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Traumatic brain injury (TBI) is a major leading cause of death and long-term disability. Although astrocytes play a key role in neuroprotection after TBI in the early stage, the overactivation of astrocytes can lead to long-term functional deficits, and the underlying pathophysiological mechanisms remain unclear. In addition, it is unknown whether the nuclear factor erythroid 2-related factor2/haem oxygenase-1 (Nrf-2/HO-1) pathway could elicit a neuroprotective effect by decreasing astrocyte overactivation after TBI. We aimed to study the effects of tert-butylhydroquinone (TBHQ) in reducing astrocyte overactivation after TBI and explored the underlying mechanisms. We first established a controlled cortical impact (CCI) model in rats and performed Haematoxylin and eosin (H&E) staining to observe brain tissue damage. The cognitive function of rats was assessed by modified neurological severity scoring (mNSS) and Morris water maze (MWM) test. Astrocyte and microglia activation was detected by immunofluorescence staining. Oxidative stress conditions were investigated using Western blotting. An enzyme-linked immunosorbent assay (ELISA) was designed to assess the level of the proinflammatory factor tumour necrosis factor-alpha (TNF-α). Dihydroethidium (DHE) staining was used to detect reactive oxygen species (ROS). Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The results showed that the administration of TBHQ ameliorated motor function and cognitive deficits and decreased the lesion volume. In addition, TBHQ significantly decreased astrocyte overactivation, diminished the pro-inflammatory phenotype M1 and inflammatory cytokines production after TBI, increased Nrf-2 nuclear accumulation, and enhanced the levels of the Nrf-2 downstream antioxidative genes HO-1 and NADPH-quinone oxidoreductase-1 (NQO-1). Furthermore, TBHQ treatment alleviated apoptosis and neuronal death in the cerebral cortex. Overall, our data indicated that the upregulation of Nrf-2 expression could enhance neuroprotection and decrease astrocyte overactivation and might represent a new theoretical basis for treating TBI.

Reliable detection and attribution of vegetation variations is a prerequisite for the development of sustainable ecosystem management strategies. Vegetation in coastal areas plays an important role in stabilizing the surface against wind erosion and provides habitat for wildlife. In this study, we analyzed the spatial heterogeneity and seasonal variation trend of greening or browning in coastal areas of mainland China (CAMC) during 1982–2015. Socioeconomic and climate factors were included to screen the driving forces for vegetation change in CAMC at the pixel scale. Based on the Normalized Difference Vegetation Index (NDVI) dataset from Global Inventory Modeling and Mapping Study (GIMMS), Mann-Kendall (M-K) trend test indicated that 33.71% of the study area was significantly greening (restoration) and 8.88% showed significant browning (degradation) with great seasonal variation. Compared to annual NDVI greened with a rate of 0.0006/a (p

Shenkang injection (SKI), a modern preparation of Chinese patent medicine, has been widely applied to clinical therapy in the chronic renal failure patients. However, it remains elusive whether SKI can ameliorate tubulointerstitial fibrosis (TIF) in vivo. Recently, pericyte-myofibroblast transition (PMT) plays an important role in the pathogenesis of TIF in obstructive nephropathy (ON). This report thus aims to demonstrate the therapeutic mechanisms of the dose-effects of SKI on TIF by targeting PMT and its signaling activation, compared with imatinib. All rats were divided into 5 groups, the sham-operated group, the vehicle-intervened group, the high dose of SKI-treated group, the low dose of SKI-treated group and the imatinib-treated group. The ON model rats were induced by unilateral ureteral obstruction (UUO), and administered with either the different doses of SKI or imatinib before and after modeling and for a period of 4 weeks. The changes before and after drugs intervention in TIF and PMT markers, and in platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways activation in the kidneys were analyzed, respectively. As a result, PMT trigger was persistently accompanied with TIF exasperation in the obstructed kidneys after UUO, and that SKI definitely targeted PMT and significantly diminished TIF in vivo. In addition, the high dose of SKI, superior to imatinib, specifically blocked PMT through inhibiting the activation of PDGFR and VEGFR signaling in the kidneys of the UUO model rats. Overall, these findings may further suggest that targeting PMT can provide new strategies for ON treatment.

Previous work indicated that conformational changes of β-lactoglobulin (β-LG) induced by dynamic high pressure microfluidization (DHPM) was related to the increase of antigenicity. In this study, β-LG glycated with 1-kestose and combined with DHPM decreased the antigenicity of β-LG. The antigenicity of control, β-LG-kestose (0.1 MPa) and β-LG-kestose (80 MPa) were 100, 79 and 42 μg/mL respectively. The molecular weight of β-LG conjugated to kestose increased from 18.4 to 19.6 kDa and its conformation scarcely changed. Conversely, combined with DHPM treatment (80 MPa), β-LG conjugated to kestose formed two conjugates with molecular weight of 18.8 and 19.8 kDa, respectively. Furthermore, the unfolding of β-LG as a result of the treatments is reflected by a decrease of intrinsic and synchronous fluorescence intensity and changes to the secondary structure. The conformational changes induced by DHPM and glycation treatments synergistically decrease the antigenicity of β-LG due to more masked or disrupted epitopes.

To observe changes in the morphology and activity of astrocytes in spinal cord at different temperatures after scratches treatment, and to investigate the effect of mild hypothermia on hyperplasia of reactive astrocytes.Spinal cord astrocytes were cultured from the neonatal SD rat, and reactive astrocytes were prepared by scratches treatment. Mild hypothermia choose 33℃, cell cul-ture 48 h. Cells were divided into control group、scratches group、mild hypothermia group and scratch+mild hypothermia group. Cell mor-phology of each group were observed in 0 h、6 h、12 h、24 h、48 h、3 d、5 d、7 d. Nestin positive rate were detected by using immunofluorescence staining method. Cell activity were observed by methyl thiazolyl tetrazolium salt (MTT) assay. The degree of apoptosis was observed by using PI staining method.Compared with control group and mild hypothermia group, cell body in both scratches group and scratch+mild hypothermia group was hypertrophy, the protrusion around was increased and extend, the cytoplasm was enrich, and the growth rate was signif-icantly increased. Compared with scratches group, scratch+mild hypothermia group cells grew slowly, the protrusion around was decreased, and cells of the scratched area ingrowth significantly slowly. Nestin and PI positive rate of cells were also significantly lower. All the results had statistically significant differences (After scratch injury, astrocytes were activated to be reactive astrocytes and hyper-plasia. Mild hypothermia significantly inhibited spinal cord reactive astrocytes overgrowth and restrain astrocytes apoptosis.

