Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but ...cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.
To study the formation mechanism of rainfall‐induced soil erosion, collapse and landslides in the Loess Plateau based on the unsaturated soil seepage theory and the effective stress principle, the ...failure process of collapse with cracks under heavy and long‐term rainfall was investigated using the finite element method. The results showed that under the action of heavy rain, surface run‐off quickly gathered in cracks to form a dominant flow, resulting in a rapid increase in the water level and hydrostatic pressure in the cracks. The strength of the soil at the tip of the crack decreased rapidly under the softening effect of the water, and tensile failure occurred. The crack accelerated downward to the foot of the slope, causing the steep slope to collapse. Long‐term rainfall acts directly on the soil near the crack, resulting in faster saturation than the soil inside the slope body. When the rainfall time exceeded a certain value, the soil near the crack reached a saturated state, and the soil strength was minimized. Simultaneously, the seepage force generated when rainwater inside the collapsed body seeps from its outer edge increases the overturning moment of the collapsed body. Under the continuous action of rainfall, the cracks gradually extended to the foot of the slope, causing the collapsed body to fail. These research results provide a theoretical basis for the prevention and control of land degradation and collapse disasters on the Loess Plateau.
Tension cracks with different development degrees are widely found at the rear edge of loess collapse. Rainwater can flow along the cracks and form a dominant flow, forming water pressure inside the cracks, which makes the cracks extend downward and further reduces the stability of the collapse body. Unstable collapses not only affect the grain planting and producing but also lead to geological disasters and even threaten the safety of people's lives and property.
Key message
This study revealed that the Arabidopsis UGT75B1 plays an important role in modulating ABA activity by glycosylation when confronting stress environments.
The cellular ABA content and ...activity can be tightly controlled in several ways, one of which is glycosylation by family 1 UDP-glycosyltransferases (UGTs). Previous analysis has shown UGT75B1 activity towards ABA in vitro. However, the biological role of UGT75B1 remains to be elucidated. Here, we characterized the function of UGT75B1 in abiotic stress responses via ABA glycosylation. GUS assay and qRT-PCR indicated that
UGT75B1
is significantly upregulated by adverse conditions, such as osmotic stress, salinity and ABA. Overexpression of
UGT75B1
in Arabidopsis leads to higher seed germination rates and seedling greening rates upon exposure to salt and osmotic stresses. In contrast, the big
UGT75B1
overexpression plants are more sensitive under salt and osmotic stresses. Additionally, the
UGT75B1
overexpression plants showed larger stomatal aperture and more water loss under drought condition, which can be explained by lower ABA levels examined in
UGT75B1
OE plants in response to water deficit conditions. Consistently,
UGT75B1
ectopic expression leads to downregulation of many ABA-responsive genes under stress conditions, including
ABI3, ABI5
newly germinated seedlings and
RD29A
,
KIN1
,
AIL1
in big plants. In summary, our results revealed that the Arabidopsis UGT75B1 plays an important role in coping with abiotic stresses via glycosylation of ABA.
Conservative and nonconservative treatments are available for keloids. However, few studies have explored the effectiveness of punch excision in keloid treatment.
This study aimed to investigate the ...efficacy and safety of punch excision combined with intralesional steroid injection for keloid treatment.
In this prospective, randomized, controlled trial, 81 patients were randomly divided into 2 groups. The patients in the treatment group were initially treated with punch excision combined with intralesional steroid injection, followed by injection treatment alone. The patients in the control group received intralesional steroid injection alone. The keloid thickness before and after the punch excision was evaluated; the keloid scores at different time points and the number of injection treatments required in both groups were compared, and adverse reactions were observed.
The mean thickness after punch excision was lower (p < .05), injection treatments were fewer (p < .05), keloid scores were significantly lower (p < .05), and incidence rate of long-term adverse effects was lower in the treatment group than in the control group (p < .05).
The combination of punch excision and intralesional steroid injection has a notable therapeutic effect on keloids, shortening the treatment course without evident adverse reactions.
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•Serum PFCAs (C8-C10) declined with the increasing distance from the fluorochemical industrial plant.•The source of PFCAs in soil (C5-C9) and serum (C8-C10) was the fluorochemical ...industrial plant.•There is a potential health risk for some teenagers with high serum concentrations of PFOA.
