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Non-alcoholic fatty liver disease is associated with gut microbiota, oxidative stress, and inflammation. We aimed to investigate the possible mechanism by which noni fruit polysaccharide (NFP) improved hepatic oxidative stress and inflammation in rats under a high-fat diet (HFD) by modulating short-chain fatty acids (SCFAs), the intestinal barrier, and gut microbiota. Hepatic oxidative stress, inflammation, and gut dysbiosis in rats were induced through HFD feeding for 4 weeks, followed by intervention with NFP treatment (100 mg per kg bw) for 5 weeks. The results showed that NFP reduced body weight gain and improved lipid metabolism, hepatic oxidative stress, and inflammation in rats under a HFD. Aside from these beneficial effects, NFP positively affected the SCFA production and reversed the HFD-induced gut dysbiosis as indicated by improved microbiota diversity and composition. The levels of Lactobacillus, Ruminococcaceae_UCG_014, Parasutterella, [Eubacterium]_coprostanoligenes_group, and Ruminococcus_1 improved, whereas the levels of Prevotella_9, Collinsella, Bacteroides, and Turicibacter decreased. Furthermore, NFP maintained the colonic barrier integrity (increased the mRNA relative expression of CCL5, ZO-1, and occludin in the colon, and decreased the serum CCL5 level), and decreased the serum lipopolysaccharide level. Thus, NFP may modulate the gut microflora and SCFA production and reduce the permeability of the colonic barrier and metabolic endotoxemia, thereby alleviating hepatic oxidative stress and inflammation in rats under a HFD.

In China, Brucea javanica oil emulsion injection (BJOEI) has been used as adjuvant therapy to treat cancer for many years. Many systematic reviews (SRs) or meta-analyses (MAs) were published to evaluate its efficacy and safety. Nevertheless, uneven quality made it difficult to reach a consensus and there has been no specific review to integrate the evidence of BJOEI for cancer at present. Therefore, a comprehensive evidence map is needed to guide clinicians.We, for the first time, conducted an overview to assess the SRs/MAs of BJOEI, and provided a comprehensive evidence map to guide clinicians. Besides, this study provided a promising direction for future research to promote the generation of advanced evidence.An overview of SRs or MAs.The pre-defined search strategies were applied to 8 databases. Suitable SRs/MAs were included according to the inclusion and exclusion criteria. Methodological quality, reporting quality, and risk of bias were assessed. An evidence map was conducted to show the situation of clinical evidence.27 SRs/MAs in 7 cancer types were included in this overview. The main problems of SRs/MAs were concentrated on the following aspects: without registration or protocol, lacking gray literature retrieval and a list of excluded studies, incomplete description in the literature retrieval strategy or the methods of merging results, the bias of each synthetic result, less exploration in heterogeneity or publication bias, deficiencies in assessing evidence quality and less description in conflict, funding or access to relevant information. Based on the rules of GRADE, the evidence quality of 154 items in 27 SRs/MAs was defined as moderate quality (103 items), low-quality (44 items), and very low-quality (7 items). Especially, risk of bias (154 items), imprecision (27 items), inconsistency (20 items), and publication bias (9 items) were the main downgrading factors.BJOEI may be a promising adjuvant therapy for treating cancer, especially in the digestive system. However, high-quality SRs/MAs are expected to be carried out to improve the reliability of the above conclusion in the future.

Open-cage fullerenes with a 19-membered orifice were prepared in three steps from C60 . The key step for cage-opening is aniline mediated ring expansion of a fullerene-mixed peroxide with a ketolactone moiety on the orifice. Release of ring strain on the spherical fullerene cage served as the main driving force for the efficient cage-opening sequence. Encapsulation of oxygen could be achieved at room temperature under moderate pressure (50 atm) and the encapsulated oxygen could be released slowly under ambient conditions. The activation energy of the oxygen-releasing process is 18.8 kcal mol-1 and the half-life at 37 °C was 73 min, which makes this open-cage fullerene derivative a potential oxygen-delivery material.

The development of electrocatalysts with excellent activity for clean and sustainable H2 has been considered as an efficient way to store energy and meet the increasing energy and environmental demands. In this paper, we used zeolitic imidazolate frameworks-67 (ZIF-67) as precursors to synthesize the highly active N-doped graphene loaded with Ni and Co nanoparticles (Ni/Co/NC) for hydrogen evolution reaction (HER). The physical and electrochemical characterization of all synthesized samples were analyzed by X-ray diffraction, Raman spectra, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and HER. The results show that the organic ligands of ZIF-67 were successfully transformed into N-doped graphene after high temperature treatment. Ni element was well dispersed in the supporting graphene and can make the graphene keeping the dodecahedral morphology with hollow structure. Co nanoparticles were encapsulated by a layer of graphene. Electrochemical tests show that Ni/Co/NC800 exhibits excellent performance for hydrogen generation: the onset overpotential is only 125 mV, the Tafel slope is 57.6 mV/dec. The excellent performance of Ni/Co/NC800 makes its being a promising candidate for energy storage and conversion applications.

Fat mass and obesity associated (FTO) gene is a famous dominant predictor of obesity, and plays pivotal roles in the regulating fatty acid transport and fat metabolism. In the current study, the quantitative real-time PCR (qRT-PCR), DNA-pooled sequencing and KAspar assay were performed to detect the expression features of FTO and the polymorphisms of FTO associated with the tail fat weight related-traits of Hu sheep. The results indicated that the expression of FTO gene is widely expressed in the tissues tested, and the expression level of FTO in tail fat tissue was evidently higher compared with that in the other tissues. In addition, FTO showed the highest expression level in tail fat tissue at three months. The expression of FTO mRNA was lower in the large-tail fat group compared with that in the small-tail fat group in 6 months old. Subsequently, the polymorphism loci g. 23704451C A detected in the FTO gene was confirmed to be significantly related to the tail length and the weight of tail fat. These results suggested that the polymorphism might be regarded as novel molecular marker for the breeding of small tail sheep.

