Tunable quantum dots in monolithic Fabry-Perot microcavities for high-performance single-photon sources.

Cavity-enhanced single quantum dots (QDs) are the main approach towards ultra-high-performance solid-state quantum light sources for scalable photonic quantum technologies. Nevertheless, harnessing the Purcell effect requires precise spectral and spatial alignment of the QDs' emission with the cavity mode, which is challenging for most cavities. Here we have successfully integrated miniaturized Fabry-Perot microcavities with a piezoelectric actuator, and demonstrated a bright single-photon source derived from a deterministically coupled QD within this microcavity. Leveraging the cavity-membrane structures, we have achieved large spectral tunability via strain tuning. On resonance, a high Purcell factor of ~9 is attained. The source delivers single photons with simultaneous high extraction efficiency of 0.58, high purity of 0.956(2) and high indistinguishability of 0.922(4). Together with its compact footprint, our scheme facilitates the scalable integration of indistinguishable quantum light sources on-chip, therefore removing a major barrier to the development of solid-state quantum information platforms based on QDs.

Reconstitution of the Final Steps in the Biosynthesis of Valanimycin Reveals the Origin of Its Characteristic Azoxy Moiety.

Valanimycin is an azoxy-containing natural product isolated from the fermentation broth of Streptomyces viridifaciens MG456-hF10. While the biosynthesis of valanimycin has been partially characterized, how the azoxy group is constructed remains obscure. Herein, the membrane protein VlmO and the putative hydrazine synthetase ForJ from the formycin biosynthetic pathway are demonstrated to catalyze N-N bond formation converting O-(l-seryl)-isobutyl hydroxylamine into N-(isobutylamino)-l-serine. Subsequent installation of the azoxy group is shown to be catalyzed by the non-heme diiron enzyme VlmB in a reaction in which the N-N single bond in the VlmO/ForJ product is oxidized by four electrons to yield the azoxy group. The catalytic cycle of VlmB appears to begin with a resting µ-oxo diferric complex in VlmB, as supported by Mössbauer spectroscopy. This study also identifies N-(isobutylamino)-d-serine as an alternative substrate for VlmB leading to two azoxy regioisomers. The reactions catalyzed by the kinase VlmJ and the lyase VlmK during the final steps of valanimycin biosynthesis are established as well. The biosynthesis of valanimycin was thus fully reconstituted in vitro using the enzymes VlmO/ForJ, VlmB, VlmJ and VlmK. Importantly, the VlmB-catalyzed reaction represents the first example of enzyme-catalyzed azoxy formation and is expected to proceed by an atypical mechanism.

Fast end-to-end surface interpretation of SARS-CoV-2 variants by differentiable molecular surface interaction fingerprinting method.

Confronting the challenge of persistent mutations of SARS-CoV-2, researchers have turned to deep learning methods to predict the mutated structures of spike proteins and to hypothesize potential changes in their structures and drug efficacies. However, limited works are focused on the surface learning of spike proteins even though their biological functions are usually defined by the geometric and chemical features of 3D molecular surfaces. In addition, the current used geometric deep learning methods are based on mesh representations of proteins to identify potential binding targets for drugs. However, the use of meshes has limitations and is not applicable for many important tasks in molecular biology. To address these limitations, we adopt the differentiable molecular surface interaction fingerprinting (dMaSIF) method which is based on the 3D point clouds and a novel efficient geometric convolutional layer to fast predict the interaction sites on the protein surface. The different binding site patterns for Delta, Omicron and its subvariants are clearly visualized. We find that Delta and Omicron show the similar surface binding patterns while BA.2, BA.2.13, BA.3 and BA.4 present similar ones. BA.4 possesses higher positive interaction site ratio than the others which may account for its higher transmission and infection among humans. In addition, the positive interaction site ratios of BA.2, BA.2.13, BA.3 are higher than Delta and Omicron, which are accordant with their transmission and infection rates. Hopefully our work offers a new effective route to analyze the protein-protein interaction for the SARS-CoV-2 variants.

Bioinformatic analysis of the molecular mechanisms underlying the progression of bone defects.

