Objective Graves’disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males.Costimulatory molecules play an essential role in regulati...Objective Graves’disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males.Costimulatory molecules play an essential role in regulating autoimmune responses.The objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone(DHT)in an in vivo BALB/c mouse model of experimental autoimmune Graves’disease.Methods Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves’disease model.Three different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first immunization.Four weeks after the third immunization,the mice were euthanatized,and then the spleen and thymus were removed.Total thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay kit.Real-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and thymus.Flow cytometry was used to analyze the percentage of CD4^+T cells in splenic lymphocytes.Quantitative data were compared with unpaired t-tests.Correlation between two variables was analyzed using Analysis of Variance.Results Treatment with DHT can dramatically reduce total thyroxine and free thyroxine levels.Higher expression of programmed death-1 was found in the spleen of Graves’disease mice receiving 5 mg of DHT treatment(0.635±0.296 vs.0.327±0.212;t=2.714,P=0.014),similarly,T-cell immunoglobulin domain and mucin domain 3(TIM-3)in both the spleen(1.004±0.338 vs.0.646±0.314;t=2.205,P=0.022)and the thymus(0.263±0.127 vs.0.120±0.076;t=3.221,P=0.004)also increased after 5 mg of DHT treatment compared with the parallel placebo model mice.Moreover,the percentage of CD4^+T cells declined in the splenic lymphocytes of Graves’disease mice treated with 5 mg of DHT(19.90%±3.985%vs.24.05%±2.587%;t=2.804,P=0.012).A significant negative association was observed between expression of TIM-3 in the spleen and serum levels of total thyroxine(r=-0.7106,P=0.014)as well as free thyroxine(r=-0.6542,P=0.029).Conclusion This study demonstrates that DHT can ameliorate experimental autoimmune Graves’disease,which may occur by up-regulating expression of programmed death-1 and TIM-3 and inhibiting development of CD4^+T cells.展开更多
Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span...Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells on aspiration biopsies of kidney transplants, measured three soluble factors and whe</span><span style="font-family:Verdana;">n indicated tested their robustness in diagnosing acute rejection.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Methods</span><span style="font-family:Verdana;">: Fine-needle aspiration biopsies were performed either on days seven or 14</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">preparations were studied by the enzymatic </span><span style="font-family:Verdana;">avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Conclusions: The presence of CD16</span><sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells inside the graft emerged as a distinct player in acute rejection, confirming other previous reports whereas we first document that in human kidney transplants, ICOS and CD26 are significantly up-regulated and both reached positive predictive values for acute rejection ≥ 80%. The other costimulatory molecules, with the exception of CD40, though widely known, did not show robust association with immune events.</span>展开更多
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and...B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con-structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P<0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evalu-ating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associ-ated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.展开更多
Summary: The expression of the costimulatory molecules B7/CD28 in peripheral blood mononuclear cells (PBMC) of the patients with systemic lupus erythematosus (SLE) and its relation to the pathogenesis of SLE were stud...Summary: The expression of the costimulatory molecules B7/CD28 in peripheral blood mononuclear cells (PBMC) of the patients with systemic lupus erythematosus (SLE) and its relation to the pathogenesis of SLE were studied. The expression of the costimulatory molecules in PBMC in 30 patients with active SLE and 20 cases of healthy controls was detected by using the techniques of immunofluorescence and flow cytometer. The result showed that the expression percentage of CD28+, CD4+CD28+ in T cells of PBMC from the patients with SLE decreased significantly as compared with that in healthy control group, while the expression percentage of CD80+, CD19+CD80+ in B cells was significantly increased than that in healthy control group (P<0.01). It suggested that the abnormal expression of costimulatory molecules B7/CD28 played a role in the pathogenesis of SLE.展开更多
Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory ...Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions.Currently,modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.展开更多
Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participat...Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues.However,the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear.Here,we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s.ICOS costimulation enhanced the survival,proliferation,and capacity of ILC3s to produce cytokines(IL-22,IL-17A,IFN-γ,TNF,and GM-CSF).Via synergistic effects of ICOS and CD40 signaling,B cells promoted ILC3 functions,and ILC3-induced T-cellindependent B-cell IgA and IgM secretion primarily required CD40 signaling.Hence,ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.展开更多
