Search

In this paper, two kinds of cold-rolled 3.5Mn steels with different initial microstructures are designed. Combined with EBSD and dilatometer, the effect of Mn pre-partition on the austenite reversi...

STUDY QUESTION Does hypo-glycosylated human recombinant FSH (hFSH18/21) have greater in vivo bioactivity that drives follicle development in vivo compared to fully-glycosylated human recombinant FSH (hFSH24)? SUMMARY ANSWER Compared with fully-glycosylated hFSH, hypo-glycosylated hFSH has greater bioactivity, enabling greater follicular health and growth in vivo, with enhanced transcriptional activity, greater activation of receptor tyrosine kinases (RTKs) and elevated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling. WHAT IS KNOWN ALREADY Glycosylation of FSH is necessary for FSH to effectively activate the FSH receptor (FSHR) and promote preantral follicular growth and formation of antral follicles. In vitro studies demonstrate that compared to fully-glycosylated recombinant human FSH, hypo-glycosylated FSH has greater activity in receptor binding studies, and more effectively stimulates the PKA pathway and steroidogenesis in human granulosa cells. STUDY DESIGN, SIZE, DURATION This is a cross-sectional study evaluating the actions of purified recombinant human FSH glycoforms on parameters of follicular development, gene expression and cell signaling in immature postnatal day (PND) 17 female CD-1 mice. To stimulate follicle development in vivo, PND 17 female CD-1 mice (n = 8–10/group) were treated with PBS (150 µl), hFSH18/21 (1 µg/150 µl PBS) or hFSH24 (1 µg/150 µl PBS) by intraperitoneal injection (i.p.) twice daily (8:00 a.m. and 6:00 p.m.) for 2 days. Follicle numbers, serum anti-Müllerian hormone (AMH) and estradiol levels, and follicle health were quantified. PND 17 female CD-1 mice were also treated acutely (2 h) in vivo with PBS, hFSH18/21 (1 µg) or hFSH24 (1 µg) (n = 3–4/group). One ovary from each mouse was processed for RNA sequencing analysis and the other ovary processed for signal transduction analysis. An in vitro ovary culture system was used to confirm the relative signaling pathways. PARTICIPANTS/MATERIALS, SETTING, METHODS The purity of different recombinant hFSH glycoforms was analyzed using an automated western blot system. Follicle numbers were determined by counting serial sections of the mouse ovary. Real-time quantitative RT-PCR, western blot and immunofluorescence staining were used to determine growth and apoptosis markers related with follicle health. RNA sequencing and bioinformatics were used to identify pathways and processes associated with gene expression profiles induced by acute FSH glycoform treatment. Analysis of RTKs was used to determine potential FSH downstream signaling pathways in vivo. Western blot and in vitro ovarian culture system were used to validate the relative signaling pathways. MAIN RESULTS AND THE ROLE OF CHANCE Our present study shows that both hypo- and fully-glycosylated recombinant human FSH can drive follicular growth in vivo. However, hFSH18/21 promoted development of significantly more large antral follicles compared to hFSH24 (P LARGE SCALE DATA RNA sequencing of mouse ovaries. Data will be shared upon reasonable request to the corresponding author. LIMITATIONS, REASONS FOR CAUTION The observations that hFSH glycoforms have different bioactivities in the present study employing a mouse model of follicle development should be verified in nonhuman primates. The gene expression studies reflect transcriptomes of whole ovaries. WIDER IMPLICATIONS OF THE FINDINGS Commercially prepared recombinant human FSH used for ovarian stimulation in human ART is fully-glycosylated FSH. Our findings that hypo-glycosylated hFSH has greater bioactivity enabling greater follicular health and growth without exaggerated estradiol production in vivo, demonstrate the potential for its development for application in human ART. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by NIH 1P01 AG029531, NIH 1R01 HD 092263, VA I01 BX004272, and the Olson Center for Women’s Health. JSD is the recipient of a VA Senior Research Career Scientist Award (1IK6 BX005797). This work was also partially supported by National Natural Science Foundation of China (No. 31872352). The authors declared there are no conflicts of interest.