Background: The pathophysiology of bone defects (BDs) is complex, and the treatment for bone defects, in particular massive bone defects, remains a major clinical challenge. Our study was conducted to explore the molecular events related to the progression of bone defects a common clinical condition. Methods: First, microarray data of GSE20980 were obtained from the Gene Expression Omnibus (GEO) database, where 33 samples in total were used to analyze the molecular biological processes related to bone defects. Next, the original data were normalized and differentially expressed genes (DEGs) were identified. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Finally, a protein-protein interaction (PPI) network was constructed and the trends of the different genes were confirmed. Results: Compared with the samples of non-critical size defects (NCSD), the samples of critical size defects (CSD) had 2057, 827, and 1,024 DEGs at 7, 14, and 21 days post injury, respectively. At day 7, the DEGs were significantly enriched in metabolic pathways, at day 14 the DEGs were predominantly enriched in G-protein coupled signaling pathways and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, and at day 21 the DEGs were mainly enriched in circadian entrainment and synaptic-related functions. The PPI network showed similar results. Quantitative real-time PCR (qRT-PCR) and western blot (WB) were performed to validate the partial results of sequencing. Conclusion: This study provides some clues about the molecular mechanism behind bone defects, which should contribute to scientific research and clinical treatment of this condition.

Ultra-low threshold continuous-wave quantum dot mini-BIC lasers.

Highly compact lasers with ultra-low threshold and single-mode continuous wave (CW) operation have been a long sought-after component for photonic integrated circuits (PICs). Photonic bound states in the continuum (BICs), due to their excellent ability of trapping light and enhancing light-matter interaction, have been investigated in lasing configurations combining various BIC cavities and optical gain materials. However, the realization of BIC laser with a highly compact size and an ultra-low CW threshold has remained elusive. We demonstrate room temperature CW BIC lasers in the 1310 nm O-band wavelength range, by fabricating a miniaturized BIC cavity in an InAs/GaAs epitaxial quantum dot (QD) gain membrane. By enabling effective trapping of both light and carriers in all three dimensions, ultra-low threshold of 12 µW (0.052 kW cm-2) is achieved at room temperature. Single-mode lasing is also realized in cavities as small as only 5 × 5 unit cells (~2.5 × 2.5 µm2 cavity size) with a mode volume of 1.16(λ/n)3. The maximum operation temperature reaches 70 °C with a characteristic temperature of T0 ~93.9 K. With its advantages in terms of a small footprint, ultra-low power consumption, and adaptability for integration, the mini-BIC lasers offer a perspective light source for future PICs aimed at high-capacity optical communications, sensing and quantum information.

SIRT1 attenuates blood-spinal cord barrier disruption after spinal cord injury by deacetylating p66Shc.

Disruption of the blood-spinal cord barrier (BSCB) leads to inflammatory cell infiltration and neural cell death, thus, contributing to poor functional recovery after spinal cord injury (SCI). Previous studies have suggested that Sirtuin 1 (SIRT1), an NAD+-dependent class III histone deacetylase, is abundantly expressed in endothelial cells and promotes endothelial homeostasis. However, the role of SIRT1 in BSCB function after SCI remains poorly defined. Here, we report that SIRT1 is highly expressed in spinal cord endothelial cells, and its expression significantly decreases after SCI. Using endothelial cell-specific SIRT1 knockout mice, we observed that endothelial cell-specific knockout of SIRT1 aggravated BSCB disruption, thus, resulting in widespread inflammation, neural cell death and poor functional recovery after SCI. In contrast, activation of SIRT1 by the agonist SRT1720 had beneficial effects. In vitro, knockdown of SIRT1 exacerbated IL-1ß-induced endothelial barrier disruption in bEnd.3 cells, whereas overexpression of SIRT1 was protective. Using RNA-seq and IP/MS analysis, we identified p66Shc, a redox protein, as the potential target of SIRT1. Further studies demonstrated that SIRT1 interacts with and deacetylates p66Shc, thereby attenuating oxidative stress and protecting endothelial barrier function. Overall, our results indicate that SIRT1 decreases endothelial ROS production and attenuates BSCB disruption by deacetylating p66Shc after SCI, and suggest that SIRT1 activation has potential as a therapeutic approach to promote functional recovery against BSCB disruption following SCI.

