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The tremendous personal and economic burden worldwide caused by low back pain (LBP) has been surging in recent years. While intervertebral disc degeneration (IVDD) is the leading cause of LBP and vast efforts have been made to develop effective therapies, this problem is far from being resolved, as most treatments, such as painkillers and surgeries, mainly focus on relieving the symptoms rather than reversing the cause of IVDD. However, as stem/progenitor cells possess the potential to regenerate IVD, a deeper understanding of the early development and role of these cells could help to improve the effectiveness of stem/progenitor cell therapy in treating LBP. Single-cell RNA sequencing results provide fresh insights into the heterogeneity and development patterns of IVD progenitors; additionally, we compare mesenchymal stromal cells and IVD progenitors to provide a clearer view of the optimal cell source proposed for IVD regeneration. [ABSTRACT FROM AUTHOR]

In recent years, 4D printing has gained increasing attention in the tissue engineering field since this advanced manufacturing platform can create stimulus-responsive structures, which can change their shapes, functions, and/or properties when appropriate external stimulus/stimuli is/are applied. A number of hydrogels with swellable/shrinkable abilities have been explored for 4D printing to fabricate different shape-morphing structures for tissue engineering. Among them, gelatin methacryloyl (GelMA) has been 4D printed, which can self-fold into microtubular structures. Currently, the self-folding ability of 4D printed GelMA hydrogels is mainly based on the different cross-linking degrees (which control and govern the swelling degrees) across the thickness of hydrogels. However, this strategy alone can only form self-folding GelMA tubes with diameters at the micrometer level and cannot create self-folding GelMA tubes with diameters at the millimeter level, which is mainly due to the insufficient internal force generated in 4D printed GelMA hydrogels when they are exposed to water. To overcome this limitation, this study has investigated a new strategy to fabricate self-folding GelMA tubes with large diameters at the millimeter level for tissue engineering applications. The new strategy introduced a cross-linking degree gradient across the GelMA plane in addition to its thickness by printing a second layer of strips on the first 4D printed GelMA film. In the aqueous environment, under the current fabrication condition, such bilayer GelMA hydrogels could self-fold into tubes of larger diameters up to 6 mm. The in vitro release behavior of heparin incorporated into the 4D printed GelMA was also studied. It was shown that heparin release could be controlled by the GelMA concentration and heparin content in 4D printed GelMA. The 4D printed GelMA hydrogels with the improved self-folding ability and controlled release of a drug are promising for targeted tissue engineering applications. [ABSTRACT FROM AUTHOR]

Textile‐based generators that can convert low‐grade energy from the human body or environment into sustainable electricity have generated immense scientific interest in self‐powered wearable applications. However, their low power density and environmental suitability have extremely restricted their portable applications in complex and mutable environments. Herein, an asymmetric sandwich structure between molybdenum disulfide (MoS2)‐carbonized silks (MCs) and MoS2/MXene–Cottons (MMCs) to construct efficient thermo–hydroelectric generators (THEGs) that synergistically harvest heat‐moisture energy to generate considerable electricity is rationally designed. Notably, the large surface area of MoS2/MXene van der Waals heterojunctions (vdWhs) enables efficient charge collection, and the vertical MoS2 nanosheet arrays supply abundant nanochannels for a highly efficient hydration effect, generating an output power density of 32.26 µW cm−2 after wetting with deionized water. Combined with the sensitive temperature recognition ability with a Seebeck coefficient of 23.5 µV K−1, the application possibilities of these prepared THEGs in the mutual conversion of fingertip temperature/language, and the monitoring of the human physiological state is foresee. [ABSTRACT FROM AUTHOR]

Mitogen‐activated protein kinases (MPKs) play essential roles in guard cell signaling, but whether MPK cascades participate in guard cell ethylene signaling and interact with hydrogen peroxide (H2O2), nitric oxide (NO), and ethylene‐signaling components remain unclear. Here, we report that ethylene activated MPK3 and MPK6 in the leaves of wild‐type Arabidopsis thaliana as well as ethylene insensitive2 (ein2), ein3, nitrate reductase1 (nia1), and nia2 mutants, but this effect was impaired in ethylene response1 (etr1), nicotinamide adenine dinucleotide phosphate oxidase AtrbohF, mpk kinase1 (mkk1), and mkk3 mutants. By contrast, the constitutive triple response1 (ctr1) mutant had constitutively active MPK3 and MPK6. Yeast two‐hybrid, bimolecular fluorescence complementation, and pull‐down assays indicated that MPK3 and MPK6 physically interacted with MKK1, MKK3, and the C‐terminal region of EIN2 (EIN2 CEND). mkk1, mkk3, mpk3, and mpk6 mutants had typical levels of ethylene‐induced H2O2 generation but impaired ethylene‐induced EIN2 CEND cleavage and nuclear translocation, EIN3 protein accumulation, NO production in guard cells, and stomatal closure. These results show that the MKK1/3–MPK3/6 cascade mediates ethylene‐induced stomatal closure by functioning downstream of ETR1, CTR1, and H2O2 to interact with EIN2, thereby promoting EIN3 accumulation and EIN3‐dependent NO production in guard cells. [ABSTRACT FROM AUTHOR]

Background: Stroke carries a poor long-term prognosis for death and disability. There are few acute treatments that reduce death and disability after stroke. The ongoing international, multicenter, randomized, placebo-controlled, double-blind CHIMES trial is currently testing the hypothesis that a 3-month course of the traditional Chinese medicine MLC601 (NeuroAiD) is superior to placebo in reducing neurological deficit and improving functional outcome after acute ischemic stroke in patients receiving standard stroke care. This extension study tests the hypothesis that at 2 years, an initial 3-month administration of NeuroAiD is superior to placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction of an intermediate range of severity. Methods: Study subjects will be those who are already participants in CHIMES - aged above 21 years, had signs and symptoms of acute stroke, 6 ≤ NIHSS ≤ 14, neuroimaging consistent with ischemic stroke, and received study medication within 72 h of stroke onset. A subject will not be eligible for inclusion in CHIMES-E if they have withdrawn consent from all participation and follow-up for CHIMES. Subjects will be contacted at 6, 12, 18 and 24 months after CHIMES enrolment. After verbal consent is obtained, subjects will be assessed for functional state by the modified Rankin scale (mRS) and Barthel Index (BI), and a history of recurrent vascular events as well as medical events. The primary outcome measure will be the mRS at month 24. Secondary outcome measures will be mRS and BI at 6, 12 and 18 months, and BI at 24 months. Analysis will be based on the intention-to-treat principle. If the number of patients lost to follow-up is substantial, a sensitivity analysis based on the last observation carried forward method will be carried out, to compare the results with those from the main analysis without imputation. Based on a cumulative odds ratio of 1.5 for the NeuroAiD group, a two-sided test of 5% type I error and an expected 30% dropout rate after 2 years of follow-up for the 1,100 patients recruited into CHIMES, the 770 subjects with mRS data expected to be available at year 2 yields an 89% power to detect a difference in efficacy between NeuroAiD and placebo. Conclusions: This study will provide evidence for the longer-term efficacy of an initial course of a neurorestorative therapy after acute ischemic stroke of intermediate severity. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]