BackgroundRenal cell carcinoma (RCC) is associated with poor prognostic outcomes. The current stratifying system does not predict prognostic outcomes and therapeutic benefits precisely for RCC patients. Here, we aim to construct an immune prognostic predictive model to assist clinician to predict RCC prognosis.MethodsHerein, an immune prognostic signature was developed, and its predictive ability was confirmed in the kidney renal clear cell carcinoma (KIRC) cohorts based on The Cancer Genome Atlas (TCGA) dataset. Several immunogenomic analyses were conducted to investigate the correlations between immune risk scores and immune cell infiltrations, immune checkpoints, cancer genotypes, tumor mutational burden, and responses to chemotherapy and immunotherapy.ResultsThe immune prognostic signature contained 14 immune-associated genes and was found to be an independent prognostic factor for KIRC. Furthermore, the immune risk score was established as a novel marker for predicting the overall survival outcomes for RCC. The risk score was correlated with some significant immunophenotypic factors, including T cell infiltration, antitumor immunity, antitumor response, oncogenic pathways, and immunotherapeutic and chemotherapeutic response.ConclusionsThe immune prognostic, predictive model can be effectively and efficiently used in the prediction of survival outcomes and immunotherapeutic responses of RCC patients.

Basic helix-loop-helix (bHLH) transcription factors (TFs) participate in many physiological and cellular processes in eukaryotes. However, their functions remain unclear in the macro basidiomycete Ganoderma lucidum (G. lucidum). In this study, a gene encoding bHLH TF, GlbHLH, was identified in G. lucidum. The knockdown of GlbHLH by RNA interference reduced hyphal growth, hyphal branching, and resistant to osmotic, oxidative, and cell wall stress. The content of cell wall components β-1,3 glucan and chitin and the expression of their synthesis genes were decreased in the GlbHLH knockdown strains. The knockdown of GlbHLH led to an increase of intracellular reactive oxygen species by decreasing the enzyme activity and gene expression of antioxidant enzymes. Furthermore, the production of intracellular polysaccharides and extracellular polysaccharides was greatly decreased in the GlbHLH mutants. These results suggested that GlbHLH is involved in hyphal growth, stress response, and polysaccharide biosynthesis in G. lucidum.

China is the largest producer of the metal magnesium, which is the third largest metal after steel and aluminum, and magnesium slag (MS) discharged from magnesium production cannot be treated effectively at present. Large amounts of MS occupy the land, making the land salinized and polluting the groundwater, which will threaten the sustainable development of the inland areas of China. To realize the large-scale utilization of MS, this paper reviews the research on the comprehensive utilization of MS and proposes using MS to prepare backfill materials. Firstly, the source and physical and chemical properties of MS are introduced, and the hazards caused by MS are also pointed out. Then, the several utilization methods of MS are summarized, such as cement admixture, chemically activated cementitious materials, clinker sintering, etc. Thirdly, the effect of MS on the properties of cementitious materials and concrete is summarized, including condensation time, workability, mechanical properties, durability, etc. Finally, based on the cemented backfill mining method, MS replaces Portland cement and blast furnace slag (BFS) to prepare cementitious materials. The mechanical properties and fluidity of backfilling slurry composed of MS, gypsum, BFS, and tailings can meet the requirements of backfilling mining.

Despite the adoption of a national immunization program in China, the incidence of mumps remains high. This study aimed to describe the epidemiological characteristics, including the time, region, occupation, and age, of mumps in Wuhan from 2005 to 2018 and to evaluate its transmissibility. In this study, the susceptible–exposed–infectious–asymptomatic–recovered (SEIAR) model fitted the actual incidence data of mumps. The effective reproduction number (Rt) was used to evaluate and compare the transmission capacity in different areas. From 2005 to 2018, there were 36,415 cases. The incidence of mumps was highest among people aged 5–10 years (460.02 per 100,000). The SEIAR model fitted the reported mumps data well (P < 0.01). The median transmissibility (Rt) was 1.04 (range = 0–2.50). There were two peak spreads every year (from March to May and from October to December). The Rt peak always appeared in the first 2 months of the peak incidence rate. The peak time of the epidemic spread of mumps was 1–2 months earlier than the peak incidence rate. The prevention and control measures of vaccination for children aged 5–10 years should be taken before the peak transmission capacity each year, 2 months before the peak of the outbreak, to reduce the spread of mumps.

A green and efficient reaction route for the synthesis of pyrrolidin-2-ones via photoinduced organocatalyzed three-component cyclization of styrene, tertiary α-bromoalkyl esters and primary amines in a microchannel reactor under visible light conditions has been developed. Moreover, the overall process can be carried out under mild conditions without using a metal. In addition, a reasonable reaction mechanism was proposed based on control experiments.

