Enhancement of volatile fatty acids production through anaerobic co-digestion of navel orange residue and waste activated sludge: Effect of pre-treatment and substrate proportions.

In this study, the co-digestion system with Navel orange residues (NOR) and Waste activated sludge (WAS) was established, by pre-treating the NOR and setting different volatile solids (VS) ratios of NOR to WAS to motivate the production of volatile fatty acids (VFA). The pre-treatment method (pH 7 and temperature 70 °C) promoted the release of dissolved organic matter, and the concentration of soluble chemical oxygen demand (SCOD) increased by 45.56% compared with the untreated group (pH 3 and temperature 20 °C). In the co-digestion system, the highest VFA yield (5716.69 mg/L) was obtained at VS ratio of 2. When the VS ratio was increased to 4, the imbalance in proportions of carbon and nitrogen affected VFA production, and the high concentration of essential oils (EO) present in the NOR inhibited the methane production; the cumulative yield of methane gas decreased by 24.10% compared with the yield obtained when the VS ratio was 2. Analysis of microbial community revealed that an increase in the number of VFA-producing microbial populations and the abundance of Methanobacteria resulted in the accumulation of acetic acid. This study demonstrated that co-digestion of NOR with WAS improve VFA production, thus realizing the utilization of solid wastes and reducing environmental pollution.

Gastroprotective effects of Machilus zuihoensis Hayata bark against acidic ethanol-induced gastric ulcer in mice.

Background and aim: In traditional medicine, Machilus zuihoensis Hayata bark (MZ) is used in combination with other medicines to treat gastric cancer, gastric ulcer (GU), and liver and cardiovascular diseases. This study aims to evaluate the gastroprotective effects and possible mechanism(s) of MZ powder against acidic ethanol (AE)-induced GU and its toxicity in mice. Experimental procedure: The gastroprotective effect of MZ powder was analyzed by orally administering MZ for 14 consecutive days before AE-inducing GU. Ulcer index (UI) and protection percentage were calculated, hematoxylin and eosin staining and periodic acid-Schiff staining were performed, and gastric mucus weights were measured. The antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and possible signaling pathway(s) were studied. Results and conclusion: Pretreatment with MZ (100 and 200 mg/kg) significantly decreased 10 µL/g AE-induced mucosal hemorrhage, edema, inflammation, and UI, resulted in protection percentages of 88.9% and 93.4%, respectively. MZ pretreatment reduced AE-induced oxidative stress by decreasing malondialdehyde level and restoring superoxide dismutase activity. MZ pretreatment demonstrated anti-inflammatory effects by reducing both serum and gastric tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß levels. Furthermore, MZ pretreatment exhibited anti-apoptotic effect by decreasing Bcl-2 associated X protein/B-cell lymphoma 2 ratio. The gastroprotective mechanisms of MZ involved inactivations of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. Otherwise, 200 mg/kg MZ didn't induce liver or kidney toxicity. In conclusion, MZ protects AE-induced GU through mucus secreting, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and inhibitions of NF-κB and MAPK signaling pathways.

Antitumor Activity of Berberine by Activating Autophagy and Apoptosis in CAL-62 and BHT-101 Anaplastic Thyroid Carcinoma Cell Lines.

Introduction: Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid carcinoma. Doxorubicin (DOX) is the only drug approved for anaplastic thyroid cancer treatment, but its clinical use is restricted due to irreversible tissue toxicity. Berberine (BER), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has been proposed to have antitumor activity in many cancers. However, the underlying mechanisms by which BER regulates apoptosis and autophagy in ATC remain unclear. Thus, the present study aimed to assess the therapeutic effect of BER in human ATC cell lines CAL-62 and BHT-101 as well as the underlying mechanisms. In addition, we assessed the antitumor effects of a combination of BER and DOX in ATC cells. Methods: The cell viability of CAL-62 and BTH-101 with treatment of BER for different hours was measured by CCK-8 assay, and cell apoptosis was assessed by clone formation assay and flow cytometric analysis. The protein levels of apoptosis protein, autophagy-related proteins and PI3K/AKT/mTORpathway were determined Using Western blot. Autophagy in cells was observed with GFP-LC3 plasmid using confocal fluorescent microscopy. Flow cytometry was used to detect intracellular ROS. Results: The present results showed that BER significantly inhibited cell growth and induced apoptosis in ATC cells. BER treatment also significantly upregulated the expression of LC3B-II and increased the number of GFP-LC3 puncta in ATC cells. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed BER-induced autophagic cell death. Moreover, BER induced the generation of reactive oxygen species (ROS). Mechanistically, we demonstrated that BER regulated the autophagy and apoptosis of human ATC cells through the PI3K/AKT/mTOR pathways. Furthermore, BER and DOX cooperated to promote apoptosis and autophagy in ATC cells. Conclusion: Taken together, the present findings indicated that BER induces apoptosis and autophagic cell death by activating ROS and regulating the PI3K/AKT/mTOR signaling pathway.

Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

Common Syndromes of Cerebral Infarction Patients in Rural Areas of Eastern Henan Based on Latent Structure Model and Factor Analysis / 中国实验方剂学杂志

ObjectiveTo explore the common syndromes of patients with cerebral infarction in rural areas of eastern Henan based on latent structure model and factor analysis，and provide reference for clinical differentiation of cerebral infarction. MethodThe data samples of patients with cerebral infarction in rural areas in eastern Henan were preprocessed. With Lantern 5.0 of latent structure method and LTM-EAST algorithm of two-step latent tree analysis， the manifest variable latent structure model of related symptoms was built to interpret different latent nodes， and common syndromes of cerebral infarction were obtained via comprehensive cluster analysis. SPSS 20.0 was used for factor analysis and cluster analysis of related symptoms to infer the distribution of syndrome types. ResultThe data of 888 patients with cerebral infarction were included， involving symptoms， tongue and pulse （88 in total）. The 65 symptoms with a frequency of ≥5% were constructed into a latent structure model， and 31 latent variables were obtained. The Bayesian information criterion （BIC） score was -15 367.17. Based on professional knowledge， s6 common syndrome types were found， namely， syndrome of upward disturbance of wind-fire， Qi deficiency and blood stasis syndrome， syndrome of phlegm and blood stasis blocking collaterals， syndrome of phlegm-heat and fu-organ excess， syndrome of wind phlegm obstructing collaterals， and syndrome of stirring wind due to yin deficiency. In factor analysis， the symptoms with a frequency of >10% were selected， and 13 common factors were obtained and used for systematic cluster analysis. And 5 syndrome types were inferred： syndrome of wind phlegm obstructing collaterals， syndrome of phlegm-heat and fu-organ excess， Qi deficiency and blood stasis syndrome， syndrome of combined phlegm and blood stasis， and syndrome of yin deficiency and internal heat. According to the determination criteria of syndrome types in traditional Chinese medicine （TCM）， 6 common syndrome types of cerebral infarction were finally determined. ConclusionAccording to the severity of the disease， the common syndromes of patients with cerebral infarction in rural areas of Eastern Henan were divided into the following categories： apoplexy involving channel and collateral： syndrome of upward disturbance of wind fire， syndrome of wind phlegm obstructing collaterals， and syndrome of stirring wind due to yin deficiency. Apoplexy involving zang and fu-viscera： syndrome of phlegm-heat and fu-organ excess， and syndrome of phlegm and blood stasis blocking collaterals. Recovery period： Qi deficiency and blood stasis syndrome. This study was basically consistent with the syndrome law in TCM theory， and provided reference for further establishing syndrome diagnostic criteria of cerebral infarction.

Exploration of potential molecular mechanism of Chuanxiong in treatment of tension-type headache based on network pharmacology and molecular docking / 中国药理学通报

Aim To analyze the active ingredients of Chuanxiong, predict its target and signaling pathways in the treatment of tension-type headache, and clarify its therapeutic mechanism based on the principle of network pharmacology.Methods The effective active ingredients in Chuanxiong were retrieved from the Chinese herbal system pharmacology platform(TCMSP), and were performed by the ADME screen to collect the potential targets; the existing tension-type headache-related disease targets were collected through the GeneCards database.The targets corresponding to the active ingredients were intersected to obtain the common target as the key target.Cytoscape was used to construct and analyze the visual "drug-active ingredient-target-disease" network, and the String database was used to construct the PPI protein interaction network; through R language the GO function and KEGG pathway enrichment of common targets in the form of bubble graphs were analyzed.Lastly, molecular docking was used for preliminary verification.Results Finally 7 active ingredients, 105 compound targets and 2 139 tension-type headache-related target genes were obtained.There were 54 nodes in the protein interaction network.GO functional enrichment analysis yielded 215 entries, and KEGG pathway enrichment analysis yielded 68 signaling pathways.Molecular docking showed that FA, Chuanxiong quinone, sitosterol, ligustalin had strong affinity with CASP3, MAPK1, MAPK14.Conclusions It is suggested that Chuanxiong may treat tension-type headaches through anti-inflammatory, antioxidant and cytoprotective effects.

