Microscopic growth mechanism and edge states of monolayer 1T'-MoTe_(2)

Transition metal ditellurides(TMTDs)have versatile physical properties,including non-trivial topology,Weyl semimetal states and unique spin texture.Controlled growth of high-quality and large-scale monolayer TMTDs with preferred crystal phases is crucial for their applications.Here,we demonstrate the epitaxial growth of 1T'-MoTe_(2) on Au(111)and graphitized silicon carbide(Gr/SiC)by molecular beam epitaxy(MBE).We investigate the morphology of the grown1T'-MoTe_(2) at the atomic level by scanning tunnelling microscopy(STM)and reveal the corresponding microscopic growth mechanism.It is found that the unique ordered Te structures preferentially deposited on Au(111)regulate the growth of monolayer single crystal 1T'-MoTe_(2),while the Mo clusters were preferentially deposited on the Gr/SiC substrate,which impedes the ordered growth of monolayer MoTe_(2).We confirm that the size of single crystal 1T'-MoTe_(2) grown on Au(111)is nearly two orders of magnitude larger than that on Gr/SiC.By scanning tunnelling spectroscopy(STS),we observe that the STS spectrum of the monolayer 1T'-MoTe_(2) nano-island at the edge is different from that at the interior,which exhibits enhanced conductivity.

帕金森病患者免疫球蛋白、Th9亚群水平变化及其与IGF-1、S-100B蛋白的相关性

目的:研究帕金森病(PD)患者免疫球蛋白(IgG、IgA和IgM)、辅助性T细胞亚群Th9水平变化及其与胰岛素生长因子-1(IGF-1)、S-100B蛋白的相关性。方法:选取2020年12月至2022年12月期间在河北省中医院确诊的108例PD患者,将其作为研究组,并根据患者病变程度分为轻度组(35例)、中度组(44例)和重度组(29例);另选108例健康成人作为对照组。对比研究组和对照组免疫球蛋白和Th9亚群水平,以及轻度组、中度组及重度组免疫球蛋白、Th9亚群、IGF-1和S-100B蛋白水平,采用Pearson相关性分析免疫球蛋白、Th9亚群和IGF-1、S-100B蛋白的相关性。采用Spearman相关性分析PD患者疾病程度和所有差异指标间的相关性。结果:研究组IgM水平较对照组低,且重度组低于中度组,中度组低于轻度组(P<0.05);研究组IgG、IgA、IL-9和Th9亚群水平较对照组高,且重度组高于中度组,中度组高于轻度组(P<0.05)。重度组IGF-1水平低于中度组,中度组低于轻度组;重度组S-100B蛋白水平高于中度组,中度组高于轻度组(P<0.05)。Pearson相关性分析结果显示,PD患者IgM水平与IGF-1水平呈正相关,与S-100B蛋白水平呈负相关;IgG、IgA、IL-9和Th9亚群水平均与IGF-1水平呈负相关,与S-100B蛋白水平呈正相关(P<0.05)。Spearman相关性分析结果显示,PD患者疾病程度与IgM、IGF-1水平呈负相关,与S-100B蛋白、IgG、IgA、IL-9和Th9亚群水平呈正相关(P<0.05)。结论:PD患者IgM水平降低,IgG、IgA、Th9亚群水平升高,且其水平变化与IGF-1、S-100B明显相关,可以用于评估病情的严重程度。

Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

Optimization of growth medium for microbially induced calcium carbonate precipitation(MICP) treatment of desert sand

