Search

The high freedom of the gate drive patterns of the Si/SiC hybrid switch comprising the Si IGBT and SiC MOSFET can significantly change the loss of the Si/SiC hybrid switch based inverters. However, the loss model of the Si/SiC hybrid switch is a complex high-order and time-varying function. Therefore, it is difficult to determine an optimal delay time within a current period to ensure high efficiency operation of the inverters. In this paper, a new efficiency improvement method adopting the particle swarm optimization (PSO) algorithm is proposed to further improve the efficiency of the single-phase inverter. Experimental results verify the feasibility of the proposed method.

Purpose Recombinant human thrombopoietin (rhTPO) has been evaluated as a therapeutic intervention for radiation-induced myelosuppression. However, the immunogenicity induced by a repeated-dosing strategy raises concerns about the therapeutic use of rhTPO. In this study, single-dose administration of rhTPO was evaluated for efficacy in the hematopoietic response and survival effect on mice and nonhuman primates exposed to total body irradiation (TBI). Methods and Materials Survival of lethally (9.0 Gy) irradiated C57BL/6J male mice was observed for 30 days after irradiation. Hematologic evaluations were performed on C57BL/6J male mice given a sublethal dose of radiation (6.5 Gy). Furthermore, in sublethally irradiated mice, we performed bone marrow (BM) histologic evaluation and evaluated BM-derived clonogenic activity. Next, the proportion and number of hematopoietic stem cells (HSCs) were analyzed. Competitive repopulation experiments were conducted to assess the multilineage engraftment of irradiated HSCs after BM transplantation. Flow cytometry was used to evaluate DNA damage, cell apoptosis, and cell cycle stage in HSCs after irradiation. Finally, we evaluated the efficacy of a single dose of rhTPO administered after 7 Gy TBI in male and female rhesus monkeys. Results A single administration of rhTPO 2 hours after irradiation significantly mitigated TBI-induced death in mice. rhTPO promoted multilineage hematopoietic recovery, increasing peripheral blood cell counts, BM cellularity, and BM colony-forming ability. rhTPO administration led to an accelerated recovery of BM HSC frequency and multilineage engraftment after transplantation. rhTPO treatment reduced radiation-induced DNA damage and apoptosis and promoted HSC proliferation after TBI. Notably, a single administration of rhTPO significantly promoted multilineage hematopoietic recovery and improved survival in nonhuman primates after TBI. Conclusions These findings indicate that early intervention with a single administration of rhTPO may represent a promising and effective radiomitigative strategy for victims of radiation disasters.

As influenza viruses mutate rapidly, a prediction model for potential outbreaks of influenza-like illnesses helps detect the spread of the illnesses in real time. In order to create a better prediction model, in this study, in addition to using the traditional hydrological and atmospheric data, features, such as popular search keywords on Google Trends, public holiday information, population density, air quality indices, and the numbers of COVID-19 confirmed cases, were also used to train the model in this research. Furthermore, Random Forest and XGBoost were combined and used in the proposed prediction model to increase the prediction accuracy. The training data used in this research were the historical data taken from 2016 to 2021. In our experiments, different combinations of features were tested. The results show that features, such as popular search keywords on Google Trends, the numbers of COVID-19 confirmed cases, and air quality indices can improve the outcome of the prediction model. The evaluation results showed that the error rate between the predicted results and the actual number of influenza-like cases form Week 15 to Week 18 fell to less than 5%. The outbreak of COVID-19 in Taiwan began in Week 19 and resulted in a sharp rise in the number of clinic or hospital visits by patients of influenza-like illnesses. After that, from Week 21 to Week 26, the error rate between the predicted and actual numbers of influenza-like cases in the later period dropped down to 13%. It can be confirmed from the actual experimental results in this research that the use of the ensemble learning prediction model proposed in this research can accurately predict the trend of influenza-like cases.

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is one of the most widely used herbicides worldwide, and groundwater contamination is of concern, especially in heavily used regions and in edaphic conditions prone to leaching. Soil sorption plays an essential role in atrazine environmental fate, yet consistent atrazine risk prediction remains limited. A quantitative meta-analysis was conducted to characterize the effect of soil properties on atrazine sorption, using 378 previous observations in 48 publications from 1985 to 2015 globally, which included data on soil properties and sorption parameters. A supplemental regional study was conducted to test the derived meta-analysis models. The meta-analysis indicated that percentage organic C (OC) was the most important parameter for estimating atrazine sorption, followed by percentage silt, soil pH, and percentage clay. Meta-analysis and supplemental study models were developed for Freundlich sorption coefficients () and sorption distribution coefficients () as a function of OC. The global meta-analysis models generated positive linear trends for OC with and ( = 0.197 and 0.205, respectively). Organic C was highly correlated with and in supplemental experimental study models ( = 0.93 and 0.92, respectively), indicating accurate prediction of sorption within the evaluated region. Continental models were investigated, which improved the goodness of fit. Models developed via meta-analysis may be used to predict atrazine sorption over wide ranges of data, whereas more accurate and refined prediction can be achieved by specific regional models through experimental studies. However, such models could be improved if standardized agroclimatic conditions, soil classification, and other key variables were more widely reported.

Fungicides (azoxystrobin, propiconazole, pyraclostrobin, and thiophanate-methyl) were applied to field plots of creeping bentgrass established on a sand-based root zone substrate and maintained at a cutting height of 0.34 cm. The wetting agent, a modified alkylated polyol, was applied 24 h prior to fungicide application. Irrigation (0.51 cm) was applied to plots immediately after the fungicide spray. Turf was sampled nine times over 42 days to examine fungicide residues in three components of the turf profile: verdure/thatch, roots, and soil. Residues were extracted from samples and then quantified using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) procedure. The experiment was run twice. Wetting agent had little or no effect on fungicide distribution in any of the turf components. Postapplication irrigation had little effect on residues observed in the verdure/thatch component. Significant irrigation treatment effects were observed in root and soil components, but results varied among fungicides and sampling dates. Where significant effects were observed for the irrigation plus wetting agent treatment, results generally mirrored outcomes for irrigation treatment.