To explore a simply feasible and affordable method to establish neuritis migration model induced by Slit 2N and silk fibroin mixture in the rat hippocampal neuronsNeurons were derived from SD rat hippocampal tissues and cultured with a special cell culture-plateNeurites of the pure Slit 2N group and the mixture group became shorter, and there was no significant change in the pure silk fibroin and control groups. The results showed that the average duration and length difference before and after changed were in descending order of mixture group, Slit 2N group, silk fibroin group (There were no significant effects of Silk fibroin on induced by Slit 2N in rat hippocampal neuron migration. It had an effect on reducing Slit 2N diffusion rate and extending its working time. It provides an advantageous construction method

To explore a method of three-dimensional (3D) printing technology for preparation of personalized rat brain tissue cavity scaffolds so as to lay the foundation for the repair of traumatic brain injury (TBI) with tissue engineered customized cavity scaffolds.Five male Sprague Dawley rats[weighing (300±10) g] were induced to TBI models by electric controlled cortical impactor. Mimics software was used to reconstruct the surface profile of the damaged cavity based on the MRI data, computer aided design to construct the internal structure. Then collagen-chitosan composite was prepared for 3D bioprinter of bionic brain cavity scaffold.MRI scans showed the changes of brain tissue injury in the injured side, and the position of the cavity was limited to the right side of the rat brain cortex. The 3D model of personalized cavity containing the internal structure was successfully constructed, and cavity scaffolds were prepared by 3D printing technology. The external contour of cavity scaffolds was similar to that of the injured zone in the rat TBI; the inner positive crossing structure arranged in order, and the pore connectivity was good.Combined with 3D reconstruction based on MRI data, the appearance of cavity scaffolds by 3D printing technology is similar to that of injured cavity of rat brain tissue, and internal positive cross structure can simulate the topological structure of the extracellular matrix, and printing materials are collagen-chitosan complexes having good biocompatibility, so it will provide a new method for customized cavity scaffolds to repair brain tissue cavity after TBI.探讨3D打印技术制备个性化大鼠脑组织空腔支架方法，为组织工程化定制空腔支架进行创伤性颅脑损伤（traumatic brain injury，TBI）修复奠定基础。.取成年雄性SD大鼠5只，体质量（300±10）g，使用电子控制性脑皮质撞击仪建立TBI模型，基于MRI数据采用Mimics软件重建损伤空腔表面轮廓，计算机辅助设计构建内部结构，再用3D生物打印机以胶原-壳聚糖复合物为原料进行3D打印。对3D打印支架进行外观及扫描电镜观察。.MRI扫描显示大鼠致伤侧脑组织损伤改变，且空腔位置均限于大脑右侧皮层区。成功构建了含有内部结构的个性化空腔三维模型，并利用3D打印技术成功制备了空腔支架。支架外部轮廓与大鼠TBI后损伤区空腔相似，内部正交叉结构排列有序、孔隙连通性较好。.结合基于MRI数据的三维重建及3D打印技术定制的空腔支架与大鼠脑组织缺损空腔外形相近，内部正交叉结构可模拟细胞外基质拓扑结构，且打印材料为生物相容性较好的胶原-壳聚糖复合物，为定制空腔支架修复TBI后脑组织空腔的研究提供了一种新方法。.

In the kidney, pericyte is the major source of myofibroblast (MyoF) in renal interstitium. It is reported that pericyte-myofibroblast transition（PMT）is one of the important pathomechanisms of renal interstitial fibrosis（RIF）. Among them, the main reasons for promoting RIF formation include pericyte recruitment, activation and isolation, as well as the lack of pericyte-derived erythropoietin. During the PMT startup process, pericyte activation and its separation from microvessels are controlled by multiple signal transduction pathways, such as transforming growth factor-β（TGF-β）pathway, vascular endothelial growth factor receptor (VEGFR) pathway and platelet derived growth factor receptor (PDGFR) pathway;Blocking of these signaling pathways can not only inhibit PMT, but also suppress renal capillaries reduction and further alleviate RIF. In clinic, many traditional Chinese medicine compound prescriptions, single traditional Chinese herbal medicine (CHM) and their extracts have the clear effects in alleviating RIF, and some of their intervention actions may be related to pericyte and its PMT. Therefore, the studies on PMT and its drug intervention will become the main development direction in the research field of anti-organ fibrosis by CHM.

Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

Our previous work indicated that the antigenicity of bovine β-lactoglobulin (β-LG) decreased after conjugation with fructo-oligosaccharides (FOS) which was related to its conformational changes. In attempt to unravel further changes of β-LG antigenicity, nystose (GF3) and 1(F)-β-fructofuranosyl nystose (GF4) of FOS were used to investigate the relationship between conformation and antigenicity. The antigenicity of β-LG after conjugated with GF3 and GF4 decreased from 143.4 to 29.5 and 31.6 μg/mL, respectively. The results of mass spectrometry revealed that the molecular weight of β-LG increased from 18.4 to 19.8 and 19.1 kDa after conjugation with GF3 and GF4, respectively. It was shown that the conformational changes of β-LG after conjugation with GF3 were bigger than that with GF4, including quenching of fluorescence intensity, the red-shift of fluorescence spectra, and the increase in sulfhydryl content. However, there was no significant difference in the antigenicity between β-LG-GF3 and β-LG-GF4 conjugates (P>0.05).

Mitochondrial dynamics play a critical role in mitochondrial function and signaling. Although mitochondria play a critical role in hypoxia/ischemia, the further mechanisms between mitochondrial dynamics and ischemia are still unclear. The current study aimed to determine the role of mitofusin 2, a key regulator of mitochondrial fusion, in a hypoxic model and to explore a novel strategy for cerebral ischemia via modulation of mitochondrial dynamics. To the best of our knowledge, this is the first study to investigate both mitochondrial function and molecular pathways to determine the role of mitofusin 2 in hypoxia-induced neuronal apoptosis. In vivo, C57BL/6 mice (male, 19-25g) underwent a permanent middle cerebral artery occlusion for 12 or 24h (n=6 per group). In vitro, cobalt chloride was used to mimic hypoxia in immortalized hippocampal neurons. Down- or up-regulation of Mfn2 was induced to investigate the role of Mfn2 in hypoxia, especially in mitochondrial function and signaling pathways. The findings demonstrated that decreased mitofusin 2 occurred both in vivo and in vitro hypoxic models; second, the anti-apoptotic effect of Mfn2 may work via restoration of mitochondrial function; third, the modulation of the B Cell Leukemia 2/Bcl-2 Associated X protein and extracellular signal-regulated kinase 1/2 signaling pathways highlight the role of Mfn2 in signaling pathways beyond fusion. In summary, depletion of mitofusin 2 would lead to apoptosis both in normal or hypoxic conditions; however, mitofusin 2 overexpression could attenuate hypoxia-induced apoptosis, which represents a potential novel strategy for neuroprotection against ischemic brain damage.

