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Mucin 1 (MUC1) peptide fused with Q11 (MUC1-Q11) having 35 residues has previously been shown to form amyloid fibrils. Using time-dependent and high-resolution atomic force microscopy (AFM) imaging, it is revealed that the formation of individual MUC1-Q11 fibrils entails nucleation and extension at both ends. This process can be altered by local mechanical perturbations using AFM probes. This work reports two specific perturbations and outcomes. First, by increasing load while maintaining tip-surface contact, the fibrils are cut during the scan due to shearing. Growth of fibrils occurs at the newly exposed termini, following similar mechanism of the MUC1-Q11 nucleation growth. As a result, branched fibrils are seen on the surface whose orientation and length can be controlled by the nuclei orientation and reaction time. In contrast to the "one-time-cut", fibrils can be continuously fragmented by modulation at sufficiently high amplitude. As a result, short and highly branched fibrils accumulate and pile on surfaces. Since the fibril formation and assembly of MUC1-Q11 can be impacted by local mechanical force, this approach offers a nonchemical and label-free means to control the presentation of MUC1 epitopes, and has promising application in MUC1 fibril-based immunotherapy.

Multicomponent nanostructures with individual geometries have attracted much attention because of their potential to carry out multiple functions synergistically. The current work reports a simple method using particle lithography to fabricate multicomponent nanostructures of metals, proteins, and organosiloxane molecules, each with its own geometry. Particle lithography is well-known for its capability to produce arrays of triangular-shaped nanostructures with novel optical properties. This paper extends the capability of particle lithography by combining a particle template in conjunction with surface chemistry to produce multicomponent nanostructures. The advantages and limitations of this approach will also be addressed.

Objective To investigate the protective effect of berberine chloride on secondary damage (inflammation, oxidative damage and neuron loss) in bilateral thalami of traumatic brain injury (TBI) model mice. Methods Mice were randomly divided into 3 groups: control group (N = 6), TBI group (N = 6) and berberine group (N =6). TBI model was established by a free-falling hitting device. In control group, mice were not given free-falling hitting. Mice in berberine group were given a gavage of berberine chloride [50 mg/(kg⋅d)] for 21 d, while mice in TBI group were given the same dosage of normal saline for 21 d. Immunohistochemistry was used to count the number of neurons or gliocytes positive for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), 8-hydroxy deoxyguanosine (8-OHdG) and neuronal nuclei (NeuN), the number of astrocytes positive for glial fibrillary acidic protein (GFAP) and the number of microglias positive for ionized calcium-binding adaptor molecule 1 (Iba1). Results The number of neurons or gliocytes positive for iNOS (P = 0.015), COX-2 (P = 0.022), 8-OHdG (P = 0.000) and NeuN (P = 0.000), the number of astrocytes positive for GFAP (P = 0.024) and microglias positive for Iba1 (P = 0.000) in TBI ipsilateral thalamus were significantly different among 3 groups. In TBI group, the number of neurons or gliocytes positive for iNOS (P = 0.005), COX-2 (P = 0.011) and 8-OHdG (P = 0.000), the number of astrocytes positive for GFAP (P = 0.011) and microglias positive for Iba1 (P = 0.000) were significantly higher than those in control group, while the number of neurons positive for NeuN (P = 0.000) was significantly lower than that in control group. In berberine group, the number of neurons or gliocytes positive for iNOS (P = 0.031), COX-2 (P = 0.024) and 8-OHdG (P = 0.008), the number of astrocytes positive for GFAP (P = 0.031) and microglias positive for Iba1 (P = 0.012) were significantly lower than those in TBI group, while the number of neurons positive for 8-OHdG (P = 0.014) and microglias positive for Iba1 (P = 0.024) were significantly higher than those in control group. The number of neurons positive for NeuN in berberine group was significantly higher than that in TBI group (P = 0.016), while lower than that in control group (P = 0.027). Additionally, number of neurons or gliocytes positive for COX-2 (P = 0.029) and 8-OHdG (P = 0.000) in TBI contralateral thalamus were significantly different among 3 groups. The number of neurons or gliocytes positive for COX-2 (P = 0.011) and 8-OHdG (P = 0.000) in TBI group was significantly higher than that in control group, while the number of neurons or gliocytes positive for COX-2 (P = 0.047) and 8-OHdG (P = 0.010) in berberine group was significantly lower than that in TBI group. The number of neurons positive for 8-OHdG in berberine group was significantly higher than that in control group (P = 0.004). Conclusions TBI could cause secondary damage of bilateral thalami, especially in ipsilateral thalamus, but only cause inflammation and oxidative damage in contralateral thalamus. Berberine chloride might exert neuroprotective effect on bilateral thalami after TBI by significantly suppressing inflammation and oxidative damage. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinicopathological features and prognosis of idiopathic membranous nephropathy(IMN)in adolescents. Methods This was a retrospective study on IMN patients hospitalized between June 2012 and December 2014,and a total of 33 IMN patients aged between 13 and 24 years old were enrolled in the study.Meanwhile,33 IMN patients aged more than 24 years old were selected randomly as control group during the same period.Diagnosis was confirmed by renal biopsy,and the secondary causes of membranous nephropathy were ruled out.Data collected from medical record and biopsy were analyzed. Results In the adolescent IMN group,the mean age at renal biopsy was(20±3)years old,and the male/female ratio was 22/11.Twenty-three cases presented as nephrotic syndrome.Systolic and diastolic pressures were(127±13)mmHg and(77±9)mmHg,respectively.The median 24-hour urine protein was 5.14(3.39,9.31)g/d,and the median serum creatinine was 62(52,73)μmol/L.The positive rate of serum anti-phospholipase A2 receptor in adolescent group was 54%.Compared with control group,the adolescent patients had lower incidence of hypertension and higher baseline estimated glomerular filtration rate level [15.2% vs.39.3%,χ 2 =4.889,P=0.03;125 ml/(min·1.73m 2 )vs.100 ml/(min·1.73m 2 ),U=137.5,P<0.001].According to IMN staging criteria in electron microscopy,adolescent patients were classified as one case in stage I,21 in stage Ⅱ,and 11 in stage Ⅲ or higher.The positive rates of IgG1,IgG2,IgG3 and IgG4 subclass staining in glomeruli were 46.9%,3.1%,56.3%,and 87.5%,respectively.Compared with control group,the adolescent patients had lower incidence of renal interstitial fibrosis and arteriolar lesions(6.1% vs.66.7%,χ 2 =26.19,P<0.001;15.2% vs.66.7%,χ 2 =18.11,P<0.001).Three patients lost to follow-up while others started steroid combined with cyclosporine A(n=20),cyclophosphamide(n=7),or mycophenolate(n=1)or solely(n=2).After a median follow-up of 18(12,24)months,the median proteinuria decreased to 0.20(0.10,0.42)g/d,whereas serum creatinine level remained stable [69(56.8,81.3)μmol/L].Seventeen patients(56.7%)achieved complete remission(CR),and the remaining 13 patients(43.4%)achieved partial remission(PR).The median time of CR and PR were three and six months,respectively.Only one patient relapsed during the follow-up.Also,21 cases received maintenance therapy including cyclosporine A(n=18),azathioprine(n=2)and mycophenolate(n=1).Conclusions The immunofluorescence IgG subclass in glomeruli and distribution of serum anti-phospholipase A2 receptor in adolescent IMN patients are similar to those in older IMN patients.IMN patients in adolescents responded well to immunosuppressive therapy.Cyclosporine A in low dose as maintenance therapy is effective after achieving remission,and will not increase risk of nephrotoxicity.