Accumulating evidence shows that sirtuin 7 (SIRT7), a key mediator of many cellular activities, plays an important role in the pathogenesis of various diseases; however, little is known about the role of SIRT7 in asthma, which is characterized by airway remodeling. This study investigated the potential role of SIRT7 in regulating the proliferation and migration of airway smooth muscle (ASM) cells, which are critical events during airway remodeling in asthmatic conditions. The results demonstrated that SIRT7 expression was significantly upregulated in ASM cells treated with transforming growth factor-beta 1 (TGF-β1). Knockdown of SIRT7 inhibited the proliferation, promoted the apoptosis, and suppressed the migration of TGF-β1-treated ASM cells, while overexpression of SIRT7 had the opposite effect. Moreover, knockdown of SIRT7 inhibited protein expression of the TGF-β receptor I (TβRI), whilst overexpression of SIRT7 promoted the expression of TβRI. Importantly, knockdown of TβRI partially reversed the stimulatory effect of SIRT7 overexpression on the TGF-β1-induced proliferation and migration of ASM cells. Taken together, these results demonstrate that SIRT7 is involved in regulating TGF-β1-induced ASM cell proliferation and migration by regulating the expression of TβRI, thus indicating an important role of SIRT7 during airway remodeling in asthma.

Differentiation therapies have been proposed to overcome the impaired cell differentiation in acute myeloid leukemia (AML). However, thus far the all-trans retinoic acid-based differentiation therapy has been the only successful modality in treating acute promyelocytic leukemia. Here, we showed that vibsanin A, a novel protein kinase C (PKC) activator, sensitized AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. Vibsanin A augmented the ability of TKIs to induce growth inhibition and G1 cell cycle arrest of AML cells. Mechanistically, PKC activation was involved in the differentiation-inducing effects of combining vibsanin A with TKIs. Moreover, we found that vibsanin A enhanced TKI-induced Lyn expression and suppression of Lyn interfered with AML cell differentiation, indicating an essential role for Lyn expression in the combination-induced differentiation. Finally, combining vibsanin A and TKIs enhanced the activation of the Raf/MEK/ERK cascade. Together, this is the first study to evaluate the synergy of vibsanin A and TKIs in AML cell differentiation. Our study lays the foundation in assessing new opportunities for the combination of vibsanin A and TKIs as a promising approach for future differentiation therapy.

In China, waste sorting has been tested in eight pilot cities for more than a decade. However, these pilot programs have shown little success. Given that waste sorting is a prerequisite for waste recycling, more attention and financial resources must be provided. Considering that among the entire population undergraduate students might be the most active and willing to engage in recycling, in this paper, the waste-sorting intention and behavior of undergraduate students in Beijing are investigated in depth. By adopting a model that comprehensively incorporates the expanded Theory of Planned Behavior (TPB) and the Attitude–Behavior–Condition (A–B–C) theory, a questionnaire survey with data from 536 undergraduate students at eight universities in Beijing is analyzed by employing logistic and probit models. The estimation results indicate that the most important factors that affect students’ waste-sorting intention and behavior include the attitudes of the surrounding people, a moral sense when failing to sort waste, and knowledge based on the students’ subjective judgments. In comparison, situational factors have less impact on the dependent variables; however, some demographic factors may influence intention or actual behavior significantly.

The basic principle of donor site selection is to take skin from areas that will heal with minimal scarring while balancing the needs of the recipient site. For skin loss from the lower legs and feet, the most common harvest site for split-thickness skin grafts is the anterior or posterior thigh; grafts from the plantar areas have been mostly used to cover the volar aspect of digits and palms. Between September 2015 and September 2017, 42 patients with areas of skin loss on the legs or feet were treated with plantar skin grafts because of their cosmetic benefits and the convenience of the surgical procedure and postoperative wound care. Our technique of harvesting a single layer of split-thickness skin graft (0.014 in. thick) from a non-weight-bearing area of the foot of the injured leg is simple and provided good functional and cosmetic outcomes at both the donor and recipient sites. All patients were very satisfied with the recovery progress and final results. Therefore, in the management of skin defects in the lower legs or feet that comprise less than 1.5% of the total body surface area, our surgical method is a reliable alternative to anterior or posterior thigh skin grafting.

A diet high in sodium chloride (NaCl) can affect renal function damage and increase urinary calcium excretion, leading to bone loss. in renal tubules, Na-Cl co-transporter (NCC) and chloride channel 5 (CLC-5) are involved in regulating urinary calcium excretion. In addition, some cytokines, such as Bone morphogenetic protein 7 (BMP-7) and 1α-hydroxylase, are synthesized by renal tubules, which target on bone and play important roles on bone metabolism. However, the specific mechanisms between NaCl and these ion channels or cytokines still need investigations from many aspects. This study, in culture normal rat renal tubular epithelial NRK-52E cells, showed that high concentrations of NaCl significantly inhibited the cell viability and increased the cell apoptosis. High concentration of NaCl reduce bone mineral density (BMD), as demonstrated by the significantly increased mRNA and protein levels of NCC and osteopontin (OPN), but decreased the levels of CLC-5, BMP-7, and 1α-hydroxylase. In addition, we found that ovariectomized (OVX) rats on a high-salt diet for 12 weeks had altered levels of these indices in the renal cortices. Moreover, the BMD in fourth and fifth lumbar vertebra (LV4 and 5) and femurs were significantly decreased and bone microstructure was destroyed of these rats. We also demonstrated that high concentration of NaCl enhanced the inhibition of these cytokines which is beneficial to increase BMD, induced by modulating ion channels NCC and CLC-5. In conclusion, our results indicate that high concentration of NaCl reduce BMD by regulating ion channels NCC and CLC-5.

Over the past decade, the increasing demand for renewable energy has driven the rapid development of China's offshore wind industry. However, it is not clear to developers and management departments which types of sea areas can be used for offshore wind projects. According to the provincial marine functional zoning (MFZ), China's coastal provinces have put offshore wind zoning (OWZ) into practice. This paper clarifies the method of OWZ, collects the results from offshore wind zones (OWZs) of 10 coastal provinces, and assesses the characteristics of OWZs by area, functional attribute and distance from the coastline. The results show that most of the areas available for offshore wind are co-existence zones where offshore wind can be sited in an agricultural and fisheries zone, an industrial and urban construction zone, a special-use zone, etc. Currently, 47% of existing offshore wind projects have been located in the OWZs in the East China Sea. Moreover, parts of the coastline distance of OWZs do not meet the “double-ten principle” in China or global siting trends. Generally, the existing areas for OWZ would allow China to meet its national target by 2020, but measures still need to be taken to meet the demands of conservation and sea-use management.

