Optical-neural Stimulation in Non-human Primates:Modulating Brain Function and Behavior

Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.

Isolation of a Prodigiosin-producing Strain and Analysis of It's Pigments

[Objective] The aim was to isolate a prodigiosin producing strain and study its pigment fractions.[Method] Red pigment-producing bacteria was identified by physiological and biochemical characteristics after isolation in plate.By using column chromatography and thin-layer chromatography,pigment fractions were separated and purified from the extractives of the strain after fermentation in flask,and then pigment fractions were analyzed via UV-Vis and LC/MS.[Result] A red pigment-producing Serratia marcescens strain NS-17 sampled from soil of Nanchang was isolated and identified.2 pigment fractions showing similar UV-Vis and LC/MS characters were separated and purified,the characters of fraction 1 were identical to those of prodigiosin,while fraction 2 showed a special UV-Vis absorption spectrum that had not been reported.[Conclusion] A prodigiosin-producing Serratia marcescens strain NS-17 and its 2 pigment fractions were isolated.

红灵(下)

韩正龙与龙山深入“虎穴”．终于查出了红灵的真实功效．但他们也遭遇到了上百只丧尸的围攻。在两人携手奋力将丧尸消灭过后，龙山却露出了他的真面目……

Determination of Lycopene Concentration in Dog Plasma by RP-HPLC

A method for determination of lycopene concentration in dog plasma wasestablished. Methods RP-HPLC was used; the mobile phase consisted of methanol-acetonitrile-methylenechloride (40:30:30, V/V) , the wavelength of detection was 472 nm, the column temperature wasambient temperature, and the flow rate was 1.0 mL·min^(-1). Results The standard curve was linearin the range from 0.012 4 to 0.496 μg·mL^(-1) with r=0.9992. The average extraction recovery was97.6% +-4.2%. The intra-day and inter-day RSD were 1.52% -4.95% and 2.31% -7.38%, respectively.Conclusion This method is sensitive, rapid, reproducible, and of good selectivity for the analysisof lycopene in dog plasma.

红灵(上)

不知多久之后．我恢复了意识。揉揉眼睛，看清四周的环境：多么遥远而熟悉的场景，群山包围的荒野，灰白的月光，还透着泥土气息的乌木棺。

Trinity of Chillingworth

Chillingworth is a complicated character in The scarlet letter. His image is a synthesis, or trinity, of the images of God, man of science and Satan, and the novel demonstrates a degradation from God to man of science and finally to a Satan of hatred. In this vicious transformation, his character as man of science plays a key role. Through the development of this character, Hawthorne expresses his criticism to those who lack necessary reverence for human heart and soul.

Comparison of mechanisms and efficacies of five formulas for improving blood circulation and removing blood stasis

