Objective To develop neutralizing monoclonal antibodies (MAbs) against H10N8 avian influenza virus hemagglutinin and to identify the binding sites. Methods MAbs against hemagglutinin of H10N8 avian ...influenza virus were developed by genetic engineering. Neutralizing MAbs were screened by microneutralization assay,and then tested by enzyme-linked immunosorbent assay and Western blot to identity the binding sites.The homology modeling process was performed using Discovery Studio 3.5 software,while the binding epitopes were analyzed by BioEdit software. Results One MAb that could neutralize the H10N8 pseudovirus was obtained and characterized. Analysis about epitopes suggested that the antibody could bind to the HA1 region of hemagglutinin,while the epitopes on antigen were conserved in H10 subtypes.Conclusions One neutralizing antibody was obtained by this research.The MAb may potentially be further developed as a pre-clinical candidate to treat avian influenza H10N8 virus infection.
By analyzing gene expression data from human fetal liver cells 3, we identified 609-, 2538-, and 1139-gene signatures for gestational 10-week fetal liver cells, 17-week fetal liver cells, and mature ...hepatocytes, respectively (Supplementary Fig. Because 10- and 17-week fetal liver cells reflect different degrees of stemness of hepatic lineage, as reflected by α-fetoprotein expression (Supplementary Fig. The HS1 subtype showed higher rates of TP53 and RB1 mutations, while the HS2 subtype showed frequent IL6ST and CDKN2A mutations (Supplementary Fig. Since the HS1 subtype showed the highest microRNA expression (Supplementary Fig. In particular, YAP1 was highly activated in the HS1 subtype. Since YAP1 regulates HS and is associated with poor prognosis in HCC 7, we next examined the potential interaction of other transcription regulators with YAP1 by integrating the downstream target genes of each of the transcription regulators. S13B, C), suggesting that JQ1 can inhibit the growth and invasion of HCC cells by suppressing YAP1. Since JQ1 could inhibit most BET family members, we silenced the expression of BET members to identify the key members regulating YAP1.
By using the bifunctional ligand, 8-hydroxyquinoline-functionalized organosilane (Q-Si), the new mesoporous material Q–MCM-41 covalently bonded with 8-hydroxyquinoline was synthesized. Through the ...ligand exchange reaction, the new near-infrared (NIR) luminescent mesoporous LnQ
3–MCM-41 (Ln
=
Er, Nd, Yb) materials were prepared by linking the lanthanide quinolinate complexes to the ordered mesoporous Q–MCM-41 material. The LnQ
3–MCM-41 materials were characterized by powder X-ray diffraction and N
2 adsorption/desorption, and they all show the characteristic mesoporous structure of MCM-41 with highly uniform pore size distributions. Fluorescence spectra of these LnQ
3–MCM-41 materials were recorded and the corresponding luminescence decay analyses were measured. After ligand-mediated excitation, all the emission spectra of the LnQ
3–MCM-41 materials show the characteristic NIR-luminescence of the corresponding lanthanide ions via the intramolecular energy transfer from the ligands to the lanthanide ions. The good luminescent performances enable these NIR-luminescent mesoporous materials to have potential applications in optical amplification (operating at 1.3 or 1.5
μm) and laser systems, etc.
Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are ...involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors （PPARs） have been identified： PPARa, PPARβ/δ, and PPARγ, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats （SHR） and to understand the modulation of endogenous PPAR isoforms under inflammatory condition. Methods lssues （kidney, liver, heart, and brain） were dissected from SHR and age-matched control Wistar-Kyoto rats （WKY） to investigate the abundance of PPAR isoforms and PPAR-responsive genes （acyI-CoA oxidase and CD36）. The expression of CCAAT/enhancer-binding protein 6 （C/EBP6）, which can trans-activate PPARγ expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase （iNOS）, intercellular adhesion molecule-1 （ICAM-1）, vascular cell adhesion molecule-1 （VCAM-1）, E-selectin, interleukin-1 beta （IL-1β）, and tumor necrosis factor alpha （TNFα）, and formation of carbonyl and nitrated proteins. Results The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPARβ/δ upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARγ increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARy, the expression of C/EBPδ was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR. Conclusions These findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes （increases） in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.
