Search

Double perovskite films have been extensively studied for ferroelectric order, ferromagnetic order, and photovoltaic effects. The customized ion combinations and ordered ionic arrangements provide unique opportunities for bandgap engineering. Here, a synergistic strategy to induce chemical strain and charge compensation through inequivalent element substitution is proposed. A-site substitution of the barium ion is used to modify the chemical valence and defect density of the two B-site elements in Bi2FeMnO6double perovskite epitaxial thin films. We dramatically increased the ferroelectric photovoltaic effect to ∼135.67 μA/cm2from 30.62 μA/cm2, which is the highest in ferroelectric thin films with a thickness of less than 100 nm under white-light LED irradiation. More importantly, the ferroelectric polarization can effectively improve the photovoltaic efficiency of more than 5 times. High-resolution HAADF-STEM, synchrotron-based X-ray diffraction and absorption spectroscopy, and DFT calculations collectively demonstrate that inequivalent ion plays a dual role of chemical strain (+1.92 and −1.04 GPa) and charge balance, thereby introducing lattice distortion effects. The reduction of the oxygen vacancy density and the competing Jahn–Teller distortion of the oxygen octahedron are the main phenomena of the change in electron–orbital hybridization, which also leads to enhanced ferroelectric polarization values and optical absorption. The inequivalent strategy can be extended to other double perovskite systems and applied to other functional materials, such as photocatalysis for efficient defect control.

[Purpose] Cd contamination in agricultural soils has sparked worldwide concerns due to the threat to human health emerging from its entry into the food chain. A cost-effective and practical method is needed to minimize Cd accumulation in the edible parts of crops. However, the effects and underlying mechanisms of biosynthetic nanoselenium (bio-SeNPs) in alleviating cadmium (Cd) toxicity have not been thoroughly explored. [Methods] To address this knowledge gap, a pot experiment was conducted to investigate the interactive effects of bio-SeNPs (5, 10, 20, 40 mg·L− 1) and Cd (1, 2 and 5 mg·kg− 1) on plant growth, nutritional quality, antioxidant enzyme activity, as well as Se and Cd accumulation in pak choi (Brassica chinensisL.). [Results] The results revealed that foliar application of bio-SeNPs notably alleviated the Cd toxicity by reducing Cd accumulation, minimizing malondialdehyde (MDA) content, boosting plant growth, improving nutritional quality, and increasing the antioxidant enzyme activities. Specially, the addition of bio-SeNPs alone (< 20 mg·L− 1) significantly increased root length (RL), shoot height (SH) and shoot fresh weight (SFW), and further improved these measures under Cd stress relative to the plants grown without Se supplementation. Plants treated with bio-SeNPs had significantly lower Cd contents in shoots than those in the control, except the plants treated with high concentrations of bio-SeNPs. Furthermore, the addition of bio-SeNPs (except at a dose of 40 mg·L− 1) restored nutritional quality by counterbalancing Cd-induced changes in shoot nitrate nitrogen (NN), total soluble protein (TSP) and total soluble sugar (TSS). Supplementation of bio-SeNPs also significantly increased MDA content caused by Cd stress, except at a dose of 40 mg·L− 1. In terms of antioxidants enzyme activities, the addition of bio-SeNPs to plants growing with or without Cd stress increased catalase (CAT) and peroxidase (POD) activities, and the magnitude of these changes varied with the dose of Cd and Se. However, CAT activity was significantly lower in plants subjected to high Cd stress alone or Cd stress combined with high-dose of Se addition relative to the control. [Conclusion] These findings suggested that the application of exogenous bio-SeNPs exhibited dual effects on pak choi in Cd-contaminated soil and worked best at a dose of 10 mg·L− 1, although the mitigating effects weakened with increasing Cd levels. All of our findings demonstrated that foliar spraying bio-SeNPs counteracted the deleterious effects of Cd stress as evidenced by reducing Cd accumulation and improving pak choi growth, nutritional quality, and antioxidant enzyme activities.