基于网络 ? ? 学探讨 ? 脾补肾活血方治疗 缺血性 ? 中的作用机 / 中国药理学通报

Aim To explore the mechanism of Danshen decoction in the treatment of colon cancer using network pharmacology and molecular docking.Methods The active components and corresponding target proteins of Salvia miltiorrhiza, Santalum album and Amo-mum villosum in Danshen decoction were screened based on Traditional Chinese Medicine Systems Pharmacology database and analysis platform.The targets of colon cancer were searched by using Genecards database, and the common targets were selected.The network diagram of traditional Chinese medicine-active components-target-disease was constructed by using Cytoscape 3.7.0.The protein protein interaction network of common targets was constructed by using STRING database.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis were carried out based on R4.0.2.The important targets in the key pathways and the important active components in the network diagram of traditional Chinese medicine-active ingredients-target-disease network were selected for Surflex Dock.Results A total of 78 active components, 142 targets, 3 239 colon cancer targets, 105 overlapping targets and 69 corresponding active components were screened out.KEGG analysis showed that the key signaling pathway was PI3K/AKT.Luteolin and Tanshinone IIA with high correlation were selected to dock with protein kinase B(AKT1).Both active components had hydrogen bonding with AKT1.Conclusions Danshen decoction plays a positive role in colon cancer treatment.The mechanism may be related to the regulation of PI3K/AKT signaling pathway.

Pickering Emulsions Stabilized by Diblock Copolymer Worms Prepared via Reversible Addition-Fragmentation Chain Transfer Aqueous Dispersion Polymerization: How Does the Stimulus Sensitivity Affect the Rate of Demulsification?

Responsive Pickering emulsions exhibit promising application in industry owing to the integration of the high storage stability with on-demand demulsification. In this study, stimuli-responsive Pickering emulsions stabilized by poly[oligo(ethylene glycol) methyl ether methacrylate]15-b-poly(diacetone acrylamide)120 (E15D120) worms were indicated, in which E15D120 worms were prepared via reversible addition-fragmentation chain transfer-based aqueous dispersion polymerization using thermo-sensitive POEGMA15 as both the stabilizer block and macro-chain transfer agent. The factors influencing the morphologies of copolymers during polymerization-induced self assembly have been investigated. A series of different morphological polymer nanoparticles including spheres, worms, and vesicles could be produced through rational synthesis. E15D120 worms demonstrated excellent emulsifying performances and could be used as emulsifiers to form n-dodecane-in-water Pickering emulsions at a low content. The formed n-dodecane-in-water Pickering emulsions revealed a slow demulsification at pH 10 or 70 °C or pH 10/70 °C combinations, and several hours were needed for the demulsification of Pickering emulsions. However, n-dodecane-in-water Pickering emulsions displayed a rapid demulsification (∼10 min) at an elevated temperature, such as 90 °C. The different demulsification rates were attributed to different sensitivities of E15D120 worms to external stimuli. Pickering emulsions integrating a rapid responsive demulsification with a slow one would be well satisfactory on different occasions.

Antimelanogenesis Effects of Leaf Extract and Phytochemicals from Ceylon Olive (Elaeocarpus serratus) in Zebrafish Model.

The melanogenesis inhibition effect in zebrafish (Danio rerio) and antityrosinase activity of the ethanolic extract and its phytochemicals from Ceylon olive (Elaeocarpus serratus Linn.) leaves were investigated in this study. Among the leaf extract and four soluble fractions, the ethyl acetate soluble fraction exhibits the best antityrosinase and antimelanogenesis activities. One phenolic acid, gallic acid, and two flavonoids, myricetin and mearnsetin, are isolated from the active subfractions through the bioassay-guided isolation; their structures are elucidated based on the 1D and 2D NMR, FTIR, UV, and MS spectroscopic analyses. These compounds have significant antityrosinase activity whether using l-tyrosine or l-DOPA as the substrate; mearnsetin shows the optimal activity. In the enzyme kinetic investigation, both gallic acid and mearnsetin are the competitive-type inhibitors against mushroom tyrosinase, and myricetin acts as a mixed-type tyrosinase inhibitor. Leaf extract and an ethyl acetate soluble fraction show effective performance in the inhibition of melanin formation in zebrafish embryos. Mearnsetin also possesses a promising antimelanogenesis effect, which is superior to the positive control, arbutin. Results reveal that the Ceylon olive leaf extract and its phytochemicals, especially mearnsetin, have the potential to be used as antimelanogenesis and skin-whitening ingredients.