We present an optimal and robust quantum control method for efficient population transfer in asymmetric double quantum-dot molecules.We derive a long-duration control scheme that allows for highly efficient population...We present an optimal and robust quantum control method for efficient population transfer in asymmetric double quantum-dot molecules.We derive a long-duration control scheme that allows for highly efficient population transfer by accurately controlling the amplitude of a narrow-bandwidth pulse.To overcome fluctuations in control field parameters,we employ a frequency-domain quantum optimal control theory method to optimize the spectral phase of a single pulse with broad bandwidth while preserving the spectral amplitude.It is shown that this spectral-phase-only optimization approach can successfully identify robust and optimal control fields,leading to efficient population transfer to the target state while concurrently suppressing population transfer to undesired states.The method demonstrates resilience to fluctuations in control field parameters,making it a promising approach for reliable and efficient population transfer in practical applications.展开更多
Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adap...Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adaptation to such nutrient stresses.In this study,we used transcriptomics and proteomics to analyze how soybean(Glycine max)and its parasitizing dodder(Cuscuta australis)respond to nitrate and phosphate deficiency(-N and-P).After-N and-P treatment,the soybean and dodder plants exhibited substantial changes of transcriptome and proteome,although soybean plants showed very few transcriptional responses to-P and dodder did not show any transcriptional changes to either-N or-P.Importantly,large-scale interplant transport of mRNAs and proteins was detected.Although the mobile mRNAs only comprised at most 0.2%of the transcriptomes,the foreign mobile proteins could reach 6.8%of the total proteins,suggesting that proteins may be the major forms of interplant communications.Furthermore,the interplant mobility of macromolecules was specifically affected by the nutrient regimes and the transport of these macromolecules was very likely independently regulated.This study provides new insight into the communication between host plants and parasites under stress conditions.展开更多
The internal microbial diversity and small molecular metabolites of Nuodeng ham in different processing years(the first,second and third year sample)were analyzed by high-throughput sequencing technology and gas chrom...The internal microbial diversity and small molecular metabolites of Nuodeng ham in different processing years(the first,second and third year sample)were analyzed by high-throughput sequencing technology and gas chromatography-time of flight mass spectrography(GC-TOF-MS)to study the effects of microorganisms and small molecular metabolites on the quality of ham in different processing years.The results showed that the dominant bacteria phyla of Nuodeng ham in different processing years were Proteobacteria and Firmicutes,the dominant fungi phyla were Ascomycota and Basidiomycota,while Staphylococcus and Aspergillus were the dominant bacteria and fungi of Nuodeng ham,respectively.Totally,252 kinds of small molecular metabolites were identified from Nuodeng ham in different processing years,and 12 different metabolites were screened through multivariate statistical analysis.Further metabolic pathway analysis showed that 23 metabolic pathways were related to ham fermentation,of which 8 metabolic pathways had significant effects on ham fermentation(Impact>0.01,P<0.05).The content of L-proline,phenyllactic acid,L-lysine,carnosine,taurine,D-proline,betaine and creatine were significantly positively correlated with the relative abundance of Staphylococcus and Serratia,but negatively correlated with the relative abundance of Halomonas,Aspergillus and Yamadazyma.展开更多
Background The B7/CD28 pathway provides critical costimulatory signals for complete T cell activation, and members of this pathway have served as useful targets for immunotherapeutic strategies. In this study, we inve...Background The B7/CD28 pathway provides critical costimulatory signals for complete T cell activation, and members of this pathway have served as useful targets for immunotherapeutic strategies. In this study, we investigated the RNA interference (RNAi) effect induced by small interfering RNA (siRNA) targeting CD28 mRNA on human lymphocytes and its specificity.Methods According to CD28 gene sequence, we designed and synthysized three different siRNAs ( siRNA-1,siRNA-2, siRNA-3 ) containing 21 bases using SilencerTM siRNA construction kit. These siRNAs were transfected into freshly isolated human lymphocytes with Lipofectamine 2000 reagent. At 24-hour, 48-hour and 72-hour post transfection, these cells were collected and analyzed. The changes of surface expression of CD28 gene were detected by flow cytometry, and the changes of CD28 mRNA levels were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The cell viability of transfected lymphocytes was determined by methyl thiazolyl tetrazolium (MTT) assay and trypan blue dye exclusion assay.Results Three siRNAs (siRNA-1, siRNA-2, siRNA-3) specifically targeting CD28 mRNA were successfully designed and constructed. Flow cytometry analysis showed that a decrease in CD28 expression was detectable at 24-hour post transfection. Different siRNA showed different inhibition effects on CD28 expression. At 48-hour post transfection, the degrees of reduction with siRNA-1, siRNA-2 and siRNA-3 were 22. 