Catching high-speed targets in the flight is a complex and typically highly dynamic task. However, existing methods require manual setting of catching height or time, resulting in lack of adaptability and flexibility and cannot deal with multiple targets. To bridge this gap, we propose a planning-with-decision scheme called catch planner. For sequential decision making, a lightweight policy search method based on deep reinforcement learning is proposed. It is jointly trained with motion planning and decoupled from physics to speed up training. For motion planning, we propose a trajectory optimization method that jointly optimizes the highly coupled catching time and terminal state. The core is the flexible-terminal constraint transcription. It converts the three unique constraints of catching into differentiable metrics, including equality constraints for terminal position and time, and inequality constraints that enable reasonable terminal position offset and attitude relaxation. In addition, sparse parameterization based on MINCO class considers both dynamic feasibility and collision avoidance constraints. As a result, a generally constrained quadrotor planning problem is transformed into an unconstrained optimization that can be solved reliably and efficiently. We also propose an online iterative optimization method for predicting differentiable trajectories of targets. Catch planner provides a new paradigm for the combination of learning and planning, where all algorithms can be run in real-time onboard at $100\text{ Hz}$. Extensive experiments are carried out in real-world and simulated scenes to verify the robustness and expansibility when facing a variety of high-speed flying targets.

Invasive candidiasis has attracted global attention with a high incidence and mortality. Current antifungal drugs are limited by unfavorable therapeutic efficacy, significant hepatorenal toxicity, and the development of drug resistance. Herein, we designed the first generation of lanosterol 14α-demethylase (CYP51)/heat shock protein 90 (Hsp90) dual inhibitors on the basis of antifungal synergism. Among them, dual inhibitor MM4exhibited potent in vitroand in vivoantifungal activity against Candida albicansand effectively inhibited important fungal virulence factors (e.g., hyphae, biofilm). Therefore, CYP51/Hsp90 dual inhibitors show great promise in the development of novel antifungal drugs to combat invasive candidiasis.

Polarization rotation caused by various strains, such as substrate and/or chemical strain, is essential to control the electronic structure and properties of ferroelectric materials. This study proposes anion-induced polarization rotation with chemical strain, which effectively improves ferroelectricity. A method for the sulfurization of BiFeO3thin films by introducing sulfur anions is presented. The sulfurized films exhibited substantial enhancement in room-temperature ferroelectric polarization through polarization rotation and distortion, with a 170% increase in the remnant polarization from 58 to 100.7 μC cm−2. According to first-principles calculations and the results of X-ray absorption spectroscopy and high-angle annular dark-field scanning transmission electron microscopy, this enhancement arose from the introduction of S atoms driving the re-distribution of the lone-pair electrons of Bi, resulting in the rotation of the polarization state from the [001] direction to the [110] or [111] one. The presented method of anion-driven polarization rotation might enable the improvement of the properties of oxide materials.

Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors of FBA from Candida albicans(CaFBA). Site-directed mutagenesis, liquid chromatography–mass spectrometry, and the crystallographic structures of APO–CaFBA, CaFBA–G3P, and C157S–2a4revealed that S268 is an essential pharmacophore for the catalytic activity of CaFBA, and L288 is an allosteric regulation switch for CaFBA. Furthermore, most of the CaFBA covalent inhibitors exhibited good inhibitory activity against azole-resistant C. albicans, and compound 2a11can inhibit the growth of azole-resistant strains 103 with the MIC80of 1 μg/mL. Collectively, this work identifies a new covalent allosteric site of CaFBA and discovers the first generation of covalent inhibitors for fungal FBA with potent inhibitory activity against resistant fungi, establishing a structural foundation and providing a promising strategy for the design of potent antifungal drugs.

The prevailing view is that parvalbumin (PV) interneurons play modulatory roles in emotional response through local medium spiny projection neurons (MSNs). Here, we show that PV activity within the nucleus accumbens shell (sNAc) is required for producing anxiety-like avoidance when mice are under anxiogenic situations. Firing rates of sNAcPVneurons were negatively correlated to exploration time in open arms (threatening environment). In addition, sNAcPVneurons exhibited high excitability in a chronic stress mouse model, which generated excessive maladaptive avoidance behavior in an anxiogenic context. We also discovered a novel GABAergic pathway from the anterior dorsal bed nuclei of stria terminalis (adBNST) to sNAcPVneurons. Optogenetic activation of these afferent terminals in sNAc produced an anxiolytic effect via GABA transmission. Next, we further demonstrated that chronic stressors attenuated the inhibitory synaptic transmission at adBNSTGABA→ sNAcPVsynapses, which in turn explains the hyperexcitability of sNAc PV neurons on stressed models. Therefore, activation of these GABAergic afferents in sNAc rescued the excessive avoidance behavior related to an anxious state. Finally, we identified that the majority GABAergic input neurons, which innervate sNAcPVcells, were expressing somatostatin (SOM), and also revealed that coordination between SOM- and PV- cells functioning in the BNST → NAc circuit has an inhibitory influence on anxiety-like responses. Our findings provide a potentially neurobiological basis for therapeutic interventions in pathological anxiety.