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index Ei, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo. As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity.

Background: Venous Thromboembolism (VTE) is a leading reason of morbidity and mortality in endometrial cancer patients. There is no meta-analysis available on this topic so far. In order to identify relevant risk factors contributing to VTE and form strategies to prevent VTE, we conducted the present study to quantitatively analyze the data from studies with the incidence and risk factors among cases with endometrial cancer.Methods: PubMed, Embase and CNKI were searched for papers containing the key words “thromboembolism” “endometrial cancer” and their variants. Studies selection, data extraction, quality assessment of eligible studies were performed independently by two reviewers. Meta-analyses were conducted to determine postoperative VTE incidence rate and risk factors in endometrial cancer. Sensitivity analysis was used to verify the robustness of the results in the present study.Results: 8 studies were included in this meta-analysis totally. The pooled incidence rate for postoperative VTE was 7% (95% CI, 0.04 –0.09).The presence of age>60 (OR, 2.26), tumor size in uterine cavity(＞60mm) (OR, 5.68), tumor extension (CT/MRI) (OR, 5.59), FIGO stage (OR, 2.92), massive ascites (OR, 3.78), clear cell cancer (OR, 4.78) and CA125(＞35U/ml) (OR, 5.05) increase the likelihood of having postoperative VTE remarkably. Conclusions: The present study revealed that VTE is a prevalent complication in postoperative patients with endometrial cancer. The patients with the following risk factor including female elderly, large size of tumor, advanced endometrial cancer，massive ascites , elevated CA125 and special histology should be altered VTE occurrence.

Background As reported, preclinical animal models differ greatly from the human body. The evaluation model may be the colossal obstacle for scientific research and anticancer drug development. Therefore, it is essential to propose efficient evaluation systems similar to clinical practice for cancer research. Main body While it has emerged for decades, the development of patient-derived xenografts, patient-derived organoid and patient-derived cell used to be limited. As the requirements for anticancer drug evaluation increases, patient-derived models developed rapidly recently, which is widely applied in basic research, drug development, and clinical application and achieved remarkable progress. However, there still lack systematic comparison and summarize reports for patient-derived models. In the current review, the development, applications, strengths, and challenges of patient-derived models in cancer research were characterized. Conclusion Patient-derived models are an indispensable approach for cancer research and human health.

FOLFOX (oxaliplatin, fluorouracil and calcium folinate) is the first-line chemotherapy regimen for colon cancer therapy in the clinic. It provides superior efficacy than oxaliplatin alone, but the underlying mechanism remains unclear. In the present study, pharmacomicrobiomics integrated with metabolomics was conducted to uncover the role of the gut microbiome behind this. First, in vivo study demonstrated that FOLFOX exhibited better efficacy than oxaliplatin alone in colon cancer animal models. Second, 16S rDNA gene sequencing analysis showed that the abundance of Akkermansia muciniphila (A. muciniphila) remarkably increased in the FOLFOX treated individuals and positively correlated with the therapeutic effect. Third, further exploration confirmed A. muciniphila colonization significantly enhanced the anti-cancer efficacy of FOLFOX. Last, metabolomics analysis suggested dipeptides containing branched-chain amino acid (BCAA) might be responsible for gut bacteria mediated FOLFOX efficacy. In conclusion, our study revealed the key role of A. muciniphila in mediating FOLFOX efficacy, and manipulating A. muciniphila might serve as a novel strategy for colon cancer therapy.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high mortality worldwide. Type 2 diabetes mellitus (T2D), known as a risk factor of CRC, can promote the deterioration of CRC, but the underlying mechanism is elusive. In this study, we aimed to reveal the relationship between CRC and T2D from the perspective of small-molecule metabolism. First, a list of common dysregulated metabolites in CRC and T2D was obtained by retrieving existing metabolomics publications. Among these metabolites, oleic acid (OA) was found to be able to promote the proliferation and migration of colon carcinoma cell HCT116. Further experiments proved that insulin could significantly strengthen this promotion and showed a synergistic effect with OA. Mechanism study found that OA and insulin acted synergistically through the extracellular signal-regulated kinase (ERK)1/2/c-Myc/cyclin D1 pathway. In addition, the combination of ERK1/2 inhibitor SCH772984 and cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib showed a remarkable inhibitory effect on tumor growth in vivo. Taken together, the current study found that OA plays an important role in CRC development by using a functional metabolomics approach. More importantly, insulin and OA were confirmed to synergistically promote the deterioration of CRC in vitro and in vivo via ERK1/2/c-Myc/cyclin D1 pathway. Our findings may shed light on CRC treatment among the T2D population.