As one of the first countries to implement marine spatial planning, known in China as marine functional zoning (MFZ), China has developed MFZ into an integral part in its territorial spatial planning. Today, MFZ has become an important basis for the development, regulation and integrated management of marine space as well as an important tool for the management of its sea area, the protection of the marine environment, and development of its marine economy. This paper reviews China's MFZ system from a perspective of institutions, technologies and management requirements, and studies the resultant effects of MFZ in applications for sea-use projects, marine environmental monitoring and marine ecosystem protection by means of quantitative and comparative analysis. It is concluded that China's MFZ promotes the rational allocation of marine resources and the coordination of marine spaces for social and economic development based on its important role in sea-use project approval, marine environmental monitoring, and marine environmental protection. After three generations of evolution, it has formed a relatively mature classification system, technical system and institutional arrangement for China's MFZ with targets specified at three administrative levels and management requirements defined for different marine functional zones, which in turn facilitate the implementation of MFZ. China now is aiming to build the next generation of MFZ into a land and sea integrated zoning plan guided by the principles of ecosystem-based management. The well-established institutional arrangement and technical systems of MFZ, and the experiences accumulated in practice are available for reference by other countries.

The extrusion preform of the spray-formed 5A12 Al alloy was hot rolled using high reduction rolling technology. By means of transmission electron microscopy (TEM), electron backscatter diffraction (EBSD) and energy dispersive spectroscopy (EDS), the microstructure evolution was studied and the strengthening and toughening mechanism was thereby proposed. The results indicate that discontinuous and continuous dynamic recrystallization occurred during the hot rolling deformation of the spray-formed 5A12 Al alloy. The grain size was significantly refined and the micro-scale grains formed. Partial dynamic recrystallization leads to a significant increase of dislocation density and cellular structure. The Mg atoms were distributed in the Al matrix mainly in the presence of solid solution rather than the formation of precipitate. High solid solution of Mg atoms not only hindered the dislocation motion and increased the density of dislocation, but also exhibited a remarkable solid solution strengthening effect, which contributes to the high strength and high toughness of the as-rolled sheets. The tensile strength and elongation of spray formed 5A12 Al alloy at room temperature after 3 passes hot rolling were 622 MPa and 20%, respectively.

Icaritin (ICT), a hydrolytic product of icariin from the genus Epimedium, has many indicated pharmacological and biological activities. Several studies have shown that ICT has potential osteoprotective effects, including stimulation of osteoblast differentiation and inhibition of osteoclast differentiation. However, the molecular mechanism for this anabolic action of ICT remains largely unknown. Here, we found that ICT could enhance MC3T3-E1 subclone 14 preosteoblastic cell differentiation associated with increased mRNA levels and protein expression of the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1), osteocalcin (OC), osteoponin (OPN) and runt-related transcription factor 2 (RUNX2), and improved mineralization, confirmed by bone nodule formation and collagen synthesis. To characterize the underlying mechanisms, we examined the effect of ICT on estrogen receptor (ER) and mitogen-activated protein kinase (MAPK) signaling. ICT treatment induced p38 kinase and extracellular signal-regulated kinase 1/2 (ERK1/2) activation, but it demonstrated at the same time point no effect on activation of c-Jun N-terminal kinase (JNK). ER antagonist ICI182780, p38 antagonist SB203580 and ERK1/2 antagonist PD98059 markedly inhibited the ICT-induced the mRNA expression of ALP, COL1, OC and OPN. ICI182780 attenuated the ICT-induced phosphorylation of p38 and ERK1/2. These observations indicate a potential mechanism of osteogenic effects of ICT involving the ERK1/2 and p38 pathway activation through the ER.

Diastereoselective synthesis of bis-cyclometalated Ir(III) stereoisomers Δ/Λ-[Ir(C∧N)2(d-pro)] and Δ/Λ-[Ir(C∧N)2(l-pro)] (where C∧N is 2-phenylpyridine (Hppy), (4,6-difluorophenyl)pyridine (Hdfppy), and 2-phenylquinoline (Hpq) and pro is proline) with dual stereogenic centers at the metal and auxiliary ligand has been developed. The diastereomers Λ-l and Λ-d, and Δ-l and Δ-d exhibit distinguishable photophysical properties in both solution and the solid state. The thermodynamically stable diastereomers Λ-[Ir(ppy)2(l-pro)], Λ-[Ir(dfppy)2(l-pro)], and Λ-[Ir(pq)2(l-pro)] emit a green emission at 524 nm (Φ = 3.5% and τ = 35 ns), a blue-green emission at 480 nm (Φ = 4.5% and τ = 59 ns), and a red emission at 588 nm (Φ = 6.5% and τ = 200 ns) in DCM solution, respectively, which are blue-shifted accompanied by a large quantum yield and long lifetime relative to the corresponding unstable diastereomers Δ-[Ir(ppy)2(l-pro)] at 537 nm (Φ = 2.3% and τ = 29 ns), Δ-[Ir(dfppy)2(l-pro)] at 489 nm (Φ = 2.8% and τ = 43 ns)...

