There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with ...exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.
Increasing evidence suggests the heterogeneity of macrophage phenotype and function ultimately determines the outcome of diabetic nephropathy (DN). This study aimed to investigate the effects of ...vitamin D on macrophage M1/M2 phenotype and its role in preventing podocyte impairment in streptozotocin-induced DN rats. Calcitriol, a bioactive 1,25-dihydroxyvitamin D3, ameliorated proteinuria and renal damage as well as reversed the decline of both nephrin and podocin, crucial structural proteins in podocytes. DN rats showed increased infiltrating macrophages with M1 phenotype characterized by elevated expression of inducible nitric oxide synthase and TNF-α in glomeruli and interstitium, which were inhibited after calcitriol treatment. Interestingly, calcitriol promoted M2 macrophage activation with enhanced expression of CD163, arginase-1, and mannose receptor at week 18 but not at week 8 or 14. The ratio of CD163 to CD68, considered as the proportion of M2 macrophages, was about 2.9-fold higher at week 18 after calcitriol treatment. Furthermore, the protein expression of inducible nitric oxide synthase, a crucial marker of M1 macrophages, was negatively correlated with the expression of either nephrin or podocin, whereas CD163, indicating M2 macrophages, was positively correlated. In vitro, 1,25-dihydroxyvitamin D3 switched high-glucose–induced M1 macrophages toward an M2 phenotype in either U937-derived macrophages or RAW264.7 cells. Our results suggest that vitamin D not only reduces macrophage infiltration and inhibits M1 macrophage activation but also enhances M2 macrophage phenotype to protect against podocyte injury.
The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with ...antiphospholipid syndrome (APS) and seronegative APS (SNAPS).
One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus SLE, 29 Sjogren's syndrome SS, 30 ankylosing spondylitis AS, 38 rheumatoid arthritis RA) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-β2-glycoprotein I (anti-β2GPI) antibodies were tested by ELISA.
One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio OR=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (p<0.001). When both were positive, the OR for APS was 101.6. Notably, 91.95% (80/87) of LAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available.
Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.
Dry reforming of methane (DRM), which involves the activation of inert CH bonds and CO bonds, at mild conditions is a tremendous challenge. The sluggish mobility of oxygen during the reaction is ...known as a key issue causing low activity and poor stability of catalysts by the coke formation. Herein, a novel Cu‐CNN/Pd‐BDCNN photocatalyst that is made up of “Cu‐nanoparticle‐loaded g‐C3N4 nanosheets” and “Pd‐nanoparticle‐loaded boron‐doped nitrogen‐deficient g‐C3N4 nanosheets” is reported. The existing dual‐reaction‐sites benefit the reactive oxygen intermediates participate in the reaction directly without distant migration. The in situ characterizations and density functional theory calculations reveal a newly dual reaction pathway through simultaneous dehydrogenation of methoxy and methyl intermediates, and demonstrate the importance of metal loading, which promote the CO2 and CH4 activation from both aspects of thermodynamics and kinetics. The optimized Cu‐CNN/Pd‐BDCNN photocatalyst displays an excellent syngas formation rate of over 800 µmol g−1 h−1 with H2/CO = 1 and splendid stability in continuous flow reaction under 300 mW cm−2 xenon lamp irradiation at room temperature. The “dual‐site” and “dual‐path” strategy shed light on the design of effective photocatalysts for methane dry reforming.
Dry reforming of methane (DRM) reaction occurs at two sites and presents two reaction pathways over the catalyst. The dual‐reaction‐site and dual‐path process not only achieves high catalytic activity, stability and syngas selectivity, but also overcomes the problems arising from poor oxygen migration on non‐oxygen‐containing catalysts. The strategy of dual reaction sites provides mechanistic insights for rational design of DRM catalysts.
Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only ...US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA is currently used in less than 5% of stroke patients. Natural compounds have been widely used in the treatment of IS in China and have a wide range of therapeutic effects on IS by regulating multiple targets and signaling pathways. The keywords "ischemia stroke, traditional Chinese Medicine, Chinese herbal medicine, natural compounds" were used to search the relevant literature in PubMed and other databases over the past five years. The results showed that JAK/STAT, NF-κB, MAPK, Notch, Nrf2, and PI3K/Akt are the key pathways, and SIRT1, MMP9, TLR4, HIF-α are the key targets for the natural compounds from traditional Chinese medicine in treating IS. This study aims to update and summarize the signaling pathways and targets of natural compounds in the treatment of IS, and provide a base of information for the future development of effective treatments for IS.
Questions
Anthropogenic climate change has become a critical environmental problem and is profoundly affecting various ecosystems, especially desert ecosystems. However, very few studies have ...explored the effects of extreme precipitation on the community structure and ecosystem functions in drylands. Moreover, whether local microtopography will interact with extreme precipitation on plant growth by changing water retention and other processes is still unclear.