Yes-associated protein 1 (YAP1) is a major component of the Hippo signaling pathway. Although the exact extracellular signals that control the Hippo pathway are currently unknown, increasing evidence supports a critical role for the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. Granulosa cells (GCs) within the ovarian follicle proliferate and produce steroids and growth factors, which facilitate the growth of follicle and maturation of the oocyte. We hypothesize that YAP1 plays a role in proliferation and estrogen secretion of GCs. In the current study, we examined the expression of the Hippo signaling pathway in bovine ovaries and determined whether it was important for GC proliferation and estrogen production. Mammalian STE20-like protein kinase 1 (MST1) and large tumor suppressor kinase 2 (LATS2) were identified as prominent upstream components of the Hippo pathway expressed in granulosa and theca cells of the follicle and large and small cells of the corpus luteum. Immunohistochemistry revealed that YAP1 was localized to the nucleus of growing follicles. In vitro, nuclear localization of the downstream Hippo signaling effector proteins YAP1 and transcriptional co-activator with PDZ-binding motif (TAZ) was inversely correlated with GC density, with greater nuclear localization under conditions of low cell density. Treatment with verteporfin and siRNA targeting YAP1 or TAZ revealed a critical role for these transcriptional co-activators in GC proliferation. Furthermore, knockdown of YAP1 in GCs inhibited follicle-stimulating hormone (FSH)-induced estradiol biosynthesis. The data indicate that Hippo pathway transcription co-activators YAP1/TAZ play an important role in GC proliferation and estradiol synthesis, two processes necessary for maintaining normal follicle development.

While FOLFOX has been the preferred chemotherapeutic strategy in colon cancer treatment, the limited response rate has seriously restricted its application in clinic. The underlying mechanisms of the individual response of FOLFOX remain to be elucidated. In this study, pharmacomicrobiomics integrated with pharmacometabolomics was applied to disentangle the key role of specific gut bacteria and microbiota derived metabolites involved. As a result , significant variation of chemotherapy efficacy was observed in tumor bearing mice after FOLFOX administration. 16S rRNA gene sequencing analysis revealed the relative abundance of Staphylococcus , Jeotgalicoccus , Sphingomonas significantly increased in the FOLFOX sensitive group, whereas Prevotella was higher in the non sensitive individuals . Meanwhile, verification study o n FOLFOX combined with bacteria colonization indicates that Prevotella could attenuate the anti cancer efficacy of FOLFOX in vivo . Furthermore, gut derived metabolite 3-Oxocholic acid (3-Oxo) identified by metabolomics approach was confirmed to associate with Prevotella in fecal samples. In addition, preliminary functional exploration suggested that 3-Oxo could reverse the anti cancer effect of FOLFOX and promote malignant progression Taken together, integrated pharmacomicrobiomics and pharmacometabolomics revealed that Prevotella and related metabolite 3-Oxo may be responsible for individualized FOLFOX efficacy, which provides novel predictive biomarkers for FOLFOX precise medicine as well as targets for colon cancer therapy.