Hybrid ISTA: Unfolding ISTA With Convergence Guarantees Using Free-Form Deep Neural Networks.

It is promising to solve linear inverse problems by unfolding iterative algorithms (e.g., iterative shrinkage thresholding algorithm (ISTA)) as deep neural networks (DNNs) with learnable parameters. However, existing ISTA-based unfolded algorithms restrict the network architectures for iterative updates with the partial weight coupling structure to guarantee convergence. In this paper, we propose hybrid ISTA to unfold ISTA with both pre-computed and learned parameters by incorporating free-form DNNs (i.e., DNNs with arbitrary feasible and reasonable network architectures), while ensuring theoretical convergence. We first develop HCISTA to improve the efficiency and flexibility of classical ISTA (with pre-computed parameters) without compromising the convergence rate in theory. Furthermore, the DNN-based hybrid algorithm is generalized to popular variants of learned ISTA, dubbed HLISTA, to enable a free architecture of learned parameters with a guarantee of linear convergence. To our best knowledge, this paper is the first to provide a convergence-provable framework that enables free-form DNNs in ISTA-based unfolded algorithms. This framework is general to endow arbitrary DNNs for solving linear inverse problems with convergence guarantees. Extensive experiments demonstrate that hybrid ISTA can reduce the reconstruction error with an improved convergence rate in the tasks of sparse recovery and compressive sensing.

A prospective marker for the prediction of postoperative deep venous thrombosis: Neutrophil extracellular traps.

Deep venous thrombosis (DVT) is a common medical complication in patients with lumbar fractures. The current study aimed to investigate the predictive value of neutrophil extracellular traps (NETs) in postoperative DVT formation in patients with lumbar fractures and to develop a nomogram relating clinical admission information for prediction. Patients who underwent open reduction and pedicle screw internal fixation in the treatment of single-segment lumbar fracture in the Department of Spine Surgery, the First Affiliated Hospital of Nanjing Medical University, from December 2020 to June 2022 were enrolled in this study. Baseline data and laboratory results were collected from enrollees, and the primary study endpoint event was the occurrence of DVT in patients after surgery. Multivariable logistic regression analysis was used to identify risk factors associated with higher odds of DVT after surgery. A nomogram was constructed using the results of the multivariable model. The calibration plot and receiver operating characteristics (ROC) curve were used to show the satisfactory predictive capacity of the model. Of these 393 patients who did not have DVT preoperatively, 79 patients developed it postoperatively, and 314 did not, respectively. Multivariate analysis showed that higher body mass index (BMI) (BMI between 24 and 28: RR = 1.661, 95% CI = 0.891-3.094; BMI ≤28: RR = 5.625, 95% CI = 2.590-12.217; reference: BMI <24), neutrophils (RR = 1.157, 95% CI 1.042-1.285), D-dimer (RR = 1.098, 95% CI 1.000-1.206), and citrullinated histone H3 (CitH3) (RR = 1.043, 95% CI 1.026-1.060) were independent risk factors for postoperative DVT. Using the multivariable analysis, we then constructed a nomogram to predict DVT, which was found to have an area under the curve of 0.757 (95% CI = 0.693-0.820). Calibration plots also showed the satisfied discrimination and calibration of the nomogram. In conclusion, patients with lumbar fractures with postoperative DVT had higher levels of NETs in the circulation preoperatively compared to those without postoperative DVT. Furthermore, based on BMI, D-dimer, neutrophils, and CitH3, we developed a predictive model to predict postoperative DVT incidence in these patients.

Deciphering the Reaction Pathway of Mononuclear Iron Enzyme-Catalyzed N≡C Triple Bond Formation in Isocyanide Lipopeptide and Polyketide Biosynthesis.

Despite the diversity of reactions catalyzed by 2-oxoglutarate-dependent nonheme iron (Fe/2OG) enzymes identified in recent years, only a limited number of these enzymes have been investigated in mechanistic detail. In particular, several Fe/2OG-dependent enzymes capable of catalyzing isocyanide formation have been reported. While the glycine moiety has been identified as a biosynthon for the isocyanide group, how the actual conversion is effected remains obscure. To elucidate the catalytic mechanism, we characterized two previously unidentified (AecA and AmcA) along with two known (ScoE and SfaA) Fe/2OG-dependent enzymes that catalyze N≡C triple bond installation using synthesized substrate analogues and potential intermediates. Our results indicate that isocyanide formation likely entails a two-step sequence involving an imine intermediate that undergoes decarboxylation-assisted desaturation to yield the isocyanide product. Results obtained from the in vitro experiments are further supported by mutagenesis, the product-bound enzyme structure, and in silico analysis.