10% ± 1.63% ,73.50% ± 1.02% and 42.90% ± 0.89% respectively compared with the control ( P < 0. 001 ). Neither of the groups transfected only with siRNA or lipo showed marked reduction in CD28 expression (3.15% ± 0.75% and 4. 55% ±0. 80% ) (P >0. 05). Moreover, lymphocytes treated with siRNA-co showed no marked reduction in CD28 expression (5.07% ± 0. 96% ) (P > 0. 05 ). The results of semi-quantitative RT-PCR assay indicated CD28 mRNA level was inhibited after transfection of specific siRNAs. At least 4-fold of reduction in siRNA-2 group occurred at 48-hour post transfection compared with the control (P < 0. 001 ). MTT assay and trypan blue dye exclusion assay demonstrated that the viable cell rations of transfected lymphocytes were significantly reduced in siRNA-1, siRNA-2 and siRNA-3 groups at 48-hour post transfection (P <0.01 ). The control groups showed no marked reduction in cell viability ( P > 0.05 ).Conclusions Three different siRNAs were synthesized and transfected into lymphocytes. They could reduce the expression of CD28 and the CD28 mRNA level, siRNA-2 was the most efficient. The cell viability reduced correspondingly. Therefore, the silencing effect on CD28 mRNA induced by siRNA may contribute to costimulatory blockade. This result show that siRNA may be useful for further study on graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT).展开更多
The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and impro...The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.展开更多
Neural progenitor cells(NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplanta...Neural progenitor cells(NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox(VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR(0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition(5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6(Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs(ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease.展开更多
Chalcopyrite is a common copper-bearing mineral with antiferromagnetic properties.However,this property has rarely been considered in previous studies for detailed adsorption behaviors of molecules on chalcopyrite.Bas...Chalcopyrite is a common copper-bearing mineral with antiferromagnetic properties.However,this property has rarely been considered in previous studies for detailed adsorption behaviors of molecules on chalcopyrite.Based on density functional theory(DFT),new adsorption pathways by H_(2)O and O_(2)on the chalcopyrite metal terminated(112)surface((112)-M)is found in this work.First,through simulating the adsorption of an isolated water molecule and monolayer water molecules,it is confirmed that H_(2)O molecules tend to adsorb on the surface Fe atoms more than on the surface Cu atoms.Then,we studied various adsorption behaviors of the O_(2)molecule.It is found that the adsorption on the hollow FeAFe site is the most stable case;however,O_(2)is undissociated.Two adsorption cases will happen when H_(2)OAO_(2)adsorb simultaneously on the surface.For the S site,the H_(2)O molecule thoroughly dissociated and formed SAO species,and the other case is H_(2)O undissociated adsorbing at the Cu site.For the former case,it is interesting that H_(2)O is dissociated before O_(2).展开更多
Using quantum chemical calculations,we model the pathways for synthesizing two purine nucleobases,adenine and guanine,in the gas-phase interstellar environment,surrounded by neutral atomic hydrogen(H I).H I is found a...Using quantum chemical calculations,we model the pathways for synthesizing two purine nucleobases,adenine and guanine,in the gas-phase interstellar environment,surrounded by neutral atomic hydrogen(H I).H I is found active in facilitating a series of fundamental proton transfer processes of organic synthesis,including bond formation,cyclization,dehydrogenation,and H migration.The reactive potential barriers were significantly reduced in the alternative pathways created by H I,leading to a remarkable increase in the reaction rate.The presence of H I also lowered the reactive activation temperature from 757.8 K to 131.5–147.0 K,indicating the thermodynamic feasibility of these pathways in star-forming regions where some of the reactants have been astronomically detected.Our findings suggest that H I may serve as an effective catalyst for interstellar organic synthesis.展开更多
Developing a low-cost and high-efficiency nonprecious metal-based catalyst for hydrogen evolution reaction(HER) is of great significance for the utilization of hydrogen energy.In this work,we report a molecular-modifi...Developing a low-cost and high-efficiency nonprecious metal-based catalyst for hydrogen evolution reaction(HER) is of great significance for the utilization of hydrogen energy.In this work,we report a molecular-modification strategy to fabricate a self-supported hydrogen evolution electrode,specially by grafting the macrocyclic molecules(HHTP=2,3,6,7,10,11-hexahydroxytriphenylene) on the surface of a cobaltous dihydroxy carbonate(COC) seed layer.The HHTP-COC electrode is endowed with a rodlike structure,which provides favorable access for charge transportation and mass exchange.The macrocyclic molecule structure in HHTP can be grafted on COC and improve the electrical conductivity,while the interaction between HHTP and COC induces the rearrangement of charge configuration on the surface.Due to the combination effects of several aspects,the HHTP-COC electrode achieves astonishing HER activity,with a low overpotential of 61.0 mV(η_(10),at the current density of 10 mA cm^(-2)) and excellent stability in alkaline condition.This kind of interface engineering based on the organic molecules can be applied to the design and manufacture of electrocatalysts in the field of energy conversion and storage.展开更多
