Third-generation Al–Li alloys, represented by 2195 Al–Li alloy, have considerable application opportunities in lightweight aerospace structures. This work investigates the effect of the aging ...temperature, single/double aging strategies and pre-deformation on the precipitation behaviors of 2195 Al–Li alloy. The influence and correlation between the precipitated phase and mechanical properties, especially the tensile strength, ductility and failure fracture mode, were further studied. The results indicate that increasing the aging temperature can significantly improve the aging kinetics, thereby precipitating the large size T1 phase and decreasing the number density accordingly. Double aging is beneficial to the uniform size and distribution of the precipitated phase, which reduces the unevenness of micro-deformation. The pre-deformation increases the number of nucleation sites of the T1 phase, thereby significantly reducing the average size and increasing the number density. Pre-deformation can directly increase the strain hardening by generating dislocations while indirectly increasing the precipitation strengthening by refining the size and increasing the number density of the T1 phase. The mechanical properties and fracture mode of materials are related to the dislocation density and the type, size, distribution and number density of the precipitated phase.
Trastuzumab is a standard treatment for HER2-positive (HER2
) breast cancer, but some patients are refractory to the therapy. MicroRNAs (miRNAs) have been used to predict therapeutic effects for ...various cancers, but whether miRNAs can serve as biomarkers for HER2
metastatic breast cancer (MBC) patients remains unclear. Using miRNA microarray, we identify 13 differentially expressed miRNAs in the serum of HER2
MBC patients with distinct response to trastuzumab, and four miRNAs are selected to construct a signature to predict survival using LASSO model. Further, our data show that miR-940 is mainly released from the tumor cells and miR-451a, miR-16-5p and miR-17-3p are mainly from the immune cells. All these four miRNAs directly target signaling molecules that play crucial roles in regulating trastuzumab resistance. In summary, we develop a serum-based miRNA signature that potentially predicts the therapeutic benefit of trastuzumab for HER2
MBC patients and warrants future validation in prospective clinical trials.
Optimal nanosized drug delivery systems (NDDS) require long blood circulation and controlled drug release at target lesions for efficient anticancer therapy. Red blood cell (RBC) membrane‐camouflaged ...nanoparticles (NPs) can integrate flexibility of synergetic materials and highly functionality of RBC membrane, endowed with many unique advantages for drug delivery. Here, new near‐infrared (NIR)‐responsive RBC membrane‐mimetic NPs with NIR‐activated cellular uptake and controlled drug release for treating metastatic breast cancer are reported. An NIR dye is inserted in RBC membrane shells, and the thermoresponsive lipid is employed to the paclitaxel (PTX)‐loaded polymeric cores to fabricate the RBC‐inspired NPs. The fluorescence of dye in the NPs can be used for in vivo tumor imaging with an elongated circulating halftime that is 12.3‐folder higher than that of the free dye. Under the NIR laser stimuli, the tumor cellular uptake of NPs is significantly enhanced to 2.1‐fold higher than that without irradiation. The structure of the RBC‐mimetic NPs can be destroyed by the light‐induced hyperthermia, triggered rapid PTX release (45% in 30 min). These RBC‐mimetic NPs provide a synergetic chemophotothermal therapy, completely inhibited the growth of the primary tumor, and suppress over 98% of lung metastasis in vivo, suggesting it to be an ideal NDDS to fight against metastatic breast cancer.
Bioinspired nanoparticles with near infrared (NIR)‐controlled drug release for synergetic chemophotothermal therapy load paclitaxel in the polymeric cores and cyanine dye (DiR) in the red blood cell (RBC) membrane shells. This overcomes the limited cellular uptake and slow drug release at tumor lesions of RBC‐mimetic nanosized drug delivery systems (NDDS), integrates real‐time tracking, allows NIR‐triggered tumor‐specific drug release and synergetic chemo‐photothermal therapy, and provides new insights for optimization of mimetic NDDS.
•Five tasty peptides were isolated and identified from soy sauce.•LPEEV, AQALQAQA and EQQQQ displayed obvious umami.•ALPEEV, EAGIQ and LPEEV showed capacity of umami-enhancement.•Peptides showed ...better taste than mixtures of their constitutive amino acids.
Five tasty peptides were separated from soy sauce, by sensory-guided fractionation, using macroporous resin, medium-pressure liquid chromatography and reverse phase-high performance liquid chromatography, and identified by ultra-performance liquid chromatography tandem mass-spectrometry as ALPEEV, LPEEV, AQALQAQA, EQQQQ and EAGIQ (which originated from glycinin A1bB2-445, glycinin A1bB2-445, cobyric acid synthase, leucine-tRNA ligase and glycoprotein glucosyltransferase, respectively). LPEEV, AQALQAQA and EQQQQ tasted umami with threshold values of 0.43, 1.25 and 0.76mmol/l, respectively. ALPEEV and EAGIQ had minimal umami taste, but ALPEEV, EAGIQ and LPEEV showed umami-enhancement with a threshold estimated at 1.52, 1.94 and 3.41mmol/l, respectively. In addition, the synthetic peptides showed much better sensory taste than mixtures of their constitutive amino acids. It indicated that peptides might play an important role in the umami taste of soy sauce.