BACKGROUND Targeting of PD-1/PD-L1 immune checkpoints exhibits excellent clinical outcomes in numerous types of solid tumors, including gastric cancer. However, the tumor microenvironment of gastric cancer is very complex and the association of PD-L1 with the tumor microenvironment in gastric cancer is still not clear. MATERIAL AND METHODS This study analyzed the characteristics of PD-L1 expression and used immunohistochemistry to assess CD8 and CD4 tumor-infiltrating leucocytes (TILs) in 478 cases of gastric cancer compared with the expression patterns in 70 matched adjacent tissues, and 32 cases of benign gastric tissues. Standardized methods for TILs assessment in gastric cancer were used. RESULTS The results indicated that PD-L1 expression was increased in gastric cancer tissues (193 out of 478, 40.37%) compared with matched adjacent tissues (14 out of 70, 20.00%) and benign gastric tissues (10 out of 32, 31.25%). It was observed that in gastric cancer patients, positive PD-L1 status in tumor cells (tPD-L1) was associated with distant metastasis (χ²=3.344, P=0.044). The positive expression pattern of tPD-L1 was associated with higher density of TILs, and this pattern was most significant in the non-metastasis group, compared to the metastasis group. We also found that tPD-L1 was not prognostic for overall survival in gastric cancer patients, but tPD-L1 and tCD8 combined positive status in gastric cancer patients was strongly associated with better overall survival rates both in the univariate analysis [hazard ratio (HR)=2.341, 95% confidence interval (CI)=1.147-3.556, P

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, has gradually emerged as a public health challenge worldwide. Morinda citrifolia (noni) has been used to treat various ailments by Pacific Islanders for centuries. In this work, noni fruit polysaccharide (NFP) was obtained by hot water extraction, and its structure was initially explored. The molecular weight of NFP was approximately 456 kDa, and its monosaccharide components predominantly consisted of Gala (58.44%), Gal (4.44%), Glu (21.13%), Rha (4.84%), and Ara (2.16%) to form galacturonic acid, rhamnogalacturonan-I, arabinogalactan, and arabinan. The protective effect of NFP on the intestinal mucosal barrier was then investigated using DSS-induced IBD model mice. Whereas DSS treatment inhibited intestinal mucosal expression and destroyed the tight junction of epithelial cells, by contrast, NFP promoted mucosal and tight junction protein (zonula occludens-1 and occludin) expression. In conclusion, NFP improved the clinical diagnosis of acute colitis in IBD mice and may present a potential source of IBD treatment.

Integration of microfluidics with integrated circuit chip is a promising method to achieve lab-on-a-chip for its high-level miniaturization and portability in application. In this paper, a novel approach for integration of complementary metal–oxide–semiconductor image sensor and microwell array using the 3-D wafer-level chip scale package (3-D WLCSP) technology for biodetector is presented. The key process including silicon microwell array fabricating, wafer-level bonding, backside grinding, through-silicon via etching, redistribution layer, and ball grid array formation are developed. A high-density serpentine electrical circuit is integrated on the backside of the package to work as a temperature controller. After the fabrication process optimization, a yield rate of 94.6% is obtained. The reliability of the packages is characterized by thermal cycling and highly accelerated stress test temperature storage tests, and the results show a good package level reliability. The proposed 3-D WLCSP provides a low-cost and reliable solution for the fluidic biodetector integration.

In actual engineering, the actual road test or indoor bench test is usually used to collect the data of the road load of the parts to acquire the fatigue life estimation of the auto parts. This paper proposes a method for load spectrum construction based on the mixed distribution probability model using the data of the road load spectrum collected in the test site. Pau Ta criteria outlier elimination and wavelet signal denoising are applied to analyze the original road load spectrum data. Then the maximum likelihood estimation method is used to estimate the generalized Pareto distribution parameters of all excesses. The Pareto distribution is also employed to extrapolate the load spectrum. Through the characteristic analysis of the load spectrum, the one-dimensional and two-dimensional program load spectrum of the hub is established based on the mixed probability distribution model, which provides a theoretical basis for the life prediction of the hub. In addition, the research results of this paper provide inspirations for the fatigue life prediction and fatigue durability bench test of automotive parts subjected to the complexity and variability of random loads.

Although silica aerogel is an excellent thermal insulation material, the poor mechanical property limits its application. The glass fiber reinforced silica aerogel with excellent mechanical property through facile sol-gel process is reported. Innovatively, during the experiments, ethanol was introduced as the main solvent in the water glass based silica sol through ion concentration adjustion to get rid of the conventional solvent exchange. To improve the mechanical property of the product, glass fiber was introduced during the gelation process. Catalyzed by hydrogen chloride, hexamethyldisiloxane was utilized as the modificaton agent. The glass fiber reinforced silica aerogel with low thermal conductivity (0.024 W/m·K) was obtained after ambient pressure drying. Three-point loading tests indicated excellent anti-flexure ability of the as-prepared glass fiber reinforced silica aerogel. Moreover, the entire preparation period can be reduced to ~20 h.

A self-synthesized octa(γ-chloropropyl) polyhedral oligomeric silsesquioxanes (POSS) and its evolutionary amino-terminated hyperbranched structure were introduced onto the carbon fibers (CFs) surface (CF-Gn-POSS-NH2, n = 1, 2 and 3) by chemically and successively grafting method to improve the interfacial properties of CFs/epoxy composite. The fiber surface structures could be tuned through regulating grafting generation (n) of CF-Gn-POSS-NH2, and the polarity and roughness of CF surface increased with the incremental dendritic generation number. Interfacial shear strength (IFSS), interlaminar shear strength (ILSS) and dynamic mechanical properties of the functionalized CFs composites improved as the grafting generation increased, which may be attributed to the varying degrees of chemical interaction, mechanical interlocking and resin wettability provided by hyperbranched Gn-POSS-NH2 interface. Moreover, the interfacial structure has been also speculated and analyzed.