By employing the complexification method and velocity resonant principle to N-solitons of the(2+1)-dimensional generalized Konopelchenko–Dubrovsky–Kaup–Kupershmidt(KDKK)equation,we obtain the soliton molecules,T-br...By employing the complexification method and velocity resonant principle to N-solitons of the(2+1)-dimensional generalized Konopelchenko–Dubrovsky–Kaup–Kupershmidt(KDKK)equation,we obtain the soliton molecules,T-breather molecules,T-breather–L-soliton molecules and some interaction solutions when N≤6.Dynamical behaviors of these solutions are discussed analytically and graphically.The method adopted can be effectively used to construct soliton molecules and T-breather molecules of other nonlinear evolution equations.The results obtained may be helpful for experts to study the related phenomenon in oceanography and atmospheric science.展开更多
A scheme for storage of cold molecules in a hollow optical ring generated by a metasurface grating is proposed.The characteristics and intensity distribution related to the ring’s structural parameters and fabricatio...A scheme for storage of cold molecules in a hollow optical ring generated by a metasurface grating is proposed.The characteristics and intensity distribution related to the ring’s structural parameters and fabrication error tolerance are theoretically studied. The optical potential and dipole force required for the ring to trap magnesium monofluoride(MgF)molecules are also calculated. The dynamic behavior of MgF molecules in the storage ring is simulated by a Monte Carlo method, which shows that a metasurface-based optical storage ring can be used to trap molecules and is an interesting platform for research into ultracold quantum gases and their quantum-state manipulation.展开更多
Solubility enhancement has been a priority to overcome poor solubility with optoelectronic molecules for solution-processable devices. This study aims to obtain experimental data on the effect of particle sizes on the...Solubility enhancement has been a priority to overcome poor solubility with optoelectronic molecules for solution-processable devices. This study aims to obtain experimental data on the effect of particle sizes on the solubility properties of several typical optoelectronic molecules in organic solvents, including the solubility results of 1,3-bis(9-carbazolyl)benzene(m CP), 1,3,5-tris(1-phenyl-1H-benzimidazol-2-yl)ben zene(TPBi) and 2-(4-tert-butylphenyl)-5-(4-biphenyl)-1,3,4-oxadiazole(PBD) in ethanol and acetonitrile,respectively. Nanoparticles of m CP, TPBi and PBD with sizes from dozens to several hundred nanometers were prepared by solvent antisolvent precipitation method and their solubility were determined by using isothermal saturation method. The saturation solubility of nanoparticles of three kinds of optoelectronic molecules exhibited increase of 12.9%-25.7% in comparison to the same raw materials in the form of microparticles. The experimental evidence indicates that nanonization technology is a feasible way to make optoelectronic molecules dissolve in liquids with enhanced solubility.展开更多
Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have ...Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.展开更多
基金supported by the National Natural Science Foundation(grant number 81670725,2017.01-2020.12)Key Research and Development Project of Shaanxi Province(grant number 2017ZDXM-SF-060,2017.01-2019.12)。
文摘Objective Graves’disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males.Costimulatory molecules play an essential role in regulating autoimmune responses.The objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone(DHT)in an in vivo BALB/c mouse model of experimental autoimmune Graves’disease.Methods Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves’disease model.Three different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first immunization.Four weeks after the third immunization,the mice were euthanatized,and then the spleen and thymus were removed.Total thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay kit.Real-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and thymus.Flow cytometry was used to analyze the percentage of CD4^+T cells in splenic lymphocytes.Quantitative data were compared with unpaired t-tests.Correlation between two variables was analyzed using Analysis of Variance.Results Treatment with DHT can dramatically reduce total thyroxine and free thyroxine levels.Higher expression of programmed death-1 was found in the spleen of Graves’disease mice receiving 5 mg of DHT treatment(0.635±0.296 vs.0.327±0.212;t=2.714,P=0.014),similarly,T-cell immunoglobulin domain and mucin domain 3(TIM-3)in both the spleen(1.004±0.338 vs.0.646±0.314;t=2.205,P=0.022)and the thymus(0.263±0.127 vs.0.120±0.076;t=3.221,P=0.004)also increased after 5 mg of DHT treatment compared with the parallel placebo model mice.Moreover,the percentage of CD4^+T cells declined in the splenic lymphocytes of Graves’disease mice treated with 5 mg of DHT(19.90%±3.985%vs.24.05%±2.587%;t=2.804,P=0.012).A significant negative association was observed between expression of TIM-3 in the spleen and serum levels of total thyroxine(r=-0.7106,P=0.014)as well as free thyroxine(r=-0.6542,P=0.029).Conclusion This study demonstrates that DHT can ameliorate experimental autoimmune Graves’disease,which may occur by up-regulating expression of programmed death-1 and TIM-3 and inhibiting development of CD4^+T cells.
