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Cardiac fibrosis is an essential pathological process in pressure overload (PO)-induced heart failure. Recently, myocyte-fibroblast communication is proven to be critical in heart failure, in which, pathological growth of cardiomyocytes (CMs) may promote fibrosis via miRNAs-containing exosomes (Exos). Peli1 regulates the activation of NF-κB and AP-1, which has been demonstrated to engage in miRNA transcription in cardiomyocytes. Therefore, we hypothesized that Peli1 in CMs regulates the activation of cardiac fibroblasts (CFs) through an exosomal miRNA-mediated paracrine mechanism, thereby promoting cardiac fibrosis. We found that CM-conditional deletion of Peli1 improved PO-induced cardiac fibrosis. Moreover, Exos from mechanical stretch (MS)-induced WT CMs (WT MS-Exos) promote activation of CFs, Peli1

Copper/zinc superoxide dismutase (SOD1) can clear cisplatin- (CP-) induced excessive reactive oxygen species (ROS), but exogenous SOD1 cannot enter cells because of its low biomembrane permeability. Cell-penetrating peptides (CPPs) can rapidly cross plasma membranes. This study is aimed at identifying an efficient and stable CPP-SOD1 and investigating its effects on CP-induced nephrotoxicity. We recombined SOD1 with 14 different CPPs and purified them using an NTA-Ni2+ column. In in vitro experiments, CPPs-SOD1 cell membrane penetration ability and JNK/p38 MAPK signaling pathway were evaluated using Western blotting. ROS production, mitochondrial membrane potential (MMP), and cell apoptosis were determined using flow cytometry and immunofluorescence staining in VERO and HK-2 cells. For in vivo experiments, mice were administered PSF-SOD1 for 2 h before cotreatment with a single CP injection for an additional 4 days. Blood and kidney samples were collected for renal function assessment (creatinine, urea nitrogen, histopathology, TUNEL assay, and JNK/p38 MAPK signaling pathway). Compared with TAT-SOD1, we found that PSF-SOD1 is more efficient at crossing the cell membrane and is stable after transduction into cells. Pretreatment with PSF-SOD1 inhibited CP-induced apoptosis, ROS generation, and JNK/p38 MAPK activation and restored CP-induced MMP loss in VERO and HK-2 kidney cells. Treatment of mice with PSF-SOD1 inhibited CP-induced serum creatinine, blood urea nitrogen elevation, and JNK/p38 MAPK activation. H&E staining and TUNEL assay indicated that kidney tissue damage was alleviated following PSF-SOD1 pretreatment. Overall, PSF-SOD1 ameliorated CP-induced renal damage by partially reducing oxidative stress and cell apoptosis by regulating JNK/p38 MAPK signaling pathway and might be a better cytoprotective agent than TAT-SOD1.

Chronic inflammation is one of the definite factors leading to the occurrence and development of tumors, including prostate cancer (PCa). The androgen receptor (AR) pathway is essential for PCa tumorigenesis and inflammatory response. However, little is known about the AR-regulated NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome pathway in human PCa. In this study, we explored the expression of inflammatory cytokine and AR in high-grade PCa and observed that NLRP3 inflammasome-associated genes were upregulated in high-grade PCa compared with that in low-grade PCa and benign prostatic hyperplasia and were associated with AR expression. In addition, we identified circAR-3-a circRNA derived from the AR gene-which is involved in the AR-regulated inflammatory response and cell proliferation by activating the NLRP3 inflammatory pathway. While circAR-3 overexpression promoted cell proliferation and the inflammatory response, its depletion induced opposite effects. Mechanistically, we noted that circAR-3 mediated the acetylation modification of NLRP3 by KAT2B and then promoted NLRP3 inflammasome complex subcellular distribution and assembly. Disturbing NLRP3 acetylation or blocking inflammasome assembly with an inhibitor suppressed the progression of PCa xenograft tumors. Our findings provide the first evidence that targeting NLRP3 acetylation or inflammasome assembly may be effective in inhibiting PCa progression.