Objective: To assess the China-made equipment Mindray BS-2000M biochemical analyzer and explore the comparability between the results of the sixteen test parameters detected by Mindray BS-2000M biochemical analyzer and by imported equipment Roche cobas702 automatic biochemical analyzer. Methods: In line with the American Clinical Laboratory Standardization Committee (NCCLS) document EP9-A2, Switzerland Roche cobas702 biochemical analyzer was used as a comparison system, while the Mindray BS-2000M served as an experimental system. Sixteen biochemical parameters from forty cases at different levels were tested at the same time. The correlation coefficient(r), linearity regression equation and absolute deviation (SE) and relative deviation (SE%) of test detection system (Y) and control detection system (X) at different medical decision levels were calculated. The clinical acceptability and comparability between different detection systems were tested according to the standard of allowed total error of American Clinical Proficiency Testing Laboratory Improvement Amendments (CLIA'88). Results: The test results of the sixteen parameters between the two different biological detection systems were well-correlated (r2 ≥0.95, p

[EN] Pharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation of senolytic therapies to human disease is hampered by their suboptimal specificity for senescent cells and important toxicities that narrow their therapeutic windows. We have previously shown that the high levels of senescence-associated lysosomal beta-galactosidase (SA-beta-gal) found within senescent cells can be exploited to specifically release tracers and cytotoxic cargoes from galactose-encapsulated nanoparticles within these cells. Here, we show that galacto-conjugation of the BCL-2 family inhibitor Navitoclax results in a potent senolytic prodrug (Nav-Gal), that can be preferentially activated by SA-beta-gal activity in a wide range of cell types. Nav-Gal selectively induces senescent cell apoptosis and has a higher senolytic index than Navitoclax (through reduced activation in nonsenescent cells). Nav-Gal enhances the cytotoxicity of standard senescence-inducing chemotherapy (cisplatin) in human A549 lung cancer cells. Concomitant treatment with cisplatin and Nav-Gal in vivo results in the eradication of senescent lung cancer cells and significantly reduces tumour growth. Importantly, galacto-conjugation reduces Navitoclax-induced platelet apoptosis in human and murine blood samples treated ex vivo, and thrombocytopenia at therapeutically effective concentrations in murine lung cancer models. Taken together, we provide a potentially versatile strategy for generating effective senolytic prodrugs with reduced toxicities., Royal Society, Grant/Award Number: RG160806; Medical Research Council, Grant/Award Number: MR/R000530/1; Cancer Research UK, Grant/Award Number: C62187/A26989 and C62187/A29760; CRUK Cambridge Centre Early Detection Programme, Grant/Award Number: RG86786

Labile ferrous iron (Fe2+) plays important biochemical functions in many physiologically essential processes. It is very important to find an effective method to detect Fe2+. Herein, a simple and effective Fe2+ fluorescent probe (FeP1) has been constructed via a unique strategy of Fe2+-induced reducing reaction. As expected, FeP1 exhibited a ‘turn-on’ fluorescence response toward Fe2+ over various small analytes, with high selectivity and excellent sensitivity (DL = 18 nM) for the detection of Fe2+ in Tris-DMSO (4:1, pH = 7.4, v/v) solution. Moreover, the probe can act in different real samples, such as physiological saline and living cells.

Water extract of Gastrodia elata Blume (WGE) has great potential as an anti-depressant and could be developed as a functional food. This study aims to assess the safety of WGE using in vitro and in vivo genotoxicity assays and a 28-day oral toxicity study. Results from a bacterial reverse mutation assay (Ames test) using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) with or without metabolic activation (S9 system) showed that WGE did not induce mutagenicity. Nor did it induce clastogenic effects in Chinese hamster ovary (CHO–K1) cells with or without S9 activation. Moreover, WGE did not affect the proportion of immature to total erythrocytes or the number of micronuclei in immature erythrocytes of ICR mice. Finally, a dose-dependent 28-day repeated dose toxicity assessment of WGE (2040, 4080, and 8065 mg/kg body weight, p.o.) in mice revealed no adverse effects on behavior, mortality, body weight, haematology, clinical biochemistry, or organ weight. No toxicopathologic lesions were detected following administration of high-dose WGE compared to controls. In conclusion, WGE has no significant mutagenic or toxic properties, and the no-observed-adverse-effect level (NOAEL) of WGE can be defined as at least 8065 mg/kg/day orally for 28 days for male and female mice.

Background Fear renewal, the context‐specific relapse of a conditioned fear after extinction, is a widely pursued model of post‐traumatic stress disorder and phobias. However, its cellular and molecular mechanisms remain poorly understood. The dentate gyrus (DG) has emerged as a critical locus of plasticity with relevance to memory, anxiety disorders, and depression, and it contributes to fear memory retrieval. Here, we have identified the role of the DG in fear renewal and its molecular mechanism. Materials and Methods Muscimol (MUS), activator of cyclic adenosine monophosphate (cAMP) forskolin (FSK), inhibitor of protein kinase A (PKA), Rip‐cAMP, and a phosphodiesterase inhibitor rolipram were infused into DG of standard deviation rats before renewal testing. cAMP levels after fear renewal was measured by enzyme‐linked immunosorbent assay. The protein levels of phosphodiesterase 4 (PDE4) isoforms were tested by western blot. At last, the roles of cAMP signaling were also tested in the acquisition of fear conditioning, fear retrieval, and extinction. Results Intra‐DG treatment of MUS and Rp‐cAMP impaired fear renewal. FSK and rolipram exhibited the opposite effect, which also occurred in the retrieval of original fear memory. This change in fear renewal was regulated by PDE4 isoforms PDE4A, PDE4A5, and PDE4D. In addition, FSK and rolipram facilitated the acquisition of fear conditioning in long‐term memory, but not short‐term memory, while Rp‐cAMP impaired long‐term memory. For extinction, FSK and rolipram inhibited extinction process, while Rp‐cAMP facilitated fear extinction. Conclusion These findings demonstrated that fear renewal activated cAMP signaling in the DG through decreased PDE4 activity. Because of the role of cAMP signaling in the acquisition or retrieval of fear conditioning and encoding of extinction, it is speculated that initial learning and extinction may have similarities in molecular mechanism, especially fear retrieval and fear renewal may share cAMP signaling pathway in the DG.