文摘Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells on aspiration biopsies of kidney transplants, measured three soluble factors and whe</span><span style="font-family:Verdana;">n indicated tested their robustness in diagnosing acute rejection.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Methods</span><span style="font-family:Verdana;">: Fine-needle aspiration biopsies were performed either on days seven or 14</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">preparations were studied by the enzymatic </span><span style="font-family:Verdana;">avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Conclusions: The presence of CD16</span><sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells inside the graft emerged as a distinct player in acute rejection, confirming other previous reports whereas we first document that in human kidney transplants, ICOS and CD26 are significantly up-regulated and both reached positive predictive values for acute rejection ≥ 80%. The other costimulatory molecules, with the exception of CD40, though widely known, did not show robust association with immune events.</span>
基金supported by a grant from Hubei Provin-cial Science and Technology Key Program Foundation of China (No. 2007AA402C60).
文摘B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con-structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P<0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evalu-ating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associ-ated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.
基金ThisprojectwassupportedbyagrantfromHubeiProvincialNaturalSciencesFoundationofChina (No .2 0 0 0 j0 5 3)
文摘Summary: The expression of the costimulatory molecules B7/CD28 in peripheral blood mononuclear cells (PBMC) of the patients with systemic lupus erythematosus (SLE) and its relation to the pathogenesis of SLE were studied. The expression of the costimulatory molecules in PBMC in 30 patients with active SLE and 20 cases of healthy controls was detected by using the techniques of immunofluorescence and flow cytometer. The result showed that the expression percentage of CD28+, CD4+CD28+ in T cells of PBMC from the patients with SLE decreased significantly as compared with that in healthy control group, while the expression percentage of CD80+, CD19+CD80+ in B cells was significantly increased than that in healthy control group (P<0.01). It suggested that the abnormal expression of costimulatory molecules B7/CD28 played a role in the pathogenesis of SLE.
基金Supported by Institute of Ophthalmology“Fundacion Conde de Valenciana”Velazquez-Soto H received fellowship 294674 from CONACYT during his doctoral studies in Programa de Doctorado en Ciencias Medicas,Odontologicas y de la Salud(Farmacologia Clinica),Universidad Nacional Autonoma de Mexico(UNAM)Real F with CVU 917729,recieved fellowship from CONACYT during his master studies in Programa de Maestria en Ciencias Medicas,Odontologicas y de la Salud(Farmacologia Clinica),Universidad Nacional Autonoma de Mexico(UNAM).
文摘Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions.Currently,modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.
基金the National Key Research and Development Program(Grant 2021YFF0704800)the Science and Technology Development Program of Jilin Province(Grant 20210402009GH)+1 种基金the Science and Technology Development Program of Jilin Province(Grant YDZJ202201ZYTS098)the Norman Bethune Program of Jilin University(Grant No.2022B34).
文摘Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues.However,the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear.Here,we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s.ICOS costimulation enhanced the survival,proliferation,and capacity of ILC3s to produce cytokines(IL-22,IL-17A,IFN-γ,TNF,and GM-CSF).Via synergistic effects of ICOS and CD40 signaling,B cells promoted ILC3 functions,and ILC3-induced T-cellindependent B-cell IgA and IgM secretion primarily required CD40 signaling.Hence,ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.
基金This work was supported by the National Natural Science Foundations of China(Grant Nos.12275033,61973317,and 12274470)the Natural Science Foundation of Hunan Province for Distinguished Young Scholars(Grant No.2022JJ10070)+1 种基金the Natural Science Foundation of Hunan Province(Grant No.2022JJ30582)the Scientific Research Fund of Hunan Provincial Education Department(Grant No.20A025).
