Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy

Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. In the present study, a streptozotocin-induced diabetic animal model was given an intraperitoneal injection of tauroursodeoxycholic acid. Results from immunofluorescent co-localization experiments showed that both caspase-12 protein and c-Jun N-terminal kinase 1 phosphorylation levels significantly in- creased, which was associated with retinal ganglion cell death in diabetic retinas. The C/ERB ho- mologous protein pathway directly contributed to glial reactivity, and was subsequently responsible for neuronal loss and vascular abnormalities in diabetic retinopathy. Our experimental findings in- dicate that endoplasmic reticulum stress plays an important role in diabetes-induced retinal neu- ronal loss and vascular abnormalities, and that inhibiting the activation of the endoplasmic reticulum stress pathway provides effective protection against diabetic retinopathy.

Comparison of Postoperative Pain Following Laser-assisted Subepithelial Keratectomy and Transepithelial Photorefractive Keratectomy:a Prospective,Random Paired Bilateral Eye Study

Purpose:To compare postoperative pain following laser-assisted subepithelial keratectomy(LASEK) and transepithelial photorefractive keratectomy(T-PRK, two-step surgery) and alleviate postoperative subjective pain.Methods:.Thirty patients(60 eyes) with myopia or myopic astigmatism were consecutively recruited into this prospective,randomized paired study..Patients underwent LASEK in one eye,and T-PRK in the other. The degree of pain was rated on a scale of 0-10 on postoperative days 1,2 and 3..Uncorrected visual acuity(UCVA) and subepithelial corneal haze were assessed at postoperative 1 and 3 months.Results:.The pain was relieved on the 4th postoperative day in all patients,.healing of corneal epithelium was observed at4-5 days after surgery and contact lenses were removed promptly.At postoperative 1 day,.the mean subjective pain score in the LASEK group was 3.2±1.88 and 4.43±1.61 in TPRK group(P=0.008).No significant difference was found between two groups on postoperative 2 and 3 days. At postoperative 3 months, the percentage of UCVA ≥0.8 in the LASEK group was 100% and 96.7% in the T-PRK group.(P =0.24),93.3% of patients in the LASEK with UCVA ≥1.0 and 90%in the T-PRK group(P=0.64). In the LASEK group, the value of corneal haze was 0.26 ±0.21 and 0.27 ±0.25 in the T-PRK group(P=0.877).Conclusion:.Good visual acuity was obtained in both groups at postoperative 3 months. Compared with those in the T-PRKgroup, patients undergoing had less discomfort in the LASEK group, which may be associated with corneal epithelial activity. The changing curve of subjective pain in the T-PRK group was relatively flat and stable at postoperative 3 days.

Extracts from rabbit skin inflamed by the vaccinia virus attenuate bupivacaine-induced spinal neurotoxicity in pregnant rats

Extracts from rabbit skin inflamed by the vaccinia virus can relieve pain and promote repair of nerve injury. The present study intraperitoneally injected extracts from rabbit skin inflamed by the vaccinia virus for 3 and 4 days prior to and following intrathecal injection of bupivacaine into pregnant rats. The pain threshold test after bupivacaine injection showed that the maximum possible effect of tail-flick latency peaked 1 day after intrathecal injection of bupivacaine in the extract-pretreatment group, and gradually decreased, while the maximum possible effect in the bupivacaine group continued to increase after intrathecal injection of bupivacaine. Histological observation showed that after 4 days of intrathecal injection of bupivacaine, the number of shrunken, vacuolated, apoptotic and caspase-9-positive cells in the dorsal root ganglion in the extract-pretreatment group was significantly reduced compared with the bupivacaine group. These findings indicate that extracts from rabbit skin inflamed by the vaccinia virus can attenuate neurotoxicity induced by intrathecal injection of bupivacaine in pregnant rats, possibly by inhibiting caspase-9 protein expression and suppressing nerve cell apoptosis.

A male-ABCD algorithm for hepatocellular carcinoma risk prediction in HBs Ag carriers

Objective: Hepatocellular carcinoma(HCC) development among hepatitis B surface antigen(HBs Ag) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBs Ag-positive male adults.Methods: HBs Ag-positive males of 35-69 years old(N=6,153) were included from a multi-center populationbased liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using Bultrasonography and α-fetoprotein(AFP). We used logistic regression models to determine potential risk factors,built and examined the operating characteristics of a point-based algorithm for HCC risk prediction.Results: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT(γ-glutamyl-transpeptidase), counts of platelets, white cells,concentration of DCP(des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91(0.90-0.93), larger than existing models. At 1.5 points of risk score,26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk,with positive prediction value of 22.85% and 12.35%, respectively.Conclusions: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.