Background and Objectives. The development of network medicine provides new opportunities for disease research. Ischemic stroke has a high incidence, disability, and recurrence rate, and one of the reasons is that it is often accompanied by other complex diseases, including risk factors, complications, and comorbidities. Network medicine was used to try to analyze the characteristics of IS-related diseases and find out the differences in genetic pathways between Chinese herbs and Western drugs. Methods. Individualized treatment of traditional Chinese medicine (TCM) provides a theoretical basis for the study of the personalized classification of complex diseases. Utilizing the TCM clinical electronic medical records (EMRs) of 7170 in patients with IS, a patient similarity network (PSN) with shared symptoms was constructed. Next, patient subgroups were identified using community detection methods and enrichment analyses were performed. Finally, genetic data of symptoms, herbs, and drugs were used for pathway and GO analysis to explore the characteristics of pathways of subgroups and to compare the similarities and differences in genetic pathways of herbs and drugs from the perspective of molecular pathways of symptoms. Results. We identified 34 patient modules from the PSN, of which 7 modules include 98.48% of the whole cases. The 7 patient subgroups have their own characteristics of risk factors, complications, and comorbidities and the underlying genetic pathways of symptoms, drugs, and herbs. Each subgroup has the largest number of herb pathways. For specific symptom pathways, the number of herb pathways is more than that of drugs. Conclusion. The research of disease classification based on community detection of symptom-shared patient networks is practical; the common molecular pathway of symptoms and herbs reflects the rationality of TCM herbs on symptoms and the wide range of therapeutic targets.

In the present study we determined acute metabolic changes induced by luteinizing hormone (LH) in highly steroidogenic luteal cells. We found that LH induces rapid changes in glycolysis, TCA cycle, pentose phosphate pathway, glutamine metabolism, and hydrolysis of phospholipids. LH stimulated glucose uptake, glycolysis and incorporation of glucose-derived carbons into various metabolic pathways in luteal cells. Moreover, LH/PKA signaling stimulated post-translational modifications of enzymes involved in de novo synthesis of fatty acids. In addition, selective use of small molecule inhibitors targeting the most significantly changed pathways revealed metabolic routes fundamental for LH-stimulated progesterone production.

Luteinizing hormone (LH) via protein kinase A (PKA) triggers ovulation and formation of the corpus luteum, which arises from the differentiation of follicular granulosa and theca cells into large and small luteal cells, respectively. The small and large luteal cells produce progesterone, a steroid hormone required for establishment and maintenance of pregnancy. We recently reported on the importance of hormone-sensitive lipase (HSL, also known as LIPE) and lipid droplets for appropriate secretory function of the corpus luteum. These lipid-rich intracellular organelles store cholesteryl esters, which can be hydrolyzed by HSL to provide cholesterol, the main substrate necessary for progesterone synthesis. In the present study, we analyzed dynamic posttranslational modifications of HSL mediated by PKA and AMP-activated protein kinase (AMPK) as well as their effects on steroidogenesis in luteal cells. Our results revealed that AMPK acutely inhibits the stimulatory effects of LH/PKA on progesterone production without reducing levels of STAR, CYP11A1, and HSD3B proteins. Exogenous cholesterol reversed the negative effects of AMPK on LH-stimulated steroidogenesis, suggesting that AMPK regulates cholesterol availability in luteal cells. AMPK evoked inhibitory phosphorylation of HSL (Ser565). In contrast, LH/PKA decreased phosphorylation of AMPK at Thr172, a residue required for its activation. Additionally, LH/PKA increased phosphorylation of HSL at Ser563, which is crucial for enzyme activation, and decreased inhibitory phosphorylation of HSL at Ser565. The findings indicate that LH and AMPK exert opposite posttranslational modifications of HSL, presumptively regulating cholesterol availability for steroidogenesis.

