Adipose-derived stem cells (ASC) have been used as an alternative to bone marrow mesenchymal stem cells (BMSC) for bone tissue engineering. However, the efficacy of ASC in bone regeneration in comparison with BMSC remains debatable, since inconsistent results have been reported. Comparing ASC with BMSC obtained from different individuals might contribute to this inconsistency in results. Therefore, this study aimed to compare the bone regenerative capacity of donor-matched human ASC and BMSC seeded onto poly(L-lactide-co-ε-caprolactone) scaffolds using calvarial bone defects in nude rats. First, donor-matched ASC and BMSC were seeded onto the co-polymer scaffolds to evaluate their in vitro osteogenic differentiation. Seeded scaffolds and scaffolds without cells (control) were then implanted in calvarial defects in nude rats. The expression of osteogenesis-related genes was examined after 4 weeks. Cellular activity was investigated after 4 and 12 weeks. Bone formation was evaluated radiographically and histologically after 4, 12, and 24 weeks. In vitro, ASC and BMSC demonstrated mineralization. However, BMSC showed higher alkaline phosphatase activity than ASC. In vivo, human osteogenesis-related genes Runx2 and collagen type I were expressed in defects with scaffold/cells. Defects with scaffold/BMSC had higher cellular activity than defects with scaffold/ASC. Moreover, bone formation in defects with scaffold/BMSC was greater than in defects with scaffold/ASC, especially at the early time-point. These results suggest that although ASC have the potential to regenerate bone, the rate of bone regeneration with ASC may be slower than with BMSC. Accordingly, BMSC are more suitable for bone regenerative applications.

The colonization of land by plants was one of the most transformative events in the history of life on Earth. The transition from water, which coincided with and was likely facilitated by the evolution of three-dimensional (3D) growth, enabled the generation of morphological diversity on land. In many plants, the transition from two-dimensional (2D) to 3D growth occurs during embryo development. However, in the early divergent moss Physcomitrella patens, 3D growth is preceded by an extended filamentous phase that can be maintained indefinitely. Here, we describe the identification of the cytokinin-responsive NO GAMETOPHORES 2 (PpNOG2) gene, which encodes a shikimate o-hydroxycinnamoyltransferase. In mutants lacking PpNOG2 function, transcript levels of CLAVATA and SCARECROW genes are significantly reduced, excessive gametophore initial cells are produced, and buds undergo premature developmental arrest. Mutants also exhibit misregulation of auxin-responsive genes. Our results suggest that PpNOG2 functions in the ascorbic acid pathway leading to cuticle formation and that NOG2-related genes were co-opted into the lignin biosynthesis pathway after the divergence of bryophytes and vascular plants. We present a revised model of 3D growth in which PpNOG2 comprises part of a feedback mechanism that is required for the modulation of gametophore initial cell frequency. We also propose that the 2D to 3D growth transition in P. patens is underpinned by complex auxin-cytokinin crosstalk that is regulated, at least in part, by changes in flavonoid metabolism.

Breathing depends on pulmonary surfactant, a mixture of phospholipids and proteins, secreted by alveolar type II cells. Surfactant requires lamellar bodies (LBs), organelles containing densely packed concentric membrane layers, for storage and secretion. LB biogenesis remains mysterious but requires surfactant protein B (SP-B), which is synthesized as a precursor (pre-proSP-B) that is cleaved during trafficking into three related proteins. Here, we elucidate the functions and cooperation of these proteins in LB formation. We show that the N-terminal domain of proSP-B is a phospholipid-binding and -transfer protein whose activities are required for proSP-B export from the endoplasmic reticulum (ER) and sorting to LBs, the conversion of proSP-B into lipoprotein particles, and neonatal viability in mice. The C-terminal domain facilitates ER export of proSP-B. The mature middle domain, generated after proteolytic cleavage of proSP-B, generates the striking membrane layers characteristic of LBs. Together, our results lead to a mechanistic model of LB biogenesis.