H_(2)O_(2)mediates transcriptome reprogramming during Soybean mosaic virus-induced callose deposition in soybean

The main defense response to Soybean mosaic virus(SMV)infection in soybean[Glycine max(L.)Merr.]is thought to be blockage of intercellular virus transport by callose deposition on plasmodesmata.But the specific regulatory mechanism remains largely unknown.In this study,we found that hydrogen peroxide(H_(2)O_(2))signal downstream of NO was associated with the regulation of callose accumulation.Abundant H_(2)O_(2)was produced on the cell membrane and cell wall in the incompatible combination of soybean cultivar Jidou 7 and SMV strain N3,whereas no obvious H_(2)O_(2)was observed in the compatible combination of Jidou 7 and strain SC-8.When H_(2)O_(2)production was inhibited,callose accumulation induced by SMV infection decreased to a level insufficient to restrict virus transport in the incompatible combination.The H_(2)O_(2)-associated transcriptome dynamics of soybean during SMV infection was investigated.Transcriptome and functional analysis using virus-induced gene silencing showed that Gm SEOB and Gm PAP27,two genes regulated by H_(2)O_(2),functioned in resistance by positively regulating the accumulation of callose in response to SMV infection.These results lay a foundation for further research on the signal transduction and molecular regulation of callose deposition during soybean resistance to SMV infection.

Polymer flooding: Current status and future directions

This review presents our perspective on the factors that have brought polymer flooding to its current state. Insights are provided on why HPAM is the dominant polymer used as well as what is needed to make alternative polymers and mobility-control methods viable. Explanation is given for why large polymer banks are needed for polymer flooding, and design of the injected polymer viscosity is detailed for cases with/without crossflow. The role of fractures and horizontal wells are discussed for improving injectivity and extending polymer flooding to recover oils with viscosities as high as 10,000 cP. Operational improvements are described to minimize mechanical and oxidative stability to allow HPAM polymers to be viable to 70 °C and ATBS polymers to 120 °C. Key factors affecting polymer retention are summarized. The paper points out unresolved issues and future directions for polymer flooding.

Examination of literature on colloidal dispersion gels for oil recovery

This paper examines literature that claims,suggests,or implies that floods with"colloidal dispersion gels"(CDGs)are superior to polymer floods for oil recovery.The motivation for this report is simple.If CDGs can propagate deep into the porous rock of a reservoir,and at the same time,provide resistance factors or residual resistance factors that are greater than those for the same polymer formulation without the crosslinker,then CDGs should be used in place of polymer solutions for most/all polymer,surfactant,and ASP floods.In contrast,if the claims are not valid,(1)money spent on crosslinker in the CDG formulations was wasted,(2)the mobility reduction/mobility control for CDG field projects was under-designed,and(3)reservoir performance could have been damaged by excessive loss of polymer,face-plugging by gels,and/or excessive fracture extension.From this review,the clear answer is that there is no credible evidence that colloidal dispersion gels can propagate deep into the porous rock of a reservoir,and at the same time,provide resistance factors or residual resistance factors that are greater than those for the same polymer formulation without the crosslinker.CDGs have been sold using a number of misleading and invalid arguments.Very commonly,Hall plots are claimed to demonstrate that CDGs provide higher resistance factors and/or residual resistance factors than normal polymer solutions.However,because Hall plots only monitor injection pressures at the wellbore,they reflect the composite of face plugging/formation damage,in-situ mobility changes,and fracture extension.Hall plots cannot distinguish between these effects-so they cannot quantify in situ resistance factors or residual resistance factors.Laboratory studiesdwhere CDG gelants were forced through short cores during 2-3 h-have incorrectly been cited as proof that CDGs will propagate deep(hundreds of feet)into the porous rock of a reservoir over the course of months.In contrast,most legitimate laboratory studies reveal that the gelation time for CDGs is a day or less and that CDGs will not propagate through porous rock after gelation.A few cases were noted where highly depleted Al and/or HPAM fluids passed through cores after one week of aging.Details about these particular formulations/experiments were sparse and questions remain about their reproducibility.No credible evidence indicates that the CDG can propagate deep into a reservoir(over the course of weeks or months)and still provide a greater effect than that from the polymer alone.With one exception,aluminum from the CDG was never reported to be produced in a field application.In the exception,Chang reported producing 1-20%of the injected aluminum concentration.The available evidence suggests that some free(unreacted)HPAM and aluminum that was associated with the original CDG can propagate through porous media.However,there is no evidence that this HPAM or aluminum provides mobility reduction greater than that for the polymer formulation without crosslinker.