Previous studies have reported hypo-glycosylated FSH and fully-glycosylated FSH to be naturally occurring in humans, and these glycoforms exist in changing ratios over a woman's lifespan. The precise cellular and molecular effects of recombinant human FSH (hFSH) glycoforms, FSH21 and FSH24, have not been documented in primary granulosa cells. Herein, biological responses to FSH21 and FSH24 were compared in primary porcine granulosa cells. Hypo-glycosylated hFSH21 was significantly more effective than fully-glycosylated hFSH24 at stimulating cAMP accumulation and protein kinase A (PKA) activity, leading to the higher phosphorylation of CREB and β-Catenin. Compared to fully-glycosylated hFSH24, hypo-glycosylated hFSH21 also induced greater levels of transcripts for HSD3B, STAR and INHA, and higher progesterone production. Our results demonstrate that hypo-glycosylated hFSH21 exerts more robust activation of intracellular signals associated with steroidogenesis than fully-glycosylated hFSH24 in primary porcine granulosa cells, and furthers our understanding of the differing bioactivities of FSH glycoforms in the ovary.

Previous studies have reported that microRNAs function as key regulators in tumor development and progression. This study aims to investigate the functional effects of miR-503 expression in cervical cancer (CC) progression. We detected the expression of miR-503 in CC tissues and cell lines using quantitative real-time polymerase chain reaction. Synthesized miR-503 mimics or inhibitors were used to upregulate or downregulate the expression of miR-503 in HeLa or SiHa cells. Cell Counting Kit-8 and colony formation assay were used to detect the ability of cell proliferation. Furthermore, luciferase assay and Western blot were applied to confirm the target of miR-503 in CC cells. Here, we demonstrated that miR-503 expression was significantly downregulated in CC tissues, compared with adjacent normal tissues. miR-503 expression was significantly associated with tumor size and International Federation of Gynecology and Obstetrics stage. Furthermore, increasing miR-503 expression in CC cells dramatically inhibited cell proliferation, colony formation ability of CC. However, reducing miR-503 had reverse effects on these malignant behaviors. Moreover, we demonstrated that miR-503 inhibited cell proliferation by targeting AKT2 3'-untranslated region and affected its expression. Overexpression of AKT2 rescued the effects induced by miR-503 on cell proliferation. Therefore, our results indicated that miR-503 may serve as a tumor suppressor in CC and provide a potential value for CC treatment.

The corpus luteum is an endocrine gland that synthesizes and secretes progesterone. Luteinizing hormone (LH) activates protein kinase A (PKA) signaling in luteal cells, increasing delivery of substrate to mitochondria for progesterone production. Mitochondria maintain a highly regulated equilibrium between fusion and fission in order to sustain biological function. Dynamin-related protein 1 (DRP1), is a key mediator of mitochondrial fission. The mechanism by which DRP1 is regulated in the ovary is largely unknown. We hypothesize that LH via PKA differentially regulates the phosphorylation of DRP1 on Ser616 and Ser637 in bovine luteal cells. In primary cultures of steroidogenic small luteal cells (SLCs), LH, and forskolin stimulated phosphorylation of DRP1 (Ser 637), and inhibited phosphorylation of DRP1 (Ser 616). Overexpression of a PKA inhibitor blocked the effects of LH and forskolin on DRP1 phosphorylation. In addition, LH decreased the association of DRP1 with the mitochondria. Genetic knockdown of the DRP1 mitochondria receptor, and a small molecule inhibitor of DRP1 increased basal and LH-induced progesterone production. Studies with a general Dynamin inhibitor and siRNA knockdown of DRP1 showed that DRP1 is required for optimal LH-induced progesterone biosynthesis. Taken together, the findings place DRP1 as an important target downstream of PKA in steroidogenic luteal cells.