Electrochemical conversion of water into oxygen and hydrogen gas is a highly efficient method to meet the energy requirement on a global scale and solve the global warming problem arising from the mass consumption of fossil sources. Therefore, it is important to develop a catalyst with excellent oxygen reduction reaction (OER) activity. In this paper, we adopted the cocrystallization technology to synthesize Zn1−xCox-ZIF composites. Then, the Zn1−xCox-ZIF composites were used as precursors to prepare the Zn1−xCox/NC electrocatalyst (NC is N-doped carbon). The influence of the Zn element on the Zn1−xCox/NC electrocatalyst for the oxygen reduction reaction has been explored. All as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The results show that Zn1−xCox/NC electrocatalysts exhibit excellent OER activity. And the doping of Zn has a great influence on the structure and OER efficiency of the Zn1−xCox/NC electrocatalyst. After the pyrolysis process, the organic ligands of Zn1−xCox-ZIF are transformed into porous carbon and Zn and Co nanoparticles are formed inside the carbon. Among these Zn1−xCox/NC electrocatalysts, Zn0.2Co0.8/NC shows the highest OER activity. The carbon nanowires appearing on the surface of Zn0.2Co0.8/NC nanoparticles are much more compared to that on others. The overpotential and Tafel slope of Zn0.2Co0.8/NC are 1.52 V and 98 eV dec−1, respectively. Zn0.2Co0.8/NC also exhibits outstanding long-term electrochemical durability. This finding can not only extend the application of MOFs, but can also present a new method for fabricating highly efficient OER electrocatalysts.

Our earlier work indicated that the polysaccharides of Amauroderma rude (AR) appear to have an effect on immunoregulation. However, the pathways are not clear. In this paper, we discuss the immunomodulatory mechanisms of A. rude to provide a scientific basis for its possible use as a food. Amauroderma rude increased the expression of iNOS and P38 in the Raw246.7 cell line. When the AR concentration reached 150 μg/mL, the expressions of iNOS and P38 increased 23.0% and 191.7%, respectively. When the AR concentrations were 50 μg/mL, the concentrations of cytokines IL-2, TNF-α, and IFN-γ were 33.65 pg/mL, 12.53 pg/mL and 42.56 pg/mL. When AR reached 200 μg/mL, the lgA and lgM levels were 0.73 μg/mL and 1.5 μg/mL. When AR reached 400 μg/mL, the lgG level reached 1.65 μg/mL by ELISA assay. When 4.8 mg AR were orally administered, IL-2, TNF-α, IFN-γ, PGE2, and LTB4 increased dramatically, to 0.17 pg/mL, 0.16 pg/mL, 0.15 pg/mL, 30.71 pg/mL, and 18.68 pg/mL, respectively. The concentrations of lgA, lgM, and lgG, AA, and PLA2 also increased significantly to 2.62 pg/mL, 2.14 pg/mL, 2.06 pg/mL, 5.23 μg/mL and 3.68 ng/mL, respectively. With 4.8 mg AR p.o., iNOS protein expression increased 16.8% and P38 increased 234.0%. These results indicate that A. rude polysaccharides stimulate cytokine production and activate the iNOS, PLA2-AA, and MAPK pathways during the immunomodulatory process.

The zeolitic imidazolate framework-8 (ZIF-8), as a kind of MOF, is widely used in sensors, gas storage/separation, drug delivery, and catalysis due to its adjustable porous structure, high surface area, and excellent chemistry tunability. ZIF-8 is constructed by Zn2+ and 2-methylimidazole and synthesized in the methanol solution. In this paper, we explored the influence of the reused methanol solution for the structure and properties of the synthesized ZIF-8. The as-synthesized ZIF-8 was characterized by an X-ray diffraction instrument (XRD), a scanning electron microscope (SEM), a specific surface area analyzer (BET), and Fourier transform infrared spectroscopy (FT-IR). The results show that the reused methanol solution does not change the phase, porous structure, and BET surface area of ZIF-8. However, the particle size of ZIF-8 increases from 50 nm to 5 um and the productive rate decreases to 7.4% when the methanol solution is reused four times. This work provides new insight into the reuse of dissolvents for the synthesis of MOFs.

Kaolin clay is an inexpensive and abundant material with potential for use as a low-dielectric-constant ceramic; however, the natural metallic oxides the clay contains hinder such applications. In this study, kaolin clay ceramics with excellent physical and dielectric properties were synthesized using kaolin clay as the raw material by chemical cleaning and sintering. Characterization of the resulting samples showed that the sulfuric acid treatment has a significant influence on the metallic oxide content and dielectric properties of the kaolin clay ceramics. When the kaolin clay raw material was treated with sulfuric acid three times, the dielectric constant decreased from 5.12 to 3.75 and the Vickers hardness increased from 946 to 1,214 kg/mm2 relative to the ceramic prepared from the untreated clay. Therefore, these ceramics exhibit significant potential for use in the microelectronics industry.

Experimental results show that when the loading sequence of fatigue loads changes, the fatigue cumulative damage prediction based on Miner's rule will have a large error, even as high as 252.83%. In an effort to improve the fatigue life predictions, based on the residual strength degradation rule, a power exponential fatigue equivalent damage model is presented in this paper, which contains two material parameters. Experimental data were cited to verify the residual strength model, and the statistical results showed that this model is capable of describing the residual strength degradation of materials. Furthermore, a fatigue cumulative damage model based on residual strength is established to predict the fatigue life. The Miner's rule and other models were compared to validate the model by referring to the test data of different materials under different loading stress levels. And the accuracy of the fatigue life predicted by this model is twice as good as that predicted by others models.