Presynaptic inputs to vasopressin neurons in the hypothalamic supraoptic nucleus and paraventricular nucleus in mice.

Arginine vasopressin (AVP) neurons in the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) are involved in important physiological behaviors, such as controling osmotic stability and thermoregulation. However, the presynaptic input patterns governing AVP neurons have remained poorly understood due to their heterogeneity, as well as intermingling of AVP neurons with other neurons both in the SON and PVN. In the present study, we employed a retrograde modified rabies-virus system to reveal the brain areas that provide specific inputs to AVP neurons in the SON and PVN. We found that AVP neurons of the SON and PVN received similar input patterns from multiple areas of the brain, particularly massive afferent inputs from the diencephalon and other brain regions of the limbic system; however, PVNAVP neurons received relatively broader and denser inputs compared to SONAVP neurons. Additionally, SONAVP neurons received more projections from the median preoptic nucleus and organum vasculosum of the lamina terminalis (a circumventricular organ), compared to PVNAVP neurons, while PVNAVP neurons received more afferent inputs from the bed nucleus of stria terminalis and dorsomedial nucleus of the hypothalamus, both of which are thermoregulatory nuclei, compared to those of SONAVP neurons. In addition, both SONAVP and PVNAVP neurons received direct afferent projections from the bilateral suprachiasmatic nucleus, which is the master regulator of circadian rhythms and is concomitantly responsible for fluctuations in AVP levels. Taken together, our present results provide a comprehensive understanding of the specific afferent framework of AVP neurons both in the SON and PVN, and lay the foundation for further dissecting the diverse roles of SONAVP and PVNAVP neurons.

Risk Factors for Long-Term Death After Medullary Infarction: A Multicenter Follow-Up Study.

Background and Purpose: We investigated the risk factors for death in patients with medullary infarction (MI) during a long-term follow-up. Methods: We retrospectively examined 179 consecutive patients (130 men and 49 women) who had clinical and MRI findings consistent with MI between February 2012 and January 2017 at three university hospitals. Long-term outcomes were assessed by telephonic interview. The clinical and radiological features and risk factors for poor outcomes (modified Rankin scale score ≥ 3, all-cause death) were analyzed. Results: Mean age of patients was 58.3 ± 12.8 years (range, 25-87); mean follow-up period after stroke onset was 42.7 ± 13.2 months (range, 24-78). Basilar artery (BA) stenosis >50% was more closely related to medial medullary infarction (MMI) than other types. There was greater frequency of ipsilateral vertebral artery hypoplasia (VAH) or V4AH and V4 occlusion in lateral MI than in other types. On rostro-caudal classification, middle (M)+dorsal (D) was most frequent, followed by the ventral (V)+M+D types. 21.2% patients showed poor long-term prognosis. Age ≥ 65 years, recurrent stroke, dysphagia, >50% BA stenosis, and ventral MI were risk factors for poor long-term prognosis. All-cause mortality rate was 10.6%; age ≥ 65 years, recurrent stroke, and dysphagia were risk factors for death in the long-term. Ventral MI and MMI+cerebellar infarction, as well as stroke mechanism of artery-to-artery embolism, were potential risk factors for death in the long-term. Pneumonia and recurrent stroke were major causes of death. Conclusions: Long-term poor outcomes of MI and all-cause mortality were not infrequent. Older age, recurrent stroke, and dysphagia were common risk factors for poor prognosis and death.

Amphiphilic Double-Brush Copolymers with a Polyurethane Backbone: A Bespoke Macromolecular Emulsifier for Ionic Liquid-in-Oil Emulsion.