2.AbstractEstablishment and maintenance of pregnancy is dependent on progesterone synthesized by luteal tissue in the ovary. Our objective was to identify the characteristics of lipid droplets (LDs) in ovarian steroidogenic cells. We hypothesized that LDs are a major feature of steroidogenic luteal cells and store cholesteryl esters. Bovine luteal tissue was used for whole tissue analysis. Further analyses were performed on isolated ovarian steroidogenic cells: granulosa and theca cells of the follicle, and small/large luteal cells. Isolated luteal LDs were collected for lipid/protein analyses. Luteal tissue contained perilipins 2/3/5, hormone-sensitive lipase and abhydrolase domain containing 5. Luteal tissue was enriched in TGs compared to other tissues, except of adipose tissue. Large and small luteal cells were distinguished from follicular cells by the presence of LDs and LD-associated proteins. Furthermore, LDs from large luteal cells were numerous and small; whereas, LDs from small luteal cells were large and less numerous. Isolated LDs contained nearly all of the TGs and cholesteryl esters present in luteal tissue. Isolated luteal LDs were composed primarily of TG, with lesser amounts of cholesteryl esters, diglyceride and other phospholipids. Bovine luteal tissue LDs are distinct from LDs in other bovine tissues, including follicular steroidogenic cells.

Modified metabolites play significant roles in disease occurrence, progression and diagnosis. Sensitive and accurate analytical methods for the quantification of these metabolites are therefore of great importance. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous measurement of 13 pairs of prototypes and their modified forms covering nucleobases, nucleosides and amino acids. In order to improve the quantification sensitivity and accuracy, two structure analogs named N-dimethyl-amino naphthalene-1-sulfonyl chloride (Dns-Cl) and N-diethyl-amino naphthalene-1-sulfonyl chloride (Dens-Cl) were introduced for twins labeling derivatization. Dns-labeling was utilized to react with target analytes while the Dens-labeling of standard compounds provided one-to-one internal standards. With the introduce of naphthalene and easily ionizable moiety tertiary ammonium, chromatography retention and separation of these polar metabolites were notably improved on C18 columns and the detection sensitivity was increased up to 400 folds. The method is sensitive with the lower limit of quantification (LLOQ) values of 0.002-0.5 μg/mL. Comparisons of the performance of twins labeling derivatization and traditional chemical isotope labeling (CIL) derivatization verified the ability of our method in the absolute quantification. The established method was applied to human lung adenocarcinoma cell line A549 and its cisplatin resistant derivative A549/DDP. Significant shifts in 12 metabolites as well as 9 modified-to-prototypical ratios in A549/DDP were observed, demonstrating the utility of our method and the potential role of modified metabolites in mediating anticancer drug resistance. The method can be easily extended to determine other types of modified metabolites in various biological matrices, which will greatly expand our knowledge on these metabolites.

At present, chemotherapy is still to be the preferred and most significant therapeutic strategy for cancer patients in clinical practice. Although Camptothecin (CPT) has been discovered for over half century, a series of CPT derivatives such as Topotecan (TPT) and irinotecan (CPT-11) have been approved and are still to be the first-line medicines for clinical application. Up to now, the topoisomerase 1 inhibitor continues to be a significant drug development research field. Based on previous study of the structure-activity relationship, we consider that the introduction of lipophilic group at C7 position can prolong the retention time and the hydroxyl esterification at C20 can eliminate the hydrogen bond interaction, stabilize the E-lactone form and promote the anti-cancer effect. In this study, we carried out an optimization at C7 and C20 positions to afford two CPT derivatives 3g and 3j. Firstly, we predicted the possibly binding sites of two compounds with topoisomerase 1 by molecular docking. Then we evaluated the anti-proliferation effect of the two novel derivatives and compared the IC50 with CPT-11. Furthermore, the induction of cell cycle arrest and apoptosis was explored through karyomorphology, flow cytometry (FCM) and Western blot analysis. At last, we evaluated the anti-cancer effect and detected the mechanism in colorectal cancer xenograft model. In brief, all the data showed that the novel CPT derivatives (3g and 3j) could inhibit colorectal cancer proliferation via induction of cell cycle arrest and apoptosis in vitro and in vivo. It suggested that the two agents may be a new potential therapeutic strategy in the future.