Exploring the potential functions of nonconserved residues on the outer side of α-helices and systematically optimizing them are pivotal for their application in protein engineering. Based on the evolutionary structural conservation analysis of GH5_5 cellulases, a practical molecular improvement strategy was developed. Highly variable sites on the outer side of the α-helices of the GH5_5 cellulase from Aspergillus niger (AnCel5A) were screened, and 14 out of the 34 highly variable sites were confirmed to exert a positive effect on the activity. After the modular combination of the positive mutations, the catalytic efficiency of the mutants was further improved. By using CMC-Na as the substrate, the catalytic efficiency and specific activity of variant AnCel5A_N193A/T300P/D307P were approximately 2.0-fold that of AnCel5A (227 ± 21 versus 451 ± 43 ml/s/mg and 1,726 ± 19 versus 3,472 ± 42 U/mg, respectively). The half-life (t(1/2)) of variant AnCel5A_N193A/T300P/D307P at 75°C was 2.36 times that of AnCel5A. The role of these sites was successfully validated in other GH5_5 cellulases. Computational analyses revealed that the flexibility of the loop 6-loop 7-loop 8 region was responsible for the increased catalytic performance. This work not only illustrated the important role of rapidly evolving positions on the outer side of the α-helices of GH5_5 cellulases but also revealed new insights into engineering the proteins that nature left as clues for us to find. IMPORTANCE A comprehensive understanding of the residues on the α-helices of the GH5_5 cellulases is important for catalytic efficiency and stability improvement. The main objective of this study was to use the evolutionary conservation and plasticity of the TIM-barrel fold to probe the relationship between nonconserved residues on the outer side of the α-helices and the catalytic efficiency of GH5_5 cellulases by conducting structure-guided protein engineering. By using a four-step nonconserved residue screening strategy, the functional role of nonconserved residues on the outer side of the α-helices was effectively identified, and a variant with superior performance and capability was constructed. Hence, this study proved the effectiveness of this strategy in engineering GH5_5 cellulases and provided a potential competitor for industrial applications. Furthermore, this study sheds new light on engineering TIM-barrel proteins.

Background: Human growth hormone (hGH) is the first recombinant protein approved for the treatment of human growth hormone deficiency. However, expression in inclusion bodies and low expression levels are enormous challenges for heterologous expression of hGH in Escherichia coli. Objective: To increase the soluble expression of recombinant hGH with correct folding in E. coli. Methods: We constructed a new recombinant expression plasmid containing the coding sequence of the outer membrane protein A (ompA3) which was used for the expression in Transetta (DE3) E. coli. In order to simplify the purification process and cleavage of recombinant proteins, the fusion sequence should contain hexahistidine-tag (His6) and enterokinase recognition sites (D4K). The effect of different expression conditions on recombinant hGH expression was optimized in flask cultivations. Furthermore, the periplasmic solution containing soluble hGH was purified by Ni-NTA affinity chromatography. Circular dichroism (CD), western blot and mass spectrometry analyses were used to characterize the protein. Moreover, the growth-promoting effect of the purified hGH was also evaluated by cell proliferation assay. Results: High-level expression (800 g/mL) was achieved by induction with 0.5 mM IPTG at 30 ºC for 10 hours. The purity of hGH was over 90%. The immunological activity, secondary structure and molecular weight of the purified hGH were consistent with native hGH. The purified hGH was found to promote the growth of MC3T3-E1 cells, and was found to show the highest activity at a concentration of 100 ng/mL. Conclusion: Our research provides a feasible and convenient method for the soluble expression of recombinant hGH in E. coli, and may lay a foundation for the production and application of hGH in the industry.

Dimethyl sulfoxide (DMSO) is a universally used solvent in various synthetic reactions, and trace amounts of DMSO residual are often seen on the surface of chemical product. It is difficult to quickly determine whether the residual DMSO is washed completely. This work reports a CdII metal-organic framework (MOF) SXU-4 which can detect trace amounts of DMSO in various solvents. Fluorescence experiments reveal its turn-on fluorescence effect toward DMSO with high selectivity and sensitivity, indicating that it can be used as an effective luminescent probe for rapid chemical product purity detection by testing the washing solution. Crystallographically characterized DMSO loaded SXU-4 (DMSO@SXU-4), in combination with computational results uncover that the enhanced DMSO-MOF conjugation through multiple DMSO-MOF supramolecule interactions and charge rearrangement are the main causes of fluorescence intensification.

