Elucidation of potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa

Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper.The dynamic changes of endogenous proteases activity,free amino acids,and volatiles during dry-cured pork coppa processing were characterized.The results showed that 5 kinds of free amino acids,Glu,Lys,Val,Ala,and Leu,were identified as significant contributors to taste.Meanwhile,key volatiles,such as hexanal,nonanal,octanal,benzaldehyde,3-methyl butanoic acid,2-methyl propanoic acid,and ethyl octanoate,greatly contributed to the flavor characteristics of dry-cured pork coppa.Further partial correlation analysis was performed to better elucidate the relationship among parameters.The results revealed that close relationship between endogenous proteases and key substances.RAP not only significantly affected the accumulation of key active-amino acids,but also affected the accumulation of ethyl octanoate,2,3-pentanedione,and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu.In addition,cathepsin B and D,DPP II,DPP IV and RAP notably affected accumulation of hexanal.

Effect of proteolytic starter culture isolated from Chinese Dong fermented pork(Nanx Wudl)on microbiological,biochemical and organoleptic attributes in dry fermented sausages

The effect of a proteolytic starter culture isolated from Nanx Wudl,on microbiological,biochemical and organoleptic attributes of dry fermented sausages was investigated during processing.Based on preliminary screening,the combination of Staphylococcus xylosus SX16 and Lactobacillus plantarum CMRC6,showing excellent proteolytic activity in vitro,was selected as the multi-strain starter(starter LS).For comparison,the single-strain starter culture of L.plantarum CMRC6(starter LB)and non-inoculated control were also tested.During fermentation,lactic acid bacteria and staphylococci dominated the microbiota and suppressed the Enterobacteriaceae growth in LS-inoculated sausages.The addition of LS starter accelerated acidification and proteolysis during ripening,improving the contents of total free amino acids and several essential free amino acids(Phe,Ile and Leu).Volatile compounds analysis revealed that LS-fermented sausage showed the highest abundance of 3-methyl-1-butanol,probably due to the inoculated S.xylosus.The inoculation of LS starter improved the sensory properties of sausages,especially the flavor attribute.Therefore,S.xylosus SX16 and L.plantarum CMRC6 are promising candidates for inclusion as multi-strain starters in the manufacture of gourmet fermented dry sausage.

Genetic association of COL1A1 polymorphisms with high myopia in Asian population: a Meta-analysis

AIM: To comprehensively evaluate the potential association of COL1A1 polymorphisms with high myopia by a systematic review and Meta-analysis. METHODS: All association studies on COL1A1 and high myopia reported up to June 10, 2014 in PubMed, Embase, Web of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed for single-nucleotide polymorphisms (SNPs) using fixed- and random - effects models according to between-study heterogeneity. Publication bias analyses were conducted by Eggers test. RESULTS: A total of four studies from reported papers were included in this analysis. The Meta-analyses for COL1A1 rs2075555, composed of 2304 high myopia patients and 2272 controls, failed to detect any significant association with high myopia. A total of 971 cases and 649 controls were tested for COL1A1 rs2269336. The association of COL1A1 rs2269336 with high myopia was observed in recessive model (CC vs CG+GG, P = 0.03) and in heterozygous model (CG vsGG, P = 0.04), but not in other models. CONCLUSION: This Meta-analysis shows that COL fill rs2269336 (CC vs CG +GG) affects individual susceptibility to high myopia, whereas there is no association detected between SNPs rs2075555 and high myopia. Given the limited sample size, further investigations including more ethnic groups are required to validate the association.

Predominant yeasts in Chinese Dong fermented pork(Nanx Wudl)and their aroma-producing properties in fermented sausage condition

Yeasts are one of the predominant microbial groups in fermented meats.In this study,yeast communities of Chinese Dong fermented pork(Nanx Wudl)were investigated and the technological properties of 73 yeast isolates were evaluated.Through culture-dependent and high-throughput sequencing methods,the main yeast species identified included Pichia membranifaciens,Kazachstania bulderi,Millerozyma farinosa,Candida zeylanoides,Kazachstania exigua,Candida parapsilosis and Saccharomyces cerevisiae.Among these yeasts,P.membranifaciens,M.farinosa,K.exigua and K.bulderi were detected in fermented meats for the first time.A total of 73 yeast isolates was investigated for their lipolytic and proteolytic activities.All yeast species showed lipolytic activity,while proteolytic activity against meat protein was only detected in S.cerevisiae.Assay of aroma-producing potential was performed in a model simulating fermented sausage condition.Inoculation of yeast strains increased volatiles production,especially esters and alcohols.The highest ester production was observed in S.cerevisiae Y70 strain,followed by K.exigua Y12 and K.bulderi Y19.C.zeylanoides Y10 and S.cerevisiae Y70 were the highest producers of benzeneethanol and 3-methyl-1-butanol.S.cerevisiae Y70 with its highest production of branched alcohols and esters could be a promising candidate as aroma enhancer in the manufacture of fermented sausages.