Effects of Plant-derived Humic Acid Organic Fertilizer on Selenium Content of Rice in Northern Guangxi

This study was to find out the suitable application amount of plant-derived humic acid organic fertilizer for selenium-rich rice production in northern Guilin area by applying the fertilizer at different amounts.The results showed that plant-derived humic acid organic fertilizer could effectively activate selenium in selenium-rich soil,and then promote the uptake of selenium by rice.With costs,selenium enrichment and rice yield as the main evaluation indicators,A4 was chosen as the best treatment,that is,the application of 4 500 kg/hm^2 of plant-derived humic acid organic fertilizer as base fertilizer could achieve the best benefit.

Optimization of Extraction Process of Anthocyanins from Selenium-enriched Purple Potato by Response Surface Methodology

Ultrasound-assisted extraction method was applied to extract the anthocyanins from selenium-enriched purple potato,and the optimum extraction conditions for anthocyanins in selenium-enriched purple potato were obtained by response surface methodology:the phosphoric acid concentration of 1.0%,the solid-liquid ratio at 5,and the extraction time of 19 min.Under these conditions,the yield of anthocyanins in selenium-enriched purple potato reached(0.409±0.010)mg/g(RSD=2.51%,n=3).The extraction of anthocyanins from selenium-rich fresh purple potato with dilute phosphoric acid has the advantages of less acid consumption and good extraction effect.

Relationship between bronchial asthma and glucocorticoid receptor gene bcl-I single nucleotide polymorphism

Objective: To investigate the relationship between bronchial asthma in children and glucocorticoid receptor (GR) gene bcl-I single nucleotide polymorphism and to analyze the relationship between bronchial asthma and the plasma cortisol level. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to deter-mine the GR gene bcl-I single nucleotide polymorphism in 76 children patients with asthma and 50 healthy controls. The plasma cortisol levels were detected by radio immunoassay in two groups respectively. Results: There were three genotypes found in bcl-I gene locus of these two groups, which were genotype CC, GG and CG. The frequencies of CC, CG, GG genotypes were 48.7%, 27.6%, 23.7% in the asthma group and 76%, 20%, 4% in the control group. The difference was of statistical significance (p < .05). The frequency of G allele in the asthma group was 37.5%, which was significantly higher than 14% in the control group (p < .05), indicating that G allele was associated with asthma. Conclusions: GR gene bcl-I polymorphism is significantly associated with the occurrence of bronchial asthma. G allele may be a susceptibility gene for steroid-resistance in asthma. Steroid-resistance has no correlation to the plasma cortisol level.

Morphine pre-exposure facilitates reinstatement but attenuates retention of morphine-induced place preference

BACKGROUND： Drug-associated conditioned stimuli are a key factor to induce morphine relapse. To date, limited evidence is available regarding the impact of drug history on propensity or vulnerability to relapse after long-term abstinence. OBJECTIVE： To determine the effect of morphine pre-exposure on acquisition, maintenance and reinstatement of morphine-induced conditioned place preference （CPP） in rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Behavior Pharmacology, Institute of Psychology, the Chinese Academy of Sciences, from March to September, 2006. MATERIALS： Morphine hydrochloride was purchased from Qinghai Pharmaceutical, China; CPP software was designed and developed by Taiji Software Company, Beijing, China. METHODS： A total of 64 Sprague Dawley rats were randomly assigned to eight groups （n = 8）. Four morphine pretreatment regimens were used （subcutaneous injections, twice daily for 5 consecutive days and a total of 10 times）： （1） ＂intensive＂ （morphine injections with doses escalating from 10 to 60 mg/kg; （2） ＂moderate＂ （one morphine injection at 5 mg/kg dose and one saline injection at 1 mL/kg daily for 5 days）; and （3） ＂single＂ （nine saline injections at 1 mL/kg followed by one morphine injection at 5 mg/kg; （4） control （ten saline injections at 1 mL/kg）. At 5 days after morphine pretreatment, animals were divided into two subgroups that underwent morphine conditioned or saline conditioned training. The test for acquisition of CPP was performed 24 hours after CPP training. The retention of morphine CPP was measured by repeated tests performed weekly for 1 month after the initial test of place preference. After extinction by pairing each chamber with saline, the reinstatement of place preference by low doses of morphine （0.05, 0.15, 0.45 mg/kg） was tested. MAIN OUTCOME MEASURES： Acquisition, maintenance, and recovery response of CPP behavior. RESULTS： The acquisition magnitude of morphine-induced CPP was not affected by prior morphine exposure （F3, 56=0.17, P 〉 0.05）. However, rats treated with moderate or intensive morphine pretreatment showed a less persistent CPP （t = -1.36, P 〉 0.05; t = -1.18, P 〉 0.05）, but their place preference was reinstated by a low dose of morphine priming （t = -2.55, P 〈 0.05; t = -2.54, P 〈 0.05）. The retention and reinstatement of morphine-induced CPP did not differ between rats with single morphine pre-exposure and control rats. CONCLUSION： Morphine pretreatment enhanced reinstatement of morphine-induced CPP but with less persistence. Individuals with heavy drug exposure are more susceptible to drug relapse when re-exposed to addictive drugs.