Objective: Determine the effect of interleukin (IL)-15 on HTR-8/SVneo cells and a preeclampsia (PE) mouse model induced by LPS. Methods: Transwell and Annexin-V-FITC/PI assays were performed in HTR-8/SVneo cells transfected with IL-15 activation plasmid/siRNA prior to LPS treatment. Additionally, pregnant mice were injected with LPS and IL-15 siRNA followed by measurement of systolic blood pressure (SBP), urine protein, and serum NO. HE staining was used to observe the morphological changes of the placenta and kidney. Glycogen accumulation was detected using Best’s carmine. qRT-PCR, Western blotting, and ELISA were performed to detect mRNA and protein expression. Results: LPS increased IL-15 and IFN-γ expression in HTR-8/SVneo cells, and IL-15 positively regulated IFN-γ expression in LPS-induced HTR-8/SVneo cells. Moreover, LPS promoted apoptosis and reduced the invasion and migration of HTR-8/SVneo cells, which was, further, promoted by IL-15 overexpression but attenuated by IL-15 inhibition. Furthermore, LPS increased SBP and urine protein but decreased serum NO in mice, and these factors were reversed by IL-15 siRNA. Downregulation of IL-15 also mitigated kidney injury and improved pregnancy outcomes in LPS-induced PE mice. A significantly thicker junctional zone (JZ) and thinner labyrinth layer were found in placentas of PE mice treated with IL-15 siRNA, along with increased glycogen trophoblast cells in the JZ. Moreover, decreased IFN-γ and NKp46 were found in placentas of PE mice treated with IL-15 siRNA. Conclusion: IL-15 inhibition reduced cell apoptosis and increased the invasive and migratory abilities of LPS-induced HTR-8/SVneo cells, thereby alleviating the PE-like phenotype and improving pregnancy outcome.

A new species, Botrytis polygoni, was isolated from several species of Polygonaceae in 2011 and 2012 in Tongwei County, Gansu Province, China. The species infects Fagopyrum esculentum, F. tataricum, and Fallopia convolvulus, causing brown leaf spots and large blotches with concentric rings in the field. Botrytis polygoni is morphologically characterized by conidia spherical, unicellular, hyaline to pale brown or brown, (10.2-)14.3-21.4(-23.5) μm; and sclerotia black, spherical to subspherical, allantoid, or irregular-shaped, 0.2-4.1 × 0.1-3.0 mm. Comparison of the nuc rDNA internal transcribed spacer region (ITS1-5.8S-ITS2) sequences confirmed its placement in the genus Botrytis. Phylogenetic analysis based on the protein-coding genes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), heat shock protein 60 (HSP60), and DNA-dependent RNA polymerase subunit II (RPB2) showed that the new species is clustered close but separate from Botrytis pyriformis, which was distant from 37 other Botrytis species and 17 undescribed species. Pathogenicity tests showed that the new species has aggressive pathogenicity to four species of Polygonaceae, specifically Fag. tataricum, Fal. convolvulus, Polygonum sibiricum, and Pol. aviculare, weak pathogenicity to Vicia faba in the Fabaceae, and no pathogenicity to eight other tested plants: Amaranthus retroflexus, Cirsium arvense, Convolvulus arvensis, Kalanchoe blossfeldiana, Lagopsis supine, Mentha canadensis, Plantago asiatica, and Raphanus sativus.

In this article, an actor-centered approach was used to conceptualize marketization trends under statist-corporatist regimes and to critically examine theories on the trends and impact of marketization. A grounded theory method was used to guide data collection. A total of 65 critical incidents from the perspective of senior executives were collected from 18 nonprofit organizations in Hong Kong. Their annual budgets all exceeded US$6.5 million. Behavioral event interviews were conducted with the senior executives to understand how they conceptualized the organizational challenges and rationalized their decisions. The results show that commercialization was not a major marketization trend in statist-corporatist regimes. Nonprofit organizations were found enhancing self-governance capacities through building management competencies, articulating organizational policies and know-how, and adopting strategic management. It was not driven by institutional isomorphism. Second, strategic human resource management was revealed as another strategy to reduce resource dependence, which enriches the theory's current focus on earned-income strategies. Third, service expansions were observed as either directed at service gaps or driven by competition. By specifying the rationales for service expansion in exclusively nonprofit service markets, the study nuances the debate over the impact of marketization on nonprofit sectors. Points for practitioners For policymakers, it is important to be aware of the impact of market mechanisms on the nonprofit sector, which varies across countries due to the differences in the institutional framework for social service provision. For nonprofit managers, particularly those working in a statist-corporatist sector, they may benefit from self-governance strategies, revenue strategies such as active fundraising campaigns and regular donor programs, and strategic human resource management practices. More importantly, it is revealed that service expansions driven by competition for market shares and resources could render nonprofits, particularly those serve multiple types of target beneficiaries susceptible to the struggles of defining organizational identity and core competencies.