River piracy has been reported worldwide and was regarded as one of the main drivers for landscape evolution. In this study, we introduce an example of river piracy in the northern Qilian Shan ...(northeastern Qinghai-Tibet Plateau), and further interpret its regional geomorphological implications. Chi-map analysis, erosion potentiality evaluation, and river profile inversion are used to verify the river piracy. The results confirm that the transverse river, the Hongshuiba River, has captured the longitudinal river, the Zhulongguan River at ~0.35 Ma, due to the headward-migrating erosion of the main stem of the Hongshuiba River. The drainage reorganization, with longitudinal rivers captured by transverse rivers, is a common and continuous landform process along with the outward growth of the northern Qilian Shan. Moreover, the present Qilian Shan watershed geomorphic system could be considered as a transient stage of drainage evolution during the mountain building.
•The Hongshuiba River has captured the Zhulongguan River at ~0.35 Ma•River piracy is common phenomenon in northern Qilian Shan•The present Qilian Shan topography is in a transient stage of drainage evolution during the mountain building.
Hematologic and biochemical analytes of Sprague-Dawley rats are commonly used to determine effects that were induced by treatment and to evaluate organ dysfunction in toxicological safety ...assessments, but reference intervals have not been well established for these analytes. Reference intervals as presently defined for these analytes in Sprague-Dawley rats have not used internationally recommended statistical method nor stratified by sex. Thus, we aimed to establish sex-specific reference intervals for hematologic and biochemical parameters in Sprague-Dawley rats according to Clinical and Laboratory Standards Institute C28-A3 and American Society for Veterinary Clinical Pathology guideline.
Hematology and biochemistry blood samples were collected from 500 healthy Sprague-Dawley rats (250 males and 250 females) in the control groups. We measured 24 hematologic analytes with the Sysmex XT-2100i analyzer, 9 biochemical analytes with the Olympus AU400 analyzer. We then determined statistically relevant sex partitions and calculated reference intervals, including corresponding 90% confidence intervals, using nonparametric rank percentile method.
We observed that most hematologic and biochemical analytes of Sprague-Dawley rats were significantly influenced by sex. Males had higher hemoglobin, hematocrit, red blood cell count, red cell distribution width, mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, neutrophils, lymphocytes, monocytes, percentage of neutrophils, percentage of monocytes, alanine aminotransferase, aspartate aminotransferase, and triglycerides compared to females. Females had higher mean corpuscular hemoglobin concentration, plateletcrit, platelet count, eosinophils, percentage of lymphocytes, percentage of eosinophils, creatinine, glucose, total cholesterol and urea compared to males. Sex partition was required for most hematologic and biochemical analytes in Sprague-Dawley rats. We established sex-specific reference intervals, including corresponding 90% confidence intervals, for Sprague-Dawley rats.
Understanding the significant discrepancies in hematologic and biochemical analytes between male and female Sprague-Dawley rats provides important insight into physiological effects in test rats. Establishment of locally sex-specific reference intervals allows a more precise evaluation of animal quality and experimental results of Sprague-Dawley rats in our toxicology safety assessment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alzheimer's disease (AD), also known as senile dementia, is a progressive neurodegenerative disease. The etiology and pathogenesis of AD have not yet been elucidated. We examined common ...differentially expressed genes (DEGs) from different AD tissue microarray datasets by meta-analysis and screened the AD-associated genes from the common DEGs using GCBI. Then we studied the gene expression network using the STRING database and identified the hub genes using Cytoscape. Furthermore, we analyzed the microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and single nucleotide polymorphisms (SNPs) associated with the AD-associated genes, and then identified feed-forward loops. Finally, we performed SNP analysis of the AD-associated genes. Our results identified 207 common DEGs, of which 57 have previously been reported to be associated with AD. The common DEG expression network identified eight hub genes, all of which were previously known to be associated with AD. Further study of the regulatory miRNAs associated with the AD-associated genes and other genes specific to neurodegenerative diseases revealed 65 AD-associated miRNAs. Analysis of the miRNA associated transcription factor-miRNA-gene-gene associated TF (mTF-miRNA-gene-gTF) network around the AD-associated genes revealed 131 feed-forward loops (FFLs). Among them, one important FFL was found between the gene
, hsa-miR-27a, and the transcription factor MYC. Furthermore, SNP analysis of the AD-associated genes identified 173 SNPs, and also found a role in AD for miRNAs specific to other neurodegenerative diseases, including hsa-miR-34c, hsa-miR-212, hsa-miR-34a, and hsa-miR-7. The regulatory network constructed in this study describes the mechanism of cell regulation in AD, in which miRNAs and lncRNAs can be considered AD regulatory factors.