Due to the evolution and development of antifungal drug resistance, limited efficacy of existing drugs has led to high mortality in patients with serious fungal infections. To develop novel antifungal therapeutic strategies, herein a series of carboline fungal histone deacetylase (HDAC) inhibitors were designed and synthesized, which had potent synergistic effects with fluconazole against resistant Candida albicansinfection. In particular, compound D12showed excellent in vitroand in vivosynergistic antifungal efficacy with fluconazole to treat azole-resistant candidiasis. It cooperated with fluconazole in reducing the virulence of C. albicansby blocking morphological mutual transformation and inhibiting biofilm formation. Mechanism studies revealed that the reversion of drug resistance was due to downregulation of the expression of the azole target gene ERG11and efflux gene CDR1. Taken together, fungal HDAC inhibitor D12offered a promising lead compound for combinational treatment of azole-resistant candidiasis.

Invasive fungal infections (particularly candidiasis) are emerging as severe infectious diseases worldwide. Because of serious antifungal drug resistance, therapeutic efficacy of the current treatment for candidiasis is limited and associated with high mortality. However, it is highly challenging to develop novel strategies and effective therapeutic agents to combat drug resistance. Herein, the first generation of lanosterol 14α-demethylase (CYP51)-histone deacetylase (HDAC) dual inhibitors was designed, which exhibited potent antifungal activity against azole-resistant clinical isolates. In particular, compounds 12hand 15jwere highly active both in vitroand in vivoto treat azole-resistant candidiasis. Antifungal mechanism studies revealed that they acted by blocking ergosterol biosynthesis and HDAC catalytic activity in fungus, suppressing the function of efflux pump, yeast-to-hypha morphological transition, and biofilm formation. Therefore, CYP51-HDAC dual inhibitors represent a promising strategy to develop novel antifungal agents against azole-resistant candidiasis.

Depression is a major mental health condition and is expected be the most debilitating and widespread health disorder by 2030. Tuberculosis (TB) is also a leading cause of morbidity and mortality worldwide and interestingly, is a common comorbidity of depression. As such, much attention has been paid to the association between these 2 pathologies. Based on clinical reports, the association between TB and depression seems to be bidirectional, with a substantial overlap in symptoms between the 2 conditions. TB infection or reactivation may precipitate depression, likely as a consequence of the host's inflammatory response and/or dysregulation of the hypothalamic–pituitary–adrenal axis. Nevertheless, few studies have considered whether patients with depression are at a higher risk for TB. In this review, we discuss the hypotheses on the association between depression and TB, highlighting the immuno‐inflammatory response and lipid metabolism as potential mechanisms. Improving our understanding of the interplay between these 2 disorders should help guide TB clinical care and prevention both in patients with comorbid depression and in the general population. Review on the association between depression and tuberculosis, includes a potential mechanism underlying depression's role in increasing the risk for tuberculosis.

A uracil DNA glycosylase (UDG) from Mycobacterium smegmatis(MsmUdgX) shares sequence similarity with family 4 UDGs and forms exceedingly stable complexes with single-stranded uracil-containing DNAs (ssDNA-Us) that are resistant to denaturants. However, MsmUdgX has been reported to be inactive in excising uracil from ssDNA-Us and the underlying structural basis is unclear. Here, we report high-resolution crystal structures of MsmUdgX in the free, uracil- and DNA-bound forms, respectively. The structural information, supported by mutational and biochemical analyses, indicates that the conserved residue His109 located on a characteristic loop forms an irreversible covalent linkage with the deoxyribose at the apyrimidinic site of ssDNA-U, thus rendering the enzyme unable to regenerate. By proposing the catalytic pathway and molecular mechanism for MsmUdgX, our studies provide an insight into family 4 UDGs and UDGs in general. Structural analysis of uracil DNA glycosylase reveals that its high affinity with DNA substrates derives from a stable intermediate that is formed by conservative H109 in a protruding loop covalently binding to the abasic site after uracil is excised.