This study addresses the research question of how the tensions between urban commons and ‘the public’ might be resolved through boundary spanning. Urban commons offers a new lens for public managers and politicians to rethink ways that urban resources could be governed to enhance public problem-solving and co-create public-value outcomes. Through in-depth case analyses of commoning initiatives at five public markets in Hong Kong, we find that tensions with bureaucratic modes of governance, marketisation of public space, land politics, and little trust in the government were major barriers of commoning. The results also pointed to the unique boundary spanning strategies to facilitate commoning such as using co-creation and political framing to align community interests and public agenda and using legal framing to enable the reallocation of property rights among property owners and community actors. This research also revealed distinct dynamics of boundary spanning in illiberal democratic systems.

Abstract: Superoxide dismutase (SOD) is a well-known cellular antioxidant enzyme. However, exogenous SOD cannot be used to protect tissues from oxidative damage due to the low permeability of the cell membrane. Cell-penetrating peptides (CPPs) are a class of short peptides that can cross the cell membrane. Recombinant fusion protein that fuses SOD protein with CPP (CPP-SOD) can cross various tissues and organs as well as the blood-brain barrier. CPP-SODs can relieve severe oxidative damage in various tissues caused by radiation, ischemia, inflammation, and chemotherapy by clearing the reactive oxygen species, reducing the expression of inflammatory factors, and inhibiting NF-κB/MAPK signaling pathways. Therefore, the clinical application of CPP-SODs provides new therapeutic strategies for a variety of oxidative stress-related disorders, such as Parkinson’s disease, diabetes, obesity, cardiac fibrosis, and premature aging.

This article explores the relationship between meta-governance, uncertainty and governance network responses. A social network analysis was conducted on the interlocking directorate network among nonprofits before and after a market-oriented collibration triggered by a new public management reform to the corporatist social service provision system in Hong Kong. By unpacking and showing the distinct processes of network formation in response to substantive and strategic uncertainty arising from the market-oriented collibration, the study shows that although more nonprofit actors were directly included in the formalized policy venues after the reform, the network density and clustering coefficient dropped after the reform, potentially reducing the self-coordinating capacity of the governance network. However, for some nonprofit actors, node betweenness centrality increased and node degree centrality decreased, creating an enabling condition for adaption. Points for practitioners The uncertainties in meta-governance may bring about network processes at variance with the original intentions of public meta-governors that actors with complementary resources and competences combine their efforts in the provision of services and service innovation. To manage substantive and strategic uncertainties, public meta-governors need to find ways to increase the shared understandings of social problems, enhance the clarity of policy goals, and find a balance when collaborating between collaborative and market modes of governance.