Surprise signals a discrepancy between past and current beliefs. It is theorized to be linked to affective experiences, the creation of particularly resilient memories, and segmentation of the flow of experience into discrete perceived events. However, the ability to precisely measure naturalistic surprise has remained elusive. We used advanced basketball analytics to derive a quantitative measure of surprise and characterized its behavioral, physiological, and neural correlates in human subjects observing basketball games. We found that surprise was associated with segmentation of ongoing experiences, as reflected by subjectively perceived event boundaries and shifts in neocortical patterns underlying belief states. Interestingly, these effects differed by whether surprising moments contradicted or bolstered current predominant beliefs. Surprise also positively correlated with pupil dilation, activation in subcortical regions associated with dopamine, game enjoyment, and long-term memory. These investigations support key predictions from event segmentation theory and extend theoretical conceptualizations of surprise to real-world contexts.

Substantial evidence has revealed that abnormalities in synaptic plasticity play important roles during the process of depression. LASP1 (LIM and SH3 domain protein 1), a member of actin-binding proteins, has been shown to be associated with the regulation of synaptic plasticity. However, the role of LASP1 in the regulation of mood is still unclear. Here, using an unpredictable chronic mild stress (UCMS) paradigm, we found that the mRNA and protein levels of LASP1 were decreased in the hippocampus of stressed mice and that UCMS-induced down-regulation of LASP1 was abolished by chronic administration of fluoxetine. Adenosine-associated virus-mediated hippocampal LASP1 overexpression alleviated the UCMS-induced behavioral results of forced swimming test and sucrose preference test in stressed mice. It also restored the dendritic spine density, elevated the levels of AKT (a serine/threonine protein kinase), phosphorylated-AKT, insulin-like growth factor 2, and postsynaptic density protein 95. These findings suggest that LASP1 alleviates UCMS-provoked behavioral defects, which may be mediated by an enhanced dendritic spine density and more activated AKT-dependent LASP1 signaling, pointing to the antidepressant role of LASP1.

Sex differences in METH use exist among human METH users and in animal models of METH addiction. Herein, we tried to identify potential differences in gene expression between female and male rats after Methamphetamine self-administration (METH SA). Rats were trained to self-administer METH using two 3-hours daily sessions for 20 days. Cue-induced drug seeking was measured on withdrawal days 3 (WD3) and 30 (WD30). Rats were euthanized twenty-four hours after WD30. Prefrontal cortex (PFC) and hippocampus (HIP) were dissected to measure mRNA expression. Both female and male rats increased their METH intake and showed increased METH seeking during withdrawal. Female had higher basal level expression of hypocretin receptor 1 (Hcrtr1) and prodynorphin (Pdyn) mRNAs in the PFC and HIP. Basal corticotropin releasing hormone receptor 1 (Crhr1), Crh receptor 2 (Crhr2), hypocretin receptor 2 (Hcrtr2) and opioid receptor kappa 1 (Oprk1) mRNA levels were higher in the PFC of females. Male rats had higher basal levels of Crh and Crhr1 in HIP. METH SA was associated with increased Crh and Crhr1 in the HIP of both sexes and Crhr2 only in female HIP. Importantly, increased Crh and Crhr1 mRNA levels correlated positively with incubation of METH craving in both sexes, supporting their potential involvement, in part, in the regulation of this behavioral phenomenon. When taken together, our results identified sexual dimorphic baseline differences in rats. We also detected dimorphic responses in animals that had self-administered METH. These observations highlight the importance of understanding the molecular neurobiology of sex differences when therapeutic interventions are planned against METH addiction.