To investigate the effects of Huaiqihuang Granules (槐杞黄颗粒, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms. Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers. HQH ameliorated the rat’s general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis. HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

The ends of coiled-coil tropomyosin molecules are joined together by nine to ten residue-long head-to-tail “overlapping domains”. These short four-chained interconnections ensure formation of continuous tropomyosin cables that wrap around actin filaments. Molecular Dynamics simulations indicate that the curvature and bending flexibility at the overlap is 10 to 20% greater than over the rest of the molecule, which might affect head-to-tail filament assembly on F-actin. Since the penultimate residue of striated muscle tropomyosin, Ser283, is a natural target of phosphorylating enzymes, we have assessed here if phosphorylation adjusts the mechanical properties of the tropomyosin overlap domain. MD simulations show that phosphorylation straightens the overlap to match the curvature of the remainder of tropomyosin while stiffening it to equal or exceed the rigidity of canonical coiled-coil regions. Corresponding EM data on phosphomimetic tropomyosin S283D corroborate these findings. The phosphorylation-induced change in mechanical properties of tropomyosin likely results from electrostatic interactions between C-terminal phosphoSer283 and N-terminal Lys12 in the four-chain overlap bundle, while promoting stronger interactions among surrounding residues and thus facilitating tropomyosin cable assembly. The stiffening effect of D283-tropomyosin noted correlates with previously observed enhanced actin-tropomyosin activation of myosin S1-ATPase, suggesting a role for the tropomyosin phosphorylation in potentiating muscle contraction.

This study investigated the protective effects and mechanisms of crocin, an extract of saffron, on brain damage after traumatic brain injury (TBI) in mice. C57BL/6 mice were subjected to controlled cortical impact (CCI)-induced TBI. Pretreatment with crocin (20mg/kg) had protective effects against TBI, demonstrated by improved neurological severity score (NSS) and brain edema, decreased microglial activation and release of several pro-inflammatory cytokines, and decreased cell apoptosis. TBI activated Notch signaling, as shown by upregulated levels of Notch intracellular domain (NICD) and Hes1 mRNA, and pretreatment with crocin further increased Notch activation. However, pretreatment with DAPT (100mg/kg), a gamma-secretase inhibitor, significantly suppressed crocin-induced activation of Notch signaling and attenuated the ability of crocin to protect mice against TBI-induced inflammation and apoptosis. Therefore, these results suggest that crocin has neuroprotective effects against TBI in mice, and these effects are at least partially dependent on activation of Notch signaling.

Glioma is one of the most malignant forms of brain tumor, and has been of persistent concern due to its high recurrence and mortality rates, and limited therapeutic options. As a cardiac glycoside, ouabain has widespread applications in congestive heart diseases due to its positive cardiac inotropic effect by inhibiting Na+/K+-ATPase. Previous studies have demonstrated that ouabain has antitumor activity in several types of human tumor, including glioma. However, the exact underlying mechanism remains to be elucidated. The purpose of present study was to elucidate the effect of ouabain on human glioma cell apoptosis and investigate the exact mechanism. U-87MG cells were treated with various concentrations of ouabain for 24 h, following which cell viability and survival rate were assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The dynamic changes and cell motility were observed using digital holographic microscopy. Additionally, western blot analysis and high-content screening assays were used to detect the protein expression levels of phosphorylated (p-)Akt, mammalian target of rapamycin (mTOR), p-mTOR and hypoxia-inducible factor (HIF)-1α, respectively. Compared with the control group, ouabain suppressed U-87MG cell survival, and attenuated cell motility in a dose-dependent manner (P

The heavy use of non-persistent pesticides, resulting in the accumulation of environment and destroy the aquatic environment. This paper presents the research status of using CWs to treat non-persistent pesticides in water. The removal mechanisms are mainly physical deposition, chemical hydrolysis and plant absorption. Analysis of the factors that affect the removal effect are mainly the nature of pesticides, HRT, plants. Some scholars have proposed that secondary products of non-persistent pesticides may be more harmful to the environment, However, the relevant reports are scarce.

Objectives. We investigated the action of triptolide in rats with adriamycin-induced nephropathy and evaluated the possible mechanisms underlying its protective effect against podocyte injury.Methods. In total, 30 healthy male Sprague-Dawley rats were randomized into three groups (normal group, model group, and triptolide group). On days 7, 28, 42, and 56, 24 h urine samples were collected. All rats were sacrificed on day 56, and their blood and renal tissues were collected for determination of biochemical and molecular biological parameters. Expression of miRNAs in the renal cortex was analyzed by a biochip assay and RT-PCR was used to confirm observed differences in miRNA levels.Results. Triptolide decreased proteinuria, improved renal function without apparent adverse effects on the liver, and alleviated renal pathological lesions. Triptolide also elevated the nephrin protein level. Furthermore, levels of miR-344b-3p and miR-30b-3p were elevated in rats with adriamycin-induced nephropathy, while triptolide treatment reversed the increase in the expression of these two miRNAs.Conclusions. These results suggest that triptolide may attenuate podocyte injury in rats with adriamycin-induced nephropathy by regulating expression of miRNA-344b-3p and miRNA-30b-3p.

Background/Aims: Current therapies for spinal cord injury (SCI) have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2. Methods: To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen’s method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CE). Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test. Results: Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes. Conclusion: These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI.

Both chemical and physical microenvironments appear to be important for lineage specification of umbilical cord mesenchymal stem cells (UCMSCs). However, physical factors such as the elastic modulus in traumatic brain injury (TBI) are seldom studied. Intracranial hypertension and cerebral edema after TBI may change the brain's physical microenvironment, which inhibits neural lineage specification of transplanted UCMSCs. The purpose of this study is to investigate the potential regulatory effect of mild hypothermia on the elastic modulus of the injured brain. First, we found that more UCMSCs grown on gels mimicking the elastic modulus of the brain (0.5 kPa) differentiated into neural cells, which were verified with the formation of branched cells and the expression of neural markers. Then, UCMSCs were transplanted into TBI rats, and we observed that mild hypothermia resulted in the differentiation of more neurons and astrocytes from transplanted UCMSCs. To demonstrate that more neural specification of UCMSCs was due to the regulation of the elastic modulus, we monitored intracranial pressure and cerebral edema. The results showed that mild hypothermia significantly reduced intracranial pressure and brain water content, indicating modulation of the elastic modulus by mild hypothermia. An examination with atomic force microscopy (AFM) in a cell injury model in vitro further verified hypothermia-regulated elastic modulus. In this study, we found a novel role of mild hypothermia in modulating the elastic modulus of the injured brain, resulting in the promotion of neural lineage specification of UCMSCs, which suggested that the combination of mild hypothermia had more advantages in cell-based therapy after TBI.