Silybum marianum is a traditional Chinese medicine that has been used for treating liver disease. Silybin consisting of silybin A and silybin B, is a member of Silybum marianum, and exerts a therapeutic effect on many diseases. However, the protective effect of silybin on cisplatin-induced neurotoxicity and the stereoisomer contributing to the effect remain unknown.The present study aimed to study the effect of silybin on cisplatin-induced neuronal injury, compare the difference of protective effect between silybin A and silybin B, and the potential mechanism.High performance liquid chromatography (HPLC) was used to separate silybin A and silybin B. X-ray crystallographic analysis in combination with experimental and calculated ECD were performed to identify the structure of silybin A and silybin B. The toxicity of the silybin or cisplatin against murine hippocampal neuronal HT22 cells was determined through MTT assay. The cell cycle and cell apoptosis were measured by PI staining and Annexin V-FITC/PI staining, respectively, and then subjected to flow cytometry. Western blot analysis was conducted to quantify the expression of proteins related to apoptosis and DNA damage. Immunofluorescence was used to evaluate the expression of DNA damage marker. In vivo experiment, the behavioral analysis was determined through pole test, swimming test and Morris water maze test. The index of superoxide dismutase (SOD), reduced glutathione (GSH), total antioxidant capacity (T-AOC) and lipid peroxidation (LPO) were examined to evaluate the antioxidant capacity in mice brain. Nissl staining and Tunel assay were used to detect the neuronal viability and apoptosis in hippocampus.We successfully separated and identified silybin A and silybin B. We found both silybin A and silybin B alleviated cisplatin-induced apoptosis and cell cycle arrest in HT22 cells, and silybin B was more effective. We chose silybin B for further mechanism investigation, and found silybin B alleviated DNA damage by enhancing phosphorylation of ATR and decreasing expression of γ-H2AX. In the in vivo experiment, we observed that silybin B markedly improved the behavioral abnormalities in cisplatin-treated mice, reduced LPO level while increased SOD, GSH and T-AOC in mice brain tissue. Nissl staining and Tunel assay showed that silybin B alleviated cisplatin-induced hippocampal damage.These results suggest that silybin B might serve as a promising drug candidate in mitigating cisplatin-induced neural injury in the brain and thereby improving the chemotherapeutic outcomes.

Background: Due to their close relationship, the efficacy of major depressive disorder (MDD) drugs in the treatment of Alzheimer's disease (AD) has received widespread attention in recent years. Methods: In this study, we explored the potential therapeutic value of traditional Chinese medicine (TCM) and multitarget components on both MDD and AD by using a comprehensive strategy with network pharmacology and molecular docking technology. Results: In total, 234 MDD-related TCM prescriptions were analyzed and the 10 most commonly used Chinese herbs, correlating to 198 active ingredients, were identified. Through a comparative analysis of 144 prospective ingredient targets, 1095 MDD-related targets, and 1684 AD-related targets, network pharmacology identified 30 common targets, 9 key targets, and 7 representative compounds. The results of GO and KEGG enrichment analysis revealed that common targets were required to regulate multiple pathways related to MDD and AD. In addition, network analysis demonstrated that the combination of Xiangfu (Cyperi Rhizoma)-Gancao (Licorice)-Chaihu (Radix Bupleuri) constituted the major part of the representative ingredients and could be used to treat both diseases. Moreover, ALB, AKT1, ESR1, CASP3, and NOS3 were also chosen as prospective targets for synthetic multitarget ingredient screening. Further docking studies revealed that various natural chemicals exhibited binding affinity with the 5 targets, including quercetin, kaempferol, β-sitosterol, stigmasterol, isorhamnetin, naringenin, and 8-isopentenyl-kaempferol. Conclusion: Taken as a whole, the current study indicates a TCM combination with positive advantages in the combined treatment of AD and MDD.

Worldwide, cancer is a serious threat to the health of citizens of every country, with the incidence and mortality increasing year by year. Cisplatin is the first-line anticancer drug commonly used in clinics and is widely used for the treatment of solid tumors including lung, gastric, liver, bladder, and ovarian cancer. Although cisplatin-based chemotherapy has a high clinical response efficacy, patients will inevitably develop drug resistance after repeated using, leading to severe restrictions of its application. Circular RNAs (circRNAs) are a promising class of non-coding RNAs capable of promoting or suppressing cancer via functioning as miRNAs sponges. Recently, an increasing amount of evidence shows that circRNAs are closely related to the cisplatin resistance of cancers. Therefore, standing at the perspective of the cisplatin chemotherapy resistance, this paper reviews the research progress of circRNAs related to cisplatin resistance of various cancers.