Cryptococcus neoformans(C. neoformans) and Candida albicans(C. albicans) are classified as the critical priority groups among the pathogenic fungi, highlighting the urgent need for developing more effective antifungal therapies. On the basis of antifungal natural product sampangine, herein, a series of tricyclic oxime and oxime ether derivatives were designed. Among them, compound WZ-2showed excellent inhibitory activity against C. neoformans(MIC80= 0.016 μg/mL) and synergized with fluconazole to treat resistant C. albicans(FICI = 0.078). Interestingly, compound WZ-2effectively inhibited virulence factors (e.g., capsule, biofilm, and yeast-to-hypha morphological transition), suggesting the potential to overcome drug resistance. In a mouse model of cryptococcal meningitis, compound WZ-2(5 mg/kg) effectively reduced the brain C. neoformansH99 burden. Furthermore, compound WZ-2alone and its combination with fluconazole also significantly reduced the kidney burden of the drug-resistant strain (0304103) and sensitive strain (SC5314) of C. albicans.

Clinical treatment of cryptococcal meningitis (CM) remains a significant challenge because of the lack of effective and safe drug therapies. Developing novel CM therapeutic agents with novel chemical scaffolds and new modes of action is of great importance. Herein, new β-hexahydrocarboline derivatives are shown to possess potent anticryptococcal activities. In particular, compound A4showed potent in vitro and in vivo anticryptococcal activity with good metabolic stability and blood–brain barrier permeability. Compound A4was orally active and could significantly reduce brain fungal burdens in a murine model of CM. Moreover, compound A4could inhibit several virulence factors of Cryptococcus neoformansand might act by a new mode of action. Preliminary mechanistic studies revealed that compound A4induced DNA double-stranded breaks and cell cycle arrest at the G2 phase by acting on the Cdc25c/CDK1/cyclin B pathway. Taken together, β-hexahydrocarboline A4represents a promising lead compound for the development of next-generation CM therapeutic agents.

Water stress and interspecific interaction will change the growth characteristics and photosynthetic parameters of wetland plants. The net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), water use efficiency (WUE), plant height (PH), biomass of Typha orientalis Presl were analyzed by pot experiments. Pot experiments were conducted utilizing the plant species, Typha orientalis Presl alone, and Typha orientalis Presl along with Phragmites australis coexisting under the same water stress and water abundant conditions. Water stress was divided into four scenarios as W1i, W2i, W3i and W4i that ranged from mild to severe stress. In addition, the control experiment (CKi) was also conducted. The results showed that Pn, Gs, Tr, WUE, PH and biomass were reduced with the increase in severity of water stress. There were large differences in WUE among water stress treatments at the end of the experiment. The trend showed that W2i > W3i > W1i > CKi, while there was a decrease under W4i’s scenario. Therefore, the data suggested that a moderate increase in water stress could increase WUE. The growth and photosynthetic parameters of Typha orientalis Presl recovered after rewatering, but not under CKi’s scenario. The threshold soil moisture for Typha orientalis Presl was approximately 30% below, which demonstrated that recovery could be difficult even after rewatering. Coexistence with Phragmites australis had significant effects on the growth of Typha orientalis Presl and photosynthetic parameters. It was negative for biomass of Typha orientalis Presl, and positive for shoot heights in the same water stress treatments. The photosynthetic parameters were higher than single species in coexistence conditions.

Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as a key brain region for mediating visceral-pain-cognitive interactions. Recently, we characterized impairments of long-term potentiation and spike-field coherence in the basolateral amygdala (BLA)-ACC network in association with a decision-making deficit in rats with visceral hypersensitivity (VH). Now, by combining integrative neurobiological approaches, we show that ACC-reactive astrogliosis and activity-dependent impairment of lactate release occur in VH rats. Exogenous lactate supply rescues chronic-visceral-pain-caused impairments of ACC phase locking and decision making, which can be mimicked by optogenetic activation of ACC astrocytes. Large-scale electrophysiological recordings in free-moving animals during a decision-making task indicate that optogenetic astrocytic activation improves decision-making performance and engages ACC phase locking and BLA-to-ACC information flow. Collectively, these observations support the idea of an “astrocyte-neuron l-lactate shuttle” and suggest that targeting astrocytes may help with cognitive dysfunctions under chronic visceral pain.

Candida glabratahas emerged as an important opportunistic pathogen of invasive candidiasis due to increasing drug resistance. Targeting Pdr1-KIX interactions with small molecules represents a potential strategy for treating drug-resistant candidiasis. However, effective Pdr1-KIX inhibitors are rather limited, hindering the validation of target druggability. Here, new Pdr1-KIX inhibitors were designed and assayed. Particularly, compound B8possessed a new chemical scaffold and exhibited potent KIX binding affinity, leading to enhanced synergistic efficacy with fluconazole to treat resistant C. glabratainfection (FICI = 0.28). Compound B8acted by inhibiting the efflux pump and down-regulating resistance-associated genes through blocking the Pdr1-KIX interaction. Compound B8exhibited excellent in vitroand in vivoantifungal potency in combination with fluconazole against azole-resistant C. glabrata. It also had direct antifungal effect to treat C. glabratainfection, suggesting new mechanisms of action independent of Pdr1-KIX inhibition. Therefore, compound B8represents a promising lead compound for antifungal drug development.

