The role of fibronectin in multiple sclerosis and the effect of drug delivery across the blood-brain barrier

Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.

Ambiguous roles of innate lymphoid cells in chronic development of liver diseases

Innate lymphoid cells(ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs(including natural killer(NK) cells and ILC1 s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs(ILC2 s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin(IL)-5 and IL-13; and, group 3 ILCs(including lymphoid tissue-like cells and ILC3 s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets.

Prediction of T cell and B cell epitopes of the 22-, 47-, 56-, and 58-kDa proteins of Orientia tsutsugamushi

Objective:To predict B cell and T cell epitopes of 22-kDa,47-kDa,56-kDa and 58-kDa proteins.Methods:The sequences of 22-kDa,47-kDa,56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA,DNAstar,Bcepred,ABCpred,NetMHC,NetMHCⅡand IEDB.The 58-kDa tertiary structure model was built by MODELLER9.17.Results:The 22-kDa B-cell epitopes were located at positions 194-200,20-26 and 143-154,whereas the T-cell epitopes were located at positions 154-174,95-107,17-25 and 57-65.The 47-kD a protein B-cell epitopes were at positions 413-434,150-161 and 283-322,whereas the T-cell epitopes were located at positions 129-147,259-267,412-420 and 80-88.The 56-kDa protein B-cell epitopes were at positions 167-173,410-419 and 101-108,whereas the T-cell epitopes were located at positions 88-104,429-439,232-240 and 194-202.The 58-kDa protein B-cell epitopes were at positions 312-317,540-548 and 35-55,whereas the T-cell epitopes were located at positions 415-434,66-84 and 214-230.Conclusions:We identified candidate epitopes of 22-kDa,47-kDa,56-kDa and 58-kDa proteins from Orientia tsutsugamushi.In the case of 58-kDa,the dominant antigen is displayed on tertiary structure by homology modeling.Our findings will help target additional recombinant antigens with strong specificity,high sensitivity,and stable expression and will aid in their isolation and purification.

Global Functional Network Connectivity Disturbances in Parkinson’s Disease with Mild Cognitive Impairment by Resting-State Functional MRI

Examining the spontaneous BOLD activity to understand the neural mechanism of Parkinson’s disease(PD)with mild cognitive impairment(MCI)is a focus in resting-state functional MRI(rs-fMRI)studies.This study aimed to investigate the alteration of brain functional connectivity in PD with MCI in a systematical way at two levels:functional connectivity analysis within resting state networks(RSNs)and functional network connectivity(FNC)analysis.Using group independent component analysis(ICA)on rs-fMRI data acquired from 30 participants(14 healthy controls and 16 PD patients with MCI),16 RSNs were identified,and functional connectivity analysis within the RSNs and FNC analysis were carried out between groups.Compared to controls,patients with PD showed decreased functional connectivity within putamen network,thalamus network,cerebellar network,attention network,and self-referential network,and increased functional connectivity within execution network.Globally disturbed,mostly increased functional connectivity of FNC was observed in PD group,and insular network and execution network were the dominant network with extensively increased functional connectivity with other RSNs.Cerebellar network showed decreased functional connectivity with caudate network,insular network,and self-referential network.In general,decreased functional connectivity within RSNs and globally disturbed,mostly increased functional connectivity of FNC may be characteristics of PD.Increased functional connectivity within execution network may be an early marker of PD.The multi-perspective study based on RSNs may be a valuable means to assess functional changes corresponding to specific RSN,contributing to the understanding of the neural mechanism of PD.

Fate of nitrogen in subsurface infiltration system for treating secondary effluent

The concentration of total nitrogen(TN) is reported to vary between 20 and 35 mg/L in domestic wastewater. In raw wastewater, ammonia nitrogen eNHt4-NT is the main nitrogen form, accounting for 70%e82% of the TN concentration. Organic nitrogen, nitrite nitrogen eNOà2-NT,and nitrate nitrogen eNOà3-NT are present as well. For years, due to the lack of regulatory limits on nitrogen concentration in surface waters,nitrogen from secondary effluent has posed a significant threat to the health of aquatic ecosystems. Researchers have made substantial efforts to reduce the nitrogen concentration in secondary effluent. As a kind of advanced wastewater treatment technology, the subsurface infiltration(SI)system has been widely used, owing to its advantages, which include low operation cost, easy maintenance, and low energy consumption. This review discusses the fate of various forms of nitrogen in SI treatment, including organic nitrogen, NHt4-N, NOà2-N, and NOà3-N. Major biological processes involved in nitrogen removal and the main factors influencing its transformation are suggested. Finally, it is shown that ammonification followed by nitrification-denitrification plays a major role in nitrogen removal. Further research needs to focus on the emission characteristics of gaseous nitrogen(generated from the nitrification, denitrification, and completely autotrophic nitrogen-removal over nitrite(CANON) processes) with respect to their greenhouse effects.

Magnetic resonance imaging apparent diffusion coefficient before and after neoadjuvant chemotherapy in patients with breast cancer and its correlation with tumor load