文摘We present an optimal and robust quantum control method for efficient population transfer in asymmetric double quantum-dot molecules.We derive a long-duration control scheme that allows for highly efficient population transfer by accurately controlling the amplitude of a narrow-bandwidth pulse.To overcome fluctuations in control field parameters,we employ a frequency-domain quantum optimal control theory method to optimize the spectral phase of a single pulse with broad bandwidth while preserving the spectral amplitude.It is shown that this spectral-phase-only optimization approach can successfully identify robust and optimal control fields,leading to efficient population transfer to the target state while concurrently suppressing population transfer to undesired states.The method demonstrates resilience to fluctuations in control field parameters,making it a promising approach for reliable and efficient population transfer in practical applications.
基金supported by the National Natural Science Foundation of China (31970274 (J.W.), 32170272 (X.W.), 32100251 (J.Z.), 32000179 (Y.X.))the Special Research Assistant of Chinese Academy of Sciences (J.Z. and Y.X.), China Postdoctoral Science Foundation (2022M713224 (J.Z.))+6 种基金the Strategic Priority Research Program of Chinese Academy of Sciences (XDPB16 (J.W.))the Yunnan Innovation Team Project (202105AE160013 (J.W.))CAS “Light of West China” Program (G.S.)Yunnan Revitalization Talent Support Program “Young Talents” Project (XDYC-QNRC-2022-0301 (J.Z.), XDYC-QNRC-2022-0001 (G.S.))the General and Key Project of the Applied Basic Research Program of Yunnan (202001AS070021(J.W.))Yunnan Fundamental Research Projects-General Project (202101AT070457 (S.L.))Yunnan Fundamental Research Projects-Youth Talent Project (202101AU070021(S.L.))
文摘Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adaptation to such nutrient stresses.In this study,we used transcriptomics and proteomics to analyze how soybean(Glycine max)and its parasitizing dodder(Cuscuta australis)respond to nitrate and phosphate deficiency(-N and-P).After-N and-P treatment,the soybean and dodder plants exhibited substantial changes of transcriptome and proteome,although soybean plants showed very few transcriptional responses to-P and dodder did not show any transcriptional changes to either-N or-P.Importantly,large-scale interplant transport of mRNAs and proteins was detected.Although the mobile mRNAs only comprised at most 0.2%of the transcriptomes,the foreign mobile proteins could reach 6.8%of the total proteins,suggesting that proteins may be the major forms of interplant communications.Furthermore,the interplant mobility of macromolecules was specifically affected by the nutrient regimes and the transport of these macromolecules was very likely independently regulated.This study provides new insight into the communication between host plants and parasites under stress conditions.
基金supported by Major Science and Technology Projects of Yunnan Science and Technology Plan(2019ZG003)Yunnan Young and Middle-aged Academic and Technical Leader Reserve Talent Project(202105AC160068)。
文摘The internal microbial diversity and small molecular metabolites of Nuodeng ham in different processing years(the first,second and third year sample)were analyzed by high-throughput sequencing technology and gas chromatography-time of flight mass spectrography(GC-TOF-MS)to study the effects of microorganisms and small molecular metabolites on the quality of ham in different processing years.The results showed that the dominant bacteria phyla of Nuodeng ham in different processing years were Proteobacteria and Firmicutes,the dominant fungi phyla were Ascomycota and Basidiomycota,while Staphylococcus and Aspergillus were the dominant bacteria and fungi of Nuodeng ham,respectively.Totally,252 kinds of small molecular metabolites were identified from Nuodeng ham in different processing years,and 12 different metabolites were screened through multivariate statistical analysis.Further metabolic pathway analysis showed that 23 metabolic pathways were related to ham fermentation,of which 8 metabolic pathways had significant effects on ham fermentation(Impact>0.01,P<0.05).The content of L-proline,phenyllactic acid,L-lysine,carnosine,taurine,D-proline,betaine and creatine were significantly positively correlated with the relative abundance of Staphylococcus and Serratia,but negatively correlated with the relative abundance of Halomonas,Aspergillus and Yamadazyma.