Formation of arsenic−copper-containing particles and their sulfation decomposition mechanism in copper smelting flue gas

The heat recovery steam generator(HRSG)of copper smelting generates a large number of arsenic−coppercontaining particles,and the in-situ separation of arsenic and copper is of importance for cutting off environmental risk and realizing resource recovery.The formation of arsenic−copper-containing particles was simulated,the method of in-situ decomposition of arsenic−copper-containing particles by pyrite was proposed,and the decomposition mechanism was confirmed.It was found that particles with high arsenic content were formed in the simulated HRSG,and copper arsenate was liable for the high arsenic content.Pyrite promoted the sulfation of copper,leading to the in-situ decomposition of copper arsenate.In this process,gaseous arsenic was released,and thus the separation of arsenic and copper was realized.

Anticancer Effect of Ginseng Leaves Crude Polysaccharides on Human Hepatoma Cell SMMC-7721

Background: Polysaccharides extracted from the medicinal herbs are known to possess antitumor effects. Although there is a significant number of evidences implicated on the beneficial effects of the ginseng leaves ginsenoside with diverse associated mechanisms, reports on the anticancer by the ginseng leaves crude polysaccharides (GLCP) are not sufficient. Experiments were carried out to unravel the anticancer effects of GLCP. Methods: Cells were treated with GLCP (0.5 - 2 mg/ml) for 48h. MTT method was used to detect the cell viability. Western blot and flow cytometry were used to detect apoptotic rate. Western blot and acridine orange staining were used to detect the cell autophagy. Results: Compared with the normal human liver cell (Chang liver), GLCP (1.5 - 2 mg/ml) significantly reduction cell viability, promote apoptosis-related proteins expression, promote cell apoptosis and autophagy in SMMC-7721 cells. But caveolin-1 gene silencing could inhibit the anticancer effect of GLCP. Conclusions: These data suggest that GLCP promote autophagy and apoptosis in human hepatoma cell SMMC-7721. We speculate that its mechanism may be associated with the caveolin-1 which is an essential structural molecule of caveolae. Although the effect of GLCP inhibited of liver cancer is not very strong, we are more interested in the GLCP which plays a tumor suppressor role in health care.

Deep Sc-RNA sequencing decoding the molecular dynamic architecture of the human retina

The human retina serves as a light detector and signals transmission tissue.Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events.Here,we sequenced the m RNA of over 0.6 million single cells from human retinas across six regions at nine different ages.Sixty cell sub-types have been identified from the human mature retinas with unique markers.We revealed regional and age differences of gene expression profiles within the human retina.Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells.Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types.Some of the gene’s expression,such as DKK3,are elevated in aged retinas.A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability.Overall,decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system.

Short- and long-term effect of complete versus culprit-only revascularization in patients undergoing primary PCI for multivessel disease： a meta-analysis

Objective The optimal strategy during primary percutaneous coronary intervention （PCI） in patients with acute myocardial infarction and multivessel disease is still controversial. Therefore, the aim of our study is to evaluate the short- and long-term effect of complete revas- cularization （CR） versus infarct-related artery revascularization （IR） following primary PCI. Methods We identified randomized controlled studies （RCTs） by systematic search of PubMed, EMBASE, Web of Science, ClinicalTrials.gov Website, Cochrane Library and Google scholar Database. Primary outcome was major adverse cardiac events （MACE）. Result Nine RCTs （2198 patients） with mean follow-up of 21.1 months were retrieved. Overall, CR was associated with significantly lower risk of MACE compared with IR therapy when followed by long-term duration （≥ 12 months） （RR： 0.56; 95% Ch 0.47-0.68; I^2 = 58.5%）. Additionally, CR was associated with equivalent rates of all-cause mortality （RR： 0.76; 95% CI： 0.53-1.08; I^2= 0.0%） and myocardial infarction （RR： 0.81; 95% CI： 0.57-1.16; I^2= 26.4%） compared with control. Meanwhile, risk of stroke was similar between groups （RR： 0.73; 95% CI： 0.24-2.19; I^2= 0.0%）. However, rates of cardiac death and target vessel revascularization were significantly decreased in the CR group （RR： 0.41; 95% CI： 0.23-0.72; I^2 = 0.0% and RR： 0.46; 95% CI： 0.37-0.57; I^2= 47.4%）. Conclusion Complete revascularization appears to have long-term clinical benefit with regard to adverse cardiac events following primary PCI. However, more studies are needed to confirm these findings.