Degradation rate is an important index for evaluating biomaterials. The authors’ aim was to determine whether the degradation rate of biomaterials is different in distinct tissues and to clarify the underlying mechanism of degradation. The collagen-chitosan (CG-CS) composite scaffolds were prepared using freeze-drying technology. The porosity, water absorption and swelling ratio of the scaffolds were tested in vitro. The scaffolds were implanted into the subcutis, spinal cord and brain tissues of SD rats, the rate of degradation was assessed by continuous monitoring of weight loss, the pathological changes of target areas were observed by histological staining, and matrix metalloproteinase 9 (MMP-9) and lysozyme were detected at the rapid stage of degradation of the scaffolds. Physical and chemical property testing confirmed that CG-CS composite scaffold components can meet the biological requirements of in vivo transplantation. The in vivo experimental results showed that the scaffolds were completely absorbed in the subcutis at 12 days, the scaffolds in the spinal cord and brain groups exhibited progressive mass loss starting from the 3rd week, and a substantial fraction of the scaffold was degraded at 12 weeks. HE staining found that compared with the spinal cord and brain groups, macrophages and capillaries appeared earlier in the subcutis group, and the number was significantly higher (P

To explore the effects and molecular mechanisms of triptolide（TP）on improving podocyte epithelial-mesenchymal transition（EMT）induced by high dose of D-glucose（HG）, the immortalized podocytes of mice

The gut microbiota dysbiosis is one of the risk factors in the progression from the advanced chronic kidney disease（CKD）to uremia, characterized by the reduction of probiotics and the increase of opportunistic pathogens including urease-related microbes, endotoxin-related microbes and toxin-related microbes, which can produce uremic toxins. According to the core point of "the gut-kidney axis" theory and "the chronic kidney disease-colonic axis" concept, the gut microbiota dysbiosis aggravates renal damage by accumulating uremic toxins and inducing the systemic micro-inflammation. The preliminary clinical trials and animal experiments show that the probiotics biologicals from Lactobacillus acidophilus or Bifidobacterium, and the prebiotics including inulin and galactooligosaccharides, as well as lubiprostone and activated carbon adsorbents can be used for improving dysfunction of CKD patients with the gut microbiota dysbiosis via reducing uremic toxins and inhibiting the systemic micro-inflammation. But not only that, it is reported that, to some extent, a number of the single Chinese herbal medicine（CHM）, the CHM prescriptions and the CHM extracts（emodin, etc.）with oral or enema administration can also regulate the gut microbiota dysbiosis, protect the intestinal epithelial barrier, reduce uremic toxins accumulation and delay CKD progression. Thereinto, Dahuang Gancao Decoction（the concentrated granule TJ-84）, a classical CHM prescription of rhubarb, can ameliorate uremic toxins accumulation in the animal models with renal failure probably through targeting the gut-kidney axis triggered from gut microbiota, but not targeting the kidney. Based on these results, the interventional studies targeting the gut microbiota-related pathological factors such as tight junction proteins, helper T cells and regulatory T cells in the intestinal tract of the advanced CKD patients will become one of the key development directions in the future.

Aging is a gradual process during the loss of functions in cells,organs and tissues by time. The molecular mechanisms of aging-related theories include the classical ones such as telomere,oxygen radical and nonenzymatic glycosylation,as well as the newly proposed ones such as DNA methylation,mitochondrial DNA （mtDNA）and autophagy. The latest study showed the anti-aging effect of autophagy in hematopoietic stem cells. In recent years,based on the molecular regulative mechanisms of aging,a number of the promising anti-aging drugs have been found,including nicotinamide mononucleotide（NMN）and FOXO4-DRI,a peptide of anti-aging. In addition,there are many new discoveries in the field of plant extracts,in which,the extracts from Chinese herbal medicine（CHM）,some single CHMs and the classical prescriptions of CHM,represented by curcumin and resveratrol,have the partial anti-aging effects by regulating the molecular mechanisms of aging both in vivo and in vitro. In brief,developing or exploring anti-aging drugs,especially the natural drugs,is one of the main development directions in the field of anti-aging research in the basis of the molecular regulative mechanisms of aging.

Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells. We found that, autophagic activation accompanied with renal fibrosis in rats with Ade-induced renal tubular injury, and both autophagy and renal fibrosis were attenuated by rhubarb. In addition, we observed that rhein could inhibit autophagy through regulating the key molecules in the AMPK-dependent mTOR signaling pathways, as well as the Erk and p38 MAPKs signaling pathways. These findings may partly explain the therapeutic mechanisms of rhubarb and rhein in treating CKD patients in clinic, and further suggest that targeting autophagy and related signaling pathways may provide new strategies for the treatment of renal fibrosis in CKD.

Although hypothermic-targeted temperature management (HTTM) holds great potential for the treatment of traumatic brain injury (TBI), translation of the efficacy of hypothermia from animal models to TBI patientshas no entire consistency. This study aimed to find an ideal time window model in experimental rats which was more in accordance with clinical practice through the delayed HTTM intervention. Sprague-Dawley rats were subjected to unilateral cortical contusion injury and received therapeutic hypothermia at 15mins, 2 h, 4 h respectively after TBI. The neurological function was evaluated with the modified neurological severity score and Morris water maze test. The brain edema and morphological changes were measured with the water content and H&E staining. Brain sections were immunostained with antibodies against DCX (a neuroblast marker) and GFAP (an astrocyte marker). The apoptosis levels in the ipsilateral hippocampi and cortex were examined with antibodies against the apoptotic proteins Bcl-2, Bax, and cleaved caspase-3 by the immunofluorescence and western blotting. The results indicated that each hypothermia therapy group could improve neurobehavioral and cognitive function, alleviate brain edema and reduce inflammation. Furthermore, we observed that therapeutic hypothermia increased DCX expression, decreased GFAP expression, upregulated Bcl-2 expression and downregulated Bax and cleaved Caspase-3 expression. The above results suggested that HTTM at 2h or even at 4h post-injury revealed beneficial brain protection similarly, despite the best effect at 15min post-injury. These findings may provide relatively ideal time window models, further making the following experimental results more credible and persuasive.

Tungsten(VI) oxide (WO3) nanoplates were successfully synthesized by microwave intercalation. Through microwave processing, an intermediate product H2W2O7·xH2O was prepared quickly to greatly decrease the time used to prepare WO3 nanoplates. The crystal structure and morphology of WO3 were characterized by x-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, and selected-area electron diffraction. The morphology of WO3 changed with an increase in calcining temperature. A mixed-potential NO x sensor using planar yttria-stabilized zirconia and WO3 as the sensing electrode (SE) was fabricated, and its performance in NO x detection at high temperature was examined. It was determined that at 500 °C, the sensor with the WO3-nanoplate SE had higher sensitivity to NO than the sensor with a SE consisting of WO3 microparticles. The response of the NO sensor with a WO3-nanoplate SE was linear with the logarithm of NO concentration in the range of 100-1000 ppm. The electrochemical impedance measurements indicate that the electrode reaction that occurred at the triple-phase boundary (TPB) of the sensor with WO3-nanoplate SE was stronger than the reaction that occurred at the TPB of the sensor with WO3-microparticle sensing electrode.