文摘Background The B7/CD28 pathway provides critical costimulatory signals for complete T cell activation, and members of this pathway have served as useful targets for immunotherapeutic strategies. In this study, we investigated the RNA interference (RNAi) effect induced by small interfering RNA (siRNA) targeting CD28 mRNA on human lymphocytes and its specificity.Methods According to CD28 gene sequence, we designed and synthysized three different siRNAs ( siRNA-1,siRNA-2, siRNA-3 ) containing 21 bases using SilencerTM siRNA construction kit. These siRNAs were transfected into freshly isolated human lymphocytes with Lipofectamine 2000 reagent. At 24-hour, 48-hour and 72-hour post transfection, these cells were collected and analyzed. The changes of surface expression of CD28 gene were detected by flow cytometry, and the changes of CD28 mRNA levels were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The cell viability of transfected lymphocytes was determined by methyl thiazolyl tetrazolium (MTT) assay and trypan blue dye exclusion assay.Results Three siRNAs (siRNA-1, siRNA-2, siRNA-3) specifically targeting CD28 mRNA were successfully designed and constructed. Flow cytometry analysis showed that a decrease in CD28 expression was detectable at 24-hour post transfection. Different siRNA showed different inhibition effects on CD28 expression. At 48-hour post transfection, the degrees of reduction with siRNA-1, siRNA-2 and siRNA-3 were 22. 10% ± 1.63% ,73.50% ± 1.02% and 42.90% ± 0.89% respectively compared with the control ( P < 0. 001 ). Neither of the groups transfected only with siRNA or lipo showed marked reduction in CD28 expression (3.15% ± 0.75% and 4. 55% ±0. 80% ) (P >0. 05). Moreover, lymphocytes treated with siRNA-co showed no marked reduction in CD28 expression (5.07% ± 0. 96% ) (P > 0. 05 ). The results of semi-quantitative RT-PCR assay indicated CD28 mRNA level was inhibited after transfection of specific siRNAs. At least 4-fold of reduction in siRNA-2 group occurred at 48-hour post transfection compared with the control (P < 0. 001 ). MTT assay and trypan blue dye exclusion assay demonstrated that the viable cell rations of transfected lymphocytes were significantly reduced in siRNA-1, siRNA-2 and siRNA-3 groups at 48-hour post transfection (P <0.01 ). The control groups showed no marked reduction in cell viability ( P > 0.05 ).Conclusions Three different siRNAs were synthesized and transfected into lymphocytes. They could reduce the expression of CD28 and the CD28 mRNA level, siRNA-2 was the most efficient. The cell viability reduced correspondingly. Therefore, the silencing effect on CD28 mRNA induced by siRNA may contribute to costimulatory blockade. This result show that siRNA may be useful for further study on graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT).
文摘The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.
基金supported by the National Natural Science Foundation of China,No. 81771381 (to CQL)Anhui Provincial Key Research and Development Project,Nos. 2022e07020030 (to CQL), 2022e07020032 (to YG)+2 种基金Science Research Project of Bengbu Medical College,No. 2021byfy002 (to CQL)the Natural Science Foundation of the Higher Education Institutions of Anhui Province,No. KJ2021ZD0085 (to CJW)the Undergraduate Innovative Training Program of China,Nos. 202110367043 (to CQL), 202110367044 (to YG)。
文摘Neural progenitor cells(NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox(VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR(0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition(5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6(Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs(ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease.
基金The authors are grateful for the financial support provided by the National Natural Science Foundation of China(NSFC)(Nos.51974094,51964004,and U20A20269).
文摘Chalcopyrite is a common copper-bearing mineral with antiferromagnetic properties.However,this property has rarely been considered in previous studies for detailed adsorption behaviors of molecules on chalcopyrite.Based on density functional theory(DFT),new adsorption pathways by H_(2)O and O_(2)on the chalcopyrite metal terminated(112)surface((112)-M)is found in this work.First,through simulating the adsorption of an isolated water molecule and monolayer water molecules,it is confirmed that H_(2)O molecules tend to adsorb on the surface Fe atoms more than on the surface Cu atoms.Then,we studied various adsorption behaviors of the O_(2)molecule.It is found that the adsorption on the hollow FeAFe site is the most stable case;however,O_(2)is undissociated.Two adsorption cases will happen when H_(2)OAO_(2)adsorb simultaneously on the surface.For the S site,the H_(2)O molecule thoroughly dissociated and formed SAO species,and the other case is H_(2)O undissociated adsorbing at the Cu site.For the former case,it is interesting that H_(2)O is dissociated before O_(2).
基金supported by the National Natural Science Foundation of China (11964002)。
文摘Using quantum chemical calculations,we model the pathways for synthesizing two purine nucleobases,adenine and guanine,in the gas-phase interstellar environment,surrounded by neutral atomic hydrogen(H I).H I is found active in facilitating a series of fundamental proton transfer processes of organic synthesis,including bond formation,cyclization,dehydrogenation,and H migration.The reactive potential barriers were significantly reduced in the alternative pathways created by H I,leading to a remarkable increase in the reaction rate.The presence of H I also lowered the reactive activation temperature from 757.8 K to 131.5–147.0 K,indicating the thermodynamic feasibility of these pathways in star-forming regions where some of the reactants have been astronomically detected.Our findings suggest that H I may serve as an effective catalyst for interstellar organic synthesis.