In order to reduce the cost of hot stamping of aluminum alloys and develop high-strength aluminum alloy parts for light-weight car body, short-time solid solution (SS) followed by shot-time ...artificial aging process was implemented for 6061 aluminum alloy with salt bath furnace and silicone oil bath. X-ray diffraction (XRD), optical microscope (OM), scanning electron microscope (SEM-EDS) and high-resolution transmission electron microscope (HR-TEM) were used to characterize the microstructural evolution in details. The holding time for SS can be reduced by 80 % with short-time SS treatment because of the decreased vacancy generation energy and effective boundary areas. Peak aging can be obtained at 200 °C for only 60 min, and the microstructure was characterized by a lot amount of acicular nano-size β’’ phase in the coherent with matrix, while precipitate-free-zone (PFZ) also appeared along the grain boundaries. All tensile properties such as 327 MPa yield strength, 362 MPa tensile strength and 13.1 % elongation meet the 6061 T6-standard. The micro stress introduced by superheated degree along with short-time treatment should be attributed to the accelerated diffusion of magnesium and silicon atoms, which greatly affects the diffusion hermodynamics and kinetics, especially nearby the grain boundaries.
•The microstructural evolution during short-time solid solution followed by shot-time artificial aging was investigated.•Holding time for SS can be reduced by 80 % with short-time SS treatment.•Peak aging was obtained at 200 °C for only 60 min. The micro stress was considered to be the main reason.
To understand the clinical characteristics of tsutsugamushi disease in Suqian Municipality, Jiangsu Province so as to guide the diagnosis and treatment of this disease.
The clinical data of 32 ...patients diagnosed as tsutsugamushi disease in our hospital during the past 2 years were analyzed retrospectively.
Tsutsugamushi disease occurred frequently between August and December. All the 32 patients had the history of contacting grass and brushwood, and all of them showed the signs of pyrexia, eschar, ulcer, swelling of lymph nodes and rash. Liver damages were observed in 30 cases (93.75%). Pulmonary imaging changes were observed in 14 cases (43.75%). Heart damages were noticed in 9 cases (28.13%). Kidney damages were noticed in 6 cases (18.75%). One case was complicated by multiple organ dysfunction syndromes (MODS) and disseminated intravascular coagulation (DIC). The OX19 and OX2 antigen agglutination reaction of bacillus proteus were negative in all the cases. The OXK antigen agglutination reaction of bacillu
In this data, we present the details of the cross-sectional study from Mackay Memorial Hospital, Taipei, Taiwan that examined the relationship between three-dimensional (3D) peri-aortic root fat ...(PARF) volumes, cardiometabolic risk profiles, carotid artery morphology and remodeling. Our sample is composed of a total 1492 adults who underwent an annual cardiovascular risk survey in Taiwan.
PARF was measured using images of gated non-contrast cardiac computed tomography (CT) and a dedicated workstation (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). The stratified analyses were performed in order to assess the association between carotid morphology, remodeling and PARF by tertile. For further analyses and discussion, please see “The Association among Peri-Aortic Root Adipose Tissue, Metabolic derangements and Burden of Atherosclerosis in Asymptomatic Population” by Yun et al. (2015) 1.
Much attention has been paid to carbazole derivatives for their potential applications as optical materials. For the first time, the blue-light-emitting carbazole chromophore has been covalently ...bonded to the ordered mesoporous SBA-15 (The resultant hybrid mesoporous materials are denoted as carbazole–SBA-15) by co-condensation of tetraethoxysilane (TEOS) and prepared compound 3-
N-3-(triethoxysilyl)propylureyl-9-ethyl-carbazole (denoted as carbazole–Si) in the presence of Pluronic P123 surfactant. The results of
1H NMR and Fourier transform infrared (FTIR) reveal that carbazole–Si has been successfully synthesized. Small-angle X-ray diffraction patterns (XRD) and Nitrogen (N
2) adsorption/desorption measurements were employed to characterize the mesostructure of carbazole–SBA-15. Solid-state
29Si magic-angle spinning (MAS) NMR was used to confirm the preservation of the carbazole group and estimate the degree of hydrolysis-condensation. Photoluminescence (PL) measurements show that carbazole–SBA-15(0.07) carbazole–Si:(TEOS+carbazole–Si) molar ratio is 0.07 hybrid mesoporous material exhibits a monomeric emission in the “light blue” region with a PL quantum yield ∼31%. Compared with carbazole–Si, the
I
car/
C
car (relative luminescence intensity divided by the content of carbazole) of carbazole–SBA-15(0.07) increases 24 times. The luminescence decays for 3-amino-9-ethyl-carbazole (denoted as carbazole–NH
2) and carbazole–Si are single-exponential functions of time, while those for carbazole–SBA-15 mesoporous materials are fitted by double-exponential functions. The stability studies on carbazole–Si and carbazole–SBA-15(0.07) show that the carbazole chromophore in the resultant hybrid mesoporous material exhibits better thermal stability than in carbazole–Si compound. The excellent luminescent properties and thermal stability enable the hybrid mesoporous material to have potential use as blue-light-emitting material in optical field.
Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival ...in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.
In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 years, or 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery) plus one dose of 1 mg/kg of ipilimumab intravenously concurrently with the first preoperative dose of nivolumab, followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for up to 2 years plus 1 mg/kg of ipilimumab intravenously every 6 weeks for up to four cycles. Patients were randomly assigned to the treatment groups by use of block randomisation with a random block size. The primary endpoint was the safety and tolerability of nivolumab with or without ipilimumab. Secondary endpoints were the proportion of patients with an overall response, time to progression, and progression-free survival. This trial is registered with ClinicalTrials.gov (NCT03222076) and is completed.
Between Oct 30, 2017, and Dec 3, 2019, 30 patients were enrolled and 27 were randomly assigned: 13 to nivolumab and 14 to nivolumab plus ipilimumab. Grade 3-4 adverse events were higher with nivolumab plus ipilimumab (six 43% of 14 patients) than with nivolumab alone (three 23% of 13). The most common treatment-related adverse events of any grade were increased alanine aminotransferase (three 23% of 13 patients on nivolumab vs seven 50% of 14 patients on nivolumab plus ipilimumab) and increased aspartate aminotransferase (three 23% vs seven 50%). No patients in either group had their surgery delayed due to grade 3 or worse adverse events. Seven of 27 patients had surgical cancellations, but none was due to treatment-related adverse events. Estimated median progression-free survival was 9·4 months (95% CI 1·47-not estimable NE) with nivolumab and 19·53 months (2·33-NE) with nivolumab plus ipilimumab (hazard ratio HR 0·99, 95% CI 0·31-2·54); median time to progression was 9·4 months (95% CI 1·47-NE) in the nivolumab group and 19·53 months (2·33-NE) in the nivolumab plus ipilimumab group (HR 0·89, 95% CI 0·31-2·54). In an exploratory analysis, three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumour area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab.
Perioperative nivolumab alone and nivolumab plus ipilimumab appears to be safe and feasible in patients with resectable hepatocellular carcinoma. Our findings support further studies of immunotherapy in the perioperative setting in hepatocellular carcinoma.
Bristol Myers Squibb and the US National Institutes of Health.
The hypertension is one of chronic vascular diseases, which often implicates multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A growing body of evidence suggests that ...inflammatory mechanisms are important participants in the pathophysiology of hypertension. In this study, the inflammatory status of these tissues (kidney, liver, heart, and brain) in spontaneously hypertensive rats (SHR) was analyzed and its molecular mechanism was explored. The tissues were dissected from SHR and age-matched control Wistar-Kyoto (WKY) rats to investigate the abundance of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma). mRNA levels were determined by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blot. To evaluate the oxidative stress of tissues, carbonyl protein content and total antioxidant capacity of tissues were detected by spectrophotometry and ferric reduction ability power (FRAP) method. The results suggest that: (1) Expressions of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma) in SHR were higher compared with those in WKY rats except no evident increase of IL-1beta mRNA in liver and brain in SHR. (2) Tissues in SHR contained obviously increased carbonyl protein (nmol/mg protein) compared to that in WKY rats (8.93+/-1.08 vs 2.27+/-0.43 for kidney, 2.23+/-0.23 vs 0.17+/-0.02 for heart, 13.42+/-1.10 vs 5.72+/-1.01 for brain, respectively, P<0.05). However, no evident difference in the amount of carbonyl protein in liver was detected between SHR and WKY rats. (3) Total antioxidant capacities of kidney, liver, heart and brain were markedly lower in SHR than that in WKY rats (P<0.05). Thus, the present data reveal a higher inflammatory status in the important tissues in SHR and indicate that inflammation might play a potential role in pathogenesis of hypertension and secondary organ complications.
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