Objective:To study the magnetic resonance imaging apparent diffusion coefficient (ADC) before and after neoadjuvant chemotherapy in patients with breast cancer and its correlation with tumor load.Methods: Patients with stage II-III breast cancer who intended to receive radical operation for breast cancer in our hospital between May 2015 and February 2018 were selected and divided into the experimental group who accepted neoadjuvant chemotherapy and the control group who received surgery directly according to the adoption of preoperative neoadjuvant chemotherapy or not in the history data. Experimental group underwent magnetic resonance imaging before and after neoadjuvant chemotherapy to measure the ADC, and control group underwent magnetic resonance imaging before surgery to measure the ADC;the tumor tissues surgically removed from the two groups of patients were collected to measure the expression of oncogenes and invasion genes.Results:ADC value of experimental group after neoadjuvant chemotherapy was higher than that before neoadjuvant chemotherapy, ADC value of experimental group before neoadjuvant chemotherapy was not significantly different from that of control group whereas ADC value after neoadjuvant chemotherapy was significantly higher than that of control group;MCM3, CyclinD1, TC-1,β-catenin, YAP and MMP2 mRNA expression levels in surgically removed tumor tissues of experimental group were significantly lower than those of control group whereas CCN5, ARID1A and PDCD4 mRNA expression levels were significantly higher than those of control group;MCM3, CyclinD1, TC-1,β-catenin, YAP and MMP2 mRNA expression levels in tumor tissues with high ADC value were significantly lower than those in tumor tissues with low ADC value whereas CCN5, ARID1A and PDCD4 mRNA expression levels were significantly higher than those in tumor tissues with low ADC value.Conclusion:The increase of ADC after breast cancer neoadjuvant chemotherapy is related to the activity of cancer cell proliferation and invasion, and can be used to evaluate the changes of tumor load before and after chemotherapy.

High-rate performance and super long-cycle stability of Na_(3)V_(2)(PO_(4))_(3)cathode material coated by diatomic doped carbon

Na_(3)V_(2)(PO_(4))_(3)is considered as one of the most promising cathodes for sodium ion batteries due to its excellent thermal stability,long cycle life and high energy density.However,the inferior intrinsic electronic conductivity which brings about the poor rate capability and cycling performance hinders its commercial application.Herein,the S-N co-doped carbon-coated Na_(3)V_(2)(PO_(4))_(3)(NVP@SNC)has been synthesized to resolve the problem.The prepared NVP@SNC forms a hierarchical structure assembled with nanosheets,which is in favor of the electrolyte infiltration and shortening the Na^(+)transmission distance.Numerous lattice defects can be induced in carbon layer by the co-doped elements(S-N),which reduce the Na^(+)diffusion energy barriers and provide adequate Na^(+)migration channels,thus jointly boosting the Na^(+)diffusion coefficient.Consequently,the NVP@SNC cathode shows a high reversible capacity with outstanding rate performance and super long-cycle stability.When discharged at 2.0C,it delivers the capacity near to the theoretical value with a capacity retention of 88.7%after 400cycles.Even if the current is as high as 50.0C,a high capacity of 58.6 mAh·g^(-1)has been released,and41.4 mAh·g^(-1)has been remained after the super long cycling of 4000 circles.This study is expected to supply a new thought of developing high-performance cathodes by diatomic doping for sodium ion battery.

丝素蛋白膜在高电场下的介电性能

丝素蛋白的分子结构兼具软段和硬段,且其结构单元具有较大的偶极矩(3.5D),在介电储能领域可能具有应用潜力.本文表征了丝素蛋白薄膜的在高电场下的介电性能,并研究了丝素蛋白的分子结构与高电场下介电性能的关系.结果显示,丝素蛋白的二级结构变化与其高场介电行为关系密切,β-折叠结构增加有利于提高击穿强度,降低介电损耗.通过调整薄膜的制备工艺优化了丝素蛋白薄膜的高场介电性能,优化后的丝素蛋白膜在500 MV/m的电场下放电能量密度可达7.43 J/cm^(3),充-放电效率为79.8%.本工作为开拓丝素蛋白在介电领域的应用提供了基础数据,并为进一步优化分子结构提供了参考.

Expression of BSE-associated proteins in the CNS and lymphoreticular tissues of cattle and buffalo

Bovine spongiform encephalopathy(BSE),which has been documented in 190,000 cases of BSE-infected cattle,to our knowledge,has not been reported in buffalo.Prion protein(PrP) is critical to susceptibility and development of BSE.Moreover,a new PrP-like protein,Shadoo(Sho),has been shown to have overlapping expression patterns and shared functions with PrP.Therefore,we hypothesize that differences in expression at the transcriptional level and/or the post-transcriptional level of the two genes may be associated with these specific differences between cattle and buffalo.We compared the relative mRNA expression of the prion protein gene(PRNP) and the Shadoo gene(SPRN) in 3% RNA samples using real-time PCR.We also analyzed PrP/Sho protein from 96 samples by Western blot.Our results demonstrated significantly lower PrP expression in the cerebellum,obex,mesenteric lymph node,and bronchial lymph node tissues,but higher relative expression of Sho in the cerebrum and spleen in buffalos compared with catties.Although these results support our primary assumption,Sho and PrP expressions did not correlate with corresponding mRNA expression,suggesting that the biological modulations of both PrP and Sho proteins are at post-translational levels.Moreover,positive correlations between PRNP and SPRN were found in cattle and buffalo cerebrum as well as in buffalo obex.Conversely,negative correlations between PrP and Sho were detected in buffalo cerebellum and obex tissues.These findings suggest that additional post-transcriptional studies are warranted to elucidate mechanisms behind prion diseases.

Generalized Lagrangian Duality in Set-valued Vector Optimization via Abstract Subdifferential

In this paper,we investigate dual problems for nonconvex set-valued vector optimization via abstract subdifferential.We first introduce a generalized augmented Lagrangian function induced by a coupling vector-valued function for set-valued vector optimization problem and construct related set-valued dual map and dual optimization problem on the basic of weak efficiency,which used by the concepts of supremum and infimum of a set.We then establish the weak and strong duality results under this augmented Lagrangian and present sufficient conditions for exact penalization via an abstract subdifferential of the object map.Finally,we define the sub-optimal path related to the dual problem and show that every cluster point of this sub-optimal path is a primal optimal solution of the object optimization problem.In addition,we consider a generalized vector variational inequality as an application of abstract subdifferential.