In recent years, some laboratories have been able to prepare calcium hydrobromide (CaHBr) by melting hydride and anhydrous bromide or metal and bromide in a hydrogen atmosphere at 900°C and have studied some of its properties. But there are few theoretical studies, especially the theoretical studies of monolayer CaHBr. We use the first-principles method to calculate the structure, elastic properties, and lattice thermal conductivity of the monolayer CaHBr based on the Boltzmann transport equation. We obtain a stable crystal structure by the optimization of monolayer CaHBr. By calculating the elastic constant of monolayer CaHBr, its mechanical stability is proved, and the elastic limit of monolayer CaHBr is obtained by biaxial tensile strain on monolayer CaHBr. And the corresponding phonon spectra show no imaginary frequency, indicating the dynamic stability of the monolayer CaHBr. By the ShengBTE code, we calculate the lattice thermal conductivity of the monolayer CaHBr, the iterative solution of BTE and RTA at 300 K–1200 K is obtained, and the lattice thermal conductivity at room temperature is κ ι BTE = 2.469 W / m ⋅ K and κ ι RTA = 2.201 W / m ⋅ K , respectively. It can be seen that the lattice thermal conductivity of monolayer CaHBr is low. And by analyzing the phonon spectrum, the scattering rate, and the mean free path of the phonons, the lattice thermal conductivity of monolayer CaHBr mainly depends on the acoustic modes. We hope this study can provide theoretical guidance for the experiments and practical application of monolayer CaHBr.

How to extract useful and key information from the original big wave data with large volume and low information density and establish a wave climate datasets is still in a blank status, which is also urgently needed in the ocean navigation, deep sea development, marine resource development, offshore construction, and disaster prevention and mitigation, etc. Based on the ERA-interim wave data for 1979–2018 and ERA-40 wave reanalysis from the European Centre for Medium-Range Weather Forecasts (ECMWF), this study adopts the climate statistical analysis methods to establish the first open and public wave climate dataset for the Maritime Silk Road, systematically including the prevailing wave direction and significant wave height (SWH), wave period, swell index (SI), rough sea occurrence, wave direction occurrence, co-occurrence of wave height and wave direction, co-occurrence of wave height and wave period, and extreme wave height. It is hoped that the results can provide a data support for the safe and efficient deployment of marine development and construction.

Objective The objective of this paper was to investigate hub genes of postmenopausal osteoporosis (PO) utilizing benchmarked dataset and gene regulatory network (GRN). Materials and methods To achieve this goal, the first step was to benchmark the dataset downloaded from the ArrayExpress database by adding local noise and global noise. Second, differentially expressed genes (DEGs) between PO and normal controls were identified using the Linear Models for Microarray Data package based on benchmarked dataset. Third, five kinds of GRN inference methods, which comprised Zscore, GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation coefficient with Information Theory (PCIT), and GEne Network Inference with Ensemble of trees (Genie3), were described and evaluated by receiver operating characteristic (ROC) and precision and recall (PR) curves. Finally, GRN constructed according to the method with best performance was implemented to conduct topological centrality (closeness) for the purpose of investigate hub genes of PO. Results A total of 236 DEGs were obtained based on benchmarked dataset of 20,554 genes. By assessing Zscore, GeneNet, CLR, PCIT, and Genie3 on the basis of ROC and PR curves, Genie3 had a clear advantage than others and was applied to construct the GRN which was composed of 236 nodes and 27,730 edges. Closeness centrality analysis of GRN was carried out, and we identified 14 hub genes (such as TTN, ACTA1, and MYBPC1) for PO. Conclusion In conclusion, we have identified 14 hub genes (such as TN, ACTA1, and MYBPC1) based on benchmarked dataset and GRN. These genes might be potential biomarkers and give insights for diagnose and treatment of PO.

Human growth hormone (hGH) is the first recombinant protein approved for the treatment of human growth hormone deficiency. However, expression in inclusion bodies and low expression levels are enormous challenges for heterologous expression of hGH in Escherichia coli.To increase the soluble expression of recombinant hGH with correct folding in E. coli.We constructed a new recombinant expression plasmid containing the coding sequence of the outer membrane protein A (ompA3) which was used for the expression in Transetta (DE3) E. coli. In order to simplify the purification process and cleavage of recombinant proteins, the fusion sequence should contain hexahistidine-tag (HisHigh-level expression (800 μg/mL) was achieved by induction with 0.5 mM IPTG at 30°C for 10 hours. The purity of hGH was over 90%. The immunological activity, secondary structure and molecular weight of the purified hGH were consistent with native hGH. The purified hGH was found to promote the growth of MC3T3-E1 cells, and was found to show the highest activity at a concentration of 100 ng/mL.Our research provides a feasible and convenient method for the soluble expression of recombinant hGH in E. coli, and may lay a foundation for the production and application of hGH in the industry.