All-optical graph representation learning using integrated diffractive photonic computing units.

Photonic neural networks perform brain-inspired computations using photons instead of electrons to achieve substantially improved computing performance. However, existing architectures can only handle data with regular structures but fail to generalize to graph-structured data beyond Euclidean space. Here, we propose the diffractive graph neural network (DGNN), an all-optical graph representation learning architecture based on the diffractive photonic computing units (DPUs) and on-chip optical devices to address this limitation. Specifically, the graph node attributes are encoded into strip optical waveguides, transformed by DPUs, and aggregated by optical couplers to extract their feature representations. DGNN captures complex dependencies among node neighborhoods during the light-speed optical message passing over graph structures. We demonstrate the applications of DGNN for node and graph-level classification tasks with benchmark databases and achieve superior performance. Our work opens up a new direction for designing application-specific integrated photonic circuits for high-efficiency processing large-scale graph data structures using deep learning.

Fatty acids derived from apoptotic chondrocytes fuel macrophages FAO through MSR1 for facilitating BMSCs osteogenic differentiation.

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate peroxisome proliferator-activated receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD+/SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments.

Kindlin-2 Promotes Chondrogenesis and Ameliorates IL-1beta-Induced Inflammation in Chondrocytes Cocultured with BMSCs in the Direct Contact Coculture System.

The osteoarthritis caused by trauma or inflammation is associated with severe patient morbidity and economic burden. Accumulating studies are focusing on the repair of articular cartilage defects by constructing tissue-engineered cartilage. Recent evidence suggests that optimizing the source and quality of seed cells is one of the key points of cartilage tissue engineering. In this study, we demonstrated that Kindlin-2 and its activated PI3K/AKT signaling played an essential role in promoting extracellular matrix (ECM) secretion and ameliorating IL-1beta-induced inflammation in chondrocytes cocultured with bone marrow stem cells (BMSCs). In vivo experiments revealed that coculture significantly promoted hyaline cartilage regeneration. In vitro studies further uncovered that chondrocytes cocultured with BMSCs in the direct contact coculture system upregulated Kindlin-2 expression and subsequently activated the PI3K/AKT signaling pathway, which not only increases Sox9 and Col2 expression but also restores mitochondrial membrane potential and reduces ROS levels and apoptosis under inflammatory conditions. Overall, our findings indicated that direct contact BMSC-chondrocyte coculture system could promote chondrogenesis, and identified Kindlin-2 represents a key regulator in this process.

N6-Methyladenosine Regulator-Mediated Immue Patterns and Tumor Microenvironment Infiltration Characterization in Glioblastoma.

Background: Epigenetic modifications, according to emerging evidence, perform a critical role for cellular immune response and tumorigenesis. Nonetheless, the role of N6-methyladenosine modification in shaping of the glioblastoma tumor microenvironment is unknown. Methods: N6-methyladenosine(m6A) methylation patterns in GBM patients were evaluated via multiple omics analysis of 15 m6A regulators and systematically correlated with tumor immune features. For quantification of N6-methyladenosine methylation patterns of individual patients, GM-score was developed and correlated with clinical and immunological characteristics. Results: Glioblastoma has two different m6A methylation patterns that are strongly associated with TME characteristics, tumor subtype, immunotherapy response, and patient prognosis. High-GM-score is associated with an immune tolerance phenotype dominated by the IDH1 wild molecular subtype and the Mesenchymal tissue subtype, as well as a high infiltration of immune cells and stromal cells and a poor prognosis. Furthermore, despite higher immune checkpoint expression, individuals with a high-GM-score have a poorer response to anti-CTLA4 immunotherapy regimens due to T-cells dysfunctional. Low-GM-score individuals had an immunodeficient phenotype dominated by IDH mutant molecular subtypes and Proneural tissue subtypes, with less immune cell infiltration and a better prognosis. Furthermore, patients with low-GM-scores had higher microsatellite instability (MSI) and t-cell exclusion scores, as well as a better response to anti-CTLA4 immunotherapy regimens. Conclusion: This study demonstrated that m6A modification patterns play an important role in the shaping of TME complexity and diversity. The GM-score could identify m6A modification patterns in individual patients, resulting in a more personalization and efficacious anti-tumor immunotherapy strategy.

Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis.

Subtalar osteoarthritis (STOA) is often secondary to chronic ankle sprains, which seriously affects the quality of life of patients. Due to its etiology and pathogenesis was not studied equivocally yet, there is currently a lack of effective conservative treatments. Although they have been used for tissue repair, platelet-rich plasma-derived exosomes (PRP-Exo) have the disadvantage of low retention and short-lived therapeutic effects. This study aimed to determine whether incorporation of PRP-Exo in thermosensitive hydrogel (Gel) increased their retention in the joint and thereby playing a therapeutic role on STOA due to chronic mechanical instability established by transecting lateral ligaments (anterior talofibular ligament (ATFL)/calcaneal fibular ligament (CFL)). PRP-Exo incorporated Gel (Exo-Gel) system, composed of Poloxamer-407 and 188 mixture-based thermoresponsive hydrogel matrix in an optimal ratio, was determined by its release ability of Exo and rheology of Gel response to different temperature. The biological activity of Exo-Gel was evaluated in vitro, and the therapeutic effect of Exo-Gel on STOA was evaluated in vivo. Exo released from Exo-Gel continuously for 28 days could promote the proliferation and migration of mouse bone mesenchymal stem cells (mBMSCs) and chondrocytes, at the same time enhance the chondrogenic differentiation of mBMSCs, and inhibit inflammation-induced chondrocyte degeneration. In vivo experiments confirmed that Exo-Gel increased the local retention of Exo, inhibited the apoptosis and hypertrophy of chondrocytes, enhanced their proliferation, and potentially played the role in stem cell recruitment to delay the development of STOA. Thus, Delivery of PRP-Exo incorporated in thermosensitive Gel provides a novel approach of cell-free therapy and has therapeutic effect on STOA.

Can Housing Assets Affect the Chinese Residents' Willingness to Pay for Green Housing?

As the development trend of the future housing field, green housing is an effective way to reduce pollution, save energy, and promote industrial upgrading. At the same time, the green house is of great significance to change the development mode of the construction industry and promote the sustainable development of the social economy. This study proposes a comprehensive research model to examine the influencing mechanism of residents' intention to purchase green buildings. The proposed model is empirically tested using data collected from 1,338 urban residents in China. Based on logit, probit, and ivprobit models, factors such as personal characteristics, housing price, and the number of real estate ownership are selected to conduct empirical analysis and mechanism analysis on willingness that affects consumers' purchase of green houses. The results show that housing assets significantly affect the willingness of householders to pay for green houses. The more houses they own, the higher their willingness to pay for a green house will be. Similarly, if the housing prices are higher, householders are more willing to buy a green house. The amount of housing assets will affect the willingness of householders to pay for green housing through the way of individual happiness. In terms of the characteristics of the householder, if the householder is more educated, unmarried, his willingness to buy a green house will be stronger, and owning housing assets may affect the individual happiness due to the housing wealth effect brought by rising housing prices. People with more housing assets are more likely to have the happiness brought by higher wealth, which may affect the purchase intention of householders.

Enhanced antitumour effect for hepatocellular carcinoma in the advanced stage using a cyclodextrin-sorafenib-chaperoned inclusion complex.