The study on ionic liquid (IL)-based emulsions is very interesting due to the "green" quality and potential wide applications of ILs, whereas the emulsifiers for the formation of IL-based emulsions are extremely limited and mainly centered on low molecular weight surfactants. In this work, synthesis of amphiphilic double-brush copolymers (DBCs) and their application as bespoke macromolecular emulsifiers for the formation of IL-containing non-aqueous emulsions are described. DBCs consisted of a polyurethane (PU) backbone and poly(N,N-dimethyl acrylamide) (PDMA) and poly(methyl methacrylate) (PMMA) chains that were grafted simultaneously at the same reactive site along the PU backbone (PU-g-PDMA/PMMA), which were synthesized through the combination of polyaddition and the reversible-deactivation radical polymerization reactions. Highly stable [Bmim][PF6]-in-benzene emulsions could be gained by adopting PU-g-PDMA/PMMA DBCs as macromolecular emulsifiers at a low content, such as 0.025 wt %. On the basis of the stability and the size of emulsion droplets, PU-g-PDMA/PMMA DBCs exhibited much better emulsifying performances than their analogues, including PU-g-PDMA, PU-g-PMMA, and PDMA-b-PMMA copolymers. Such excellent emulsifying performances of PU-g-PDMA/PMMA DBCs were due to high interfacial activities. PU-g-PDMA/PMMA DBCs exhibited higher capabilities in lowering the interfacial tension of the [Bmim][PF6]-benzene interface than their analogues. A large energy barrier to desorption of adsorbed PU-g-PDMA/PMMA DBCs from the interface contributed to high stability of the [Bmim][PF6]-in-benzene emulsion.

Effects of Body Weight-supported Treadmill Training on Neuropathic Pain and Expression of Glutamate Decarboxylase (GAD)-65/67 in Spinal Dorsal Horn of Rats with Spinal Cord Injury / 中国康复理论与实践

Objective:To investigate the effect of body weight-supported treadmill training on neuropathic pain and expression of glutamate decarboxylase-65/67 (GAD-65/67) in spinal dorsal horn of rats with spinal cord injury (SCI). Methods:A total of 24 Sprague-Dawley rats were randomly divided into sham group, SCI-sedentary (SCI-Sed) group and SCI-Exercise (SCI-Ex) group, with eight rats in each group. Allen's method was used to make T10 incomplete SCI model. Seven days after SCI, SCI-Ex group was given body weight-supported treadmill training. Before SCI, and seven days, 14 days, 21 days, 28 days and 35 days after SCI, the von Frey filaments and thermal stimulation pain tester were used to evaluate the mechanical and thermal pain thresholds. Then, Western blotting and immunohistochemical analysis were performed on the spinal cord of all rats to detect the expression of GAD-65 and GAD-67. Results:The mechanical and thermal pain thresholds were higher in SCI-Ex group than in SCI-Sed group 21 days, 28 days and 35 days after SCI (P < 0.01). Compared with the sham group, the expression of GAD-65 and GAD-67 decreased in SCI and SCI-Ex groups (P < 0.05), and increased in SCI-Ex group compared with that of SCI-Sed group (P < 0.05). Conclusion:Body weight-supported treadmill training could increase the synthesis of GAD-65/67 in the distal spinal cord dorsal horn of incomplete SCI rats, and improve the pain thresholds of hind limbs in rats with SCI.

Effects of Different Upper Extremity Fixing Approaches on Elbow Flexor Activities and Balance for Stroke Patients / 中国康复理论与实践

Objective:To observe the affected elbow flexor activities and balance of stroke patients in standing and walking as fixing the affected upper extremity with different methods. Methods:From September to December, 2018, 14 stroke patients from Affiliated Suzhou Science ＆ Technology Town Hospital of Nanjing Medical University were included. They were measured elbow flexor contraction ratio (integrated electromyogram of flexor/integrated electromyogram of antagonist) with wireless surface electromyography as standing and walking in normal speed, and sway index with Biodex as standing, in four conditions: the affected arm without fixing, and fixed with elbow orthosis, and with unaffected hand backwards and forwards. Results:The contraction ratio was the most as the arm fixed with elbow orthosis in both standing and walking (F > 2.687, P < 0.05). The sway index was the most as the arm fixed with unaffected hand forwards (F = 21.091, P < 0.05). Conclusion:The elbow orthosis restraint may lead to increased contraction of the affected elbow flexor, which is unsatisfactory to inhibit flexor activity of the upper extremities; while restraint of unaffected hand forwards may lead to instable balance.

Selection signature reveals genes associated with susceptibility loci affecting respiratory disease due to pleiotropic and hitchhiking effect in Chinese indigenous pigs.

BACKGROUND: Porcine respiratory disease is one of the most important health problems which causes significant economic losses. OBJECTIVE: To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 SNPs in a total of 249 individuals based on genome-wide sequencing data. METHODS: Genome comparison of three susceptibility to swine EP pig breeds (Jinhua, Erhualian and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using XP-EHH and FST statistical approaches identified 691 positively selected genes. Based on QTLs, GO terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. RESULTS: Most of these genes were tested by several methods including transcription analysis and candidated genes association study. Among these genes: CYP1A1 and CTNNB1 are involved in fertility; TGFBR3 plays a role in meat quality traits; WNT2, CTNNB1 and TCF7 take part in adipogenesis and fat deposition simultaneously; PLAUR (completely linked to AXL, r2=1) plays an essential role in the successful ovulation of matured oocytes in pigs; CLPSL2 (strongly linked to SPDEF, r2=0.848) is involved in male fertility. CONCLUSION: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provide insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.

