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Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKCγ-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKCγ knockdown remarkably increased neuronal death after OGD. We also found that cPKCγ knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKCγ could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKCγ knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKCγ knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKCγ partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2’,3’-O-(2,4,6-trinitrophenyl)-adenosine 5’-triphosphate), a nonspecific P2X1–7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4–L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

Based on the tree-ring increment cores of基于阴山东部油松树轮样芯,建立采样区域树轮宽度年表,并计算器测时期(AD 1952—2007)月均温和月降水量与树轮宽度年表的相关系数。结果表明: 树轮宽度年表与上一年9月至当年6月降水量变化的相关性最高(

Objective(s): A2 adenosine receptor (A2AR) is a novel promising target for the treatment of inflammatory and allergic diseases. However, its role in the development of cow’s milk protein allergy (CMPA) has not been elucidated. The present study was designed to investigate the function of A2AR in CMPA development. Materials and Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic responses. The model was assessed by detecting allergic responses and plasma-specific IgE levels. The levels of A2AR were measured by PCR and flow cytometry. The subpopulation of Treg cells was analysed. Results: The mice sensitized and challenged with OVA showed classic allergic symptoms, such as acute allergic skin responses, increased anaphylactic shock symptom scores, and higher levels of total IgE, OVA-specific IgE, IgG1 and IgG2a. OVA-sensitized mice and CMPA patients showed decreased levels of A2AR and Treg cells. Interestingly, we observed a positive correlation between A2AR expression and Treg levels in CMPA patients. Further study showed that the A2AR agonist CGS21680 blocked OVA-induced allergic reactions, and the A2AR antagonist KW-6002 amplified allergic responses. Interestingly, CGS21680 not only activated the A2AR-mediated signalling pathway but also caused an increase in the population of Treg cells. In contrast, KW-6002 therapy decreased the levels of Tregs in allergic mice. Conclusion: A2AR expression is downregulated in CMPA. The A2AR-mediated pathway negatively regulates the development of CMPA, at least in part, by amplifying the differentiation of Tregs.

Pulmonary fibrosis (PF) is a difficult clinical condition with no effective treatment and a high mortality rate. Patients usually die of respiratory failure. In the present, we hypothesized that resveratrol (Res) could suppress bleomycin (BLM)-induced PF in rats and examined the detailed mechanism.The successfully established BLM-induced PF rat models and normal healthy rats were randomly assigned into the control, model, Res-low, Res-medium, and Res-high groups. The extent of PF in rats was determined by Masson and HE staining. ELISA was used to detect changes in the inflammatory factors IL-1β, IL-6, TNF-α, SOD, and GSH-PX in lung tissue. Microscopic lung fibrosis scoring was done using the Ashcroft scale. Western blotting and RT-qPCR assays were used to analyze the effects of Res on the epithelial-mesenchymal transition (EMT).The administration of Res ameliorated the BLM-induced PF in vivo. Res could inhibit pro-inflammatory factors and regulates oxidative stress levels. It also revealed that Res downregulated Vimentin and upregulated E-cadherin expression. Res inhibited fibrosis and inflammatory responses in rat lung tissue. The activation of the TLR4/NF-κB and TGF-β1/smad3 signaling pathways were inhibited following Res treatment.The present study suggested that Res may protect against BLM-induced PF by inhibiting the EMT and down-regulating the TLR4/NF-κB and TGF-β1/smad3 signaling pathways.

Flower-like ZnO microstructures were successfully produced using a hydrothermal method employing ZnSO4/(NH4)2SO4 as a raw material. The effect of the operating parameters of the hydrothermal temperature, OH−/Zn2+ molar ratio, time, and amount of dispersant on the phase structure and micromorphology of the ZnO particles were investigated. The synthesis conditions of the flower-like ZnO microstructures were: hydrothermal temperature of 160°C, OH−/Zn2+ molar ratio of 5:1, reaction time of 4 h, and 4 mL of dispersant. The flower-like ZnO microstructures were comprised of hexagon-shaped ZnO rods arranged in a radiatively. Degradation experiments of Rhodamine B with the flower-like ZnO microstructures demonstrated a degradation efficiency of 97.6% after 4 h of exposure to sunshine, indicating excellent photocatalytic capacity. The growth mechanism of the flower-like ZnO microstructures was presented.