Retinal ganglion cell death in a DBA/2J mouse model of glaucoma Microglial activation and intraocular pressure

BACKGROUND： Retinal microglia has been shown to reactivate in a murine model of pigmentary glaucoma. However, the relationship between microglial activation and intraocular pressure （lOP） elevation and retinal ganglion cell （RGC） death is still unclear. OBJECTIVE： To verify that microglial activation and tumor necrosis factor alpha （TNF-α） expression is involved in RGC death with elevated lOP and prolonged time of glaucomatous optic nerve lesion in a DBA/2J mouse model of glaucoma. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed at the Peking University Third Hospital, Peking University Eye Center, China between December 2006 and May 2008.MATEFIiALS： DBA/2J mice and C57BL/6J mice （Jackson Laboratory, USA）, rat anti-mouse CD11 b monoclonal antibody （Serotec, UK）, and goat anti-TNF-α polyclonal antibody （Sigma, USA） were used in this study.METHODS： A total of 100 female, DBA/2J mice at 3, 6, 9, 12, and 14 months of age （20 mice per age group） were used for the glaucoma model, and 18 C57BL/6J mice at 3, 9, 14 months of age （6 mice per age group） were used as normal controls. The anterior segment of the eye was observed using a slit-lamp biomicroscope, lOP was measured using a microneedle system. Morphology and number of retinal microglia were observed using immunohistochemistry. RGCs were quantified using Nissl staining. Co-localization of TNF-α and microglia was observed using double-labeling immunofluorescence. Excavation of the optic nerve head was observed utilizing hematoxylin-eosin staining. MAIN OUTCOME MEASURES： The following parameters were measured： lOP levels, numbers of RGCs and activated microglia, and TNF-α expression. RESULTS： In 6-month-old DBA/2J mice, dispersed pigment was observed, and some mice developed increased IOP. At 9 months of age, lOP levels reached a peak. In 3-month-old DBA/2J mice, microglia were activated. In 6-month-old DBA/2J mice, the number of activated microglia was significantly increased and migrated to the outer retinal layer. In 9-month-old mice, TNF-a expression was co-localized with microglia. Significant RGC loss occurred in mice aged 9 to 14 months, with the presence of optic nerve fiber loss and optical nerve head excavation, lOP returned to normal levels at 12 months of age, but microglia remained activated, which was consistent with RGC loss. CONCLUSION： Retinal microglial activation was partially attributed to increased lOP. Activated microglia might be mainly responsible for RGC loss. TNF-α expression was evident in the inner retinal layer. However, the relationship between TNF-α and RGC loss remains poorly understood.

TRAF7 enhances degradation of ubiquitinated KLF4 to promote hepatocellular carcinoma progression

Objective:The tumor necrosis factor receptor-associated factor 7(TRAF7)is one of the components of the tumor necrosis factor alpha(TNF-α)/nuclear factor kappa B(NF-κB)pathway and a putative E3-ubiquitin ligase.This study aims to explore the biologic effects and the molecular mechanisms of deregulated TRAF7 signaling in hepatocellular carcinoma(HCC)progression.

XCL1/Glypican-3 fusion protein induces potent CD8^+ T-cell generation and enhances the anti-PD1 effect to suspend hepatocellular carcinoma development

Objective:To induce potent CD8^+T-cells against glypican-3(GPC3),which is overexpressed in hepatocellular carcinoma(HCC),to suspend tumor development.Methods:Since the chemokine receptor XCR1 is selectively expressed on professional cross-presenting CD8α^+dendritic cells(DCs).