Hepatocellular carcinoma (HCC) is a hypervascular tumour characterized by tumour-driven neovascularization. The degrees of blood oxygen saturation (DBOS), microvessel density (MVD) and tumour size (TS) are indicators in identifying the development stage of HCC. Herein, we proposed an HCC staging model using HepG2 tumour-bearing mice based on DBOS, MVD and TS. According to the patterns of these three criteria, HCC was classified into four stages: early, intermediate, advanced and end stages. The advanced stage was characterized by MVD of 50-90 (number per mm2), DBOS of 12-16% and TS of 250-600 mm3, which poses a critical challenge in HCC therapy. In order to efficiently control and treat HCC in the advanced stage, we developed a cyclodextrin (CD)-based chaperoned inclusion complex using Sorafenib (Sor), ß-CD and γ-CD (SCD) via the co-crystallization method. The structural study manifested that CDs could encapsulate Sor with the hydrophobic cavities at a 1 : 1 stoichiometry ratio. The crystallographic analysis indicated that Sor-ß-CD presented a diagonal stacking pattern, while Sor-γ-CD possessed a channel-type structure. The resultant chaperoned inclusion complexes significantly improved the solubility, dissolution rate and drug release of Sor, leading to superior pharmacokinetics, biodistribution and biosafety through oral administration. The antitumour effect was then evaluated on a mouse model with advanced HCC through oral administration and intratumour injection. The treatment involving the oral administration of SCDs showed a promising therapeutic effect on advanced HCC, which efficiently blocked angiogenesis and inhibited tumour progression. For the treatments using intratumour injections, only Sor-γ-CD exhibited a satisfactory anti-tumour effect with reduction in TS, MVD and DBOS. The enhanced therapeutic performance of Sor-γ-CD was attributed to its channel-type structure, which had an impact on the dissociation and release of the drug. Thus, Sor-γ-CD can be used as a potential pro-drug for clinical medicine and basic research to treat HCC.

[Expression level and Clinical Significance of Serum SE-CAD and Matriptase in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To analyze the expression level of the serum soluble E cadherin (SE-CAD) and Matriptase and its clinical significance for evaluation of the disease condtions and prognosis in patients with acute myeloid leukemia (AML). METHODS: One hundred and ten patients diagnosed as AML in our hospital were divided into 3 groups: newly diagnosed group (38 cases), remission group (40 cases) and recurrence group (32 cases). The expression levels of serum matriptase were detected by Western blot, and the expression levels of serum SE-CAD were detected by ELISA. The serum levels of serum SE-CAD and matriptase among 3 groups were compared. Followin-up for one year, according to the outcome of patients, all the patients were divided into 2 groups: the survival group and death group. The serum levels of SE-CAD and Matriptase were compared between 2 groups. The correlation of serum levels of SE-CAD and matriptase with the survival of AML patients was analyzed by multivariate Logistic analysis. The evaluation value of the serum levels of SE-CAD and matriptase for the prognosis of the patients with AML were analyzed by receiver operating characteristic curves (ROC). RESULTS: The serum levels of SE-CAD and matriptase were siginificantly different among 3 groups (P＜0.05). The serum levels of SE-CAD and matriptase in remission group were lowest (P＜0.05), and the serum levels of SE-CAD and matriptase were not different between newly diagnoses and recurrence groups (P＞0.05). Multivariate Logistic analysis showed that the serum levels of SE-CAD and matriptase were independent risk factors for the prognosis of AML patients (OR=3.157, P＜0.05, OR=2.426, P＜0.05). By follow-up for 1 year, the serum expression levels of SE-CAD and Matriptase in survival group were lower than that in death group. ROC curve showed that when the cut-off value of matriptase level was 0.73 and SE-CAD level was 3.42 ng/ml, the AUC of predictions for the poor prognosis in AML patients was 0.849 (P＜0.05), the sensitivity was 85.6% (95%CI: 0.810~0.924) and specificity was 89.6% (95%CI: 0.849~0.941). CONCLUSION: The serum levels of SE-CAD and matriptase can perfectly evaluate the condition and short-term prognosis of the patients with AML.

Protective effects of 2,3,5,4-tetrahydroxystilbene-2-o-ß-D-glucoside against osteoporosis: Current knowledge and proposed mechanisms.