Location
The Gurbantunggut Desert in Central Asia.
Methods
We conducted a two‐year field experiment to assess the effect of extreme precipitation (+65% of ambient growing‐season precipitation amounts) on the composition and productivity of a desert ephemeral plant community growing in sand dunes of the Gurbantunggut Desert in Central Asia. We further determined how much slope position modulates this response.
Results
We found that the cover, density, height, species richness, and biomass of ephemeral plants increased with an increase in precipitation, and the strongest direct effect of biomass was a positive effect on density of ephemeral plants. Additionally, no significant differences in the sensitivity of biomass to the increased precipitation were found between slope positions.
Conclusions
The results indicate that extreme precipitation primarily increased the above‐ground net primary production by increasing the density, rather than the height and species richness, of the ephemeral community; no interactive effects were observed between sand dune slope positions and the sensitivity of biomass to the extreme precipitation treatment.
Extreme precipitation significantly increased the species richness and biomass of a desert ephemeral plant community growing in sand dunes of the Gurbantunggut Desert in Central Asia, but the proportion of biomass for dominant species remained unchanged. There were no significant differences in the sensitivity of biomass to the increased precipitation between western and eastern aspect.
Selective condensation/bicycloaromatization of two different arylalkynes is firstly developed under ligand-free copper(
i
)-catalysis, which allows the direct synthesis of C-N axial biaryl compounds ...in high yields with excellent selectivity and functional group tolerance. Due to the critical effects of Cu(
i
) catalyst and HFIP, many easily occurring undesired reactions are suppressed, and the coupled five-six aromatic rings are constructed
via
the selective formation of two C(sp
2
)-N(sp
2
) bonds and four C(sp
2
)-C(sp
2
) bonds. The achievement of moderate enantioselectivity verifies its potential for the simplest asymmetric synthesis of atropoisomeric biaryls. Western blotting demonstrated that the newly developed compounds are promising targets in biology and pharmaceuticals. This unique reaction can construct structurally diverse C-N axial biaryl compounds that have never been reported by other methods, and might be extended to various applications in materials, chemistry, biology, and pharmaceuticals.
Selective condensation/bicycloaromatization of two different arylalkynes is firstly developed under ligand-free copper(
i
)-catalysis, which allows the direct synthesis of C-N axial biaryl compounds in high yields with excellent selectivity and functional group tolerance.
The atom‐economic and one‐pot regio‐ and stereoselective addition of sodium arenesulfinates to either alkynes or alkenes can be achieved with an iron(III) chloride hexahydrate FeCl3⋅6 H2O catalytic ...system to afford β‐haloalkenyl and β‐chloroalkyl sulfones in moderate to good yields.
A copper‐catalyzed aerobic oxidative amidation reaction of inert CC bonds with tertiary amines has been developed for the synthesis of tertiary amides, which are significant units in many natural ...products, pharmaceuticals, and fine chemicals. This method combines CC bond activation, CN bond cleavage, and CH bond oxygenation in a one‐pot protocol, using molecular oxygen as the sole oxidant without any additional ligands.
All in one pot! A novel copper‐catalyzed aerobic oxidative amidation reaction of inert CC bonds with tertiary amines has been developed for the synthesis of tertiary amides (see scheme). This method successfully combines CC bond activation, CN bond cleavage, and CH bond oxygenation in one pot using molecular oxygen as the sole oxidant without any additional ligands.
Developing new pharmaceuticals is a costly and time-consuming endeavor fraught with significant safety risks. A critical aspect of drug research and disease therapy is discerning the existence of ...interactions between drugs and proteins. The evolution of deep learning (DL) in computer science has been remarkably aided in this regard in recent years. Yet, two challenges remain: (i) balancing the extraction of profound, local cohesive characteristics while warding off gradient disappearance and (ii) globally representing and understanding the interactions between the drug and target local attributes, which is vital for delivering molecular level insights indispensable to drug development. In response to these challenges, we propose a DL network structure, MolLoG, primarily comprising two modules: local feature encoders (LFE) and global interactive learning (GIL). Within the LFE module, graph convolution networks and leap blocks capture the local features of drug and protein molecules, respectively. The GIL module enables the efficient amalgamation of feature information, facilitating the global learning of feature structural semantics and procuring multihead attention weights for abstract features stemming from two modalities, providing biologically pertinent explanations for black-box results. Finally, predictive outcomes are achieved by decoding the unified representation via a multilayer perceptron. Our experimental analysis reveals that MolLoG outperforms several cutting-edge baselines across four data sets, delivering superior overall performance and providing satisfactory results when elucidating various facets of drug–target interaction predictions.
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