Gliomas are the most common and aggressive malignant brain tumors and are associated with high mortality and incidence in humans. Despite rigorous multi-modal therapy, including surgery, chemotherapy and radiotherapy, patients with malignant glioma survive an average of 12–15 months following primary diagnosis. Therefore, new molecular biomarkers are urgently needed for diagnosis and targeted therapy. Here, we find that suppression of CKAP4 might inhibit glioma growth through regulation of Hippo signaling. We examined the expression levels of CKAP4 through analysis of RNA sequencing data from GEPIA and CGGA databases. Then, Lentivirus was used to construct stable cell lines with knockout or overexpression of CKAP4. Next, the function of CKAP4 on glioma was investigated in vitro and in an orthotopic brain tumor model in mice. Lastly, luciferase reporter assay, immunofluorescence and immunoblotting were performed to explore the potential mechanism of how CKAP4 affects gliomas. CKAP4 is highly upregulated in glioma and high CKAP4 expressing tumors were associated with poor patient survival. And CKAP4 promotes malignant progression of gliomas via inhibiting Hippo signaling. CKAP4 has potential as a promising biomarker and can predict the prognosis of patients with gliomas. And targeting CKAP4 expression may be an effective therapeutic strategy for the treatment of human gliomas.

Prostate cancer (PCa) is one of the most common malignancies for males, but very little is known about its pathogenesis. This study aimed to identify novel biomarkers associated with PCa prognosis and elucidate the underlying molecular mechanism. First, The Cancer Genome Atlas (TCGA) RNA-sequencing data were utilized to identify differentially expressed genes (DEGs) between tumor and normal samples. The DEGs were then applied to construct a co-expression and mined using structure network analysis. The magenta module that was highly related to the Gleason score (r = 0.46, p = 3e–26) and tumor stage (r = 0.38, p = 2e–17) was screened. Subsequently, all genes of the magenta module underwent function annotation. From the key module, CCNA2, CKAP2L, NCAPG, and NUSAP1 were chosen as the four candidate genes. Finally, internal (TCGA) and external data sets (GSE32571, GSE70770, and GSE141551) were combined to validate and predict the value of real hub genes. The results show that the above genes are up-regulated in PCa samples, and higher expression levels show significant association with higher Gleason scores and tumor T stage. Moreover, receiver operating characteristic curve and survival analysis validate the excellent value of hub genes in PCa progression and prognosis. In addition, the protein levels of these four genes also remain higher in tumor tissues when compared with normal tissues. Gene set enrichment analysis and gene set variation analysis for a single gene reveal the close relation with cell proliferation. Meanwhile, 11 small molecular drugs that have the potential to treat PCa were also screened. In conclusion, our research identified four potential prognostic genes and several candidate molecular drugs for treating PCa.

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation has emerged as a central mediator of kidney inflammation in diabetic kidney disease (DKD). However, the mechanism underlying this activation in DKD remains poorly defined. In this study, we found that kidney-enriched microRNA-10a and -10b (miR-10a/b), predominantly expressed in podocytes and tubular epithelial cells, were downregulated in kidney from diabetic mice and patients with DKD. High glucose decreased miR-10a/b expression in vitro in an osmolarity-independent manner. miR-10a/b functioned as negative regulators of the NLRP3 inflammasome through targeting the 3′untranslated region of NLRP3 mRNA, inhibiting assembly of the NLRP3 inflammasome and decreasing caspase-1-dependent release of pro-inflammatory cytokines. Delivery of miR-10a/b into kidney prevented NLRP3 inflammasome activation and renal inflammation, and it reduced albuminuria in streptozotocin (STZ)-treated mice, whereas knocking down miR-10a/b increased NLRP3 inflammasome activation. Restoration of miR-10a/b expression in established DKD ameliorated kidney inflammation and mitigated albuminuria in both db/db and STZ-treated mice. These results suggest a novel intervention strategy for inhibiting kidney inflammation in DKD by targeting the NLRP3 inflammasome.

Salvia miltiorrhiza Bunge has been widely used in the treatment of cardiovascular and cerebrovascular diseases, due to the pharmacological action of its active components such as the tanshinones. Plasma membrane (PM) H+-ATPase plays key roles in numerous physiological processes in plants. However, little is known about the PM H+-ATPase gene family in S. miltiorrhiza (Sm). Here, nine PM H+-ATPase isoforms were identified and named SmPHA1–SmPHA9. Phylogenetic tree analysis showed that the genetic distance of SmPHAs was relatively far in the S. miltiorrhiza PM H+-ATPase family. Moreover, the transmembrane structures were rich in SmPHA protein. In addition, SmPHA4 was found to be highly expressed in roots and flowers. HPLC revealed that accumulation of dihydrotanshinone (DT), cryptotanshinone (CT), and tanshinone I (TI) was significantly reduced in the SmPHA4-OE lines but was increased in the SmPHA4-RNAi lines, ranging from 2.54 to 3.52, 3.77 to 6.33, and 0.35 to 0.74 mg/g, respectively, suggesting that SmPHA4 is a candidate regulator of tanshinone metabolites. Moreover, qRT-PCR confirmed that the expression of tanshinone biosynthetic-related key enzymes was also upregulated in the SmPHA4-RNAi lines. In summary, this study highlighted PM H+-ATPase function and provided new insights into regulatory candidate genes for modulating secondary metabolism biosynthesis in S. miltiorrhiza.