An improved method of (NH4)2SO4 roasting followed by water leaching to utilize zinc oxidized ores was studied. The operating parameters were obtained by investigating the effects of the molar ratio of (NH4)2SO4 to zinc, roasting temperature, and holding time on zinc extraction. The roasting process followed the chemical reaction control mechanism with the apparent activation energy value of 41.74 kJ·mol−1. The transformation of mineral phases in roasting was identified by X-ray diffraction analysis combined with thermogravimetry-differential thermal analysis curves. The water leaching conditions, including the leaching temperature, leaching time, stirring velocity, and liquid-to-solid ratio, were discussed, and the leaching kinetics was studied. The reaction rate was obtained under outer diffusion without product layer control; the values of the apparent activation energy for two stages were 4.12 and 8.19 kJ·mol−1. The maximum zinc extraction ratio reached 96% while the efficiency of iron extraction was approximately 32% under appropriate conditions. This work offers an effective method for the comprehensive use of zinc oxidized ores.

NH4HCO3 conversion followed by HCl leaching was performed and proven to be effective in extracting Pb and Sr from zinc extracted residual. The mechanism and operating conditions of NH4HCO3 conversion, including molar ratio of NH4HCO3 to zinc extracted residual, NH4HCO3 concentration, conversion temperature, conversion time, and stirring velocity, were discussed, and operating conditions were optimized by the orthogonal test. Experimental results indicate that NH4HCO3 conversion at temperatures ranging from 25 to 85°C follows the shrinking unreacted core model and is controlled by inner diffusion through the product layer. The extraction ratios of Pb and Sr under optimized conditions reached 85.15% and 87.08%, respectively. Moreover, the apparent activation energies of Pb and Sr were 13.85 and 13.67 kJ·mol−1, respectively.

Employing zinc sulfate solution obtained from zinc oxide ore as raw material, sodium hydroxide as precipitant and PEG20000 as dispersant, ultrafine ZnO powders with different morphologies were successfully synthesized through hydrothermal method. The influences of the dosage of PEG20000 solution, molar ratio of OH−/Zn2+, reaction temperature, reaction time and Zn2+ concentration on the structures and morphologies of the ZnO powders were discussed in detail. The reaction conditions of synthesizing ZnO powders with flower-like structure were obtained as below: dosage of PEG20000 with 10% mass fraction 5 mL, molar ratio of OH− to Zn2+ 5, reaction temperature 150 °C, reaction time 8 h at Zn2+ concentration 1 mol L−1. The growth mechanism of ZnO particles with different morphologies was proposed. The ZnO powder with flower-like structure are composed of multiple micro-rods with hexagon morphology and has good photocatalytic degradation ability to degrade RhB. 20 mL RhB solution with 15 mg L−1 could be completely degraded over flower-like ZnO powder 300 mg within 3 h.

Although electrospinning of nanofibrous scaffolds benefit to wound healing have been developed at a fast pace, achieving nanofibrous scaffolds with high absorptivity by green electrospinning and crosslinking techniques is still a great challenge. Here, we developed a maleilated hyaluronate/methacrylated poly (vinyl alcohol) (MHA) (MaPVA) composite nanofibers by electrospinning from pure water solvent and followed by photopolymerization to form crosslinking nanofibers network. Electrospinnability of MHA/MaPVA blend systems were investigated and the results shows that the morphology and diameter of the nanofibers were mainly affected by MHA/MaPVA weight ratios by changing viscosity and conductivity of the blend solutions. The crystalline microstructure of the electrospun fibers was not well developed due to intermolecular hydrogen bonding interaction between the molecules of MHA and MaPVA. The photocrosslinking MHA/MaPVA nanofibrous mats can swell to form fibrous hydrogels with high water absorption, meanwhile it is cytocompatible and capable of promoting the cell attachment, which render it great potential for wound dressings.