Ethnopharmacological relevance Dahuang Fuzi Decoction (DFD) is a traditional well-prescribed formula for the treatment of chronic kidney disease (CKD) in China. This study was carried out to examine the effects of DFD in adenine-induced tubular epithelial apoptosis and renal damage, in comparison with allopurinol (AP), then to clarify the therapeutic mechanisms in vivo. Materials and methods A rat model of renal damage was created by adenine. Rats in Normal and Vehicle groups received distilled water, while rats in DFD and AP groups received DFD and AP, respectively. Proteinuria; urinary N-acetyl-β- d -glucosaminidase (NAG) levels; the blood biochemical parameters; renal histopathology damage; transferase-mediated dUTP nick-end labeling (TUNEL)-staining; the key molecular protein expressions in mitochondrial and transforming growth factor (TGF)-β1-c-JunNH2-terminal kinase (JNK) pathways were examined, respectively. Results Adenine administration induced severe renal damages, as indicated by the mass proteinuria, the heavy urinary NAG, and the marked histopathological injury in tubules and interstitium. This was associated with the activation of TGF-β1-JNK signaling pathway and tubular epithelial apoptosis. DFD treatment, however, significantly prevented proteinuria and urinary NAG elevation, and attenuated tubular epithelial apoptosis. It suppressed the protein expressions of Bax and cleaved caspase-3, whereas it enhanced the protein expression of Bcl-2. Furthermore, it also suppressed the protein levels of TGF-β1 as well as phosphorylated-JNK (p-JNK). Conclusion DFD alleviated adenine-induced tubular epithelial apoptosis and renal damage in vivo, presumably through the suppression of TGF-β1-JNK pathway activation.

Baicalin is one bioactive flavone with anti-inflammatory and neuroprotective activities. The neuroprotective effects of baicalin on pathological changes and behavioral deficits were explored in a mouse model of amyloid β (Aβ)(1-42) protein-induced Alzheimer's disease (AD). Mice received a bilateral injection of Aβ(1-42) protein into the hippocampus, then they were treated with baicalin (30, 50 and 100 mg/kg body weight, orally) or Tween 80. The therapeutic effects of baicalin were monitored by Morris water maze trial and probe test. Then mice were sacrificed for immunohistochemistry and western blot analysis. After a relatively short-term treatment of 14 days, 100 mg/kg of baicalin significantly ameliorated memory impairment in the Morris water maze test and probe test, and also attenuated glial cell activations and increase of TNF-α and IL-6 expressions induced by Aβ(1-42) protein. These results suggest that baicalin ameliorated Aβ(1-42) protein-related pathology and cognitive dysfunction via its anti-neuroinflammatory activity, and may be a potential candidate for the treatment of AD.

The combined effect of previous dynamic high-pressure microfluidization treatment (40, 80, 120, and 160MPa) and subsequent glycation with galacto-oligosaccharides (GOS) on the antigenicity of β-lactoglobulin (β-LG) was investigated. The antigenicity of β-LG-GOS decreased at relatively low pressure (≤120MPa). Surface sulfhydryl group content of β-LG-GOS increased and surface hydrophobicity of β-LG-GOS decreased. Additionally, protein unfolding in β-LG-GOS samples was reflected by quenching of fluorescence intensity, the red-shift of fluorescence spectra, decreased UV absorption, and circular dichroism analysis, indicating tertiary and secondary structural changes of β-LG. The conformational changes may contribute to the alteration of antigenicity.

Layered Molybdenum trioxide MOO3, with a two-dimensional (2D) structure was successfully delaminated into colloidal nanosheets in n-butanol via a soft-chemical process involving intercalation of dodecylamine. X-ray diffration (XRD) showd that: after intercalation spacing of the layered material expend from 1.38nm to 2.69nm. Furthermore, stable nanosheet sol was obtained after exfoliation under ultrasonic condition, Characterizations by transmission electron microscopy (TEM) and scan electron microscopy (SEM) confirmed the formation of unilamellar 2D nanosheet crystallites with an average lateral size of 400 nm, those also suggests that the samples we got is Lamellar structured. Selected Area Electron Diffraction (SEDA) indicates that the obtained nanosheets were crystalline. And the obtained nanosheets exhibited photo-catalytic decolorization properties. Which was evaluated by monitoring the degradation of Methylene Blue, after 40 minutes 90% methylene blue was degradated.

Constructed wetlands have been successfully applied to the removal of various pollutants in recent decades. The treatment effect of constructed wetlands on domestic sewage is affected by the type of wetland, plant species, temperature, pollutant concentration and environmental factors. The seasonal variation of the removal rate of domestic sewage and the removal rate of main pollutants (TN, TP, COD, NH4 +-N) were studied under the mixed conditions of four plants, and the degradation effect of pollutants along the course was explored. Clarifying the comprehensive purification ability of various wetland plants on domestic sewage and defining the effect of temperature on removal rate. The results showed that temperature had a great influence on the removal efficiency, which was significantly higher in summer than in winter. Temperature had the greatest effect on TP removal, ranging from 88.1% to 42.4%, and COD was the lowest, ranging from 57.11% to 44.47%. The degradation rate increased gradually along the path in summer and winter, and the closer to the intake, the more obvious the degradation effect was, and the degradation rate was much higher in summer than in winter. Compared with other pollutants, TP had a higher removal effect in the middle and tail positions of the wetland.

Ethnopharmacological relevance Transforming growth factor (TGF)-β1/Smad signaling pathway plays a critical role in the prolonged glomerulosclerosis (GS), which is an important determinant during the progression in chronic kidney disease (CKD). For recent 30 years, multi-glycoside of Tripterygium wilfordii Hook. f. (GTW), an extract from Chinese herbal medicine has been proved clinically effective in improving GS in CKD in China. However, therapeutic mechanisms involved in vivo are still unclear. In this study, we aimed to explain the dose-effects and molecular mechanisms of GTW on GS by regulating TGF-β1/Smad signaling activity in adriamycin (ADR)-induced nephropathy (ADRN). Materials and methods Rats with ADRN, created by unilateral nephrectomy and twice adriamycin injections (ADR, 4 mg/kg and 2 mg/kg) within 4 weeks, were divided into four groups, the Sham group, the Vehicle group, the low-dose GTW-treated group, and the high-dose GTW-treated group, and that, sacrificed at the end of the 6th week after administration. Proteinuria, blood biochemical parameters, glomerulosclerotic morphological makers, podocyte shape, and nephrin expression were examined, respectively. Protein expressions of key signaling molecules in TGF-β1/Smad pathway, such as TGF-β1, Smad3, phosphorylated-Smad2/3 (p-Smad2/3), and Smad7, were also evaluated individually. Results The results indicated that the characterizations of ADRN involved the typical prolonged GS, a small amount of abnormal proteinuria, and the failing renal function; TGF-β1/Smad signaling molecules, especially Smad3, p-Smad2/3, and Smad7 were activated in vivo, accompanied by the exasperation of glomerulosclerotic lesion; GTW at high-dose (100 mg/kg) and low-dose (50 mg/kg) could slightly ameliorate the prolonged GS and nephrin expression, furthermore, the anti-proliferative action of GTW at high-dose was superior to that at low-dose, but caused the significant liver injury; in ADRN model rats, protein expressions of TGF-β1, p-Smad2/3, and Smad7 in the kidneys could be regulated with the treatment of GTW at low-dose. Conclusion This study farther demonstrated that the low-dose of GTW, as a natural regulator in vivo, could effectively and safely ameliorate the prolonged GS in FSGS model, via the potential molecular mechanisms involving the reduction of ECM components and the suppression of TGF-β1 over-expression, as well as the bidirectional regulation of TGF-β1/Smad signaling activity.