Background. To evaluate whether the overexpression of chemokine receptor-7 (CXCR7) in prostatic tissues obtained from men with Castration-Resistant Prostate Cancer (CRPC) is associated with resistance to enzalutamide (Enza). Methods. Based on the inclusion criteria of CRPC in EAU guidelines, all eligible patients treated in our hospital from January 2015 to December 2019 were included. Cases underwent radical prostatectomy, docetaxel-based chemotherapy, or new endocrine therapies (including Enza or abiraterone), and cases with severe cardiopulmonary disease or other malignant tumors were excluded. After immunohistochemical staining for CXCR7 expression in prostatic biopsy tissues, all enrolled cases were divided into two groups, namely, the CXCR7-positive group and the CXCR7-negative group. And then, PSA response to Enza treatment was recorded in detail and comparatively analyzed. In addition, the Cox proportional hazard modeling and the Kaplan-Meier analysis were used to determine PSA progression-free survival (PSAP-FS) and clinical or radiographic progression-free survival (CRP-FS) in this cohort. Results. A total of 79 CRPC individuals were enrolled and evaluated in this study. Median follow-up durations were 24 months (range, 12-42) in the CXCR7-positive group ( n = 47 ) and 28.5 months (range, 12-42) in the CXCR7-negative group ( n = 32 ). The patients with lower CXCR7 expression showed much better PSA response to Enza treatment. There was 84.4% of CXCR7- cases showing decreasing PSA response, while there were 71.4% in the CXCR7/1+ group and 31.2% in the CXCR7/2+ group, respectively. All patients in the CXCR7/3+ group showed increasing PSA response to Enza treatment. And the percentage of patients whose PSA decreased over 50% is significantly higher in the CXCR7-negative group than in the CXCR7-positive group (68.8% vs. 8.5%, P < 0.001 ), and the percentage of patients whose PSA decreased over 90% is also remarkably higher in the CXCR7-negative group (43.8% vs. 0, P < 0.001 ). The Kaplan-Meier analysis demonstrated that the oncologic outcomes of CXCR7-negative patients were improved much significantly by Enza treatment in comparison with those of CXCR7-positive patients. Significantly increased median PSAP-FS (21 months vs. 6 months, P < 0.0001 ) and CRP-FS (27 months vs. 9 months, P < 0.0001 ) were obtained in the CXCR7-negative group. The further stratified analysis in all CXCR7-positive patients demonstrated that the patients with higher CXCR7 expression showed much worse outcome. The median time of PSAP-FS was 21 months in the CXCR7/1+ group, 9 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, while the median time of CRP-FS was 21 months in the CXCR7/1+ group, 12 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, respectively. Conclusion. Overexpression of CXCR7 induced by an AR antagonist in CRPC patients displays much better treatment response to Enza. CXCR7 might be a novel therapeutic target gene for CRPC patients.

Micron-sized hydrophobic SiO

Ozone (O3) exposure can lead to airway inflammation, hyperreactivity and airway remodeling. Liver X receptors (LXRs) play an important role in attenuating inflammation. The therapeutic effects of LXRs on ozone-induced pulmonary inflammation and airway remodeling were examined. C57/BL6 mice were exposed to ozone for 1 or 6 weeks. LXR agonist T0901317 was administered to mice at one hour before ozone exposure. As expected, ozone-exposed mice developed lung inflammation with augmented neutrophil, macrophage, TNF-α, IL-6, IL-8 and G-CSF in the bronchoalveolar lavage fluid and serum. The increase in MMP-9 and α-SMA expression, and collagen deposition around airway reflected the airway remodeling in ozone-exposed mice. Compared with ozone-exposed mice, LXR agonist T0901317 inhibited the ozone-induced inflammation after 1 and 6 weeks in the ozone exposure model. In addition, the treatment with the LXR agonist prevented alveolar enlargement and reduced airway remodeling in 6-week ozone-induced mice. Therefore, LXRs may repress pulmonary inflammation and attenuate the progression of airway remodeling.

Activated carbons (AC) were prepared by carbonization and KOH activation using rice husk as feedstock. The effects of impregnation ratios and activation temperatures on the properties of AC were investigated. Under optimum conditions, BET surface area, total pore volume and micropore volume of AC are as high as 1495.52 m

With the rise of intelligent driving market, automotive CMOS image sensor is more and more widely used. Compared with cameras in mobile phones, automotive CMOS image sensor need to pass critical reliability test, namely, AEC-Q100. In this paper, a novel and highly reliable wafer level packaging technology using through via technology (TSV) was developed for automotive CMOS image senor. Several new key process such as wafer level bonding, backside grinding, via etching, low temperature PECVD, spray coating passivation layer, RDL formation and ball drop were investigated. Reliability of the developed WLCSP based on AEC-Q100 was characterized by Temperature Humidity Bias Test (THB), Temperature Humidity Test (THS), Temperature Cycling Test (TC), High Temperature Storage Life Test (HTS) and Low Temperature Storage Life Test (LTS). No failure was found after the reliability rest. Good package reliability results demonstrate that WLCSP technology can meet the requirements of low cost and high reliability for automotive CMOS image sensors.