Objective Invasive pulmonary candidiasis is a disease with high incidence, difficult treatment, poor prognosis, and high mortality. The present study analyzed the influence of cinnamaldehyde on 1,3-β-D-glucans in the cell wall of Candida albicans in order to provide a theoretical basis for the research of antifungal drugs. Methods An immunosuppressed BALB/c mouse model with invasive pulmonary candidiasis was established by nasal perfusion of 50 µL of C. albicans suspension (107 cfu/mL). 1,3-β-D-glucans examination and electron microscopy were carried out. Fluconazole was used as the control. Results Cinnamaldehyde was administered at a dose of 240 mg/kg/d for 14 consecutive days, and the measured value of 1,3-β-D-glucans was (1160.62 ± 89.65) pg/mL, whereas that of fluconazole was (4285.87 ± 215.62) pg/mL. The difference between the two groups was statistically significant (P Conclusion Cinnamaldehyde demonstrated special efficacy on 1,3-β-D-glucans in the cell wall of C. albicans.

Objectives To explore the clinical characteristics of hematologic disease complicated by rhino-orbital-cerebral mucormycosis (HD-ROCM) and improve the understanding, diagnosis and treatment of M-ROC. Methods For mastering the clinical characteristics, treatment and prognosis of HD-ROCM, the medical records of 6 HD-ROCM patients admitted from 2009 to 2015 were analyzed retrospectively, and related literatures were also retrieved and reviewed. Results All the patients had bone marrow transplantation, 2 out of 6 patients had neutropenia, 5 had endoscopic debridement in a few days to several months after the onset of symptoms, and 1 had open debridement. 3 out of 6 achieved local debridement, and the other 3 had radical debridement. Out of them, one died 8 days postoperation, 1 died at 1 month, 2 at 2 months and 2 at 6 months. Conclusion Early diagnosis and timely surgical treatment are the key points for improving the survival rate of HD-ROCM patients. DOI: 10.11855/j.issn.0577-7402.2017.07.13

Nowadays concrete has become the most widely-employed construction material in civil engineering. But at present stage, not all internal factors’ effects on this material’s axial and transverse mechanical behaviors have been comprehensively understood, and highly-accurate formulas to predict its mechanical properties are still lack. This prevents designers and engineers to well construct structural components, and also separates people to better know the failure mechanism and strength rule of other types of concrete materials (such as the recycled aggregate concrete and the recycled lump concrete). Considering such situations, a series of discrete element simulations were conducted in this study. In current works, concrete was at mesoscopic level modeled as composed by coarse aggregates, mortar and interfacial transition zones (ITZs). The influences of each constituted phase’s attribution and content (including the shape, size, location, volume content and attribution of coarse aggregates, the mortar’s water-to-cement ratio as well as the property of the ITZs) on the concrete’s crack development process, failure pattern as well as longitudinal and lateral mechanical responses were analyzed carefully. The factors most important in determining concrete’s tensile and compressive strengths together with elastic modulus were identified, and accurate expressions for relating concrete’s uniaxial mechanical properties with the attributions of its components were also proposed. The present study showed that mesoscopic discrete element simulation is an ideal tool for expressing the concrete’s the development of internal damages/cracks and understanding its lateral deformation features under uniaxial loadings. The compressive strength of concrete is primarily governed by the mortar’s strength, the aggregate content and the bonding strength of aggregate-mortar ITZs, and its elastic modulus is notably affected by the mortar’s modulus and the aggregate content, while the tensile strength is greatly influenced by the strengths of mortar and ITZs. Expressions are proposed which usefully predict concrete’s properties based on its constituents, and they may be further extended to investigate the mechanical properties of other types of concrete.

