Peripheral nerve injury has seriously affected patient’s health and life. Schwann cells play an important role in peripheral nerve regeneration. However, the effect of the current tissue engineered ...scaffolds for promoting Schwann cells growth is still not as good as that of autologous graft. In this study, new developed three-dimensional gellan gum/starch (GG/ST) scaffolds with various printing gap for Schwann cells growth were prepared by 3D printing technology. Various physiochemical characterizations of the printed scaffolds were performed including morphology, rheological behavior, swelling ratio, and degradation behavior. The cytotoxicity and biocompatibility of the scaffolds were evaluated using L929 fibroblasts and RSC96 Schwann cells, respectively. The results displayed that the GG/ST scaffold exhibited a porous network structure. The cross-sectional pore density of the hydrogel had a tendency to increase with the ascending printing gap. The swelling rate and degradation rate of the hydrogel gradually increased and eventually reached an equilibrium state. The rheological test results showed that the scaffolds had good printability. MTT cytotoxicity test and CCK-8 cell proliferation test displayed that the scaffold was nontoxic, and Schwann cells could grow well on the scaffold after 5 days of culture, whereas the number of cells on the scaffold with the printing gap of 3 mm was the largest. These results indicated that the GG/ST scaffold prepared by 3D printing technology may have a potential application in peripheral nerve regeneration.
Peripheral nerve injury (PNI) seriously affects the health and life of patients, and is an urgent clinical problem that needs to be resolved. Nerve implants prepared from various biomaterials have ...played a positive role in PNI, but the effect should be further improved and thus new biomaterials is urgently needed. Ovalbumin (OVA) contains a variety of bioactive components, low immunogenicity, tolerance, antimicrobial activity, non-toxicity and biodegradability, and has the ability to promote wound healing, cell growth and antimicrobial properties. However, there are few studies on the application of OVA in neural tissue engineering. In this study, OVA implants with different spatial structures (membrane, fiber, and lyophilized scaffolds) were constructed by casting, electrospinning, and freeze-drying methods, respectively. The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity, and can promote vascularization, show good histocompatibility, without excessive inflammatory response and immunogenicity. The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells, while the in vivo results confirmed that OVA implants (the E5/70% and 20 kV 20 μL/min groups) could effectively regulate the growth of blood vessels, reduce the inflammatory response and promote the repair of subcutaneous nerve injury. Further on, the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α (TNF-α), phosphatidylinositide 3-kinases/protein kinase B (PI3K-Akt) signaling pathway, axon guidance, cellular adhesion junctions, and nerve regeneration in Schwann cells. The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.
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•OVA implants with different spatial structures (membrane, fiber, and lyophilized scaffolds) were constructed.•OVA implants had excellent physicochemical properties and were biocompatible.•OVA implants could promote the proliferation and migration of Schwann cells.•OVA implants could reduce the inflammatory response and promote the repair of subcutaneous nerve injury.•The study will provide experimental and theoretical basis for the development nerve regeneration biomaterials.
Genetic testing for breast cancer (BC) patients may shift the paradigm towards more personalized management and treatment strategies. While gene alterations may be ethnic-specific in breast cancer, ...our understanding of genetic epidemiology of BC remains mainly driven by data from Caucasian populations and further limited to selected handful of genes.
We collected whole blood samples from 356 BC patients at metastatic first line BC and primary stage IV disease at Beijing Cancer Hospital between Jan. 2013 to Dec. 2019. A comprehensive 600-gene cancer panel was used to detect germline variants in the covered genes with a median 300x sequencing depth. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance, likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. Pathogenic and likely pathogenic variants were considered as deleterious mutations.
The median age of 356 BC patients was 49 years (range, 21-87 years) at the first diagnosis of BC. Deleterious germline mutations across 48 cancer-related genes were identified in 21.6% (77/356) of the patients. The most prevalent mutations were BRCA1/2 mutations (7.0%), followed by ATM and RAD50 mutations (1.4% each). In addition, patients with family history were more likely to carry BRCA1 mutations (P=0.04). Moreover, patients with triple-negative breast cancer (TNBC) were more likely to harbor BRCA1 mutations than those with HR+ or HER2+ breast cancer (P=0.006). While there was no significant survival difference observed in BRCA1/2 carriers relative to non-carriers, patients with DNA damage repair (DDR) gene mutations (mostly frequently BRCA, ATM, RAD50) had worse disease-free survival (P=0.02).