Chemotherapy is the preferred and most common treatment for cancer in clinical practice. An increasing number of researchers all over the world are focusing on natural medicines to find new antitumor drugs, and several reports have shown that Camellia nitidissima (C. nitidis-sima) Chi could reduce blood-lipid, decrease blood pressure, resist oxidation, prevent carcinogenesis and inhibit tumors. Therefore, the pharmacodynamics of the chemical constituents in C. nitidissima need to be investigated further. In the present study, 16 chemical constituents were isolated from the leaves of C. nitidissima, of which 6 compounds are reported to be found in this plant for the first time. Furthermore, all these phytochemicals were screened for antitumor activity on 4 common cancer cell lines, while compound 3, one oleanane-type triterpene, exhibited the most potential antitumor effects. Interestingly, to our knowledge, this was the first report that compound 3 inhibits cancer cells. Compound 3 inhibited EGFR-mutant lung cancer cell line, NCI-H1975 via apoptosis effect, with an IC50 of 13.37±2.05 µM at 48 h. Based on the data, compound 3 showed potential for antitumor drug development, suggesting the scientific basis for the antitumor activity of C. nitidissima.

Over the last decade, demand has increased for developing the hot-galvanized quenching and partitioning (Q&P) steel to overcome the disadvantages associated with vehicle safety, fuel consumption and corrosion resistant. The present work aims to elucidate the effects of quenching temperature on phase transformation kinetics, microstructure evolutions and mechanical properties of a hot-galvanized Q&P steel (0.225C-0.85Si-2.02Mn-0.91Al, in wt.%) by combining modeling and experimental research. Using dilatometry, SEM, EBSD, EPMA, TEM, PED, XRD and Image-Pro Plus (IPP) software, we quantitatively investigated the microstructure evolution at different quenching temperatures. Results indicated that a larger fraction of primary martensite at lower quenching temperature could strongly promote subsequent bainite transformation kinetics, which is attributed to more martensite-austenite interfaces and defect density. By fitting the dilatometer curves and establishing the equation of transformation rate vs. quenching temperature, a Kolmogorov-Johnson-Mehl-Avram (KJMA) equation was established to describe insufficient bainite formation kinetics during high-temperature short-time overaging. Furthermore, a modified CCE model taking into account intercritical ferrite and short-time bainite transformation was proposed and the predicted RA fractions are more consistent with the experimental values. As the quenching temperature decreases, small-sized blocky RA along martensite boundaries and filmy RA between martensite laths increase, while coarse lath/blocky RA inside bainite structures or at bainite boundaries decreases gradually. In addition, the YS decreases from 763 MPa to 431 MPa with the increase of quenching temperature, while the UTS varies in a narrow range between 967 MPa and 1036 MPa. A stable TEL of 22.6–25.7% can be obtained at a wide range quenching temperature (150–275 °C), which is attributed to the joint effects of TRIP effect and multiphase structure. This research would be of guiding significance for the industrial practice.

With the aid of first principle calculations, structural characteristics, mechanical stability, and electronic and electrochemical properties of two polymorphs of manganese-based pyrophosphate α- and β-phases of Li2MnP2O7 and their relevant delithiated structures are explored for comparison. Our results indicate that, although these two polymorphs of Li2MnP2O7 belong to the monoclinic space group, considerable differences are discovered in Mn local environment of crystal structures. The cell voltage vs Li/Li+ are 4.68 and 4.16 V for α- and β-phases of the Li2MnP2O7/LiMnP2O7 platform, respectively, comparable to the experimental values (4.45 and 4.00 V) for first voltage plateaus. All of the lithium atoms are practically fully ionized in the α- and β-Li2MnP2O7 and their relative half delithiated states, charge transfer mainly concentrated upon Mn and O, which leads to the oxidization state of Mn from Mn2+ to Mn3+ and then from Mn3+ to Mn4+. The band gaps of delithiated configurations decrease gradually wit...