Objective This study aimed to compare the mechanisms and efficacies of five formulas that improve blood circulation and remove blood stasis.Methods(1)A network pharmacology method was used to determine the targets of five formulas that promote circulation and remove blood stasis.Compounds of the five formulas,namely Danshen Yin(丹参饮,DSY),Huoluo Xiaoling Dan(活络效灵丹,HLXLD),Shixiao San(失笑散,SXS),Taohong Siwu Tang(桃红四物汤,THSWT),and Xuefu Zhuyu Tang(血府逐瘀汤,XFZYT),were retrieved from the Traditonal Chinese Medicine System Pharmacology Database(TCMSP),the Shanghai Institute of Organic Chemistry of CAS,and the TCM Integrated Database.Drug target network was constructed by searching the Swiss Target Prediction database and the STITCH database.The target network of stasis was extracted from the PharmGKB database,the Online Mendelian Inheritance in Man(OMIM)database,the Genetic Association Database(GAD),and the Therapeutic Target Database(TTD).Candidate targets were determined using protein-protein interaction(PPI)network extension and topology selection.Thereafter,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was used to determine the differentiation of the mechanism of the five formulas.(2)Animal experiments were conducted to explore the efficacies of the five formulas in treating blood stasis.Seventy New Zealand rabbits were exposed to high-fat feeding+epinephrine injection to construct a blood stasis syndrome model.The rabbits were evenly divided into control,model,DSY,HLXLD,SXS,THSWT,and XFZYT groups.The latter five groups were orally administered the corresponding formulas[DSY:3.92 g/(kg·d),XFZYT:7.10 g/(kg·d),SXS:1.12 g/(kg·d),HLXLD:5.60 g/(kg·d),THSWT:4.48 g/(kg·d)].Serum lipid and blood rheology were analyzed,and pathology slices were observed.Results(1)A total of 269,358,288,370,and 376 candidate targets of DSY,HLXLD,SXS,THSWT,and XFZYT were obtained among which were 232 shared candidate targets.Fluid shear stress and atherosclerosis were the biological processes common to the five formulas.HLXLD,SXS,DSY,and THSWT regulated lipolysis in adipocytes,and XFZYT,HLXLD,SXS,and THSWT regulated the AGE-RAGE signaling pathway and complement and coagulation cascades.HLXLD,SXS,and XFZYT regulated the HIF-1 signaling pathway,DSY regulated the cGMP-PKG signaling pathway,HLXLD reduced platelet activation,SXS regulated the calcium signaling pathway,and XFZYT regulated the PPAR signaling pathway.(2)In the animal experiments,the values of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL),high density lipoprotein cholesterol(HDL),TC/HDL,and TG/HDL in each group decreased,among which the ones seen in XFZYT,HLXLD,and SXS groups were statistically significant(P<0.05).XFZYT presented the best effect,followed by HLXLD and SXS.XFZYT and HLXLD decreased apolipoprotein B100(apoB100)and increased apolipoprotein A1/apoB100(P<0.05).XFZYT decreased all the values of hematocrit(HCT),plasma viscosity,whole blood viscosity(WBV);HLXLD and SXS affected HCT;and DSY and THSWT regulated WBV(P<0.05).All the five formulas decreased the values of optical density and area of plaque,among which XFZYT and HLXLD showed statistical significance(P<0.05).Conclusion Adjusting fluid shear stress and alleviating the injury of endothelial cells might be the common mechanisms by which the five formulas promote blood circulation and remove blood stasis.Different formulas also have unique targets,which may provide guidance for clinical drug selection.By regulating different indices,the five formulas can regulate blood lipid and hemorheology,improve the state of blood stasis,and decrease the degree of aortic plaque in the blood stasis model rabbits.XFZYT and HLXLD had higher efficacies than DSY,THSWT,and SXS.