Thise study is aimed to identify the biomarkers for predicting refractory Mycoplasma pneumoniae pneumonia in Chinese children at the time of the hospital admission.
The case control study ...retrospectively analyzed the clinical characteristics and laboratory results of Chinese pediatric patients presenting with common and refractory Mycoplasma pneumoniae pneumonia (CMPP and RMPP). Overall, there were 216 cases in the CMPP group and 88 cases in the RMPP group. Venous blood was collected, and serum ferritin (SF), lactate dehydrogenase (LDH), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte count (NLR), and other indexes were measured. A single factor analysis, an ROC curve analysis, and a logistic regression analysis were used to determine the independent risk factors of RMPP and find combination of initial markers for RMPP.
There were significant differences between the RMPP group and the CMPP group in mean SF (529.82 357.86 vs. 147.22 122.68 ng/mL), LDH (522.08 389.08 vs. 286.85 101.02 U/L), D-dimer (6.65 5.66 vs. 1.46 2.45 μg/mL), CRP (62.80 52.15 vs. 19.03 24.50 mg/L), PCT (0.80 2.61 vs. 0.16 0.44) ng/mL, and NLR (4.14 2.52 vs. 2.62 1.55), with P < 0.05 for each comparison. ROC cut-off values of the above indexes were 329.01 ng/mL, 375.50 U/L, 2.10 μg/mL, 43.08 mg/L, 0.08 ng/mL, and 2.96, respectively. The logistic regression analysis showed that SF, D-dimer, and CRP are independent risk factors to predict RMPP.
SF, D-dimer, and CRP are statistically significant biomarkers to predict RMPP in Chinese children patients in the settings of pediatric emergency department.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The cell‐specific targeting drug delivery and controlled release of drug at the cancer cells are still the main challenges for anti‐breast cancer metastasis therapy. Herein, the authors first report ...a biomimetic drug delivery system composed of doxorubicin (DOX)‐loaded gold nanocages (AuNs) as the inner cores and 4T1 cancer cell membranes (CMVs) as the outer shells (coated surface of DOX‐incorporated AuNs (CDAuNs)). The CDAuNs, perfectly utilizing the natural cancer cell membranes with the homotypic targeting and hyperthermia‐responsive ability to cap the DAuNs with the photothermal property, can realize the selective targeting of the homotypic tumor cells, hyperthermia‐triggered drug release under the near‐infrared laser irradiation, and the combination of chemo/photothermal therapy. The CDAuNs exhibit a stimuli‐release of DOX under the hyperthermia and a high cell‐specific targeting of the 4T1 cells in vitro. Moreover, the excellent combinational therapy with about 98.9% and 98.5% inhibiting rates of the tumor volume and metastatic nodules is observed in the 4T1 orthotopic mammary tumor models. As a result, CDAuNs can be a promising nanodelivery system for the future therapy of breast cancer.
The biomimetic gold nanocages composed of doxorubicin in the cores and the 4T1 cancer cell membranes as the shells, utilizing the homotypic targeting ability of the natural cancer cell membranes and the photothermal property of gold nanocages, can realize the selective targeting of the homotypic tumor cells, NIR‐triggered drug release, and synergetic chemo/photothermal therapy to inhibit metastatic breast cancer.
In order to explore the processing and application potential of Chinese yam starch, nine kinds of Chinese yam starch (GY11, GY5, GY2, GXPY, LCY, SFY, MPY, SYPY, ASY) from South China were collected ...and characterized. The chemical composition, rheological properties, thermal properties, and in vitro starch digestion were compared, and the correlation between the structure and processing properties of these yam starches was analyzed using Pearson correlation. The results show that GY2 had the highest amylose content of 28.70%. All the yam starches were similarly elliptical, and all the yam starch gels showed pseudoplastic behavior. Yam starches showed similar pasting temperatures and resistant starch content, but SYPY showed the largest particle size (28.4 μm), SFY showed the highest setback (2712.33 cp), and LCY showed the highest peak viscosity (6145.67 cp) and breakdown (2672.33 cp). In addition, these yam starches also showed different crystal types (A-type, B-type, C-type), relative crystallinity (26.54-31.48%), the ratios of 1045/1022 cm
(0.836-1.213), pasting properties, and rheological properties, so the yam starches have different application potentials. The rheological and pasting properties were related to the structural properties of starch, such as DI, Mw, and particle size, and were also closely related to the thermodynamic properties. The appropriate processing methods and purposes of the processed products of these yam starches can be selected according to their characteristics.
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