Colorectal cancer (CRC) is a global disease with high incidence and mortality rate. Hsp90 inhibitors induce cell death in various cancers, including CRC. However, the underlying mechanisms need to be clarified further. In this study, Caco-2 cells were treated with 0.25 μM SNX-2112, an Hsp90 inhibitor, for 48 h; subsequently, whole-transcriptome sequencing was performed. At the mRNA level in SNX-2112-treated Caco-2 cells, 1588 genes were upregulated, and 433 genes were downregulated. Six genes were found to be associated with necroptosis and apoptosis, and these 6 upregulated genes were validated by RT-qPCR. Hundred and six miRNAs were upregulated, and 48 miRNAs were downregulated in SNX-2112-treated Caco-2 cells. Eleven downregulated miRNAs were found to interact with the 6 upregulated genes. Moreover, 676 circRNAs were upregulated, and 291 circRNAs were downregulated in SNX-2112-treated Caco-2 cells. Among them, 126 circRNAs were found to be the target of the 11 downregulated miRNAs. The circRNA-miRNA-mRNA regulatory network of Hsp90 inhibitor-induced cell death in colorectal cancer was constructed. This regulatory network extends the underlying mechanism of Hsp90 and improves our understanding of Hsp90 inhibitors as potential targeted therapeutic agents.

This case presents a restaurant chain and franchise company Eighteen Chefs Pte Ltd, founded by an ex-offender, Mr. Benny Se Teo in 2007. Eighteen Chefs provided employment opportunities to marginalized groups of ex-convicts and youth at risk, helping them to integrate into the working community and a normal life rather than fall through the cracks and back into crime. About half of their staff was from their target beneficiary group. This case traces Se Teo’s background and journey in starting up Eighteen Chefs while illustrating how he had overcome numerous obstacles, leveraged setbacks and seized opportunities for growth. The case analyses how the operating model of Eighteen Chefs, which largely follows that of the work integration social enterprise (WISE) model, pursues the twin goals of financial profitability and social inclusion. It also looks at Eighteen Chefs’ continuous innovations and new initiatives. As competition heated up in the food and beverage industry with disruptions offered by new food delivery services, Eighteen Chefs had to assess its threats and opportunities and formulate his responses options. Should the social venture subscribe to the services of external food delivery service providers or build its own in-house food dispatch services?

The optically active Ir(III) complex Λ-[Ir(ppy)2(MeCN)2](PF6) (ppy is 2-phenylpyridine) with a chiral-at-metal was first demonstrated to preferentially react with (R)-configuration sulfoxides 2-(alkylsulfinyl)phenol (HLO-R, R = Me, Et, iPr, and Bn) rather than (S)-configuration sulfoxides under thermodynamic equilibrium due to the hydrogen-bonding interaction and the differences in the steric interference, and thus act as a highly efficient enantioreceptor for resolution of sulfoxide enatiomers. Treatment of Λ-[Ir(ppy)2(MeCN)2](PF6) with 2 equiv of rac-HLO-R offered (S)-HLO-R in yields of 46–47% with 97–99% enantiomeric excess (ee) values and Λ-[Ir(ppy)2{(S)-LO-R}] complex in yields of 89–93% with 98% diastereomeric excess (de). The (R)-HLO-R chiral sulfoxides were obtained by the acidolysis of Λ-[Ir(ppy)2{(S)-LO-R}] complexes with trifluoroacetic acid (TFA) in the presence of coordinated solvent MeCN in yields of 45–47% with 98–99% ee values. Moreover, the enantioreceptor Λ-[Ir(ppy)2(MeCN)2](PF6) can be ...

The microscopic morphology of fatigue crack initiation and propagation behavior was investigated for B93пч high strength aluminum using optical microscopy, scanning electron microscopy and transmission electron microscopy. The results show that, the fatigue micro-crack generally initiates on the surface from broken coarse particle, interface between particle and matrix and grain boundary. The micro-crack initiation has the characteristics of randomness and diversity and the main crack is generally formed on the surface of the specimen. Fatigue crack propagation path may deviate from the direction with the max loading and appear in the form of deflection, fork, convergences and bridge connectivity. This can be attributed to the influence of microstructural characteristics, which also affect the fatigue crack propagation direction and growth rate.

Hypoxia deprives cells of energy and induces severe physical damage in embryophytes. Under hypoxia, the equilibrium between ethylene and H2O2 affects the response of the transcription factor AtERF73/HRE1. To evaluate the role of AtERF73/HRE1 during hypoxia signaling, we used three independent AtERF73/HRE1 knockout lines to detect H2O2 accumulation. The results revealed that under hypoxia, H2O2 accumulation in the AtERF73/HRE1 knockout lines decreased, indicating that AtERF73/HRE1 uses a negative feedback regulation mechanism to influence the production of H2O2 induced through hypoxia signal transduction. Quantitative RT-PCR analyses showed that oxygen deficiency had different effects on the expression of the hypoxia-induced genes Rboh B, D, G, and I in the AtERF73/HRE1 knockout lines. In particular, Rboh B and D expression were increased, whereas Rboh G expression was decreased. The expression of Rboh I was increased at 1 h but decreased at 3 h during hypoxia treatment in the AtERF73/HRE1 knockout lines. Similarly, the transcript levels of antioxidant and hypoxia-induced/ethylene response genes in the AtERF73/HRE1 knockout lines were affected by hypoxic stress, indicating that AtERF73/HRE1 is essential to hypoxia signal transduction in embryophytes. Additionally, in histochemical analysis, AtERF73/HRE1 promoter-induced GUS expression was detected in various plant parts throughout the plant growth process (e.g., leaves, inflorescences, siliques), particularly in the edges of mature leaves and guard cells. Taken together, our results confirm that AtERF73/HRE1 plays a role in H2O2 production by affecting the hypoxia-induced expression of Rboh genes in hypoxia signal transduction.

Background Patterns of scapular dyskinesis have unique scapular kinematics and associated muscular activation. The characteristics of unique dyskinesis patterns may be associated with functional disability. Objectives To investigate whether the shoulder function level and primary dysfunction items were different in unique dyskinesis pattern. The factors associated with shoulder dysfunction in different dyskinesis patterns were identified. Design Cross-sectional study. Methods Fifty-one participants with unilateral shoulder pain were classified as having a single dyskinesis pattern (inferior angle prominence, pattern I; medial border prominence, pattern II) or a mixed dyskinesis pattern (patterns I + II). Clinical measurements with the Flexilevel Scale of Shoulder Function (FLEX-SF), shoulder range of motion and pectoralis minor index were recorded. These clinical measurements, 3-D scapular kinematics (electromagnetic-based motion analysis), and associated muscular activation (electromyography on the upper/middle/lower trapezius and serratus anterior muscles) during arm elevation were analyzed for associations with functional disability. Results We found FLEX-SF scores and primary dysfunction items were similar among the patterns of dyskinesis. In inferior angle prominence, increased shoulder function was associated with decreased upper trapezius activity (R 2 = 0.155, p = 0.035), which accounted for approximately 16% of the variance of FLEX-SF scores. In medial border prominence, increased shoulder function was associated with increased lower trapezius activity (R 2 = 0.131, p = 0.017), which accounted for approximately 13% of the variance of FLEX-SF scores. Conclusion Upper and lower trapezius activities are important to consider in the evaluation of patients with pattern I and II, respectively. No other factors were related to shoulder dysfunction due to insufficient challenge of arm elevation tasks.