Chitosan is a potent biopolymer having promising antimicrobial properties against phytopathogens. Recently, engineered nanomaterials (ENMs) have gained much attention due to their potential application in the plant disease management. In this study, we reported the green synthesis of chitosan-magnesium (CS-Mg) nanocomposite and its antimicrobial activity against two rice pathogens namely Acidovorax oryzae and Rhizoctonia solani for the first time. The green MgO nanoparticles synthesized by using a native Bacillus sp. strain RNT3, were used to fabricate CS-Mg nanocomposite utilizing one-pot synthesis method. The synthesis of CS-Mg nanocomposite was further confirmed by using UV-vis spectroscopy, whereas, FTIR and XRD analysis showed the capping of CS-Mg nanocomposites by different functional groups together with their crystalline structure, respectively. Besides, SEM and TEM images revealed the spherical shape along with the particles size ranging from 29 to 60 nm. Moreover, EDS analysis confirmed the elemental purity of nanocomposite. The CS-Mg nanocomposite showed remarkable antimicrobial activity against A. oryzae and R. solani and significantly inhibited the growth as compared to non-treated control. The ultrastructure studies showed damaged structure of cell wall and internal cellular organelles after treatment with 100 μg mL-1 CS-Mg nanocomposite. The results of this study indicated that CS-Mg nanocomposite-based antimicrobial agents could be considered as promising nanopesticides against phytopathogens in plant disease management.

Using restructuring technology, A- or B-type crystalline granular potato starch was produced from amorphous granular potato starch (AGPS). AGPS was prepared using ethanol-heat processing, and hydrothermal treatments were performed with different moisture contents (18, 29, 200% d.b.) and temperatures (4, 25, 40, 60, 80 °C) for 3 weeks. AGPS showed no endothermic peak in a DSC thermogram, while hydrothermally treated AGPS (HAGPS) revealed endothermic peaks. In X-ray diffraction, AGPS displayed an amorphous pattern, and HAGPS displayed A- or B-type crystalline patterns depending on treatment temperature and moisture content. Neither AGPS nor HAGPS had typical RVA pasting curves, and their viscosities gradually increased. Raman spectroscopy and FT-IR confirmed that ordered structure and crystalline regions increased in HAGPS. Resistant starch (RS) and slowly digestible starch (SDS) contents of HAGPS increased but rapidly digestible starch (RDS) content decreased compared to AGPS. These results elucidated that hydrothermal treatment could change the physicochemical properties of AGPS and produce an identical material, such as granular potato starch with A-type and B-type crystalline granular potato starch.

This study aimed at determining the effects of saffron on depression as well as its neuroprotective and pharmacological effects on the intestinal function of crocetin in mice exposed to chronic restraint stress.

Unravelling the anti-diabetic mechanism of action of L. leonurus at adipose, liver, muscle and pancreatic level.

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. Despite the importance of toxoplasmosis, there is no comprehensive strategy to control this disease. Hence, applying the new methods such as the poly-epitope vaccine can be successful. In the current project, to engineer a potent poly-epitope vaccine, 10 antigenic proteins including BiP, GRA1, GRA2, GRA5, MIC8, MIC13, P30, PI1, SOD and Rop2 were selected based on the database. Then, B cell, MHCI and MHCII epitopes of the selected antigenic proteins were isolated by the most accurate servers. The best predicted epitopes along with a molecular adjuvant were employed to engineer a poly-epitope vaccine. After engineering, different physicochemical features, secondary and tertiary structures, molecular docking of the designed vaccine were assessed. The results of this project revealed that the designed vaccine with 730 amino acids in length and molecular weight of 77.67 kDa was a soluble protein which could bind to its receptor with an energy of 6223.43. According to the achievements of this study, it seems the designed vaccine can be an appropriate candidate to apply.

To identify the factors associated with perceived COVID-19 risk among people living in the US.