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

The nuclear transcription factors κB (NF-κB) is widely existing in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor alpha 36 (ER-α36), is a novel variant of ERα (as known ER-α66) which can transduce both estrogenand antiestrogen-dependent activation of MAPK signal pathway and stimulate cell growth. Here, we aimed to detect the effect of ER-α36 gene silencing on the expression of NF-κB in normal cultured PC12 cells and to provide an experimental foundation for understanding the function of ER-α36 innerve cells. PC12 cells with ER-α36 expression knocked down by the shRNA method. Then Western blot and immunocytochemical staining were performed to detect the expression and translocation of NF-κB after transfection. The results showed that NF-κB expression was significantly higher comparing with the control group after transfection (P 0.01). Also, NF-κB subunit entered nuclear after transfection;Immunofluorescence staining and immunocytochemical staining of PC12 cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and on the cell nucleus membrane. These data indicate that ER-α36 gene silencing can increase the expression of NF-κB and promote its nuclear translocation in PC12 cells.

Enhanced degradation of refractory organics in ORR-EO system with a blue TiO_(2)nanotube array modified Ti-based Ni-Sb co-doped SnO_(2)anode

Recently,a novel 2-electron oxygen reduction reaction(ORR)based electro-oxidation(EO)system was developed,which utilizes a H_(2)O_(2)generation cathode instead of H_(2)evolution cathode.A Ti-based Ni-Sb co-doped SnO_(2)(Ti/NATO)anode was selected for efficient degradation of refractory organics and O_(3)production.The synergistic reaction of O3/H_(2)O_(2)further accelerated the generation of hydroxyl radicals(·OH)in the ORR-EO system.However,the catalytic activity and long-term effectiveness of the Ti/NATO anode limited the large-scale application of the ORR-EO process.In this study,a blue TiO_(2)nanotube array(blue-TiO_(2)-NTA)inter-layer was introduced into the fabrication process between the Ti substrate and NATO catalyst layer.Compared to the Ti/NATO anode,the Ti/blue-TiO_(2)-NTA/NATO anode achieved higher efficiency of organic removal and O_(3)generation.Additionally,the accelerated lifetime of the Ti/blue-TiO_(2)-NTA/NATO anode was increased by 7 times compared to the Ti/NATO anode.When combined with CNTs-C/PTFE air cathode in ORR-EO system,all anodic oxidation and O_(3)/H_(2)O_(2)processes achieved higher•OH production.Over 92%of TOC in leachate bio-effluent was effectively eliminated with a relatively low energy cost of 45 kWh/t.

Whole exome sequencing identifies mutations of multiple genes in a Chinese cohort of 95 sporadic probands with presumptive retinitis pigmentosa

Retinitis pigmentosa(RP),a major cause of inherited blindness worldwide,is highly heterogeneous.This study aimed to identify mutations in a Chinese cohort of sporadic probands with presumptive RP.Whole exome sequencing represents a considerable advancement in the identification of mutations associated with Mendelian diseases,such as RP.In this study,whole exome sequencing analysis was performed in a Chinese cohort of 95 sporadic probands who were initially diagnosed with RP,in order to identify disease mutations.All detected variations were confirmed by direct Sanger sequencing,and potential pathogenicity was assessed by predictions of the mutations’functions.The overall mutation rate of presumptive RP genes for this cohort was 30.5%(n=29 of 95 probands).Forty-four mutations were identified in 19 RP genes,among which 40 mutations were novel.Eleven probands carried mutations in autosomal dominant genes(38.0%),16 probands carried mutations in autosomal recessive genes(55.2%),and 2 probands carried mutations in X-linked genes(6.9%).Twenty-eight mutations in 18 genes linked to other retinal diseases in 23 probands were also identified.Overall,mutations were detected in 52 probands(54.7%).The recurrent and novel mutations reported here will expand potential understanding of the pathogenesis of RP and other retinal diseases.