Aim To determine whether the Comprehensive Reminder System based on the Health Belief Model improves health belief, health behaviors, medication adherence and blood pressure control as a means of decreasing the rate of stroke recurrence among hypertensive ischemic stroke. Background Hypertensive patients having experienced recent ischemic strokes are at high risk for stroke recurrence. Several trials attempted to improve secondary stroke prevention via patient education, however, patient outcomes remained poor. Long-term follow-up studies regarding secondary stroke prevention are limited. Design A multi-center, 12-month, assessor-blinded, parallel-group, randomized controlled longitudinal trial. Methods Hypertensive patients having experienced an ischemic stroke are the target population. The intervention consists of health belief education, a calendar handbook, a weekly automated short-message service and four telephone follow-up interviews. Outcomes will be assessed at baseline and at 3, 6 and 12 months following discharge. The primary outcome is blood pressure control. The secondary outcomes include health belief, health behaviors and medication adherence. The clinical endpoint is the rate of stroke recurrence. Discussion Although many efforts to improve secondary stroke prevention have been undertaken, research indicates that improvements remain possible and warranted. This research protocol based on the Health Belief Model will improve our understanding of stroke education and transitional care needed in China and with the world-wide target population. Trial registration Chinese clinical trials registry: ChiCTR-IPR-15005946. Ethical approval received in December 2014. This article is protected by copyright. All rights reserved.

Background Adopting healthy behaviors is critical for secondary stroke prevention, but many patients fail to follow national guidelines regarding diet, exercise, and abstinence from risk factors. Compliance often decreases with time after hospital discharge, yet few studies have examined programs promoting long-term adherence to health behaviors. Goal setting and telephone follow-up have been proven to be effective in other areas of medicine, so this study evaluated the effectiveness of a guideline-based, goal-setting telephone follow-up program for patients with ischemic stroke. Methods This was a multicenter, assessor-blinded, parallel-group, randomized controlled trial. Ninety-one stroke patients were randomized to either a control group or an intervention group. Intervention consisted of predischarge education and 3 goal-setting follow-up sessions conducted by phone. Data were collected at baseline and during the third and sixth months after hospital discharge. Results Six months after discharge, patients in the intervention group exhibited significantly higher medication adherence than patients in the control group. There were no statistically significant differences in physical activity, nutrition, low-salt diet adherence, blood pressure monitoring, smoking abstinence, unhealthy use of alcohol, and modified Rankin Scale (mRS) scores between the 2 groups. Conclusions Goal-setting telephone follow-up intervention for ischemic stroke patients is feasible and leads to improved medication adherence. However, the lack of group differences in other health behavior subcategories and in themRS score indicates a need for more effective intervention strategies to help patients reach guideline-recommended targets.

Ovulation is a critical inflammation-like event that is central to ovarian physiology. IL-1β is an immediate early pro-inflammatory cytokine that regulates production of several other inflammatory mediators, such as cyclooxygenase 2 (COX)-2 and IL-8. NS-398 is a selective inhibitor of COX-2 bioactivity and thus this drug is able to mitigate the COX-2-mediated production of downstream prostaglandins and the subsequent inflammatory response. Here we have investigated the action of NS-398 using a human ovarian granulosa cell line, KGN, by exploring IL-1β-regulated COX-2 and IL-8 expression. First, NS-398, instead of reducing inflammation, appeared to further enhance IL-1β-mediated COX-2 and IL-8 production. Using selective inhibitors targeting various signaling molecules, MAPK and NF-κB pathways both seemed to be involved in the impact of NS-398 on IL-1β-induced COX-2 and IL-8 expression. NS-398 also promoted IL-1β-mediated NF-κB p65 nuclear translocation but had no effect on IL-1β-activated MAPK phosphorylation. Flow cytometry analysis demonstrated that NS-398, in combination with IL-1β, significantly enhanced cell cycle progression involving IL-8. Our findings demonstrate a clear pro-inflammatory function for NS-398 in the IL-1β-mediated inflammatory response of granulosa cells, at least in part, owing to its augmenting effect on the IL-1β-induced activation of NF-κB.

Chiral precursors Λ-[Ir(ppy)2(l-pro)] (Λ-L, where ppy is 2-phenylpyridine; pro is proline), Λ-[Ir(ppy)2(MeCN)2](PF6) (Λ-1), Δ-[Ir(ppy)2(d-pro)] (Δ-D), and Δ-[Ir(ppy)2(MeCN)2](PF6) (Δ-1) were synthesized from rac-[(Ir(ppy)2)2Cl2] and l-pro or d-pro by means of the auxiliary ligand strategy with 99% de values. The enantiopure mono complexes Λ/Δ-[Ir(ppy)2(L)](PF6) (L is 2,2'-bipyridine, Λ/Δ-2; L is 2,2'-dipyrimidine (dpm), Λ/Δ-3; L is 2,2'-bibenzimidazole (H2bbim), Λ/Δ-4) with 99% ee values and binuclear complexes ΛΛ/ΔΔ-[(Ir(ppy)2)2(dpm)](PF6)2 (ΛΛ-5 and ΔΔ-5) and ΛΛ/ΔΔ-[(Ir(ppy)2)2(bbim)] (ΛΛ-6 and ΔΔ-6) with 99% de values were synthesized in one step using the corresponding chiral precursors. The absolute configurations at Ir(III) centers of precursor Δ-1, mononuclear Λ-3, and binuclear ΔΔ-6 were confirmed by single-crystal structural analysis and characterized by circular dichroism (CD) spectroscopy. The correlation between the absolute configuration at Ir(III) center and CD spectra was established. The configurations at Ir(III) centers are stable during the reactions, and the chiral precursors can be used for the asymmetric synthesis of enantiomerically pure mono- and polynuclear Ir(III) complexes. Moreover, meso ΛΔ-[(Ir(ppy)2)2(dpm)](PF6)2 (meso-5) and ΛΔ-[(Ir(ppy)2)2(bbim)] (meso-6) were also synthesized using these precursors.