With the rise of artificial intelligence, automatic driving, 5G, Internet of things and other emerging industries, the demand of 3D integrated packaging technology is increasing strongly to meet the ever-increasing market demands of high performance, small size, high reliability and ultra-low power consumption. This paper presents a new 3D system integrated packaging technology named embedded system in chip (eSinC®) technology. This technology is a combination of TSV technology and eSiFO technology which has been reported in 2016 [1]-[4]. After finishing the standard eSiFO process, backside RDLs and via last TSV process were fabricated by using laser temporary bonding technology. A totally three stacking package including five chips with two layer frontside and backside RDLs was fabricated successfully. Individual package was connected by micro bumps and TSVs. The packaging size is 5×5mm with an overall 0.78mm packaging thickness, while the individual eSinC packaging thickness is 0.28mm. Several key technologies were developed to achieve eSinC package, including high aspect ratio TSVs, wafer thin and handling, low temperature PECVD process, as well as temporary bonding. Good electrical yield was achieved after process optimization.

We previously reported that Amauroderma rude polysaccharides (AR) displayed strong immunomodulatory tumor-suppressive effects in mice. The current study was designed to explore the potential mechanism by which AR polysaccharides inhibit tumor growth. We found that AR could effectively induce cell death in 4T1 and MDA-MB-231 breast cancer cells. AR could also inhibit tumor cell migration and invasion, significantly promote apoptosis in 4T1 cells, and significantly increase CDK4, CDK6, cylinD1, and P27 mRNA expression in mice. Additionally, AR was able to significantly increase FOXO3a expression and decrease p-AKT expression both in vitro and in vivo, indicating that the AKT/FOXO3a signaling pathway had been activated during the inhibitory process.

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

The preparation of hierarchically porous carbon via a low-cost way for gaseous benzene adsorption remains a challenge that needs to be addressed urgently. In this study, crayfish shell from kitchen garbage was employed as the precursor for synthesis of activated carbon (AC) via chemical activation strategy, which could be potential in synthesis because of the cost-effective precursor and simple way. Orthogonal design test and various characterization techniques were adopted to explore the optimal preparation conditions of AC. As a result, AC7 with the large specific surface area (2669.40 m2/g) and well-developed pore volume (1.42 cm3/g) has been synthesized successfully. Compared with other adsorbents, AC7 exhibited more excellent adsorption performance for gaseous benzene (684.6 mg/g) in the dynamic adsorption experiments. The influences of preparation factors by the range analysis method and environmental conditions via the single factor method on the adsorption performance of AC7 for gaseous benzene were investigated and analyzed, comprehensively. Based on the isotherm and thermodynamic models, the adsorption experiment data were fitted, analyzed and evaluated to figure out the adsorption mechanism. The results showed that the adsorption process was exothermic, and mainly physical. The partition coefficient and breakthrough volume were also applied to evaluate the benzene adsorption performance objectively. In addition, the reusability tests were carried out. In the eleventh cycle, the adsorption capacities under different initial concentrations were higher than 96.92% of the initial adsorption capacities, showing that AC7 possessed the good reusability. These results showed that AC7 would be an attractive and potential adsorbent for the gaseous benzene adsorption.

BACKGROUND The relevance of c-Met expression as a prognostic or predictive clinical indicator in chemotherapy-resistant breast cancer remains unknown. The aims of this study were to investigate the expression of c-Met in breast cancer tissues and its association with expression of type II topoisomerase (TOPO II), including in patients who received neoadjuvant chemotherapy (NAC), and to investigate chemotherapy resistance in vitro in breast cancer cell lines. MATERIAL AND METHODS Tissue samples from 255 patients with breast cancer, with matched adjacent normal breast tissue, were used in tissue microarrays (TMAs). c-Met protein expression levels were determined using immunohistochemistry. Forty-five cases of breast cancer treated with NAC were studied to investigate the association between c-Met and TOPO II expression and clinical outcome. Chemotherapy resistance was evaluated in vitro in the MCF-7 and MDA-MB-231 breast cancer cell lines. RESULTS Expression of c-Met protein was increased in breast cancer tissue compared with normal breast tissue. In breast cancer tissue samples, increased c-Met expression was significantly associated with increased Ki-67 expression, tumor size, tumor stage, and TOPO II expression, and with reduced overall survival (OS) rates. Increased c-Met expression and reduced TOPO II expression were associated with chemotherapy resistance. In breast cancer cell lines, knockdown of c-Met expression induced TOPO II expression and increased tumor cell sensitivity to chemotherapy. CONCLUSIONS The findings of this study support a role for c-Met as a clinical prognostic marker and for c-Met and TOPO II as predictive markers for response to chemotherapy in patients with breast cancer.

An increasing amount of waste sodium-based slag was generated during the purification process of metallurgical silicon that causes a posed problem to the environment. Here, a simple but effective approach was developed for the synthesis of mesoporous silicon from waste sodium-based slag. The as-received slag was leached and then calcined to fabricate silica as a precursor. Subsequently, the nanostructured silicon was produced through the reduction of the silica in a magnesium (Mg) vapor. The mechanism suggested that the Mg-containing phases (Mg2Si, MgSiO3, and MgO) were performed as an intermediary agent and facilitated the formation of nano-scale silicon. Nitrogen (N2) adsorption study of the final silicon product showed a BET surface area of 75.5 m2/g and a distributional BJH pore size of 3.7 nm. Significantly, the N2 absorption capacity of the mesoporous silicon reached 200 m3/g. The aim of this study is to recycle the waste sodium-based slag and provide an alternative for the synthesis of mesoporous silicon materials.