Transcriptome and Metabolome Revealed the Mechanism of NtBRL3 Overexpression Tobacco(Nicotiana tabacum L.K326)in Response to Drought Stress

Drought has severely affected the yield and quality of commercial crops.The BRI1 family plays an important role in plant response to drought stress,and BRL3 gene plays an important role in the study of drought in Arabidopsis thaliana.In this study,NtBRL3 was constructed as a vector and genetically transformed to obtain‘N.Tobacco K326’overexpression of NtBRL3.The enzyme activities of transgenic tobacco and wild-type tobacco were measured and transcriptome and metabolome analyses were performed.The results showed that the antioxidant enzymes of transgenic tobacco were more active under drought conditions,and 85 significantly differentially metabolites and 106 significantly differentially expressed genes were identified in the metabolome and transcriptome analyses,respectively.Transgenic tobacco NtBRL3ox demonstrated an excessive accumulation of droughtrelated metabolites,sugars such as sucrose and maltotetraose,and amino acids such as proline,compared with WT.We discovered drought-related differential genes in the root transcriptome,among which LOX6,RD22,WSD1,CCD8,and UGT were key genes which play an important role in plant response to drought stress.Our results demonstrate that NtBRL3 overexpression in K326 enhances drought resistance in transgenic tobacco.

Transcriptome Profiling of the Salt-Stress Response in Paper Mulberry

Paper mulberry is a high-quality woody feed resource plant with high crude protein content.It is widely distributed in China and has excellent characteristics of salt and alkali tolerance.Paper mulberry has ecological and economic importance.Salt stress has become a critical factor with the increasing degree of soil salinity that restricts plant growth.In the saline-alkali environments,transcriptome expression is altered leading to phenotypic defects in most plants.However,the regulatory mechanism related to paper mulberry’s salt-stress(SS)response is not clearly understood.In the present study de novo transcriptomic assembly was performed,and gene expression levels were measured between different SS and natural conditions(25℃)as a control for paper mulberry plants.According to the results of our study,under NaCl stress conditions,the differential gene expression was observed in the leaves of paper mulberry compared with the control.A total of 2126 differentially expressed unigenes were observed.Among these unigenes the expression of 812 DEGs was up-regulated and the expression of 1,314 DEGs was down-regulated.Additionally,The GO and KEGG analyses regarding differentially expressed unigenes(DEUs)revealed that the observed critical transcriptomic alterations under salt stress(SS)conditions were associated with primary and secondary metabolism,photosynthesis,and plant hormone signaling pathways.Further investigations such as gene function studies regarding the unigenes depicting altered expression under salt stress conditions in paper mulberry will help understand the mechanism of salt tolerance,and this information can be utilized in paper mulberry breeding and improvement programs.

Management Models and Development Strategies of the Farmers’ Professional Cooperatives in the Western Poor Counties and Regions of China: A Case Study of Long’an County,Guangxi

In the new era,an important task is how farmers’professional cooperatives to better adapt to new development environment and effectively solve the problems that"who will cultivate land"and"who does agriculture depend on"in the future.In this paper,model and development direction of farmers’professional cooperatives in Long’an County of Guangxi are analyzed and studied based on realistic development background of Guangxi.

Standardized Production Technology of Selenium-enriched Hylocereus undatus(pitaya) in Natural Selenium-rich Areas

With the adjustment of the tropical and subtropical fruit industry organizations in southern China, the Hylocereus undatus(pitaya) industry is growing rapidly in subtropical Guangxi and other places. Guangxi is also the largest natural selenium-rich region in the country, and selenium-enriched pitaya is increasingly sought after by the general public. This paper described in detail the selection of selenium-enriched pitaya production fields, key planting techniques and core selenium enrichment techniques, with a view to providing technical guidance for the standardized production of selenium-enriched pitaya and providing technical support for improving the quality and efficiency of pitaya production in natural selenium-rich areas.

Spectra of Harmonic Oscillators with GUP and Extra Dimensions

In this paper, we address the spectra of simple harmonic oscillators based on the generalized uncertainty principle (GUP) with a Kaluza-Klein compactified extra dimension. We show that in this scenario, to make the results compatible with experiments, the minimal length scale equals to the radius of compact extra dimension.

Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection

Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities.Methods: The AlCl3colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti-oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18column(2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase(PDB ID: 2CDU) by molecular docking.Results: Combined with the results of activity screening in vitro, the anti-oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatographymass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile.Conclusion: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.