Over the last decade, China's annual average reclamation area has been approximately 100 km2. Sea reclamation provides a space guarantee for industrialization and urbanization and is a motivating force for China's rapid economic growth. Meanwhile, the rapid expansion of sea reclamation has caused problems due to the oversized scale and extensive use of the sea, resulting in the loss of large quantities of coastal shoal wetlands and natural shorelines and leading to continued deterioration of marine ecological environment. China has attached great importance to sea reclamation management. In order to strengthen sea reclamation management and to protect the marine environment, China has developed seven management system measures. These measures include a sea reclamation plan, marine functional zoning, regional sea use planning, a plane design for sea reclamation, a control index of the sea area for projects, sea area use demonstration and environmental impact evaluations, as well as an examination and approval administration with the management philosophy of total amount control and intensive use. At present, China's economic development faces a “new normal”, as industrial and urban demands on sea reclamation will gradually become more reasonable, and the primary application of sea reclamation will transition to coastal tourism, construction of the area close to sea, and recovery and repair of the coastal zone. In the future, China will continue to implement strict sea reclamation management based on ecological system recovery and public participation. In this essay, the system, experience and future development trends of sea reclamation management in China is comprehensively introduced in an effort to provide reference sea reclamation management plans to other countries around the world.

Cadmium is an environmental metal pollutant that has been a focus of research in recent years, which is reported to cause bone disease; however, its skeletal toxicity and the mechanism involved are not yet fully known. Therefore, this study used MC3T3-E1 subclone 14 cells to determine the mechanism of cadmium toxicity on bone. Cadmium chloride (Cd) significantly reduced cell viability in a concentration-dependent manner. Exposure to Cd inhibited osteoblast-related proteins (Runx2, Col-1, STC2) and decreased alkaline phosphatase (ALP) activity. Cd caused Exportin-1 accumulation and induced DNA damage. Cd significantly down-regulated caspase 9 and induced cleaved-PARP, cleaved-caspase 3 protein level. Treatment with JNK inhibitor, SP600125, suppressed cadmium-induced elevation in the ratio of phosphorylation of JNK to JNK. Inhibition of caspase with pan-caspase inhibitor, Z-VAD-FMK, prevented MC3T3-E1 subclone 14 cells from cadmium-induced reduction of Runx2, STC2, caspase 9, and accumulation of cleaved PARP and cleaved caspase 3. Cd-induced cell survival enhanced by SP600125 but rescued by Z-VAD-FMK or KPT-335. These results suggest that cadmium cytotoxicity on bone involved exportin 1 accumulation, phosphorylation of JNK, induction of DNA damage and pro-apoptosis, which was induced by activation of caspase-dependent pathways.

Vegetable crops of the genus Cucumis are very popular worldwide and have great market value. However, their fruit quality and yield are hindered by viral diseases. C. metuliferus is considered a wild species with resistance to viral diseases that is lacking in cultivated crops of the Cucumis genus, such as melon. The C. metuliferus line L37 shows extreme resistance against Papaya ringspot virus (PRSV-HA), whereas line L35 is a susceptible line. In this study, reciprocal grafting experiments between L35 and L37 were performed, and the PRSV-HA strain was pre-inoculated in the rootstock leaves. The results revealed that the resistance signal in the L37 rootstock could transmit and provide resistance to the L35 scion. Subsequently, double sandwich grafting was performed using the pre-inoculated L35 as the rootstock, which was then grafted onto the L37 intermediate and the L35 scion. The results showed that PRSV-HA RNA accumulated in the L35 rootstock leaf, petiole, and stem tissues, whereas PRSV-HA RNA accumulated in some intermediate and scion petiole and stem tissues. No HCPro RNA was detected in the L35 scion leaves. The results showed that the suppression of the virus occurred in the leaves, and the resistance effect spread from the rootstock in the scion direction. Hence, this study has demonstrated that RNA silencing of systemic signals is responsible for L37 resistance against PRSV. C. metuliferus L37 could provide a valuable resistance source for crops of the Cucumis species against viral diseases through grafting.

Wound-induced hair follicle neogenesis (WIHN) has been demonstrated in laboratory mice (Mus musculus) after large (>1.5 × 1.5 cm(2)) full-thickness wounds. WIHN occurs more robustly in African Spiny mice (Acomys cahirinus), which undergo autotomy to escape predation. Yet, the non-WIHN regenerative ability of the spiny mouse skin has not been explored. To understand the regenerative ability of the spiny mouse, we characterized skin features such as hair types, hair cycling, and the response to small and large wounds. We found that spiny mouse skin contains a large portion of adipose tissue. The spiny mouse hair bulge is larger and shows high expression of stem cell markers, K15 and CD34. All hair types cycle synchronously. To our surprise, the hair cycle is longer and less frequent than in laboratory mice. Newborn hair follicles in anagen, are more mature than C57Bl/6 and demonstrate molecular features similar to C57Bl/6 adult hairs. The second hair cycling wave begins at week 4 and lasts for 5 weeks, then telogen lasts for 30 weeks. The third wave has a 6-week anagen, and even longer telogen. After plucking, spiny mouse hairs regenerate in about 5 days, similar to that of C57Bl/6. After large full-thickness excisional wounding, there is more de novo hair formation than C57Bl/6. Also, all hair types are present and pigmented, in contrast to the unpigmented zigzag hairs in C57Bl/6 WIHN. These findings shed new light on the regenerative biology of WIHN and may help us understand the control of skin repair versus regeneration.