基金funded by grants from the National Natural Science Foundation of China (21771101, 52201258)the Natural Science Foundation of Jiangsu Province, China (BK20210651 and BK20210650)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (21KJB430003)。
文摘Developing a low-cost and high-efficiency nonprecious metal-based catalyst for hydrogen evolution reaction(HER) is of great significance for the utilization of hydrogen energy.In this work,we report a molecular-modification strategy to fabricate a self-supported hydrogen evolution electrode,specially by grafting the macrocyclic molecules(HHTP=2,3,6,7,10,11-hexahydroxytriphenylene) on the surface of a cobaltous dihydroxy carbonate(COC) seed layer.The HHTP-COC electrode is endowed with a rodlike structure,which provides favorable access for charge transportation and mass exchange.The macrocyclic molecule structure in HHTP can be grafted on COC and improve the electrical conductivity,while the interaction between HHTP and COC induces the rearrangement of charge configuration on the surface.Due to the combination effects of several aspects,the HHTP-COC electrode achieves astonishing HER activity,with a low overpotential of 61.0 mV(η_(10),at the current density of 10 mA cm^(-2)) and excellent stability in alkaline condition.This kind of interface engineering based on the organic molecules can be applied to the design and manufacture of electrocatalysts in the field of energy conversion and storage.
基金Jiangsu Provincial Natural Science Foundation of China(Grant Nos.BK20221508,11775116,BK20210380,and JSSCBS20210277)SRT(Grant No.202210307165Y)Jiangsu Qinglan High-level Talent Project.
文摘By employing the complexification method and velocity resonant principle to N-solitons of the(2+1)-dimensional generalized Konopelchenko–Dubrovsky–Kaup–Kupershmidt(KDKK)equation,we obtain the soliton molecules,T-breather molecules,T-breather–L-soliton molecules and some interaction solutions when N≤6.Dynamical behaviors of these solutions are discussed analytically and graphically.The method adopted can be effectively used to construct soliton molecules and T-breather molecules of other nonlinear evolution equations.The results obtained may be helpful for experts to study the related phenomenon in oceanography and atmospheric science.
基金supported by the National Natural Science Foundation of China (Grant Nos. 12174115, 11974434, 91836103, and 11374100)the Natural Science Foundation of Guangdong Province, China (Grant No. 2020A1515011159)+1 种基金the Science and Technology Program of Guangzhou (Grant No. 202102080380)Shanghai Pujiang Program (Grant No. 20PJ1403400)。
文摘A scheme for storage of cold molecules in a hollow optical ring generated by a metasurface grating is proposed.The characteristics and intensity distribution related to the ring’s structural parameters and fabrication error tolerance are theoretically studied. The optical potential and dipole force required for the ring to trap magnesium monofluoride(MgF)molecules are also calculated. The dynamic behavior of MgF molecules in the storage ring is simulated by a Monte Carlo method, which shows that a metasurface-based optical storage ring can be used to trap molecules and is an interesting platform for research into ultracold quantum gases and their quantum-state manipulation.
基金financial support from National Natural Science Foundation of China (22288102)the Fundamental Research Funds for the Central Universities of China (buctrc202016)。
文摘Solubility enhancement has been a priority to overcome poor solubility with optoelectronic molecules for solution-processable devices. This study aims to obtain experimental data on the effect of particle sizes on the solubility properties of several typical optoelectronic molecules in organic solvents, including the solubility results of 1,3-bis(9-carbazolyl)benzene(m CP), 1,3,5-tris(1-phenyl-1H-benzimidazol-2-yl)ben zene(TPBi) and 2-(4-tert-butylphenyl)-5-(4-biphenyl)-1,3,4-oxadiazole(PBD) in ethanol and acetonitrile,respectively. Nanoparticles of m CP, TPBi and PBD with sizes from dozens to several hundred nanometers were prepared by solvent antisolvent precipitation method and their solubility were determined by using isothermal saturation method. The saturation solubility of nanoparticles of three kinds of optoelectronic molecules exhibited increase of 12.9%-25.7% in comparison to the same raw materials in the form of microparticles. The experimental evidence indicates that nanonization technology is a feasible way to make optoelectronic molecules dissolve in liquids with enhanced solubility.
基金the MRC Laboratory of Molecular Biology (to MR)。
文摘Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.
