing scheme is proposed to find the global maximum of the focus curve by iteratively comparing image qualities of specific locations. On the autofocused images, the multiway graph cut (GC) is performed globally on the a* channel enhanced image to obtain cytoplasm segmentation. The nuclei, especially abnormal nuclei, are robustly segmented by using GC adaptively and locally. Two concave-based approaches are integrated to split the touching nuclei. To classify the segmented cells, features are selected and preprocessed to improve the sensitivity, and contextual and cytoplasm information are introduced to improve the specificity. Experiments on 26 consecutive image stacks demonstrated that the dynamic autofocusing accuracy was 2.06 μm. On 21 cervical cell images with nonideal imaging condition and pathology, our segmentation method achieved a 93% accuracy for cytoplasm, and a 87.3% F-measure for nuclei, both outperformed state of the art works in terms of accuracy. Additional clinical trials showed that both the sensitivity (88.1%) and the specificity (100%) of our system are satisfyingly high. These results proved the feasibility of automation-assisted cervical cancer screening in MLBC slides with HE stain, which is highly desirable in community health centers and small hospitals.

A silicon doped calcium phosphate coating was obtained successfully on AZ31 alloy substrate via pulse electrodeposition. A novel dual-layer structure was observed with a porous lamellar-like and outer block-like apatite layer. In vitro immersion tests were adopted in simulated body fluid within 28 days of immersion. Slow degradation rate obtained from weight loss was observed for the Si-doped Ca-P coating, which was also consistent with the results of electrochemical experiments showing an enhanced corrosion resistance for the coating. Further formation of an apatite-like layer on the surface after immersion proved better integrity and biomineralization performance of the coating. Biological characterization was carried out for viability, proliferation and differentiation of MG63 osteoblast-like cells. The coating showed a good cell growth and an enhanced cell proliferation. Moreover, an increased activity of osteogenic marker ALP was found. All the results demonstrated that the Si-doped calcium phosphate was perspective to be used as a coating for magnesium alloy implants to control the degradation rate and enhance the bioactivity, which would facilitate the rapidity of bone tissue repair.

Abstract Considerable evidence indicates an enhanced sympathetic innervation of resistance arterial smooth muscle in the spontaneously hypertensive rat (SHR) compared with its normotensive Wistar-Kyoto (WKY) control. In addition to sympathetic hyperinnervation, an increased vascular innervation by neuropeptide Y–containing fibers, which are known to exert a vasoconstrictive and trophic action in vascular smooth muscle, has also been described. In addition to genetic hypertension, the SHR expresses hyperactive behavior and hyperreactivity to stress. To determine whether the enhanced neuropeptide Y–immunoreactive vascular innervation is specifically associated with hypertension and/or these behavioral abnormalities, four genetically related, inbred rat strains were used: SHR, which are hypertensive and hyperactive; WKY rats, which are neither hypertensive nor hyperactive; WKHA, which are hyperactive but normotensive; and WKHT, which are hypertensive but not hyperactive. The present study demonstrated that whereas the hypertensive strains (SHR and WKHT) exhibited smooth muscle hypertrophy in both superior mesenteric and caudal arteries in adulthood (10 months) but not at a prehypertensive age (1 month), both arteries exhibited significantly increased neuropeptide Y–immunoreactive innervation at both ages. It was further observed that the mesenteric artery in WKHA, a normotensive strain, had significant smooth muscle hypertrophy at 10 months; however, neuropeptide Y innervation in this artery was no different from that of WKY controls. The findings indicate that there is a cosegregation of neuropeptide Y hyperinnervation of the vasculature with the hypertensive phenotype, evident as early as 1 month of life in the hypertensive strains, and this should be considered further as a contributory factor in genetic hypertension. Vascular smooth muscle hypertrophy, while evident in adult hypertensive rats, was also observed in the mesenteric artery (but not the caudal artery) of adult WKHA rats, suggesting that other factors besides genetic hypertension, possibly hyperreactivity to stress, are responsible for this specific hypertrophic change in WKHA rats.

Supported by: National Natural Science Foundation of China, No.81172282; National Natural Youth Science Foundation of China, No.81302151; Shenzhen Peacock Plan, No.KQCX20130621101141669; Planned Science and Technology Project of Shenzhen, No.GJHS20120621142654087; the Key Laboratory Project of Shenzhen, No.ZDSY20130329101130496; Technological innovation group of SZU grants, No.T201202; NIH grants DK087454, CA146799, CA173390; an American Cancer Society Clinical Research Professorship. Gastric cancer (GC) remains a major health threat worldwide, and is one of the leading causes of cancer-related deaths in China. The discovery of microRNAs (miRNAs) has provided a new and powerful tool for studying diagnostic biomarkers and effective therapeutic targets in GC. By using microarray analyses of benign and malignant gastric epithelial cell lines (HFE145, NCI-N87, MKN28, RF1, KATO III and RF48), we discovered dysregulated 16 miRNAs, of which 11 were validated by real-time qRT-PCR. Based on miRWalk online database scans, 2532 potential mRNA targets of these 16 miRNAs were identified. Bioinformatic analyses suggested that these predicted targets were principally involved in tumor pathogenesis, MAPK signaling, and apoptosis. Finally, miRNA-gene network analyses identified miRNA- 125b as being potentially vitally important in GC. Citation Format: Xiaojing Zhang, Xianling Feng, Yin Peng, Mengting Yang, Yong Huang, Xinmin Fan, Stephen J. Meltzer, Zhe Jin. Integrated analysis of miRNA profiling and bioinformatics reveals the potential key miRNAs in gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3996. doi:10.1158/1538-7445.AM2015-3996