Icariin (ICA) is a major active ingredient in Herba epimedii, which is commonly used as a Chinese herbal medicine for the treatment of osteoporosis. Previous studies have revealed that ICA exerted a protective effect against bone loss and increased bone regeneration; however, the association between ICA and estrogen receptor (ER) signaling remains unclear. The aim of the present study was to determine the effect of ICA on rat bone marrow stromal cells (rBMSCs). Cell Counting Kit‑8 assays were conducted to measure proliferation, alkaline phosphatase (ALP) activity was evaluated to assess osteoblast differentiation, and reverse transcription‑quantitative polymerase chain reaction as well as western blotting were performed to detect the expression of cellular and molecular markers of osteogenic or adipogenic differentiation. The results demonstrated that treatment of rBMSCs with 10‑6 M ICA stimulated rBMSC proliferation and ALP activity. Furthermore, ICA treatment increased the expression of the osteogenic markers runt‑related transcription factor 2, collagen type 1 and bone morphogenetic Protein 2; however, it also decreased the expression of the adipogenic differentiation markers peroxisome proliferator‑activated receptor gamma and CCAAT/enhancer‑binding protein α. Treatment of rBMSCs with ICI182780, an ER antagonist, blocked the effects of ICA. Taken together, these findings indicated that ICA may stimulate osteoblast differentiation and inhibit adipogenic differentiation via the activation of the ER signaling pathway. Therefore, ICA has the potential to serve as a therapeutic alternative for the prevention and treatment of osteoporosis.

(Deoxy)guanosine-5′-triphosphate (5′-(d)GTP), the precursor for synthesizing DNA or RNA in vivo, is an important raw material for various modern biotechnologies based on PCR. In this study, we investigated the application of whole-cell catalysts constructed by bacterial cell surface display in biosynthetic reactions of 5′-(d)GTP from (deoxy)guanosine-5′-monophosphate (5′-(d)GMP). By N-terminal or N- and C-terminal fusion of the ice nucleation protein, we successfully displayed the GMP kinase of Lactobacillus bulgaricus and the acetate kinase of E. coli on the surface of E. coli cells. A large amount of soluble target protein was obtained upon induction with 0.2 mM IPTG at 25 °C for 30 h. The conversion of dGMP was up to 91% when catalysed by the surface-displayed enzymes at 37 °C for 4 h. Up to 95% of the GMP was converted after 3 h of reaction. The stability of the whole-cell catalyst at 37 °C was very good. The enzyme activity was maintained above 50% after 9 rounds of recovery. Our research showed that only one-twentieth of the initial substrate concentration of added ATP was sufficient to meet the reaction requirements.

Ethnopharmacological relevance For the past millennium, water extract from Epimedium (dried leaves of Epimedium brevicornu Maxim.) has been widely used for bone disease therapy in traditional Chinese medicine and has been reported to exhibit salutary effects on osteoporosis in clinical trials. The therapeutic effect of Epimedium is associated with the function of the brain in traditional Chinese medicine theory. Study aim To determine the potential relationship between treating osteoporosis with Epimedium and neuropeptide regulation. Materials and methods Water extract from Epimedium was qualitatively and quantitatively analyzed with HPLC-TOF-MS. Ovariectomized rats were used as an osteoporosis model and were treated orally with water extract from Epimedium 16 weeks after surgery to mimic clinical therapy. After treatment, gene expression and protein levels of four neuropeptides, as well as their main receptors or receptor precursors including; neuropeptide Y (NPY) and its receptors NPY 1 (NPYR1) and 2; calcitonin gene-related peptide and its receptor precursor calcitonin receptor-like receptor (CRLR); vasoactive intestinal peptide (VIP) and its receptor VIP 1 (VIP1R) and 2; and substance P (SP) and its receptor neurokinin 1 receptor (NK1R) were detected in samples taken from bone, brain and spinal cord. Results Treatment with water extract from Epimedium prevented bone mineral loss and reduced femoral bone strength decline associated with osteoporosis. Detection of neuropeptides showed that treatment also affected neuropeptide in the brain/spinal cord/bone axis; specifically, treatment increased brain NPY, bone NPY1R, bone CRLR, bone and spinal cord VIP and VIP2R, bone SP, and brain and spinal cord NK1R. Conclusion The effects of osteoporosis can largely be reduced by treatment with Epimedium most likely through a mechanism associated with several neuropeptides involved in regulation of the brain/spinal cord/bone axis. These novel results contribute to existing literature regarding the possible mechanisms of habitual use of Epimedium in the treatment of osteoporosis.

A one-pot process of enzymatic synthesis of deoxythymidine-5'-triphosphate (5'-dTTP) employing whole cells of recombinant Escherichia coli coexpressing thymidylate kinase (TMKase) and acetate kinase (ACKase) was developed. Genes tmk and ack from E. coli were cloned and inserted into pET28a(+), and then transduced into E. coli BL21 (DE3) to form recombinant strain pTA in which TMKase and ACKase were simultaneously overexpressed. It was found that the relative residual specific activities of TMKase and ACKase, in pTA pretreated with 20 mM ethylene diamine tetraacetic acid (EDTA) at 25°C for 30 min, were 94% and 96%, respectively. The yield of 5'-dTTP reached above 94% from 5 mM deoxythymidine 5'-monophosphate (5'-dTMP) and 15 mM acetyl phosphate catalyzed with intact cells of pTA pretreated with EDTA. The process was so effective that only 0.125 mM adenosine-5'- triphosphate was sufficient to deliver the phosphate group from acetyl phosphate to dTMP and dTDP.

The hot deformation behavior of 2060 alloy has been studied using thermal simulation test, EBSD technique and transmission electron microscopy. The flow stress could be described by a Zener-Hollomon parameter in hyperbolic sine function with the hot deformation activation energy of 205 kJ/mol. Dynamic recovery is the main dynamic soften mechanism of 2060 alloy. The relative volume fraction of subgrains increases from about 30% to 90% as the temperature rises from 350 °C to 400 °C. When the temperature is higher than 400 °C, both the relative volume fraction of the deformed grains and subgrains remain steady. The processing maps are similar in the strain ranging from 0.1 to 0.5, and the unsafe domains increase with the increase of strain. The optimum hot-working condition for 2060 alloy is 380–500 °C and 0.01–3 s−1.