[Effect of modified Buyang Huanwu Decoction on hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with super early cerebral infarction].

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.

The Notch signaling pathway inhibitor Dapt alleviates autism-like behavior, autophagy and dendritic spine density abnormalities in a valproic acid-induced animal model of autism.

Autism spectrum disorders (ASDs) comprise a number of heterogeneous neurodevelopmental diseases. Recent studies suggest that the abnormal transmission of neural signaling pathways is associated with the pathogenesis of autism. The aim of this study was to identify a link between the Notch signaling pathway and the pathogenesis of autism. In this study, we demonstrated that prenatal exposure to valproic acid (VPA) resulted in autistic-like behaviors in offspring rats and that the expression of the Notch signaling pathway-related molecules Notch1, Jagged1, Notch intracellular domain (NICD) and Hes1 increased in the prefrontal cortex (PFC), hippocampus (HC) and cerebellum (CB) of VPA rats compared to those of controls. However, inhibiting the Notch pathway with (3,5-Difluorophenacetyl)-L-alanyl-S-phenylglycine-2-butyl Ester (Dapt) reduced the overexpression of Notch pathway-related molecules in offspring rats. Notably, Dapt improved autistic-like behaviors in a VPA-exposed rat model of autism. Furthermore, we investigated whether Dapt improved autistic-like behavior in a VPA rat model by regulating autophagy and affecting the morphology of dendritic spines. We found that the expression of the autophagy-related proteins Beclin 1, LC3B and phospho-p62 in the PFC, HC and CB of VPA model rats increased after Notch signal activation and was inhibited by Dapt compared to those of controls. Moreover, postsynaptic density-95 (PSD-95) protein expression also increased significantly compared to that of VPA model rats. The density of dendritic spines decreased in the PFC of VPA rats treated with Dapt compared to that of VPA model rats. Our present results suggest that VPA induces an abnormal activation of the Notch signaling pathway. The inhibition of excessive Notch signaling activation by Dapt can alleviate autistic-like behaviors in VPA rats. Our working model suggests that the Notch signaling pathway participates in the pathogenesis of autism by regulating autophagy and affecting dendritic spine growth. The results of this study may help to elucidate the mechanism underlying autism and provide a potential strategy for treating autism.

Exploring the Structure of Haplotype Blocks and Genetic Diversity in Chinese Indigenous Pig Populations for Conservation Purpose.

Chinese indigenous pigs in the Taihu Lake region are well known for their high fecundity and other excellent characteristics. To better understand the characteristics of these breeds in this area as well as to provide the government and breeders the molecular basis for formulating a reasonable conservation policy, we explored the structure of haplotype blocks and genetic diversity of the 7 populations which is relevant for the management and conservation of these important genetic resources using next-generation sequencing data. In this study, a total of 131 300 single-nucleotide polymorphisms with minor allele frequencies ⩾0.05 were obtained for further analysis. In general, there are similar within-breed genetic diversities (He, Ho, Pn, Ar) among these 7 pig populations in the Taihu Lake region. Average values for the inbreeding coefficients estimates in the 7 populations are 0.110 (F1), 0.056 (F2), and 0.078 (F3). All the breeds have seen a continuous decline in Ne estimates over time with FJ and SW populations having a very similar curve. Moreover, the Ne of SMS pig breeds were smaller than other Chinese pig breeds, indicating that SMS pig breeds underwent stronger selection pressure than other Chinese pig breeds. The average genetic distances among the 7 populations in the Taihu Lake region were 0.235 (MMS), 0.240 (SMS), 0.269 (EH), 0.248 (MI), 0.221 (FJ), 0.254 (JX), and 0.212 (SW). A summary of the number of haplotype blocks and haplotype diversity was also presented. This study provide a deep understanding of the current situation of conservation in this region, thereby uncovering the pertinent insight to better formulate more reasonable preservation policies for the government departments and breeding planners to follow-up.

Effect of modified Buyang Huanwu Decoction on hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with super early cerebral infarction / 中国中药杂志

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.