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Application of Extrusion-Based Hydrogel Bioprinting for Cartilage Tissue Engineering
Extrusion-based bioprinting (EBB) is a rapidly developing technique that has made substantial progress in the fabrication of constructs for cartilage tissue engineering (CTE) over the past decade. With this technique, cell-laden hydrogels or bio-inks have been extruded onto printing stages, layer-by-layer, to form three-dimensional (3D) constructs with varying sizes, shapes, and resolutions. This paper reviews the cell sources and hydrogels that can be used for bio-ink formulations in CTE application. Additionally, this paper discusses the important properties of bio-inks to be applied in the EBB technique, including biocompatibility, printability, as well as mechanical properties. The printability of a bio-ink is associated with the formation of first layer, ink rheological properties, and crosslinking mechanisms. Further, this paper discusses two bioprinting approaches to build up cartilage constructs, i.e., self-supporting hydrogel bioprinting and hybrid bioprinting, along with their applications in fabricating chondral, osteochondral, and zonally organized cartilage regenerative constructs. Lastly, current limitations and future opportunities of EBB in printing cartilage regenerative constructs are reviewed.
Journal Article
Synthesis and Biological Evaluation of Quinoline Derivatives as a Novel Class of Broad-Spectrum Antibacterial Agents
Nineteen new quinoline derivatives were prepared via the Mannich reaction and evaluated for their antibacterial activities against both Gram-positive (G+) and Gram-negative (G−) bacteria, taking compound 1 as the lead. Among the target compounds, quinolone coupled hybrid 5d exerted the potential effect against most of the tested G+ and G− strains with MIC values of 0.125–8 μg/mL, much better than those of 1. Molecular-docking assay showed that compound 5d might target both bacterial LptA and Top IV proteins, thereby displaying a broad-spectrum antibacterial effect. This hybridization strategy was an efficient way to promote the antibacterial activity of this kind, and compound 5d was selected for the further investigation, with an advantage of a dual-target mechanism of action.
Journal Article
Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis
Backgrounds
The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer.
Methods
We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values.
Results
A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275,
p
< 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365,
p
< 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score.
Conclusions
High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.
Journal Article
Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where
ERBB2
focal amplifications positively correlate with prognosis and
EGFR
focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the
ERBB2
focal amplifications may represent a good prognostic marker in GCA patients.
The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, the authors identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, as well as the potential associations of these alterations with prognosis and dietary habits.
Journal Article
Intra-assemblage variation in the macro-blade assemblage from the 1963 excavation at Shuidonggou locality 1, northern China, in the context of regional variation
The emergence of the Upper Paleolithic and regional variability in early Upper Paleolithic industries are prominent topics in Paleolithic archaeology, with special relevance to the dispersal and differentiation of early modern human cultures across Eurasia. The so-called Initial Upper Paleolithic (IUP) has been considered a key element in the emergence of the Upper Paleolithic in northern Asia. Here, we examine the intra-assemblage variation in the collection from the 1963 excavation at Shuidonggou locality 1, a major IUP site in northern China. We combine technological and quantitative attribute analyses to investigate the variety of core reduction sequences and tool manufacture behaviors at the site. A range of core reduction sequences have been documented at Shuidonggou locality 1, including both simple core reduction and prepared core reduction yielding laminar (blade-like) products. The simple core reduction component may due to mixed non-IUP assemblages from different archaeological layers. Among the laminar core reduction sequences, the main strategy involves asymmetrical exploitation of the broad face of core blank, producing blades and elongate flakes, and resembling a recurrent Levallois blade method sensu lato. We compare Shuidonggou laminar blank production with that of IUP assemblages in the Siberian Altai, northern Mongolia, and the Transbaikal region. The comparison demonstrates a general consistency to the basic blank production in IUP assemblages across northern Asia, with some regional variation. The results suggest a multi-directional model of diffusion of the IUP in northeast Asia.
Journal Article
PBRM1 deficiency oncogenic addiction is associated with activated AKT–mTOR signalling and aerobic glycolysis in clear cell renal cell carcinoma cells
The PBRM1 (PB1) gene which encodes the specific subunit BAF180 of the PBAF SWI/SNF complex, is highly mutated (~ 40%) in clear cell renal cell carcinoma (ccRCC). However, its functions and impact on cell signalling are still not fully understood. Aerobic glycolysis, also known as the ‘Warburg Effect’, is a hallmark of cancer, whether PB1 is involved in this metabolic shift in clear cell renal cell carcinoma remains unclear. Here, with established stable knockdown PB1 cell lines, we performed functional assays to access the effects on 786‐O and SN12C cells. Based on the RNA‐seq data, we selected some genes encoding key glycolytic enzymes, including PFKP, ENO1, PKM and LDHA, and examined the expression levels. The AKT–mTOR signalling pathway activity and expression of HIF1α were also analysed. Our data demonstrate that PB1 deficiency promotes the proliferation, migration, Xenograft growth of 786‐O and SN12C cells. Notably, knockdown of PB1 activates AKT–mTOR signalling and increases the expression of key glycolytic enzymes at both mRNA and protein levels. Furthermore, we provide evidence that deficient PB1 and hypoxic conditions exert a synergistic effect on HIF 1α expression and lactate production. Thus, our study provides novel insights into the roles of tumour suppressor PB1 and suggests that the AKT–mTOR signalling pathway, as well as glycolysis, is a potential drug target for ccRCC patients with deficient PB1.
Journal Article
Experimental optimization of user-habit-oriented daily products via integrated innovation and functional parameter analysis
Daily products (DPs) are frequently used in synergy due to lifestyle preferences and usage habits, evolving in response to shifting living needs. Given this dynamic, the integration of existing product functionalities emerges as a sustainable approach to innovative development. In this study, a novel user-habit-oriented hybrid Taguchi method is proposed, coupled with experimental frameworks designed to assess usability. Through rigorous experimentation, significant design parameters that enhance usability are identified and utilized to optimize the integration of multiple DPs. Validation experiments confirm that the proposed hybrid Taguchi method effectively integrates and optimizes the functions of multiple daily products, offering a promising pathway for sustainable product innovation. The design scheme determined by this method not only has high usability performance, but also suits the user’s lifestyle habits.
Journal Article