Discharges released from fluorochemical industrial plants lead to severe contamination of the environment with per- and polyfluoroalkyl substances (PFASs), which may pose risks to human health. In this study, 187 serum samples from teenagers (age = 14 years), 22 tap water samples and 40 soil samples were collected in areas within 0–11 km of a fluorochemical industrial plant in Huantai County, Shandong Province, and concentrations of 18 PFASs were quantified by UPLC-MS/MS. Perfluorooctanoic acid (PFOA) was found to be predominant, concentrations of which ranged from 40.4 to 845 ng/mL in serum, from 2.88 to 19.3 ng/L in tap water, from 4.40 to 189 ng/g in soil, and accounting for 84.1–98.6%, 15.9–79.8%, and 73.8–96.7% of the total PFASs, respectively. Statistical analysis demonstrated that concentrations of perfluorinated carboxylic acids (PFCAs) in soil (C5-C9) and serum (C8-C10) were associated with the industrial plant. And PFOA concentrations in tap water were not relevant to the industrial plant, which were comparable with the non-contaminated area and lower than the threshold value recommended by U.S. EPA (70 ng/mL), indicating that the contribution to the high concentration of serum PFOA of local teenagers by drinking water was limited. Moreover, PFCAs in soil only made a limited contribution to the serum PFCAs of local residents by direct inhalation and dermal exposure, but the potential health risk by the soil via food chain should be paid attention to. Furthermore, health risk assessment demonstrated that high concentrations of PFOA in serum could pose potential health risk to local teenagers. Therefore, effective measures should be taken to attenuate the health risks caused by the industrial plant to local residents, and further epidemiological studies should be carried out in the future.
Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has ...been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis.
Herein, we have prepared a new donut-like metal-organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers.
Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.
Snail is a master inducer of epithelial-mesenchymal transition (EMT) and metastasis, however, Snail protein is labile and is quickly degraded through the predominate ubiquitination-mediated ...proteasome pathway. Deubiquitinases (DUBs) can counteract the Snail degradation process to maintain high level of Snail protein in cancer cells. In this study, we screened a cDNA library containing 79 DUBs, and discovered that a panel of DUBs consisting of USP13, USP28, USP29, USP37, OTUD6A, and DUB3 can markedly stabilize Snail protein, with USP29 displaying the strongest activity to prevent Snail degradation. Mechanistically, USP29 enhances the interaction of Snail and SCP1, resulting in simultaneous dephosphorylation and deubiquitination of Snail and thereafter cooperative prevention of Snail degradation. Biologically, ectopic expression of USP29 promotes gastric cancer cell migration, and depletion of Snail abolishes USP29-mediated cell migration; and USP29 can be induced by major EMT and metastatic inducing factors such as TGFβ, TNFα, and hypoxia. More importantly, high expression levels of Snail, USP29, and SCP1 are associated with poor survival and prognosis. Collectively, these data indicate that Snail is a crucial substrate for USP29 to promote cell migration and USP29/SCP1 complex may be new therapeutic targets to treat metastatic cancer.
Metabolic associated fatty liver disease (MAFLD) due to excess weight and obesity threatens public health worldwide. Gut microbiota dysbiosis contributes to obesity and related diseases. The ...cholesterol-lowering, anti-inflammatory, and antioxidant effects of wild rice have been reported in several studies; however, whether it has beneficial effects on the gut microbiota is unknown. Here, we show that wild rice reduces body weight, liver steatosis, and low-grade inflammation, and improves insulin resistance in high-fat diet (HFD)-fed mice. High-throughput 16S rRNA pyrosequencing demonstrated that wild rice treatment significantly changed the gut microbiota composition in mice fed an HFD. The richness and diversity of the gut microbiota were notably decreased upon wild rice consumption. Compared with a normal chow diet (NCD), HFD feeding altered 117 operational taxonomic units (OTUs), and wild rice supplementation reversed 90 OTUs to the configuration in the NCD group. Overall, our results suggest that wild rice may be used as a probiotic agent to reverse HFD-induced MAFLD through the modulation of the gut microbiota.
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