// Xin Cheng 1, * , Yong-Qiang Liu 1, * , Gui-Zhen Wang 1, * , Li-Na Yang 2, * , Yong-Zhi Lu 3 , Xin-Chun Li 1 , Bo Zhou 1 , Li-Wei Qu 1 , Xiao-Lu Wang 1 , Yong-Xian Cheng 4 , Jinsong Liu 3 , Sheng-Ce Tao 2 , Guang-Biao Zhou 1 1 Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China 2 Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China 3 Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China 4 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China * These authors have contributed equally to this work Correspondence to: Guang-Biao Zhou, email: gbzhou@ioz.ac.cn Sheng-Ce Tao, email: taosc@sjtu.edu.cn Keywords: proteome microarray, 6-O-angeloylplenolin, STAT3 inhibitor, Skp2, lung cancer Received: July 25, 2016 Accepted: October 14, 2016 Published: November 7, 2016 ABSTRACT The S phase kinase-associated protein 1 (Skp1), an adaptor protein of the Skp1-Cul1-F-box protein complex, binds the ubiquitin E3 ligase Skp2 and is critical to its biological functions. Targeting of Skp1 by a small compound 6-O-angeloylplenolin (6-OAP) results in dissociation and degradation of Skp2 and mitotic arrest of lung cancer cells. Here, by using a proteome microarray containing 16,368 proteins and a biotinylated 6-OAP, we identified 99 proteins that could bind 6-OAP, with Skp1 and STAT3 sitting at the central position of the 6-OAP interactome. 6-OAP formed hydrogen bonds with Ser611/Ser613/Arg609 at the SH2 domain of STAT3 and inhibited the constitutive and interleukin-6-induced phosphorylated STAT3 (pSTAT3), leading to inhibitory effects on lung cancer cells and suppression of Skp2 transcription. STAT3 was overexpressed in tumor samples compared to counterpart normal lung tissues and was inversely associated with prognosis of the patients. 6-OAP inhibited tumor growth in SCID mice intravenously injected with lung cancer cells, and downregulated both STAT3 and Skp2 in tumor samples. Given that 6-OAP is a Skp1 inhibitor, our data suggest that this compound may target Skp1 and STAT3 to suppress Skp2, augmenting its anti-lung cancer activity.

Background Although great achievements have been made in the field of cancer therapy, chemotherapy and radiotherapy remain the mainstay cancer therapeutic modalities. However, they are associated with various side effects, including cardiocytotoxicity, nephrotoxicity, myelosuppression, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, mucositis, and alopecia, which severely affect the quality of life of cancer patients. Plants harbor a great chemical diversity and flexible biological properties that are well-compatible with their use as adjuvant therapy in reducing the side effects of cancer therapy. Purpose This review aimed to comprehensively summarize the molecular mechanisms by which phytochemicals ameliorate the side effects of cancer therapies and their potential clinical applications. Methods We obtained information from PubMed, Science Direct, Web of Science, and Google scholar, and introduced the molecular mechanisms by which chemotherapeutic drugs and irradiation induce toxic side effects. Accordingly, we summarized the underlying mechanisms of representative phytochemicals in reducing these side effects. Results Representative phytochemicals exhibit a great potential in reducing the side effects of chemotherapy and radiotherapy due to their broad range of biological activities, including antioxidation, antimutagenesis, anti-inflammation, myeloprotection, and immunomodulation. However, since a majority of the phytochemicals have only been subjected to preclinical studies, clinical trials are imperative to comprehensively evaluate their therapeutic values. Conclusion This review highlights that phytochemicals have interesting properties in relieving the side effects of chemotherapy and radiotherapy. Future studies are required to explore the clinical benefits of these phytochemicals for exploitation in chemotherapy and radiotherapy.

Compared with hesitant fuzzy linguistic term set (HFLTS), double hierarchy hesitant fuzzy linguistic term set (DHHFLTS) has a second hierarchy linguistic term set, which is a detailed supplementary of each linguistic term included in the first hierarchy linguistic term set. Thus, DHHFLTS can express more complex and sufficient evaluation information than HFLTS. To solve multiple attribute group decision making (MAGDM) problems in which the assessment values of alternatives and the preference relations between alternatives are denoted by double hierarchy hesitant fuzzy linguistic elements, this paper extends the traditional LINMAP method under double hierarchy hesitant fuzzy linguistic environment. A practical example is provided to demonstrate the applicability of the proposed method.