PurposeOne increasingly popular financing option for entrepreneurial ventures is to attract corporate venture capital (CVC) investments. Prior research tends to take a CVC-centric perspective assessing the benefits and contingencies for incumbent firms or corporate investors to engage with entrepreneurial ventures. Few studies have taken the opposite perspective of investigating factors that entrepreneurial ventures need to take into account when engaging with CVC investments. As such, this study aims to investigate pre- and post-IPO entrepreneurial venture performance that partners with CVC providers or corporate investors, as well as to assess organizational and environmental contingencies.Design/methodology/approachThis study draws on a sample of 631 entrepreneurial ventures from the CSMAR database ranging from 2009 to 2019, along with CVC financing data from the CVSource database and financial data in entrepreneurial ventures’ annual reports from the Juchao Network. This study applies multiple linear regression modelling and fixed effect panel data analyses to test the proposed hypotheses.FindingsThe results show that CVC investment contributes to entrepreneurial ventures’ financial performance, both pre- and post-IPO. However, while research and development (R&D) intensity and geographic proximity strengthen the positive relationship between CVC investment and entrepreneurial ventures’ performance pre-IPO, R&D intensity has a negative moderating effect on the relationship between CVC investment and entrepreneurial ventures’ performance post-IPO.Practical implicationsFirst, in emerging economies, adopting a CVC financing strategy is an important strategic choice for entrepreneurial ventures that have a great demand for external capital, resources and technology support. Second, leveraging the relationship between external financing and internal R&D investment is essential for them to maintain their core competitiveness and sustainable growth. Moreover, entrepreneurial ventures should deal with the coopetitive relationship with incumbent companies and manage their dependency on other market participants in the external environment.Originality/valueThis study focuses on the performance implications for entrepreneurial ventures engaging with CVC investments pre- and post-IPO. First, this study broadens and expands prior research on the mechanism of the relationship between CVC and entrepreneurial ventures’ financial performance. Second, the research conducts a comparative study of the moderating effects of different timings. Third, this study applies learning theory to the field of CVC in emerging economies.

Interleukin 17A (IL-17A), vascular endothelial growth factor A (VEGF-A) and tumour necrosis factor alpha (TNF-α) are important cytokines detected mostly within two weeks after stroke in previous clinical studies. Longer clinical studies investigating these cytokines are lacking. We aimed to explore the roles of these cytokines in patients within 35 days after cerebral infarction.Thirty patients with cerebral infarction and 30 healthy individuals were enrolled. Venous blood was collected from each patient at specific times and from each healthy individual only once. Coma and neurological functional deficits of the patients were evaluated by the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS), respectively. Three cytokines were measured. The correlations among the three cytokines and between each cytokine and the GCS/NIHSS scores were analysed.IL-17A and TNF-α began to increase on day 1 after cerebral infarction, peaked on day 4, then decreased, and increased again on day 18. IL-17A returned to normal on day 35, but TNF-α remained higher than normal on day 35. VEGF-A began to increase on day 1, peaked on day 7, and returned to normal on day 35. From days 18 to 35, IL-17A was positively correlated with the GCS scores, and both IL-17A and VEGF-A were negatively correlated with the NIHSS scores.After cerebral infarction, VEGF-A from the acute phase and IL-17A from the early stage of recovery may be important for nerve protection and repair; TNF-α plays a complex role within 35 days.

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 10(4) cells/3 μL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4–6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,β-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca(2+) imaging analysis revealed that the EA stimulation decreased the percentage of α,β-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,β-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA’s analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.

Evaluating the impacts of human activity on river runoff has important implications for regional water resource management. Here, we used seven tree-ring width chronologies to establish a regional mean tree-ring width chronology from the northern mountain of Delingha, Qaidam Basin. We conducted the correlation, moving correlation and regression analysis of regional mean tree-ring width chronology with runoff data from Bayin River gauge station. Then, we stimulated the June runoff of Bayin River from 1956 to 2002. The results showed that the highest correlation coefficient was found for June runoff (评估人类活动对径流的影响,对区域水资源开发管理有借鉴和指导意义。利用柴达木盆地北部山区7个祁连圆柏树轮宽度数据,建立区域平均树轮宽度年表。通过对区域平均树轮宽度年表与巴音河水文站径流量进行相关、滑动相关和回归分析,模拟了巴音河1956—2002年6月天然径流量变化,进而分析出人类活动对径流量的影响。结果表明: 树轮平均年表与6月径流量的相关性最强(

Background: As a life-saving therapy for patients with acute respiratory failure (ARF)Mechanical ventilation has catalyzed the development of modern emergency medicine and intensive care units.Another way to support respiratory or cardiac functions is extracorporeal membrane oxygenation (ECMO).Based on previous studies, the increased pre-ECMO time of mechanical ventilation is a significant independent predictor of the poorer outcome . Removal or maintaining of mechanical ventilation during ECMO is still debatable. Methods: We analyzed the clinical data of 23 patients veno-venous ECMO therapy with acute respiratory failure due to adult community-acquired pneumonia.They were divided into two groups: group A (removed of mechanical ventilation, n=10) and group B ( maintaining of mechanical ventilation,n=13).Demographic data, including gender, age, smoking habits were collected. General characteristics and Clinical characteristics of patients were also recorded, in order to discuss whether the retention or removal of trachea cannula and continued mechanical ventilation during ECMO can affect patients’ prognosis. Results: After analysis, patients in the Group B were older than the Group A (61.0 y [54.5-67.5] vs 39.0 y [24.0-61.8], P=0.021). The median APACHE Ⅱ score of 23 patients before ECMO therapy was 25.0 (IQR, 21.0-28.0), and the Group A had a lower initial APACHE Ⅱ score than the Group B (21.5 [20.8-24.3] vs 28.0 [24.0-29.0], P=0.005)(Table 1).The group A with a survival rate of 80% , and the group B presenting a survival rate of 23.1%.The difference in the survival rate between the two groups was statistically significant (P=0.012).No differences in other items were found between the two groups.Conclusions: The final results showed that the removing of mechanical ventilation during ECMO can improve the survival rate and prognosis in patients with ARF.

Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.

A major challenge in rice (Oryza sativa L.) production is to cope with increasing grain yield and fertilizer use efficiency without compromising grain quality. This study was designed to determine if optimizing integrative cultivation management in rice could improve grain quality while increase yield and nitrogen use efficiency (NUE). An indica-japonica hybrid rice cultivar and a japonica rice cultivar were grown in the field, with five cultivation managements including no N application (0 N), local farmer's practice (LFP), and three optimizing integrative cultivation managements, reducing N rate and increasing plant density (ND), ND+alternate wetting and moderate soil drying irrigation (NDW), and NDW+applying rapeseed cake fertilizer (NDWR). The results showed that the optimizing integrative cultivation managements could not only increase grain yield, but also enhance NUE compared to LFP. Compared to LFP, NDWR significantly increased brown, milled, head milled rice rate, ratio of the kernel length to breadth and breakdown value of starch, whereas decreased amylose content, gel consistency, prolamin content, setback value, percentage of chalky kernels, and chalkiness. The three optimizing integrative cultivation managements increased contents of total proteins, albumin and glutelin, activities of the key enzymes involved in the sucrose-starch conversion in grains, root oxidation activity, and malic and succinic acid concentrations in root exudates during the grain-filling period. The results suggested that optimizing integrative cultivation managements could improve grain quality meanwhile increase grain yield and NUE by enhancing physiological activities of rice plants.

ZnO@SiO2 composite with flower-like structure was successfully prepared with molar ratio of ZnO/SiO2 = 1:1 based on the optimized synthesizing parameters of spherical SiO2 and flower-like ZnO. SiO2 particles were coated on the flower-like ZnO to form a homogeneous film through the multidimensional polycondensation of Si(OH)4. The photocatalytic degradation ability of ZnO@SiO2 composite for rhodamine B (RhB) obtained at different ZnO/SiO2 molar ratio and the comparison to that of flower-like ZnO showed that ZnO@SiO2 composite with ZnO/SiO2 molar ratio of 1:1 displayed a relatively good photocatalytic degradation ability to degrade RhB, but it was weaker than that of flower-like ZnO. Twenty millilitres of RhB solution at a concentration of 15 mg·L−1 could be completely degraded by 300 mg flower-like ZnO powder within 3 h, while the degrading efficiency was only 82.5% by 300 mg ZnO@SiO2 composite. But ZnO@SiO2 composite showed a better photocatalytic activity than flower-like ZnO at a lower pH value of 4.5.

Non-tuberculous mycobacteria (NTM) refers to the mycobacteria other than M. tuberculosis complex and M. leprae complex, which is widely distributed in the natural environment and people can infect NTM from the environment. With the increased number of acquired immunodeficiency syndrome (AIDS) and the continuous use of immunosuppressants around the world, the number of diseases caused by NTM are also increasing continuously. However, NTM related intracranial infection is still a rare or even rare disease in clinic, which is often misdiagnosed or even missed diagnosis since the negative results of cerebrospinal fluid bacteria culture, the poor effect of anti-tuberculosis treatment and the high mortality. In present paper, we intend to summarize the documents that have been reported so far in order to review the definition of NTM, the susceptible population, classification, diagnosis and treatment of NTM related intracranial infection for further strengthening and improving awareness of such a kind of the disease. DOI: 10.11855/j.issn.0577-7402.2019.10.15