In this study, we report an ultrasensitive western blotting method by introducing gold nanoparticles (AuNPs) onto modified polyvinylidene fluoride (PVDF) membranes via atom transfer radical polymerization (ATRP). AuNPs can prevent protein or peptide transfer across the PVDF membrane to reduce target loss. The results suggest that the improved western blotting method can be used to detect target biomarkers with a satisfactory limit of detection (LOD).

β-Amyloid (Aβ) accumulation has been proved to be responsible for the pathogenesis of Alzheimer's disease (AD). However, it is not yet clear what makes Aβ accumulate and become toxic in the AD brains. Our previous studies demonstrated that glycated Aβ (Aβ-AGE) could be formed, and it exacerbated the authentic Aβ-mediated neurotoxicity in vitro, but we did not show the role of Aβ-AGE in vivo and the underlying mechanism. In the current study, we synthesized Aβ-AGE by incubating Aβ with methylglyoxal in vitro, and then stereotactically injected Aβ-AGE into lateral ventricle of Sprague-Dawley (SD) rats. We found that Aβ-AGE aggravated Aβ-induced cognitive impairment, which was characterized by higher speed of deterioration of long-term potentiation (LTP), more decrease of dendritic spines density and more down-regulation of synaptic proteins. We also observed the overexpression of receptor for advanced glycation endproducts receptor for AGEs (RAGE) and the activation of downstream molecular (GSK3, NF-κB, p38) in RAGE-mediated pathways. On the other hand, simultaneous application of RAGE antibody or GSK3 inhibitor LiCl reversed the cognitive decline amplified by Aβ-AGE. Our data revealed that in vivo the Aβ-AGE is more toxic than Aβ, and Aβ-AGE could lead to the aggravation of AD-like pathology though the RAGE pathway, suggesting that Aβ-AGE and RAGE may be new therapeutic targets for AD.

Layered Molybdenum trioxide MOO3, with a two-dimensional (2D) structure was successfully delaminated into colloidal nanosheets in n-butanol via a soft-chemical process involving intercalation of dodecylamine. X-ray diffration (XRD) showd that: after intercalation spacing of the layered material expend to 2.69nm from 1.38nm, and Characterizations by transmission electron microscopy (TEM) and scan electron microscopy (TEM) confirmed the formation of unilamellar 2D nanosheet crystallites with an average lateral size of 400 nm. The obtained nanosheets exhibited photochromic properties upon UV-VIS excitation. The chromogenic nanosheet obtained in this study features the intense UV absorption and optically switchable Visible-to-IR absorption, which may be useful for window applications such as heat-absorbing films.

Ethnopharmacological relevance Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases in China. Huangkui capsule (HKC), an extract from AM, has been proved clinically effective in improving renal inflammation and glomerular injury in chronic kidney disease (CKD). However, the dose-effects and the mechanisms involved in vivo are still unclear. Aim of the study This study was performed to examine the dose-effects of HKC on renal inflammation and glomerular lesion in adriamycin-induced nephropathy (ADRN), then to clarify the mechanisms in vivo of HKC by investigating its actions on modulating the activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. Materials and methods The rats with chronic ADRN, created by the unilateral nephrectomy and twice adriamycin injections (ADR, 4 mg/kg and 2 mg/kg) within 4 weeks, were divided into four groups, a Sham group, a Vehicle group, a high-dose HKC group, and a low-dose HKC group, and that, sacrificed at the end of the 4th week after the administration. The rat's general status, renal morphological appearance, proteinuria, blood biochemical parameters, glomerular morphological changes, podocyte shape, and macrophage (ED1+ and ED3+ cells) infiltration in glomeruli were examined, respectively. The protein expressions of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-2, as well as p38MAPK signaling molecules such as transforming growth factor (TGF)-β1, p38MAPK, and phosphorylated-p38MAPK (p-p38MAPK), were also evaluated individually. Results HKC at high dose of 2 g/kg/d not only significantly ameliorated the rat's general status, renal morphological appearance, proteinuria, albumin, and glomerulosclerosis, but also obviously reduced the infiltrated ED1+ and ED3+ macrophages in glomeruli and TNF-α protein expression in the kidney, in addition to these, evidently down-regulated TGF-β1 and p-p38MAPK protein expressions in ADRN rats, but had no influence on podocyte shape and renal function. Conclusion HKC could dose-dependently ameliorate renal inflammation and glomerular injury in ADRN rats, by way of reducing the infiltration and the activation of macrophages in glomeruli, and TNF-α protein expression in the kidney, as well as inhibiting p38MAPK signaling pathway activity via the down-regulation of p-p38MAPK and TGF-β1 protein expressions in vivo.

Accumulating evidence shows that Sirt1 regulates a variety of neurological functions through the deacetylation of many proteins besides histone; however, the literature on the relationship between Sirt1 and axonal outgrowth is limited. Here, we first demonstrated that Sirt1 was located in the axon, especially in the growth cone. Then, we found that genetic inhibition of Sirt1 retarded axonal development in embryonic hippocampal neurons, whereas genetic and pharmacologic upregulation of Sirt1 promoted not only the formation but also the elongation of axons. Sirt1 can deacetylate and thus activate Akt, and inhibition of Akt significantly reversed the axonogenesis induced by Sirt1 overexpression. We also found that Sirt1 inhibited the activity of glycogen synthase kinase 3 (GSK3), whereas activation of GSK3 could abolish the effect of Sirt1. These results suggest that Sirt1 promotes axonogenesis by deacetylating Akt and thereby activates the Akt/GSK3 pathway, which could be a promising therapeutic target for axonopathy.

Planar zirconia automotive oxygen sensor consists of three layers of ZrO2 tape-casting substrates which possess different function after sintering, so it is important for us to research the joining of these substrates. Through SEM and EDS measurements, the essay mainly discussed the joining of ZrO2 tape-casting substrates and the adhesive mechanism when chose ZrO2 slurry as joining materials.