Many viruses utilize molecular chaperone heat shock protein 90 (Hsp90) for protein folding and stabilization, however, the role of Hsp90 in herpesvirus lifecycle is obscure. Here, we provide evidence that Hsp90 participates in pseudorabies virus (PRV) replication. Viral growth kinetics assays show that Hsp90 inhibitor geldanamycin (GA) abrogates PRV replication at the post-penetration step. Transmission electron microscopy demonstrates that dysfunction of Hsp90 diminishes the quantity of PRV nucleocapsids. Overexpression and knockdown of Hsp90 suggest that de novo Hsp90 is involved in PRV replication. Mechanismly, dysfunction of Hsp90 inhibits PRV major capsid protein VP5 expression. Co-immunoprecipitation and indirect immunofluorescence assays indicate that Hsp90 interacts with VP5. Interestingly, Hsp70, a collaborator of Hsp90, also interacts with VP5, but doesn't affect PRV growth. Finally, inhibition of Hsp90 results in PRV VP5 degradation in a proteasome-dependent manner. Collectively, our data suggest that Hsp90 contributes to PRV virion assembly and replication via stabilization of VP5.

To elucidate the regulation of serotonin transporter (SERT) function via its membrane trafficking, we investigated the involvement of the ubiquitin E3 ligase HRD1 (HMG-CoA reductase degradation protein), which participates in endoplasmic reticulum (ER)-associated degradation (ERAD), in the functional regulation of SERT. Cells transiently expressing wild-type SERT or a SERT C-terminal deletion mutant (SERTΔCT), a SERT protein predicted to be misfolded, were used for experiments. Studies using HRD1-overexpressing or HRD1-knockdown cells demonstrated that HRD1 is involved in SERT proteolysis. Overexpression of HRD1 promoted SERT ubiquitination, the effect of which was augmented by treatment with the proteasome inhibitor MG132. Immunoprecipitation studies revealed that HRD1 interacts with SERT in the presence of MG132. In addition, HRD1 was intracellularly colocalized with SERT, especially with aggregates of SERTΔCT in the ER. HRD1 also affected SERT uptake activity in accordance with the expression levels of the SERT protein. These results suggest that HRD1 contributes to the membrane trafficking and functional regulation of SERT through its involvement in ERAD-mediated SERT degradation.

We aimed to develop a deep learning algorithm detecting 10 common abnormalities (DLAD-10) on chest radiographs, and to evaluate its impact in diagnostic accuracy, timeliness of reporting and workflow efficacy.DLAD-10 was trained with 146 717 radiographs from 108 053 patients using a ResNet34-based neural network with lesion-specific channels for 10 common radiological abnormalities (pneumothorax, mediastinal widening, pneumoperitoneum, nodule/mass, consolidation, pleural effusion, linear atelectasis, fibrosis, calcification and cardiomegaly). For external validation, the performance of DLAD-10 on a same-day computed tomography (CT)-confirmed dataset (normal:abnormal 53:147) and an open-source dataset (PadChest; normal:abnormal 339:334) was compared with that of three radiologists. Separate simulated reading tests were conducted on another dataset adjusted to real-world disease prevalence in the emergency department, consisting of four critical, 52 urgent and 146 nonurgent cases. Six radiologists participated in the simulated reading sessions with and without DLAD-10.DLAD-10 exhibited area under the receiver operating characteristic curve values of 0.895-1.00 in the CT-confirmed dataset and 0.913-0.997 in the PadChest dataset. DLAD-10 correctly classified significantly more critical abnormalities (95.0% (57/60)) than pooled radiologists (84.4% (152/180); p=0.01). In simulated reading tests for emergency department patients, pooled readers detected significantly more critical (70.8% (17/24) versus 29.2% (7/24); p=0.006) and urgent (82.7% (258/312) versus 78.2% (244/312); p=0.04) abnormalities when aided by DLAD-10. DLAD-10 assistance shortened the mean±sd time-to-report critical and urgent radiographs (640.5±466.3 versus 3371.0±1352.5 s and 1840.3±1141.1 versus 2127.1±1468.2 s, respectively; all p<0.01) and reduced the mean±sd interpretation time (20.5±22.8 versus 23.5±23.7 s; p<0.001).DLAD-10 showed excellent performance, improving radiologists' performance and shortening the reporting time for critical and urgent cases.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal disease caused by defective production of the enzyme α-N-acetylglucosaminidase. It is characterized by severe and complex central nervous system degeneration. Effective therapies will likely target early onset disease and overcome the blood-brain barrier. Modifications of adeno-associated viral (AAV) vector capsids that enhance transduction efficiency have been described in the retina. Herein, we describe for the first time, a transduction assessment of two intracranially administered adeno-associated virus serotype 8 variants, in which specific surface-exposed tyrosine (Y) and threonine (T) residues were substituted with phenylalanine (F) and valine (V) residues, respectively. A double-mutant (Y444 + 733F) and a triple-mutant (Y444 + 733F + T494V) AAV8 were evaluated for their efficacy for the potential treatment of MPS IIIB in a neonatal setting. We evaluated biodistribution and transduction profiles of both variants compared to the unmodified parental AAV8, and assessed whether the method of vector administration would modulate their utility. Vectors were administered through four intracranial routes: six sites (IC6), thalamic (T), intracerebroventricular, and ventral tegmental area into neonatal mice. Overall, we conclude that the IC6 method resulted in the widest biodistribution within the brain. Noteworthy, we demonstrate that GFP intensity was significantly more robust with AAV8 (double Y-F + T-V) compared to AAV8 (double Y-F). This provides proof of concept for the enhanced utility of IC6 administration of the capsid modified AAV8 (double Y-F + T-V) as a valid therapeutic approach for the treatment of MPS IIIB, with further implications for other monogenic diseases.