AIM: The aim of this study was to explore the mechanism underlying the protective effects of 2,3,5,4-tetrahydroxystilbene-2-o-ß-D-glucoside (TSG) against osteoporosis. METHOD: MC3T3-E1 mouse osteoblast precursor cells were used to analyze the protective effects of TSG on osteoblast apoptosis and differential inhibition induced by oxidative stress to determine the gene expression of forkhead transcription factor FKHRL1 (FoxO3a), T cell factors (TCFs), and downstream genes. A mouse model was used to assess the protective effects of TSG on ovariectomy-induced osteoporosis as well as on Cell Counting Kit-8 (CCK) gene expression, including that of FoxO3a. The mechanism underlying the protective effects of TSG against osteoporosis was further explored using high-throughput sequencing data. RESULTS: A CCK-8 assay in MC3T3-E1 cells and hematoxylin and eosin staining in mouse tissue indicated that cell viability and bone tissue development were inhibited by oxidative stress and ovariectomy and that TSG neutralized or attenuated this effect. The expression levels of FoxO3a, TCF, and downstream genes and the indices of oxidative stress were the same in MC3T3-E1 cells and the bone tissues of the mouse model. Bioinformatics analysis indicated that the cardiac muscle contraction and chemokine signaling pathway were disturbed in MC3T3-E1 cells treated with hydrogen peroxide. Gene ontology-biological process analysis revealed the influence of TSG treatment. CONCLUSION: Osteoporosis and cardiac diseases appear to share a common mechanism. In addition to Wnt/FoxO3a signaling, the immune system and the chemokine signaling pathway may contribute to the protective mechanism of TSG.

Perfluorooctane sulfonate induced neurotoxicity responses associated with neural genes expression, neurotransmitter levels and acetylcholinesterase activity in planarians Dugesia japonica.

As a persistent and widespread toxic organic pollutant in the environment, perfluorooctane sulfonate (PFOS) has the potential to cause great harm to wildlife. In our study, the effects of PFOS on neurodevelopment gene expression, neurotransmitter content, neuronal morphology, acetylcholinesterase (AChE) activity were examined, and the potential neurotoxicity mechanisms of PFOS were also investigated in planarians, Dugesia japonica. Using quantitative real-time PCR analysis, five neurodevelopmental related genes were measured, among which, DjotxA, DjotxB, DjFoxD, and DjFoxG were found to be down-regulated, while Djnlg was found to be up-regulated, following exposure to PFOS for 10 days compared with control groups. In addition, the neurotransmitters including dopamine, serotonin, and γ-aminobutyricacid as well as the acitivity of AChE were altered by PFOS exposure. Furthermore, PFOS exposure altered brain morphology as well as smaller cephalic ganglia which displayed reduced nerve fiber density decreased brain branches compared to controls. Our results demonstrate that neurotransmission was disturbed after exposure to PFOS and that exposure to this pollutant can cause neurotoxic defects. Results from this study provide valuable information regarding the neuro- and ecological toxicity of PFOS in aquatic animals and aquatic environments.

The Fusarium Graminearum virulence factor FGL targets an FKBP12 immunophilin of wheat.

Wheat scab, caused by the fungal pathogen Fusarium graminearum is a devastating disease worldwide. Despite an extensive and coordinated effort to investigate this pathosystem, little progress has been made to understand the molecular basis of host-pathogen interactions, for example how the pathogen causes disease in plant. Recently, a secreted lipase (FGL1) has been identified from the fungus and shown to be an important virulence factor; however, the intrinsic function of FGL1 in plant is unknown. Here, we report the identification of the molecular components that may possibly be involved in the FGL virulence pathway using yeast two hybrid system. FGL gene was amplified from a local virulent strain (F15) and shown to be 99.5% identical to the original published FGL at the amino acid level. We showed that transient expression of this FGL gene by Agroinfiltration in tobacco leaves causes cell death further implicating the role of FGL in virulence. To identify FGL initial physical target in plant, we screened two wheat cDNA libraries using the FGL protein as the bait. From both libraries, a small FKBP-type immunophilin protein, designated wFKBP12, was found to physically interact with FGL. The direct interaction of FGL with wFKBP12 was confirmed in living onion epidermal cells by biomolecular fluorescence complementation (BiFC) assay. To investigate further, we then used wFKBP12 protein as bait and identified an elicitor-responsive protein that contains a potential Ca(2+) binding domain. Semi-quantitative PCR showed that this elicitor-responsive gene is down-regulated during the F. graminearum infection suggesting that this protein may be an important component in FGL virulence pathway. This work serves as an initial step to reveal how fungal lipases act as a general virulence factor.