To investigate the protective effect of hypothermia (HT) on brain injury in moderate traumatic brain injury (TBI) rat models and the potential mechanisms, especially the involvement of RIPK1 in apoptosis and necroptosis.Adult Sprague-Dawley rats were randomized to four groups: sham+normothermia (sham+NT), sham+hypothermia (sham+HT), moderate TBI+normothermia (TBI+NT) and moderate TBI+hypothermia (TBI+HT). The sham+HT and TBI+HT groups were submitted to 32°C for 6 hours. The regional cerebral blood flow (rCBF) was assessed 24 hours after TBI; 24 and 48 hours after TBI, the modified neurological severity score (mNSS) was assessed. Immediately after behavioural tests, rats were sacrificed to harvest the brain tissues.mNSS scores were lower in the TBI+HT group compared with the TBI+NT group (p0.01) and cerebral blood flow was better (p0.01). HE staining of the cortex and ipsilateral hippocampus showed pyknotic and irregularly shaped neurons in TBI+NT rats, which were less frequent in TBI+HT rats. The TBI+NT and TBI+HT groups showed higher TNF-α, TRAIL, FasL, FADD, caspase-3, caspase-8, PARP-1, RIPK-1 and RIPK-3 levels than the sham+NT group (all p0.05), but the levels of these proteins were all lower in the TBI+HT group compared with the TBI+NT group (all p0.01).HT treatment significantly reduced RIPK-1 upregulation, which may inhibit necroptosis and apoptosis pathways after moderate TBI.

Baby raising is not only related to psychology or pedagogy seeking for the “best” and “evidence-based” practices but it is embedded in particular cultural practices. Family interaction in baby raising is a process of cultural transmission influenced by family members’ position in the social structure. The present study focused on how two generations resolve the intergenerational conflicts and transmit their value orientations when grandparents are involved in baby raising. Ten typical families are sampled according to family background and conflict coping style. It was found that in Chinese families, the intergenerational conflict about baby raising is essentially a struggle for family authority to define the boundaries of different role identity, where the generation having a higher position in the social structure has more possibilities to gain authority and therefore the chance to transmit their value orientations in raising young babies.

Effective treatments promoting axonal regeneration and functional recovery for spinal cord injury (SCI) are still in the early stages of development. Most approaches have been focused on providing supportive substrates for guiding neurons and overcoming the physical and chemical barriers to healing that arise after SCI. Although collagen has become a promising natural substrate with good compatibility, its low mechanical properties restrict its potential applications. The mechanical properties mainly rely on the composition and pore structure of scaffolds. For the composition of a scaffold, we used heparin sulfate to react with collagen by crosslinking. For the structure, we adopted a three-dimensional (3D) printing technology to fabricate a scaffold with a uniform pore distributions. We observed that the internal structure of the scaffold printed with a 3D bioprinter was regular and porous. We also found that both the compression modulus and strengths of the scaffold were significantly enhanced by the collagen/heparin sulfate composition compared to a collagen scaffold. Meanwhile, the collagen/heparin sulfate scaffold presented good biocompatibility when it was co-cultured with neural stem cells in vitro. We also demonstrated that heparin sulfate modification significantly improved bFGF immobilization and absorption to the collagen by examining the release kinetics of bFGF from scaffolds. Two months after implantating the scaffold into transection lesions in T10 of the spinal cord in rats, the collagen/heparin sulfate group demonstrated significant recovery of locomotor function and according to electrophysiological examinations. Parallel to functional recovery, collagen/heparin sulfate treatment further ameliorated the pathological process and markedly increased the number of neurofilament (NF) positive cells compared to collagen treatment alone. These data suggested that a collagen/heparin sulfate scaffold fabricated by a 3D bioprinter could enhance the mechanical properties of collagen and provide continuous guidance channels for axons, which would improve the neurological function after SCI. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1324-1332, 2017.

The kidney is the target organ of insulin with abundant insulin receptors. Thereinto,the renal intrinsic cells including glomerular podocytes,endothelial cells,mesangial cells,renal tubular epitheliums and collecting duct epithelial cells are all highly sensitive to insulin as the effector cells. Furthermore,the structural and functional abnormalities of these cells are closely related to insulin and its receptors activity. It is reported that the chronic kidney disease（CKD）patients have systemic or renal insulin resistance（IR）. IR is not only the pathogenic factor of CKD but also one of the mechanisms of CKD progression. The pathogenic factors of IR in the CKD patients include the systemic factors and the local factors in muscles and fat cells. The pathogenesis of IR is related to glomeruli,proximal tubules,collecting ducts and corresponding renal intrinsic cells such as podocytes,mesangial cells,renal tubular epitheliums and collecting duct epithelial cells. IR-related signaling pathways include insulin receptor substrate（IRS）/phosphatidylinositol 3 kinase（PI3K）/serine threonine kinase（Akt）pathway,adenosine monophosphate activated protein kinase（AMPK）pathway,glucose transporter4（GLUT4）pathway,nuclear factor（NF）-κB pathway and mitogen activated protein kinase（MAPK）pathway. Among them,IRS1/PI3K/Akt2 is the main signaling pathway of IR in podocytes of glomeruli, thus intervening its activity can improve podocyte injury. In clinic,some classical oral hypoglycemic agents and diuretic including metformin,rosiglitazone,glibenclamide,thiazolidinedione and spironolactone,as well as some extracts from Chinese herbal medicines including astragalus polysaccharides,quercetin,puerarin,emodin,berberine,curcumin and geniposide can both affect insulin and its receptor activity,and regulate IR-related signaling pathways,thereby ameliorating IR and CKD progression. Overall,the pharmacological studies based on IR-related signaling pathways in the renal intrinsic cells of CKD will become one of the developmental directions in the future.

Aging is the gradual functional recession of the living tissues or organs caused by a variety of genetic and environmental factors together. Autophagy is a process of degrading cytoplasmic components mediated by lysosomes in eukaryotic cells. Kidney is a typical target organ of aging. Autophagy regulates renal aging. Decrease in autophagy can accelerate renal aging,whereas,increase in autophagy can delay renal aging. During the process of regulating renal aging,the mammalian target of rapamycin (mTOR) and its related signaling pathways including the adenosine monophosphate activated protein kinase (AMPK)/mTOR,the phosphatidylinositol 3-kinase (PI3K)/ serine-threonine kinase(Akt)/mTOR,the AMPK/silent information regulation 1 (Sirt1) and transforming growth factor β (TGF-β) play the important roles in renal aging. Regulating the key signaling molecules in these pathways in vivo can control renal aging. Some Chinese herbal medicine (CHM) and their extracts with the effects of nourishing kidney or activating stasis, such as Cordyceps sinensis, curcumin and resveratrol have the beneficial effects on renal aging and/or autophagy. Therefore,revealing the pharmacological effects of CHM in anti-renal aging based on the molecular mechanisms of autophagy will become one of the development trends in the future study.