Identification of small molecules in a biological sample remains a major bottleneck in molecular biology, despite a decade of rapid development of computational approaches for predicting molecular structures using mass spectrometry (MS) data. Recently, there has been increasing interest in utilizing other information sources, such as liquid chromatography (LC) retention time (RT), to improve identifications solely based on MS information, such as precursor mass-per-charge and tandem mass spectrometry (MS2).

This study seeks to dissect the basic factors that can elucidate the efficiency and innovation in biomass utilization to control carbon dioxide (CO2) emission and economic growth nexus particularly at the time that the worldwide CO2 emission is at an all-time high and COVID-19 is ravaging the word. We use data principally from the World Bank Indicators covering the period 1990-2016 to study the nexus among biomass utilization, economic growth, and CO2 emission based on the moderating role of biotechnology in China. On the basis of the results of our preliminary tests, we apply the autoregressive distributed lag (ARDL) for this analysis and employ the nonlinear autoregressive distributed lag (NARDL) as a robust check and also deploy the vector error correction model (VECM) to determine the direction of causality. We find that long-run relationship exists among the factors in this study. We additionally find that biotechnology has a critical but negative relationship with CO2 emission in China. Through hierarchical multiple regression analysis and PROCESS macro for mediation, moderation, and conditional process, we establish that biotechnology significantly moderates the relationship between biomass utilization and CO2 emission in China. Again, we discover that biomass utilization significantly decreases CO2 emission in China. Through the ARDL, NARDL, and VECM, we find empirical support for the growth hypothesis in China. We conduct a series of diagnostic tests that prove the robustness of our estimates. Based on our empirical evidence, this study recommends that China seeks sustainable economic development and environmental sustainability simultaneously by prioritizing biomass utilization and biotechnological innovation in the country.

Two cases of myopericytosis combined with pericytoma originating within the lung are reported. These are rare pulmonary tumors. The differential diagnosis for hemangiopericytoma and pericytic tumors with glomus elements is discussed. Both myopericytic lesions mimic other lesions, which are more commonly seen in the lung. Based on the expression of vascular growth factor receptors 2 and 3, an antiangiogenic therapy was suggested for the patient with the myopericytoma. A treatment with an angiogenesis inhibitor resulted in a regression of the tumor, but not the precursor lesion. Probably a more specific therapy using tyrosine kinase inhibitors for VEGFR2/3 might better control these myopericytic proliferations.

Apatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced gastric cancer. There was a tendency for patients with lymph node metastasis to have prolonged median progression-free survival and median overall survival, compared with patients with liver metastasis.