Appropriate autophagy has protective effects on ischemic nerve tissue, while excessive autophagy may cause cell death. The inflammatory response plays an important role in the survival of nerve cells ...and the recovery of neural tissue after ischemia. Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke. This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows. (1) Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR, the AMPK pathway, and inhibition of inflammasome activation. (2) Activation of inflammation triggers the formation of autophagosomes, and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1. Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK, reducing the flux and autophagy level, thereby inducing inflammatory activity. (3) By blocking the activation of autophagy, the activation of inflammasomes can alleviate cerebral ischemic injury. Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway, which is beneficial to the recovery of neural tissue after ischemia. Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway. These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.
3D bioprinting technology provides programmable and customizable platforms to engineer cell‐laden constructs mimicking human tissues for a wide range of biomedical applications. However, the ...encapsulated cells are often restricted in spreading and proliferation by dense biomaterial networks from gelation of bioinks. Herein, a cell‐benign approach is reported to directly bioprint porous‐structured hydrogel constructs by using an aqueous two‐phase emulsion bioink. The bioink, which contains two immiscible aqueous phases of cell/gelatin methacryloyl (GelMA) mixture and poly(ethylene oxide) (PEO), is photocrosslinked to fabricate predesigned cell‐laden hydrogel constructs by extrusion bioprinting or digital micromirror device‐based stereolithographic bioprinting. The porous structure of the 3D‐bioprinted hydrogel construct is formed by subsequently removing the PEO phase from the photocrosslinked GelMA hydrogel. Three different cell types (human hepatocellular carcinoma cells, human umbilical vein endothelial cells, and NIH/3T3 mouse embryonic fibroblasts) within the 3D‐bioprinted porous hydrogel patterns show enhanced cell viability, spreading, and proliferation compared to the standard (i.e., nonporous) hydrogel constructs. The 3D bioprinting strategy is believed to provide a robust and versatile platform to engineer porous‐structured tissue constructs and their models for a variety of applications in tissue engineering, regenerative medicine, drug development, and personalized therapeutics.
An aqueous two‐phase emulsion bioink is developed to create bioprinted porous‐structured hydrogel constructs. Interconnected micropores within the bioprinted hydrogel constructs enhance the growth, spreading, and proliferation of encapsulated living cells.
Objective To assess the associations of the Assessment of Spondyloarthritis International Society Health Index (ASAS HI) with gender and other factors in patients with ankylosing spondylitis (AS). ...Methods From November 2017 to October 2018, we measured the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and the ASAS HI score for AS patients at the Taichung Veterans General Hospital. After adjusting for disease activity (ASDAS-erythrocyte sedimentation rate ESR, ASDAS- C-reactive protein CRP, BASDAI+ESR or BASDAI+CRP), mSASSS and other potential confounders including medications, comorbidities, and laboratory data, any associations between gender and the sum score of ASDAS HI were assessed using multiple linear regression analysis, as well as any associations between gender and an ASAS HI score >5 using multivariable logistic regression analysis. Results A total of 307 AS patients (62 20.2% females, mean age 46.4 years S.D. 13.3, mean symptom duration 20.6 years S.D. 12.1) were included. Multiple linear regression analysis showed that the male gender was significantly associated with a lower ASAS HI (B = -1. 91, 95% confidence interval CI, -2.82--1.00, p 5 than females (odds ratio = 0.15, 95% CI, 0.07-0.36, p 0.001). Disease activity measures, including ASDAS-ESR, ASDAS-CRP and BASDAI, had positive correlations with ASAS HI. Conclusion This single-center, cross-sectional study revealed that a higher ASAS HI score was significantly associated with female gender and higher disease activity measures.
Fast charging of lithium ion batteries is essential for next‐generation energy‐storage systems. However, the poor ionic and electronic transport of anodes with its rather high mass loading limits the ...practical applications of this technology. Herein, a multiscale design from niobium titanium oxide anode material to electrode structure is proposed for fast charging lithium ion batteries with a practical level of areal capacity (3 mAh cm−2). At the atomic scale, the introduction of oxygen vacancy and surface carbon coating enables niobium titanium oxide (TiNb2O7−x@C) to possess excellent ionic and electronic conductivity. For the microscopic electrode structure, 1D TiNb2O7−x@C fibers are tightly assembled to form a high‐speed transport network of ions and electrons throughout the electrode. As a result, the obtained TiNb2O7−x@C electrode shows excellent rate capability (1.83 mAh cm−2 at 1 C) and cycling stability under an areal capacity of 3 mAh cm−2 (2.35 mAh cm−2 after 100 cycles at 0.5 C) in half‐cells. Significantly, a full‐cell coupled with practical level mass loading of lithium cobalt oxide cathode is demonstrated to deliver 1.55 mAh cm−2 at 3 C for the first time.
A multiscale electrode design strategy is reported to achieve fast ionic and electronic transport for improving the electrochemical performance of TiNb2O7 electrodes at high mass loading (>11 mg cm−2). Moreover, a TiNb2O7–x@C/LiCoO2 full‐cell with practical level mass loading is fabricated, which displays excellent fast‐charging performance.
Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly ...lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.
The commercial ceramic nanoparticle coated microporous polyolefin separators used in lithium batteries are still vulnerable under external impact, which may cause short circuits and consequently ...severe safety threats, because the protective ceramic nanoparticle coating layers on the separators are intrinsically brittle. Here, a nacre‐inspired coating on the separator to improve the impact tolerance of lithium batteries is reported. Instead of a random structured ceramic nanoparticle layer, ion‐conductive porous multilayers consisting of highly oriented aragonite platelets are coated on the separator. The nacre‐inspired coating can sustain external impact by turning the violent localized stress into lower and more uniform stress due to the platelet sliding. A lithium‐metal pouch cell using the aragonite platelet coated separator exhibits good cycling stability under external shock, which is in sharp contrast to the fast short circuit of a lithium‐metal pouch cell using a commercial ceramic nanoparticle coated separator.
A nacre‐inspired coating is fabricated to improve the impact tolerance of the separator in a lithium battery via efficient energy dissipation. Remarkably, the pouch cell using the nacre‐inspired porous aragonite platelet coated separator performs with much lower instantaneous open‐circuit voltage change and faster voltage recovery than the cell using the commercial ceramic nanoparticle coated separator under external impaction.
Pulmonary inflammation, which is characterized by the presence of perivascular macrophages, has been proposed as a key pathogenic driver of pulmonary hypertension (PH), a vascular disease with ...increasing global significance. However, the mechanisms of expansion of lung macrophages and the role of blood-borne monocytes in PH are poorly understood. Using multicolor flow cytometric analysis of blood in mouse and rat models of PH and patients with PH, an increase in blood monocytes was observed. In parallel, lung tissue displayed increased chemokine transcript expression, including those responsible for monocyte recruitment, such as
and
, accompanied by an expansion of interstitial lung macrophages. These data indicate that blood monocytes are recruited to lung perivascular spaces and differentiate into inflammatory macrophages. Correspondingly, parabiosis between congenically different hypoxic mice demonstrated that most interstitial macrophages originated from blood monocytes. To define the actions of these cells in PH in vivo, we reduced blood monocyte numbers via genetic deficiency of
or
in chronically hypoxic male mice and by pharmacologic inhibition of Cx
cl1 in monocrotaline-exposed rats. Both models exhibited decreased inflammatory blood monocytes, as well as interstitial macrophages, leading to a substantial decrease in arteriolar remodeling but with a less robust hemodynamic effect. This study defines a direct mechanism by which interstitial macrophages expand in PH. It also demonstrates a pathway for pulmonary vascular remodeling in PH that depends upon interstitial macrophage-dependent inflammation yet is dissociated, at least in part, from hemodynamic consequences, thus offering guidance on future anti-inflammatory therapeutic strategies in this disease.
A visible‐light‐driven radical‐mediated strategy for the in situ generation of aza‐ortho‐quinone methides from 2‐vinyl‐substituted anilines and alkyl radical precursors is described. This process ...enables an efficient multicomponent reaction of 2‐vinylanilines, halides, and sulfur ylides, and has a wide substrate scope and good functional group tolerance. Treatment of the cycloaddition products with a base leads to densely functionalized indoles in a single‐flask operation.
Aza‐ortho‐quinone methides were generated in situ from 2‐vinyl‐substituted anilines and alkyl radical precursors in a visible‐light‐driven reaction. This process enables the multicomponent coupling of 2‐vinylanilines, alkyl halides, and sulfur ylides, and ultimately generates densely functionalized indoles in a single‐flask operation.
The plant vacuole is an important organelle for storing excess iron (Fe), though its contribution to increasing the Fe content in staple foods remains largely unexplored. In this study we report the ...isolation and functional characterization of two rice genes OsVIT1 and OsVIT2, orthologs of the Arabidopsis VIT1. Transient expression of OsVIT1:EGFP and OsVIT2:EGFP protein fusions revealed that OsVIT1 and OsVIT2 are localized to the vacuolar membrane. Ectopic expression of OsVIT1 and OsVIT2 partially rescued the Fe2+‐ and Zn2+‐sensitive phenotypes in yeast mutant Δccc1 and Δzrc1, and further increased vacuolar Fe2+, Zn2+ and Mn2+ accumulation. These data together suggest that OsVIT1 and OsVIT2 function to transport Fe2+, Zn2+ and Mn2+ across the tonoplast into vacuoles in yeast. In rice, OsVIT1 and OsVIT2 are highly expressed in flag leaf blade and sheath, respectively, and in contrast to OsVIT1, OsVIT2 is highly responsive to Fe treatments. Interestingly, functional disruption of OsVIT1 and OsVIT2 leads to increased Fe/Zn accumulation in rice seeds and a corresponding decrease in the source organ flag leaves, indicating an enhanced Fe/Zn translocation between source and sink organs, which might represent a novel strategy to biofortify Fe/Zn in staple foods.
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