Mega-blowouts are very large-scale deflationary landforms, formed by wind erosion. They are abundant in the Gonghe basin, northeast margin of the Qinghai-Tibet Plateau (QTP) and little is known about the evolution, dynamics or controls on the mega-blowout development. Here we report on mega-blowouts' morphodynamic expansion rates based on 4 years of monitoring. Also presented is a remotely sensed longer-term (48 years) morphologic change record which is used to understand the initiation, growth and evolution of mega-blowouts in alpine grasslands. Links between the morphodynamics and blowout-controlling factors are analysed. The expansion rates of the monitored blowouts vary according to blowout area, with different parts of the blowouts expanding at different rates. Generally longitudinal (downwind) mega-blowout expansion is greatest, with upwind headwall expansion via collapse being particularly significant. The growth of depositional lobes downwind of mega-blowouts tends to be faster than growth of the deflation basins. Merging of adjacent blowouts is one of the key mechanisms for mega-blowout development and extension. Sediment characteristics, wind erosion, water erosion, and freeze-thaw processes also all play a part in mega-blowout initiation and expansion. However, the relative roles that these factors play may differ according to a blowout's evolutionary stage. Due to an almost unlimited depth of sand, very low water table, and short grass vegetation cover, evolution into parabolic dunes is limited. A large proportion of sand patches and small blowouts around the mega-blowouts are still developing in the Gonghe basin proving that land degradation is still ongoing. Future work will focus on the feedback mechanisms between the blowout morphodynamics, climate change and anthropogenic impacts.

Liver fibrosis is a hallmark feature of many chronic liver diseases, which is the leading cause of morbidity and mortality worldwide. Bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles have been applied in many diseases. In this study, we aimed to explore the specific mechanism of extracellular vesicles from BMSCs in liver fibrosis. Bioinformatics analysis was employed to screen miRNA and its target mRNA. Sirius Red staining was carried out to examine fibrosis in liver tissues. Extracellular vesicle morphology was assessed using Transmission Electron Microscopy. Quantitative real-time PCR (qRT-PCR) and western blotting analysis were performed to detect the expressions of miR-148a-5p, Smad4, transforming growth factor-β1 (TGF-β1), tissue inhibitor of metalloproteinase 1 (TIMP-1), Collagen I, α-smooth muscle actin (α-SMA), and extracellular vesicle markers CD9, TSG101, CD63, and calnexin. Dual-luciferase report gene assay was used for the luciferase activity analysis. Bioinformatics analysis revealed miR-148a-5p as a regulator in liver fibrosis. QRT-PCR results indicated that miR-148a-5p was lowly expressed in both thioacetamide (TAA)-induced mice and TGF-β1-activated hepatic stellate cells. Extracellular vesicles from miR-148a-5p enriched BMSCs downregulated the mRNA and protein levels of TGF-β1, TIMP-1, Collagen I, and α-SMA. Further bioinformatics analysis indicated that Smad4 was related to liver fibrosis. Furthermore, the dual-luciferase report gene assay confirmed the binding relationship between miR-148a-5p and Smad4. Extracellular vesicles from miR-148a-5p enriched BMSCs attenuated hepatic fibrosis in liver fibrosis by targeting Smad4.

Crocin is the main monomer of saffron, which is a momentous component of traditional Chinese medicine Lang Qing A Ta. Here, we tried to probe into the role of crocin in liver fibrosis. Hematoxylin-eosin staining and Sirius Red staining were used to observe the pathological changes of liver tissues. After hepatic stellate cells (HSCs) were isolated from liver tissues, lnc-LFAR1, MTF-1, GDNF, and α-SMA expressions were detected by qRT-PCR and western blot. Immunohistochemistry and immunofluorescence were used to detect α-SMA expression. Chromatin immunoprecipitation was used to analyze the binding of MTF-1 to the GDNF promoter. Moreover, the dual-luciferase reporter gene, RNA pull-down, and RNA immunoprecipitation were used to clarify the interaction between MTF-1 and GDNF, lnc-LFAR1 and MTF-1. The degree of liver fibrosis was more severe in the mice from the liver fibrosis model, while the liver fibrosis was alleviated by the injection of crocin. lnc-LFAR1, GDNF, and α-SMA were up-regulated, and MTF-1 was down-regulated in liver fibrosis tissues and cells, while these trends were reversed after the injection of crocin. Besides, lnc-LFAR1 negatively regulated MTF-1 expression, and positively regulated GDNF and α-SMA expressions, and MTF-1 was enriched in the promoter region of GDNF. Furthermore, the cellular direct interactions between MTF-1 and GDNF, lnc-LFAR1 and MTF-1 were verified. In vivo experiments confirmed the relief of crocin on liver fibrosis. Our research expounded that crocin restrained the activation of HSCs through the lnc-LFAR1/MTF-1/GDNF axis, thereby ameliorating liver fibrosis.