Wind-induced sand erosion is a natural process, and can have several negative impacts on human health, environment, and economy. To mitigate the wind-induced sand erosion, an environmental friendly technique that helps to bind soil particles is desirable. The microbially induced calcium carbonate precipitation(MICP) treatment has lately become renowned and a viable alternative to enhance the binding of sand particles(especially against wind erosion). The efficiency of Sporosarcina pasteurii bacteria in inducing calcite formation can be influenced by various factors, including the type of growth media used for bacterial culture. Most of the studies have mainly validated the efficiency of S. pasteurii bacteria usually under single growth media for the MICP treatment. However, the efficiency of S. pasteurii under different growth media on calcite formation is rarely explored. The current study explores the effect of S.pasteurii bacteria on calcite formation under the presence of three different growth media, namely,molasses(MS), tryptic soy broth(TB), and nutrient broth(NB). The three growth media have been applied in the laboratory with and without bacterial solution(control samples). Altered cementation media concentrations(0.5 and 1.0 M) with different pore volumes(PVs), namely, 0.25, 0.50, and 1.00 PV were used in sand-filled tubes for 7 and 14 treatment cycles(1 cycle=24 h). The pH and EC were measured for 12-h period in every 2 h interval, to monitor values at the time of treatment at room temperature. The calcite precipitation was confirmed using SEM(scanning electron microscope), PXRD(powder X-ray diffraction), and calcimeter tests. It was observed that MS generates lower calcite precipitation as compared with NB and TB. However, MS has the advantage of being more economical and abundant(waste product from sugar mills and refineries) as compared with other growth media(NB and TB). It was observed that the minimum and the maximum calcite precipitation using MS is 5% and 12%, respectively.The findings using MS in the present study was compared with the literature and found that precipitation of calcite using MS is effective to stabilize soil against wind erosion.

Overexpression of fibroblast growth factor 13 ameliorates amyloid-β-induced neuronal damage

Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.

Prognostic significance and relationship of SMAD3 phosphoisoforms and VEGFR-1 in gastric cancer:A clinicopathological study

BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

多奈哌齐联合丁苯酞治疗老年阿尔茨海默病的效果及对患者Hcy、CysC、VEGF的影响

目的观察多奈哌齐联合丁苯酞治疗老年阿尔茨海默病(AD)的效果及对患者血清同型半胱氨酸(Hcy)、胱抑素C(CysC)、血管内皮生长因子(VEGF)的影响。方法选取2021年1月—2022年6月福州市中医院收治的老年AD患者90例作为观察组,选择同期进行健康体检的90例健康老年人作为健康对照组,将观察组患者按随机数字表法分为Ⅰ亚组、Ⅱ亚组、Ⅲ亚组各30例,分别给予多奈哌齐、丁苯酞及多奈哌齐+丁苯酞治疗,3组均治疗24周。治疗前、治疗24周结束时对2组受试者进行血清Hcy、CysC、VEGF检测及记录简易精神状态检查量表(MMSE)、日常生活活动能力量表(ADL)评分,根据MMSE评分将患者分为轻度、中度、重度,比较不同病情程度患者治疗前血清Hcy、CysC、VEGF水平,采用Pearson相关分析探讨Hcy、CysC、VEGF与病情程度的相关性,治疗24周结束时评价临床疗效。结果观察组血清Hcy、CysC水平明显高于健康对照组,血清VEGF水平明显低于健康对照组(P均<0.01)。轻度、中度、重度患者血清Hcy、CysC、VEGF水平比较,差异有统计学意义(F/P=20.917/<0.001、37.397/<0.001、60.507/<0.001);Pearson相关分析显示,Hcy、CysC与病情程度呈正相关(r=0.853、0.864,P<0.01),VEGF与病情程度呈负相关(r=-0.901,P<0.01)。3亚组治疗总有效率比较,差异有统计学意义(χ^(2)=6.477,P=0.039);Ⅲ亚组治疗总有效率高于Ⅰ亚组、Ⅱ亚组(χ^(2)/P=5.963/0.015、4.812/0.028),但Ⅰ亚组、Ⅱ亚组治疗总有效率比较,差异无统计学意义(P>0.05)。3亚组治疗24周后MMSE评分与血清VEGF水平较治疗前升高,ADL评分与血清Hcy、CysC水平较治疗前降低,且治疗后3亚组间MMSE、ADL评分与血清Hcy、CysC、VEGF水平比较,差异有统计学意义(P<0.01),Ⅲ亚组治疗后相应指标与Ⅰ亚组、Ⅱ亚组比较差异有统计学意义(P<0.01),但Ⅰ亚组、Ⅱ亚组比较差异无统计学意义(P>0.05)。结论Hcy、CysC、VEGF参与老年AD的形成过程,Hcy、CysC与病情程度呈正相关,VEGF与病情程度呈负相关,多奈哌齐联合丁苯酞治疗老年AD能更有效降低Hcy、CysC水平,升高VEGF水平,进而提高临床治疗效果。

Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon

AIM: To investigate whether the expression of plateletderived growth factor receptor-α-positive(PDGFRα^+)-cells is altered in Hirschsprung's disease(HD).METHODS: HD tissue specimens(n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus(n = 10). Immunolabelling of PDGFRα^+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα^+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα^+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis

AIM To explore the role and mechanism of total flavone of Abelmoschus manihot(TFA) on epithelial-mesenchymal transition(EMT) progress of Crohn's disease(CD) intestinal fibrosis.METHODS First,CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial(IEC-6) cells and select the optimal concentrations of TFA for our further studies.Then cell morphology,wound healing and transwell assays were performed to examine the effect of TFA on morphology,migration and invasion of IEC-6 cells treated with TGF-β1.In addition,immunofluorescence,real-time PCR analysis(q RT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress.Moreover,western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways.Further,the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by q RTPCR,western blotting,morphology,wound healing andtranswell assays.RESULTS In this study,TFA promoted transforming growth factor-β1(TGF-β1)-induced(IEC-6) morphological change,migration and invasion,and increased the expression of epithelial markers and reduced the levels of mesenchymal markers,along with the inactivation of Smad and MAPK signaling pathways.Moreover,we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells.Importantly,co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSION These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

A novel apidaecin Api-PR19 synergizes with the gut microbial community to maintain intestinal health and promote growth performance of broilers

Background: Antibiotic growth promoters(AGPs) have been used as growth promoters to maintain animal intestinal health and improve feed efficiency in broilers by inhibiting pathogen proliferation. In view of the growing emergence of antibiotic-resistant pathogen strains and drug residue issues, novel treatments are increasingly required. This study aimed to compare two antimicrobial approaches for managing pathogen infection and maintaining animal intestinal health in broilers by supplying Apidaecin Api-PR19 and AGPs over 42 d of a feeding trial.Results: Compared with the broilers that were only fed a corn-soybean basal diet(CON group), supplementation with Api-PR19 and AGP(respectively named the ABP and AGP groups) both increased the feed conversion efficiency. When compared with the AGP group, Api-PR19 supplementation could significantly increase the organ index of the bursa of fabricius and subtype H9 antibody level in broiler chickens. Moreover, when compared with the CON group, the intestinal villus height, intestinal nutrient transport, and intestinal s Ig A content were all increased in the Api-PR19 group, while AGP supplementation was harmful to the intestinal villus height and intestinal nutrient transport. By assessing the antibacterial effect of Api-PR19 and antibiotics in vitro and in vivo, we found that Api-PR19 and antibiotics both inhibited the growth of pathogens, including Escherichia coli and Campylobacter jejuni. Furthermore, by using 16 S r RNA gene sequencing, the beneficial bacteria and microbiota in broilers were not disturbed but improved by apidaecin Api-PR19, including the genera of Eubacterium and Christensenella and the species of uncultured_Eubacterium_sp, Clostridium_asparagiforme, and uncultured_Christensenella_sp, which were positively related to improved intestinal development, absorption, and immune function.Conclusion: Apidaecin Api-PR19 treatment could combat pathogen infection and had little negative impact on beneficial bacteria in the gut compared to antibiotic treatment, subsequently improving intestinal development,absorption, and immune function.

Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling

Transforming growth factor-beta （TGF-β） type II receptor （TβRⅡ） levels are extremely low in the brain tissue of patients with Alzheimer＇s disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specific adapter protein, protects T RII from degradation and ensures the effective conduction of TGF-β 1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippocampus and investigated the regulatory effect of Dab2 protein on TGF-β1/SMAD signaling in a mouse model of Alzheimer＇s disease, and the potential neuroprotective effect. The results showed that the TβRⅡ level was lower.in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal TβRⅡ and p-SMAD2/3 levels were signifi- cantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor- and interleulin-6 levels and neuronal loss were significantly attenuated in APP/PS1 mouse brain tissue. These results suggest that Dab2 can exhibit neuroprotective effects in Alzheimer＇s disease by regulating TGF-β1/SMAD signaling.

Allelopathy of Gaseous Volatiles of Eupatorium adenophorum on Seed Germination and Seedling Growth of Pinus yunanensis

[ Objective] The paper was to understand allelopathy of gaseous volatiles of Eupatorium adenophorum stems and leaves on seed germination and seedling growth of P/nus yunnanens/s. [ Method] P. yunnanens/s seeds were treated by fresh stems and leaves of E. adenophorum in translucent airtight container under high concentration （0.069 4 g/cm3 ）, middle concentration （0.023 1 g/cm3 ） and lower concentration （0. 007 7 g/cm3 ）, respectively. [ Result] Gaseous volatiles affected seed germination process; with the increasing processing concentration, the day on which seeds began to germinate and the day reaching germination peak were delayed, and the germination quantity on the day reaching germination peak was decreased ; the day on which the germination quantity began to significantly re- duce was delayed ; the process curve was developed from sudden increase and sudden decrease to gentle change, and nearly became a beeline at high concentration. The effects of gaseous volatiles on seed germination （ seed germination rate, germination potential, germination index） and seedling growth （fresh weight, dry weight, radicle length, hypceotyl length） of P. yunnanens/s were basically consistent, showing a regularity that high concentration had stronger inhibition effect and the inhibition effect became weaker with the decreasing concentration of E. adenophorum. E. adenophorum was widely distributed under P. yunnanens/s forests, and might affect natural regeneration and growth of P. yunnanens/s via allelopathy. [ Conclusion ] The paper provides reference for scientific management of P. yunnanens/s forests.

Effects of Drought Stress Simulated by Polyethylene Glycol on Seed Germination, Root and Seedling Growth, and Seedling Antioxidant Characteristics in Job’s Tears

Two Job’s tears cultivars, yy18-1 (high resistance to drought stress) and yy12-7 (susceptible to drought stress) were used to investigate the responses of seed germination, root and seedling growth, and seedling antioxidant characteristics to drought stress simulated by polyethylene glycol (PEG) 6000 solutions with 0, -0.05, -0.1, -0.15, and -0.2 MPa osmotic potentials. The results showed that the germination energy, germination rate, germination index, root and seedling lengths, root and seedling diameters, root and seedling fresh masses, root and seedling dry masses, and seedling relative water content (RWC) decreased with the decrease of the osmotic potential of PEG 6000 solution. The contents of hydrogen peroxide (H2O2), malondialdehyde (MDA), and proline in seedling increased with the decrease of the osmotic potential of PEG 6000 solution. The activities of peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) in seedling increased and then decreased with the decrease of osmotic potential of PEG 6000 solution. -0.1 MPa was the optimal osmotic potential of PEG 6000 solution simulated drought stress at germination stage for Job’s tears. The proline content and activities of POD and CAT were important mechanisms for the maintenance of drought resistance in Job’s tears seedling.

Enriched environment elevates expression of growth associated protein-43 in the substantia nigra of SAMP8 mice

An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43（GAP-43） is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8（SAMP8） mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.