Design and make triple cannula dual-lumen vacuum extractor to improve effect of decompression in operation of intestinal obstruction.Triple cannula dual-lumen vacuum extractor was applied in 32 patients who underwent operation of intestinal obstruction from 2012 to 2015 in our hospital. The effect of intestinal decompression and patient prognosis were observed.32 patients that used triple cannula dual-lumen vacuum extractor had good recovery except for one patient abdominal incision with fatty liquefaction. The other patients had one-stage healed without any complication such as intestinal fistula, abdominal infection etc.Application of triple cannula dual-lumen vacuum extractor in operation for intestinal decompression could avoid contamination of abdomen and injury of intestinal mucosa, which had satisfied effect of intestinal decompression and promoted the effect of operation for intestinal obstruction.

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a widely distributed natural phenolic compound that is abundant in many plant tissues and foods. This study investigated possible mechanisms underlying the sedative–hypnotic effect of FA through behavioral pharmacology methods. FA showed dose-dependent sedative effects on locomotion activity in normal mice. FA also significantly potentiated pentobarbital-induced (45 mg/kg, i.p.) sleep by prolonging sleeping time and shortening sleep latency in a dose-dependent manner. These effects were augmented by the administration of 5-hydroxytryptophan (5-HTP), a precursor of 5-hydroxytryptamine (5-HT). With a sub-hypnotic dose of pentobarbital (25 mg/kg, i.p.), FA significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5 mg/kg, i.p.). Pretreatment with p -chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) significantly decreased the duration of pentobarbital-induced sleep, whereas FA significantly reversed this effect. These results suggest that FA has sedative–hypnotic activity, possibly mediated by the serotonergic system.

Calcium binding to the regulatory domain of cardiac troponin C (cNTnC) causes a conformational change that exposes a hydrophobic surface to which troponin I (cTnI) binds, prompting a series of protein-protein interactions that culminate in muscle contraction. A number of cTnC variants that alter the Ca(2+) sensitivity of the thin filament have been linked to disease. Tikunova and Davis engineered a series of cNTnC mutations that altered Ca(2+) binding properties and studied the effects on the Ca(2+) sensitivity of the thin filament and contraction [Tikunova, S. B., and Davis, J. P. (2004) J. Biol. Chem. 279, 35341-35352]. One of the mutations they engineered, the L48Q variant, resulted in a pronounced increase in the cNTnC Ca(2+) binding affinity and Ca(2+) sensitivity of cardiac muscle force development. In this work, we sought structural and mechanistic explanations for the increased Ca(2+) sensitivity of contraction for the L48Q cNTnC variant, using an array of biophysical techniques. We found that the L48Q mutation enhanced binding of both Ca(2+) and cTnI to cTnC. Nuclear magnetic resonance chemical shift and relaxation data provided evidence that the cNTnC hydrophobic core is more exposed with the L48Q variant. Molecular dynamics simulations suggest that the mutation disrupts a network of crucial hydrophobic interactions so that the closed form of cNTnC is destabilized. The findings emphasize the importance of cNTnC's conformation in the regulation of contraction and suggest that mutations in cNTnC that alter myofilament Ca(2+) sensitivity can do so by modulating Ca(2+) and cTnI binding.

Pharmacologic inhibition of matrix metalloproteinases (MMP) by doxycycline is of therapeutic potential for a number of cardiovascular diseases characterized by excessive activation of MMP. So far, long-term administration of doxycycline in the treatment of hypertensive ventricular remodeling has not been systemically investigated. Seven-week-old stroke-prone spontaneously hypertensive rats (SHRSP) were fed with doxycycline (30 mgKg(-1) daily) for 26 weeks, when the mortality rate of the control group reached 50%. Stroke incidence was recognized by daily monitoring of stroke symptoms. Left ventricular (LV) performance was measured by in-vivo pressure-volume loop analysis and ex-vivo passive pressure-volume relationship at the time of sacrifice. Collagen deposition, gelatinases activity, protein abundance of gelatinases, and tissue inhibitor of matrix metalloproteinases (TIMP) -1, -2, and related mRNA levels in the heart were determined. MMP-9 expression was not detected in all groups. Excessive activation of MMP-2 in the heart could be partially suppressed by doxycycline. Left ventricular systolic function and ventricular size was partially ameliorated by doxycycline; however, elevated collagen deposition co-existed in the heart. Moreover, doxycycline could downregulate MMP-2 and TIMP-1 expression both at mRNA and protein levels, and TIMP-2 represented opposite expression pattern. These results demonstrate that long-term administration of doxycycline during the development of hypertension has no impact on stroke death, and could partially preserve LV systolic performance and restrain LV chamber dilation, but leads to increased LV extracellular matrix accumulation. Interrupted cardiac MMP-2/TIMP-2 balance by doxycycline may play a role in this process.

Background Decompressive craniectomy is widely used for treating patients with traumatic brain injury (TBI). Usually patients have dura mater defect due to surgery or injury itself. The defective area may left open or repaired by artificial dura substitutes. A variety of artificial dura substitutes have been used for this purpose. Objective This study aimed to evaluate bovine‐derived pericardium membrane as artificial dural material for patients with decompressive craniectomy. Methods Totally 387 patients with severe TBI in our hospital were included in this study. Among them, 192 patients were treated with standard decompressive craniectomy without dura repair (control group). One hundred and ninety‐five TBI patients were treated with dura repair by artificial dura materials (ADM). Nonlyophilized bovine pericardium membranes were used as artificial dura material. The postoperative complications were compared in both groups, including infection, seizure, and cerebrospinal fluid (CSF) leakage. Results Patients in control group have higher complication rates than patients in ADM group, including subcutaneous hematoma (13.02% in control vs. 4.01% in ADM group, p = .004), infection (12.5% in control vs. 5.64% in ADM group, p = .021), CSF leakage (13.02% in control vs. 5.13% in ADM group, p = .012), and seizure (10.42% in control vs. 3.08% in ADM group, p = .007). Patients in ADM group are only associated with higher incidence of foreign body reaction (6 of 195 patients in ADM vs. none from control group). Conclusion Bovine‐derived pericardium membranes are successfully used as artificial dural substitutes for decompressive craniectomy. Patients with ADM have better clinical outcome than control group.

Myosin binding protein C (MyBP-C) is a thick-filament protein that limits cross-bridge cycling rates and reduces myocyte power output. To investigate mechanisms by which MyBP-C affects contraction, we assessed effects of recombinant N-terminal domains of cardiac MyBP-C (cMyBP-C) on contractile properties of permeabilized rat cardiac trabeculae. Here, we show that N-terminal fragments of cMyBP-C that contained the first three immunoglobulin domains of cMyBP-C (i.e., C0, C1, and C2) plus the unique linker sequence termed the MyBP-C “motif” or “m-domain” increased Ca2+ sensitivity of tension and increased rates of tension redevelopment (i.e., ktr) at submaximal levels of Ca2+. At concentrations ≥20 μM, recombinant proteins also activated force in the absence of Ca2+ and inhibited maximum Ca2+-activated force. Recombinant proteins that lacked the combination of C1 and the motif did not affect contractile properties. These results suggest that the C1 domain plus the motif constitute a functional unit of MyBP-C that can activate the thin filament.