五首活血化瘀方对血瘀证新西兰兔血常规、血沉及心、肝脏器系数的影响

目的观察五首活血化瘀方对新西兰兔血瘀证血常规、血沉及心、肝脏器系数的影响,对比其作用差异,为临床选方用药提供实验依据。方法70只新西兰兔随机分为正常组10只,造模组60只。采用“饥饿+高脂饲料+肾上腺素”方法复制血瘀证模型。造模成功后将造模组随机分为模型组、血府组、丹参组、失笑组、活络组、桃红组。各复方组分别给予相应复方灌胃治疗,正常组和模型组予以同等剂量蒸馏水灌胃作为对照。治疗结束后腹主动脉取血检测血常规及血沉,空气栓塞处死后取心脏、肝脏计算脏器系数。结果与正常组比较,模型组红细胞计数(RBC)、红细胞压积(HCT)、血红蛋白(HGB)显著降低(P<0.01),平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)、平均红细胞血红蛋白浓度(MCHC)、白细胞计数(WBC)、中间细胞计数(Mid)、粒细胞计数(Gran)、肝脏系数显著升高(P<0.05或P<0.01),红细胞体积分布宽度变异系数(RDW-CV)、淋巴细胞计数(Lymph)、血小板计数(PLT)、血小板压积(PCT)、平均血小板体积(MPV)、血小板分布宽度(PDW)、血沉(ESR)、心脏系数差异无统计学意义。与模型组比较,丹参组、血府组、桃红组RBC显著升高(P<0.05或P<0.01);与模型组比较,桃红组HCT显著升高(P<0.05);与模型组比较,丹参组、血府组、活络组、桃红组MCV显著降低(P<0.05或P<0.01);与模型组比较,丹参组、血府组、失笑组、桃红组MCH显著降低(P<0.01);与模型组比较,丹参组、血府组、活络组MCHC显著降低(P<0.05);与模型组比较,血府组Mid、Gran显著降低(P<0.05);与模型组比较,活络组肝脏系数显著升高(P<0.05);与模型组比较,各复方组RDW-CV、HGB、PLT、PCT、MPV、PDW、WBC、Lymph、ESR、心脏系数差异无统计学意义。结论五首活血化瘀方调节红细胞、血红蛋白相关指标RBC、HCT、MCV、MCH、MCHC的作用力大小不同,桃红四物汤疗效最佳,其次为血府逐瘀汤;调节炎症反应相关指标Mid、Gran效果最优的是血府逐瘀汤。

Preparation, characterization, and antifungal activity of hymexazol-linked chitosan derivatives

In this study, three hymexazol-linked chitosan derivatives （HML-CS） were synthesized and their structures confirmed by Fourier transform infrared and elemental analysis. Linkage ratios were measured by high performance liquid chromatography. The derivatives＇ antifungal activity against the plant pathogenic fimgi Rhizoctonia solani CGMCC 3.28 and Gibberella zeae CGMCC 3.42 were investigated at concentrations of 100, 200, and 400 mg/L. These HML-CS derivatives exhibited stronger antifungal activity than CS alone. HML-CS-1 showed the best antifizngal activity against G. zeae, whose antifimgal index was 65.9% at 400 mg/L, and also showed the best antifungal activity against R. solani, whose antifimgal index was 52.7% at 400 mg/L. This conjugation of CS and HML suggested the presence of synergistic effects between the moieties and indicated that these derivatives possessed great potential as novel fungicides and require further research for the development of applications in crop protection.

Metabolic engineering of Streptomyces coelicolor for enhanced prodigiosins (RED) production

Bacterial prodigiosins are red-colored secondary metabolites with multiple activities,such as anticancer,antimalarial and immunosuppressive,which hold great potential for medical applications.In this study,dramatically enhanced prodigiosins(RED) production in Streptomyces coelicolor was achieved by combinatorial metabolic engineering,including inactivation of the repressor gene ohkA,deletion of the actinorhodin(ACT) and calcium-dependent antibiotic(CDA) biosynthetic gene clusters(BGCs) and multi-copy chromosomal integration of the RED BGC.The results showed that ohkA deletion led to a 1-fold increase of RED production over the wild-type strain M145.Then,the ACT and CDA BGCs were deleted successively based on the AohkA mutant(SBJ101).To achieve multi-copy RED BGC integration,artificial ΦC31 attB site(s) were inserted simultaneously at the position where the ACT and CDA BGCs were deleted.The resulting strains SBJ102(with a single deletion of the ACT BGC and insertion of one artificial attB site) and SBJ103(with the deletion of both BGCs and insertion of two artificial attB sites) produced 1.9-and 6-fold higher RED titers than M145,respectively.Finally,the entire RED BGC was introduced into mutants from SBJ101 to SBJ103,generating three mutants(from SBJ104 to SBJ106) with chromosomal integration of one to three copies of the RED BGC.The highest RED yield was from SBJ106,which produced a maximum level of 96.8 mg g^(-1) cell dry weight,showing a 12-fold increase relative to M145.Collectively,the metabolic engineering strategies employed in this study are very efficient for the construction of high prodigiosin-producing strains.