Fiber needle felt–silica aerogel composite was successfully prepared by via sol–gel process based on water glass. The thermal conductivity show V-type variation tendency with the increase of water to Si. Thermogravimetric analysis-differential scanning calorimetry analysis revealed that the thermal stability was up to approximately 390.58 °C. It has been found that the fire hazard of the composites decreased with the increased ratio of water to Si according to the cone calorimeter test, which can be characterized by peak heat release rate, fire performance index, and fire growth rate index. The fiber needle felt/aerogels present greatly improved compressive and flexural strength (elastic modulus: 0.1–0.97 MPa; flexural modulus: 0.33–0.66 MPa) while keeping inherent properties of pure silica aerogel: low bulk density (0.166 g/cm3), low thermal conductivity of 0.0236 W/m·K, and high specific surface area (1091.62 m2/g). As a result, the as-prepared composite shows a great potential to be applied in the thermal insulation field.

This study aims to compare the therapeutic effects of noni fruit water extract (NFW) and noni fruit polysaccharide (NFP) on oxidative stress and inflammation in mice under high-fat diet. In this study, mice were induced to develop oxidative stress and inflammation through high-fat diet. Treatment was performed via the administration of NFW (10 mL per kg bw) and NFP (50, 100, and 200 mg per kg bw) for 4 weeks. The results indicated that the NFW and NFP reduced the body weight gain, liver relative weight, and abdominal fat relative weight of mice under high-fat diet. Moreover, the NFW and NFP reduced the liver malondialdehyde level and increased the liver trolox equivalent antioxidant capacity level. The NFP effectively increased the liver superoxide dismutase and glutathione peroxidase activities, and the administration of NFP at 100 and 200 mg per kg bw effectively increased the hepatic nuclear factor erythroid-2 related factor level, thus presenting improved antioxidant activity. The NFW and NFP restrained the elevation of tumor necrosis factor alpha, interleutin-6, and nitric oxide levels in the liver and serum. All NFP doses prominently decreased the hepatic nuclear factor kappa B level, and the NFP at 100 and 200 mg per kg bw presented high anti-inflammatory activity. These results suggested that the NFW and NFP alleviated oxidative stress and inflammation in mice under high-fat diet, and the NFP at 100 mg per kg bw had a better effect than NFW with a similar polysaccharide dosage, illustrating that NFP may be an important component in the NFW.

Designing efficient electrocatalysts for oxygen evolution reaction (OER) is very important for renewable energy storage and conversion devices. In this paper, we introduced a new strategy to synthesize Ni doped Co/NC catalysts (NC is the abbreviation of nitrogen-doped graphitic carbon), which were derived from ZIF-67. All catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscope (TEM) and oxygen evolution reaction (OER). The results show that Ni was well doped in the Ni/Co/NC catalysts and the doping of Ni has great influence on the OER activity of Ni/Co/NC catalysts. Among these catalysts, 0.50Ni/Co/NC exhibits the highest OER activity. The onset potential of 0.50Ni/Co/NC is 1.47 V, which is superior than the onset potential of Co/NC (1.54 V), 0.25Ni/Co/NC (1.48 V), 1.00Ni/Co/NC (1.53 V). The excellent OER activity of 0.50Ni/Co/NC catalyst makes its potential to be used on renewable energy storage.

Epstein-Barr virus-induced gene 3 (EBI3) encodes a secretory glycoprotein, and has previously been identified as upregulated in various types of tumors. The presnet study examined the clinical significance of EBI3 expression for predicting tumor recurrence and survival after resection in hepatocellular carcinoma (HCC). EBI3 expression in various HCC cell lines and in 20 pairs of tumor and peritumor tissue samples were detected using western blot analysis. Immunohistochemical staining using tissue microarray with 312 samples from randomly selected patients with HCC who underwent surgery. Survival analysis was performed using univariate and multivariate analyses. EBI3 protein level was higher in L-02 cells and in peri-tumor tissues compared with tumor tissues. Immunohistochemical staining of EBI3 was reduced in HCC tissues in comparison with adjacent normal tissues and significantly associated with tumor invasive characteristics, including tumor thrombus, poor differentiation and large size. Notably, the results suggested that EBI3 was a predictor for tumor recurrence and patient survival, and multivariate analysis indicated EBI3 to be an independent prognostic factor. Even in early-stage disease, low EBI3 expression was also independently associated with increased tumor recurrence and shortened survival. Downregulation of EBI3 in HCC indicated aggressive tumor behaviors and predicted a more severe clinical outcome, which suggests that EBI2 may be a useful biomarker to identify patients at high risk of post-operative recurrence.

Aimed at sensibility—psychopathology problem, undergraduates are selected to be research object and a correlative mechanism model for rough set and neural network of reinforced sensibility—psychopathology is proposed. Firstly, five characteristics are taken as example to analyze common psychological illnesses of undergraduates. These five characteristics include: behavior, emotional state, diet and sleep, character trait and physical illness, and four common psychological illnesses of undergraduates are selected as training to construct BP neural network evaluation model; then, upper and lower approximation of rough set and boundary region theory are adopted for noise removal of noise sample, which can solve sample noise interference of BP network pattern recognition effectively and reduce error recognition rate of BP network significantly. Finally, performance advantage of algorithm is verified through simulation experiment.

An effective method for bonding carbon nanotubes (CNTs) onto carbon fibers (CFs) surface via layer-by-layer (LBL) grafting method is reported here. The CNTs have been chemically grafted as confirmed by X-ray photoelectron spectroscopy (XPS). Scanning electron microscopy (SEM) indicates that this LBL method can increase the dispersion quality of the CNTs on CF surface. The polarity, wettability and roughness of the CFs have been significantly increased after the CNTs modifying. The interfacial shear strength (IFSS) and impact strength test suggest that the hierarchical structure can result in a remarkable improvement for the interfacial properties. The results also indicate that this LBL method is a promising technique to modify CFs with the high interfacial performance.