Over the past several decades, invasive fungal infections, especially candidiasis, have caused dramatic morbidity and mortality due to ineffective antifungal drugs and severe drug resistance. Herein, new BRD4–histone deacetylase (HDAC) inhibitors were designed to restore the susceptibility of Candida albicans(C. albicans) to fluconazole (FLC). Interestingly, several compounds showed excellent selectivity against fungal HDACs. In particular, compound B2showed excellent synergistic effect with FLC against resistant C. albicans(FICI = 0.063) with high selectivity against fungal HDACs (SI = 1653) and low cytotoxicity. Compound B2effectively synergized with FLC and prevented biofilm formation and morphological transition in resistant C. albicans, potentiating the antifungal activity of FLC in vivoand significantly reducing kidney fungal loads. Thus, this drug combination is promising in the treatment of resistant C. albicansinfections.

Punica granatum L. Pomegranate has been traditionally used as a folk fruits for centuries in Oriental countries. It extract and subsequent fractions were used to evaluate antioxidant and related activities of Punica granatum L. It were extracted by 70% acetone, and then purified by HPD-400 macroporous adsorbent resins column. The aim of this study was to verify the antioxidant properties of acetone extracts of pomegranate pericarps and their lyophilized samples, and also to study the relationship between the activity and the contents of the tannins. The effects of natural extracts on microsomal lipid of mice liver and erythrocyte membrane lipid were examined. Vc/Fe2+, Cys/Fe2+induced microsomal lipid peroxidation, UV light induced erythrocyte membrane lipid peroxidation were measured by malondialdehyde (MDA) content with spectrophotometric methods. The natural plant extracts not only diminish the Vc/Fe2+,Cys/Fe2+ induced microsomal lipid peroxidation, UV light induced erythrocyte membrane lipid peroxidation and also showed its activity in a concentration-dependent manner. Our study found that the higher tannins contents showed more effective of antioxidant properties. Keywords: Punica granatum L.; liver microsome; antioxidant activity; Lipid peroxidation

Recent progress in nanotechnology has prompted research interest in immobilised enzymes on graphene oxide (GO) nanosheets for their large specific surface area and abundant functional groups. In the present work, acid pectinase was immobilised on the GO via the cross-linking of amino groups on pectinase and functional groups (e.g. carboxyl group) on the GO surface. Acid pectinase was effectively immobilised on the support and high loading densities were obtained (2400 mg per g of support). In addition, the immobilised enzyme achieved a better catalytic efficiency (K cat/K m) than its free counterpart; 3.7 mg−1 min−1 mL for immobilised pectinase, 3.5 mg−1 min−1 mL for free pectinase. Under acidic conditions, pectinase immobilised on GO will be agglomerated, but the addition of surfactant PEG 6000 could solve the problem and afford higher catalytic activity and catalytic efficiency.

Recent progress in nanotechnology has prompted research interest in immobilised enzymes on graphene oxide (GO) nanosheets for their large specific surface area and abundant functional groups. In the present work, acid pectinase was immobilised on the GO via the cross-linking of amino groups on pectinase and functional groups (e.g. carboxyl group) on the GO surface. Acid pectinase was effectively immobilised on the support and high loading densities were obtained (2400 mg per g of support). In addition, the immobilised enzyme achieved a better catalytic efficiency (Kcat/Km) than its free counterpart; 3.7 mg−1min−1mL for immobilised pectinase, 3.5 mg−1min−1mL for free pectinase. Under acidic conditions, pectinase immobilised on GO will be agglomerated, but the addition of surfactant PEG 6000 could solve the problem and afford higher catalytic activity and catalytic efficiency.

With the level of China's power information technology increased, any information security problem appear in power system are likely to endanger the safe operation of power grid. USB dongle is a popular authentication security tool which can effectively prevent the illegal use of software. In this paper, use electrical simulation training software as an example, apply encryption lock as an important tool for the security protection of electric power simulation training software, introduce the principle and role in information security protection of encryption lock in detail.