Li- and Na-transition metal fluorosulfate materials (AFeSO4F, A = Li, Na) are proposed as highly promising novel cathode materials for Li- and Na-ion batteries. In this study, the electrochemical performance and elastic properties of AFe1-xMxSO4F (A = Li, Na; M = Co, Ni, Mg; x = 0, 0.5, 1) are investigated from the view of first-principles calculations. The computational results reveal that the substitutions of Fe by Ni, Co and Mg enhance the intercalation voltage of the fluorosulphate materials. The density of states analysis shows that transition metal-doping AFeSO4F, especially for Ni doping case, could achieve better electronic conductivity in comparison with the pure phase and Mg-doped AFeSO4F. Further bader charges calculations give a confirmation that the Fe and Co in AFe0.5Co0.5SO4F play significant role in the charge transfer during delithiated or desodiated progresses, but the relatively inert character of Ni and Mg is discovered in AFe0.5Ni0.5SO4F and AFe0.5Mg0.5SO4F. LiFeSO4F and NaFeSO4F are found to be ductile from the exploration of elastic constants, whereas their delithiated and desodiated configurations have brittle character. In addition, Young’s Modulus (E), and Poisson's Ratio (ν) for LiFeSO4F, NaFeSO4F and 50% metal-doped AFe1-xMxSO4F (A = Li, Na; M = Co, Ni, Mg) are also presented to explore the hardness, bond characteristic and stability against shear.

Collagen is not only the most abundant protein providing the scaffold for assembly of the extracellular matrix (ECM), but also considered to be the "highway" for cancer cell migration and invasion depending on the different collagen organizations. The accumulation of stabilized collagen is enhanced by different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen cross-link. Interestingly, PLOD2 is overexpressed in different cancers and closely related to a poor prognosis. To the best of our knowledge, only the mechanisms of PLOD2 regulated by HIF-1α, TGF-β and microRNA-26a/b have been elaborated. In addition, several pharmacologic inhibitors of PLOD2 have been confirmed to have an anti-metastasis effect. However, there have been no reviews about PLOD2 in cancer research published thus far. In brief, this review about PLOD2 will describe the function, regulatory mechanism, and the inhibitors of PLOD2 in cancer, suggesting the credible clinical evaluation of a prognostic signature in pathological examination and the possible development of therapeutic strategies targeting PLOD2 in the future.

Development of novel carbon-based nanoporous materials with high reversible capacity and excellent cycling stability is a hot topic in the field of hydrogen delivery and storage. In this work, first-principles calculations are carried out to discuss the hydrogen storage properties of Li-decorated porous graphene (Li-PG). The binding energies, electronic structures, storage capacities of hydrogen on different sites are investigated in details. The computational results show that with the increase of lithium doping concentration, the electron concentration of donor atoms exceeds the Nc value, and as a consequence, the PG changes from the p-type semiconductor to the n-type degenerate semiconductor. The maximum hydrogen adsorption configurations of H1a-H'1b and H2a-H'2b systems are obtained, and the average binding energy of per H2 molecule is 0.245 eV and 0.263 eV, respectively. Furthermore, ab inito MD simulation results show that the H1-H'1 and H2-H'2 systems can hold up to sixteen and fifteen H2 molecules, which corresponds to a hydrogen storage capacity of 10.89 wt% and 10.79 wt% at T = 300 K (no external pressure), respectively.

Mobile robot object recognition has attracted significant attention in the internet of things recently, in which there are many challenging tasks, such as the objects, the communication networks and the computer system. It still needs a large of computation, communication and storage capability for the whole system. In this paper, we propose a scheme of mobile robot object recognition in IOT and use edge nodes to process the data from robot vision instead of cloud computing. Besides, we adopt YOLOv3 as the main algorithm in the edge nodes to process the video data. The video from the camera on the robot is transmitted to the fog node by a Wi-Fi router. The advantages of using edge nodes for computation local robot clusters are reliability, real-time capability and flexibility compared with the cloud. In our experiment, we efficiently train the computer model using COCO database deployed to GPU. The robot using the proposed model could recognize the objects in real-time. We achieve mAP of 31.0% and response time of 52ms that illustrates the state-of-art performance of the proposed framework.