The most prevalent germline mutations in a large cohort of Chinese patients with advanced BC were BRCA1/2 mutations, followed by ATM and RAD50 mutations. In total, approximately 16.0% (57/356) of patients carry deleterious mutations in DDR pathway. Patients with breast or ovarian cancer family history were more likely to carry BRCA1/2 mutations, and ones with DDR mutations had worse survival. These findings suggest that DDR mutations are prevalent in Chinese BC patients who may potentially benefit from treatment with Poly (ADP-ribose) polymerase inhibitors.
This article discusses Dalian's bar hostesses' paradoxical model of romance: one that is both commodified and based on love. On the one hand, hostesses reject the popular media's emphasis on romantic ...love and sexual purity as a thin disguise for the ugly reality of men's sexual exploitation of women, and they actively perform and commodify romance for their instrumental purposes. On the other hand, hostesses resort to supernatural forces to determine their romantic fate and to seek out ideal love.
Apples are a rich source of polyphenols in the human diet. However, the distribution of polyphenols in different apple varieties and tissues is still largely unclear. In this study, a new liquid ...chromatography–tandem mass spectrometry (LC-MS/MS) strategy was developed to reveal the spatial distribution of polyphenols in different apple tissues and varieties. A method based on multiple reaction monitoring (MRM)-enhanced product ion (EPI) was established in the information-dependent acquisition (IDA) mode for pseudo-target screening of major apple polyphenols. A total of 39 apple polyphenolic metabolites were finally identified. Qualitative and quantitative results showed that the variety and content of polyphenols in apple peels were higher than those of other tissues. In apple roots, stems, and leaves, the highest polyphenol variety and content were found in wild species, followed by cultivars and elite varieties. Dihydrochalcone substances, one kind of major apple polyphenols, were more abundant in apple roots, stems, and leaves. This strategy can be applied as a model for other agricultural products, in addition to revealing the distribution of polyphenols in different tissues of apples, which provides a theoretical basis for the utilization of polyphenol resources and variety selection.
On August 6, 2021, a female employee at the Alibaba Company went on social media to accuse her boss and his client of sexual harassment 1. In her publicized report, she narrated that, during a ...business trip, she was demanded by her boss to drink with his client.
Current liquid biopsy assays lack sufficient sensitivity to detect copy number loss, which limits the interrogation of critical tumor suppressor gene deletions during cancer progression and ...treatment. Here we describe a liquid biopsy assay with improved sensitivity for detection of copy number loss in blood samples with low levels of circulating tumor DNA, and demonstrate its utility by profiling
PTEN
,
RB1
, and
TP53
genetic loss in metastatic prostate cancer patients.
Abstract
Background
The COVID-19 pandemic has caused an unprecedented need for accessible health care services and significantly accelerated the development processes of telehealth tools for autism ...spectrum disorder (ASD) early screening and diagnosis. This study aimed to examine the feasibility and utility of a time-efficient telehealth tool combining a structured snack time assessment activity and a novel behaviour coding scheme for identifying ASD.
Methods
A total of 134 1–6-year-old individuals with ASD (age in months: mean = 51.3, SD = 13.1) and 134 age- and sex-matched typically developing individuals (TD) (age in months: mean = 54, SD = 9.44) completed a 1-min snack time interaction assessment with examiners. The recorded videos were then coded by trained coders for 17 ASD-related behaviours; the beginning and end points and the form and function of each behaviour were recorded, which took 10–15 min. Coded details were transformed into 62 indicators representing the count, duration, rate, and proportion of those behaviours.
Results
Twenty indicators with good reliability were selected for group difference, univariate and multivariate analyses. Fifteen behaviour indicators differed significantly between the ASD and TD groups and remained significant after Bonferroni correction, including the children’s response to the examiner’s initiation, eye gaze, pointing, facial expressions, vocalization and verbalization, and giving behaviours. Five indicators were included in the final prediction model: total counts of eye gaze, counts of standard pointing divided by the total counts of pointing, counts of appropriate facial expressions, counts of socially oriented vocalizations and verbalizations divided by the total counts of vocalizations and verbalizations, and counts of children using giving behaviours to respond to the examiner's initiations divided by the total counts of the examiner's initiation of snack requisitions. The ROC curve revealed a good prediction performance with an area under the curve (AUC) of 0.955, a sensitivity of 92.5% and a specificity of 84.3%.
Conclusion
Our results suggest that the snack activity-based ASD telehealth approach shows promise in primary health care settings for early ASD screening.
Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present ...study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K(+)channel on vascular smooth muscle cells, VSMC sarc-K(ATP)) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-K(ATP) channels and reperfusion recovery.
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