Intrastriatal Gene Transfer of Vascular Endothelial Growth Factor Rescues Dopaminergic Neurons in a Rat Parkinson's Disease Model

To examine the ability of intrastriatal gene transfer of vascular endothelial growth factor 165 mediated by adenoviral vector to rescue dopaminergic neurons in a rat model of Parkinson＇s disease （PD）, we constructed recombinant replication-deficent adenoviral vectors carrying the gene of VEGF165 （Ad-VEGF）, and injected Ad-VEGF （or Ad-LacZ and PBS as controls） into the striatum of rats 7 days after the lesion by 6-hydroxydopamine. The rat rotational behavior analysis and tyrosine hydroxylase （TH） immunohistochemistry were performed to assess the change of dopaminergic neurons. Our results showed that the rats receiving Ad-VEGF injection displayed a significant improvement in apomorphine-induced rotational behavior and a significant preservation of TH-positive neurons and fibers compared with control animals, It is concluded that intrastriatal gene transfer by Ad-VEGF may rescue the dopaminergic neurons from degeneration in a rat model of PD.

Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer’s disease

Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.

Nursery practice on seed germination and seedling growth of Dalbergia sissoo using beneficial microbial inoculants

Nursery practice using microbial inoculants was performed to find out the efficacy of the inoculants on seed germination and seedling growth of sissoo（Dalbergia sissoo Roxb.）.Microbial inoculants or effective microorganisms（EM） are a mixture of many different beneficial microorganisms in a solution.The seedlings were grown in a mixture of sandy soil and cowdung（3：1） kept in polybags with pouring EM solution at different concentrations（0.1%,0.5%,1%,2%,5% and 10%） before and after a week of sowing the seeds.Seed germination rate and growth parameters of seedlings were measured,such as,shoot and root length,vigor index,fresh and dry weight of shoot and root and total biomass increment.The nodulation status influenced by EM was also observed along with the measurement of pigment contents in leaves.The highest germination rate（69%） was observed in 2% EM treatment,followed by 67% and 65% in 1% and 5% EM.The highest shoot length（33.2 cm） was in 2% EM,whereas highest root length（26.3 cm） was in 1% EM.Both fresh and dry weights from shoot and root,were maximum（4.16 g and 1.57 g;2.12 g and 0.83 g respectively） in 2% EM and were significantly（p ≤ 0.05） different from control.Vigor index was highest（4071） in 2% EM,which was significantly（p ≤ 0.05） different from control.Total dry weight increment was highest in 2% EM treatment,followed by 1% and 5% concentrations of EM.Nodulation number was higher at very low（0.1%） concentration of EM solution but it normally decreased with the increase of EM concentrations.The contents of chlorophyll a,chlorophyll b and carotenoid were highest（60.11,17.05 and 42.48 mg·L1respectively） in 2% EM treatment and lowest（39.35,13.55 and 27.29 mg·L-1 respectively） in control treatment.Therefore,low concentration of EM（up to 2%） can be used for getting maximum seed germination rate and seedling development of Dalbergia sissoo Roxb.

Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p

BACKGROUND The incidence of inflammatory bowel disease,a chronic intestinal inflammatory disorder that includes Crohn’s disease(CD)and ulcerative colitis,is rising.Circular RNAs are considered valuable diagnostic biomarkers for CD.Current evidence supports the views that epithelial-mesenchymal transition(EMT)plays an important role in CD pathogenesis,and that hsa-miR-130a-3p can inhibit transforming growth factor-β1(TGF-β1)-induced EMT.Our previous study revealed that hsa_circRNA_102610 was upregulated in CD patients.Moreover,we predicted an interaction between hsa_circRNA_102610 and hsa-miR-130a-3p.Thus,we hypothesized that hsa_circRNA_102610 may play roles in the proliferation and EMT of intestinal epithelial cells by sponging hsa-miR-130a-3p to participate in the pathogenesis of CD.AIM To explore the mechanism of hsa_circRNA_102610 in the pathogenesis of CD.METHODS The relative expression levels of hsa_circRNA_102610 and hsa-miR-130a-3p in patients were detected by quantitative reverse transcription-polymerase chain reaction.The proliferation of human intestinal epithelial cells(HIECs)and normal-derived colon mucosa cell line 460(NCM460)cells was detected by cell counting kit-8,5-ethynyl-2’-deoxyuridine staining and cell cycle assays following overexpression or downregulation of hsa_circRNA_102610.Cell proliferation assays were performed as described above in a rescue experiment with hsa-miR-130a-3p mimics.The interaction of hsa_circRNA_102610 and hsa-miR-130a-3p was verified by fluorescence in situ hybridization and dual luciferase reporter assays.The relative expression levels of CyclinD1,mothers against decapentaplegic homolog 4(SMAD4),E-cadherin,N-cadherin and Vimentin were detected by western blotting following hsa_circRNA_102610 overexpression,TGF-β1-induced EMT or hsa-miR-130a-3p mimic transfection(in rescue experiments).RESULTS Upregulation of hsa_circRNA_102610 was determined to be positively correlated with elevated fecal calprotectin levels in CD(r=0.359,P=0.007)by Pearson correlation analysis.Hsa_circRNA_102610 promoted the proliferation of HIECs and NCM460 cells,while hsa-miR-130a-3p reversed the cell proliferationpromoting effects of hsa_circRNA_102610.Fluorescence in situ hybridization and dual luciferase reporter assays showed that hsa_circRNA_102610 directly bound hsa-miR-130a-3p in NCM460 and 293T cells.An inverse correlation between downregulation of hsa-miR-130a-3p and upregulation of hsa_circRNA_102610 in CD patients was observed(r=-0.290,P=0.024)by Pearson correlation analysis.Moreover,overexpression of hsa_circRNA_102610 promoted SMAD4 and CyclinD1 protein expression validated by western-blotting.Furthermore,overexpression of hsa_circRNA_102610 promoted TGF-β1 induced EMT in HIECs and NCM460 cells via targeting of hsa-miR-130a-3p,with increased expression of Vimentin and N-cadherin and decreased expression of E-cadherin.CONCLUSION Hsa_circRNA_102610 upregulation in CD patients could promote the proliferation and EMT of intestinal epithelial cells via sponging of hsa-miR-130a-3p.

Modeling of Fatigue Crack Growth Closure Considering the Integrative Effect of Cyclic Stress Ratio,Specimen Thickness and Poisson's Ratio

Key components of large structures in aeronautics industry are required to be made light and have long enough fatigue lives.It is of vital importance to estimate the fatigue life of these structures accurately.Since the FCG process is affected by various factors,no universal model exists due to the complexity of the mechanisms.Most of the existing models are obtained by fitting the experimental data and could hardly describe the integrative effect of most existing factors simultaneously.In order to account for the integrative effect of specimen parameters,material property and loading conditions on FCG process,a new model named integrative influence factor model（IIF） is proposed based on the plasticity-induced crack closure theory.Accordingly to the predictions of crack opening ratio（γ） and effective stress intensity factor range ratio（U） with different material under various loading conditions,predictions of γ and U by the IIF model are completely identical to the theoretical results from the plane stress state to the plane strain state when Poisson＇s ratio equals 1/3.When Poisson＇s ratio equals 0.3,predictions of γ and U by the IIF model are larger than the predictions by the existing model,and more close to the theoretical results.In addition,it describes the influence of R ratios on γ and U effectively in the whole region from-1.0 to 1.0.Moreover,several sets of test data of FCG rates in 5 kinds of aluminum alloys with various specimen thicknesses under different loading conditions are used to validate the IIF model,most of the test data are situated on the predicted curves or between the two curves that represent the specimen with different thicknesses under the same stress ratio.Some of the test data slightly departure from the predictions by the IIF model due to the surface roughness and errors in measurement.Besides,based on the analysis of the physical rule of crack opening ratios,a relative thickness of specimen is defined to describe the influence of material property,specimen thickness and so forth on FCG characteristics conveniently.In conclusion,the relative thickness of specimen simplifies the expression of FCG characteristic and provides a general parameter to analyze the fatigue characteristics of different materials with various thicknesses under different loading conditions.The IIF model describes the integrative effect of existing influence factors explicitly and quantitatively,and provides a helpful tool for fatigue property estimation of practical component and experiment design.