Dynamic human retinal pigment epithelium(RPE)and choroid architecture based on single-cell transcriptomic landscape analysis

The retinal pigment epithelium(RPE)and choroid are located behind the human retina and have multiple functions in the human visual system.Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies.Here,we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages,revealing regional and age differences within the human RPE and choroid.Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types.Moreover,the transcription factors and their target genes change during aging.The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level.Moreover,we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging.The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

利用CRISPR/Cas9基因编辑技术治疗β-地中海贫血的最新进展

β-地中海贫血是β-珠蛋白基因(HBB)点突变或缺失引起的单基因遗传病,患者产生溶血性贫血,其生存主要依赖于反复输血及去铁治疗,最终导致多器官受损、衰竭,给个人、家庭和国家带来严重的经济负担.随着基因编辑技术的蓬勃发展,可能治愈基因突变性疾病的基因治疗应运而生,其中CRISPR/Cas9基因编辑技术凭其靶向特异性、经济性等优势备受关注,并已广泛应用于分子生物学以及生命科学领域的研究.如今CRISPR/Cas9基因编辑技术修复人多能干细胞HBB基因、诱导胎儿血红蛋白(HbF)合成或抑制α-珠蛋白基因(HBA基因)表达是治愈β-地中海贫血的三大可行性策略,相关临床试验已相继开展.本文就CRISPR/Cas9系统的研究进展、作用机制以及在治疗β-地中海贫血的最新研究与应用进行综述,涉及细胞实验、动物模型、临床试验等内容,并介绍了CRISPR/Cas9系统衍生的新型基因编辑工具碱基编辑器在该领域的研究应用,为促进β-地中海贫血从基础研究转向临床治疗提供新的思路和方向.

Age-related macular degeneration: Epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy

Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macula and it is classified as early stage to late stage (advanced AMD). The advanced AMD is classified into the nonexudative or atrophic form (dry AMD) and the exudative or neovascular form (wet AMD). More severe vision loss is typically associated with the wet form. Multiple genetic factors, lipid metabolism, oxidative stress and aging, play a role in the etiology of AMD. Dysregulation in genetic to AMD is established to 46%–71% of disease contribution, with CFH and ARMS2/HTRA1 to be the two most notable risk loci among the 103 identified AMD associated loci so far. Chronic cigarette smoking is the most proven consistently risk living habits for AMD. Deep learning algorithm has been developed based on image recognition to distinguish wet AMD and normal macula with high accuracy. Currently, anti-vascular endothelial growth factor (VEGF) therapy is highly effective at treating wet AMD. Several new generation AMD drugs and iPSC-derived RPE cell therapy are in the clinical trial stage and are promising to improve AMD treatment in the near future.

DMF stabilized Li3N slurry for manufacturing self-prelithiatable lithium-ion capacitors

Li3N is an excellent zero-residue positive electrode pre-lithiation additive to offset the initial lithium loss in lithium-ion capacitors. However, Li3N has an intrinsic problem of poor compatibility with commonly used aprotic polar solvents in electrode manufacture procedure due to its high reactivity with commonly used solvents like N-methy-2-pyrrolidone(NMP) and etc. It is the Valley of Death between research and large-scale commercialization of Li-ion capacitors using Li3N as prelithiation agent. In this work, Li3N containing electrode is prepared by a commercially adoptable route for the first time, using N,Ndimethylformamide(DMF) to homogenate the electrode slurry. The DMF molecular stabilizing mechanism is confirmed via experiment analysis and DFT simulation, indicating that the dehydrogenation energy for DMF is obviously larger than other commonly used solvents such as NMP and etc. The soft package lithium-ion capacitors(LIC250) with only 12 wt% Li3N addition in AC positive electrode exhibits excellent rate capability, cyclic stability and ultrahigh specific energy. Its specific energy is 2.3 times higher than the Li3N-free devices, with energy retention as high as 90% after 10,000 cycles.

3D-metal-embroidered electrodes:dreaming for next generation flexible and personalizable energy storage devices

Flexible and Personalizable battery is a promising candidate for energy storage, but suffers from the weldablity and large-scale producibility of the electrode. To address the issues, we design a nickel foam catalyzed electroless deposition (NFED) derived 3D-metal-pattern embroidered electrodes. This is the first attempt to utilize this type of electrode in battery field. It is found that the current collector can be embroidered on any selected areas of any complex-shape electrodes, with high controllability and economical feasibility. As a result, the electronic conductivity of the flexible electrodes can be improved by nearly one order of magnitude, which can be easily and firmly weldded to the metal tab using the industry generic ultrasonic heating process. The embroidered electrodes could substantially promote the electrochemical performance under bending deformation, with both Li-S and Li-Li FePO4batteries as the models. This innovation is also suitable to embroider all the VIII group elements on any electrodes with personalized shapes, which is widely attractive for the development of next generation flexible and personalizable energy storage devices.