To prevent water bursting in mining coals and boring tunnels, analysis of water abundance of aquifer has to be done firstly. Based on analysis of main factors that can influence the water abundance of aquifer, five indices were used-aquifer thickness, drilling fluid consumption, structure distribution density, specific capacity and permeability coefficient. And the fuzzy analytic hierarchy process was introduced to determine the weight of each factor. Combining the data management and spatial analysis of GIS, we calculated and estimated the characteristic of water abundance for the study area. Due to the wide variance of water abundance over the whole study area, we set five rates to show the different results. So the study area was divided into five parts whose water capacity from high to low. The division was consistent with the hydro-geological conditions. So our method could be an alternative.

Photovaltaic power generation in the future world energy consumption will occupy an important position, not only to partially replace conventional energy sources, and will become the main energy supply. But at present, compared with conventional energy generation, photovoltaic electricity does not have a competitive advantage. So develop a reasonable electrovalency is the key to promote the healthy development of China’s photovoltaic industry. This paper use the net present value method of financial analysis to learn the generating capacity and investment cost of PV system combined with system’s characteristics and performance, discuss the unit cost of PV power and analyzed the impact of PV electricity price factors.

Large diameter and super-long pile has found abroad application in high buildings, super high buildings, large bridges and port engineering, and its ultimate bearing capacity is increasingly demanding. Its ultimate bearing capacity is affected by many kinds of uncertainty factors, which is a complex grey analysis program. The influencing factors are analyzed by grey system theory such as pile diameter, pile length, socket length, the length to diameter ratio, the socket length to diameter ratio, rock strength and rock coefficient of weathering. The grey correlation analysis is combined with the tested statistical data of 19 large diameter and super-long piles in Zhejiang province based on the grey correlation model. With the objective to overcome the lack of objectivity in calculating correlation degree of the grey correlation analysis, this paper has improved the calculated formula of the correlation degree based on the distance analysis method. The paper has get and compared the corresponding result of the correlation degree and its rank of various influence factors with the improved calculated formula and the original formula respectively. The influence advantage factors found by grey correlation analysis, and the results can provide important reference for the future theoretical research and design application of large diameter and super-long pile, and show that the grey correlation method is effective and reliable.

With the C# language and Access database, Building Foundation Pit Monitoring Information System (BFPMIS) was developed. At the process of developing the excavation monitoring system, the design of the system data structures and the data types are discussed. The excavation monitoring system contains main data structure and assistant data structure. The data structure, data element and data type of projects, bids, sections, monitoring point types, point property, alert values, bore information, pile information and beam information are analyzed emphatically. The application of the tree structure in the main data structure is introduced. And the monitoring points are classified according to the monitoring objects to describe and store the monitoring data. The system set orange alarm and red alarm to every monitoring point.

Strontium ranelate is a newly approved drug that can reduce the risk of vertebral fracture, which is attributed to its dual function in increasing the bone formation and decreasing the bone resorption. Strontium‐containing hydroxyapatite was also demonstrated to stimulate the osteoblast activity and inhibit the osteoclast activity. However, the molecular mechanisms of strontium underlying such beneficial effects were still not fully understood. In this study, we investigated the effects of strontium on the osteogenic differentiation of human mesenchymal stem cells (MSCs) and its related mechanism; its osteogenic potential was also evaluated using a calvarial defect model in rats. We found that strontium could enhance the osteogenic differentiation of the MSCs, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/β‐catenin pathway. After transplanting the collagen‐strontium‐substituted hydroxyapatite scaffold into the bone defect region, histology and computed tomography scanning revealed that in vivo bone formation was significantly enhanced; the quantity of mature and remodeled bone substantially increased and ECM accumulated. Interestingly, strontium induced an increase of β‐catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the β‐catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation. STEM CELLS 2011;29:981–991

Treatment of life-threatening cryptococcal meningitis (CM) is highly challenging due to the limited efficacy of the available antifungal drugs. Antidepressant sertraline (SER) has been proposed to be a potential antifungal agent for CM. However, clinical studies indicated that SER failed to achieve the expected therapeutic effects. Herein, novel SER derivatives were designed by scaffold hopping, and they showed improved anticryptococcal activity both in vitroand in vivo. In particular, compound D16was identified as a promising anti-CM agent with a new antifungal mode of action. It acted by blocking the biosynthesis of ergosterol through the inhibition of Δ5,6-desaturase. This study provides a new target and a drug-like candidate for CM treatment.