Explore the vast range of titles available.

Background Hepatocellular carcinoma (HCC) remains a global challenge due to its high morbidity and mortality rates as well as poor response to treatment. The communication between tumor-derived elements and stroma plays a critical role in facilitating cancer progression of HCC. Exosomes are small extracellular vesicles (EVs) that are released from the cells upon fusion of multivesicular bodies with the plasma membrane. There is emerging evidence indicating that exosomes play a central role in cell-to-cell communication. Much attention has been paid to exosomes since they are found to transport bioactive proteins, messenger RNA (mRNAs) and microRNA (miRNAs) that can be transferred in active form to adjacent cells or to distant organs. However, the mechanisms underlying such cancer progression remain largely unexplored. Methods Exosomes were isolated by differential ultracentrifugation from conditioned medium of HCC cells and identified by electron microscopy and Western blotting analysis. Hepatic stellate cells (HSCs) were treated with different concentrations of exosomes, and the activation of HSCs was analyzed by Western blotting analysis, wound healing, migration assay, Edu assay, CCK-8 assay and flow cytometry. Moreover, the different miRNA levels of exosomes were tested by real-time quantitative PCR (RT-PCR). The angiogenic ability of activated HSCs was analyzed by qRT-PCR, CCK-8 assay and tube formation assay. In addition, the abnormal lipid metabolism of activated HSCs was analyzed by Western blotting analysis and Oil Red staining. Finally, the relationship between serum exosomal miRNA-21 and prognosis of HCC patients was evaluated. Results We showed that HCC cells exhibited a great capacity to convert normal HSCs to cancer-associated fibroblasts (CAFs). Moreover, our data revealed that HCC cells secreted exosomal miRNA-21 that directly targeted PTEN, leading to activation of PDK1/AKT signaling in HSCs. Activated CAFs further promoted cancer progression by secreting angiogenic cytokines, including VEGF, MMP2, MMP9, bFGF and TGF-β. Clinical data indicated that high level of serum exosomal miRNA-21 was correlated with greater activation of CAFs and higher vessel density in HCC patients. Conclusions Intercellular crosstalk between tumor cells and HSCs was mediated by tumor-derived exosomes that controlled progression of HCC. Our findings provided potential targets for prevention and treatment of live cancer.

The substantial harmful effects of tobacco smoking on fertility and reproduction have become apparent but are not generally appreciated. Tobacco smoke contains more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide, polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of tobacco smoke components, the toxicological mechanism is notably complicated. Most studies have reported reduced semen quality, reproductive hormone system dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa function in smokers compared with nonsmokers. Underlying these effects, elevated oxidative stress, DNA damage, and cell apoptosis may play important roles collaboratively in the overall effect of tobacco smoking on male fertility. In this review, we strive to focus on both the phenotype of and the molecular mechanism underlying these harmful effects, although current studies regarding the mechanism remain insufficient.

Acral melanoma (AM), as a peculiar subgroup of melanoma, is rare in Caucasians but has higher incidence in Asians. Large series of study on AM with clinicopathological features and prognostic factors is still limited, especially in Asian population. We retrospectively collected clinical, pathological and follow-up data of 142 AM cases. All patients were Chinese, with the age ranging from 24 to 87 years (mean 62.0; median 62.0). The Breslow thickness of primary lesions ranged from 0.6 to 16.3 mm (mean 4.9; median 3.7). 85.9% of the patients had acral lentiginous histologic subtype. Plantar was the most frequently involved site, followed by heels. Statistically, duration of the lesion before diagnosis (≤2.5 years), Breslow thickness >4.0 mm (T4), high mitotic index (>15 mm −2 ), presence of vascular invasion, regional lymph node metastasis at diagnosis and pathologic stage (II/III/IV) were found to be independent prognostic factors in both univariate and multivariate analyses. The prognosis of AM in Chinese is extremely poor. Our 5- and 10-year disease-specific survival (DSS) rates were 53.3% and 27.4%, respectively. Therefore, AM in Asians represents a more biologically aggressive melanoma subtype and is thought to carry a worse prognosis when compared with other races or cutaneous melanomas in other anatomic sites.

After half a billion years of evolution, arthropods have developed sophisticated compound eyes with extraordinary visual capabilities that have inspired the development of artificial compound eyes. However, the limited 2D nature of most traditional fabrication techniques makes it challenging to directly replicate these natural systems. Here, we present a biomimetic apposition compound eye fabricated using a microfluidic-assisted 3D-printing technique. Each microlens is connected to the bottom planar surface of the eye via intracorporal, zero-crosstalk refractive-index-matched waveguides to mimic the rhabdoms of a natural eye. Full-colour wide-angle panoramic views and position tracking of a point source are realized by placing the fabricated eye directly on top of a commercial imaging sensor. As a biomimetic analogue to naturally occurring compound eyes, the eye’s full-colour 3D to 2D mapping capability has the potential to enable a wide variety of applications from improving endoscopic imaging to enhancing machine vision for facilitating human–robot interactions. Insect-like biomimetic compound eyes have many technological applications. Here, the authors present a facile fabrication scheme involving microfluidics assisted 3D printing that permits to completely separate design, optimization and construction of optical and sensor components.

Background Anthracycline usage has been linked to cardiovascular adverse events (CAEs), which is unpredictable. It is critical to identify the characteristics of vulnerable populations and risk factors in order to reduce the occurrence of CAEs. Objectives This meta-analysis aimed to assess the correlation between various risk factors and CAEs induced by anthracyclines. Methods We systematically searched for studies from PubMed, Cochrane, Embase, and assessed the publication bias. Anthracyclines, hypertension, radiation therapy, diabetes, smoking, age, gender, hyperlipidemia, and obesity were meta-analyzed using a fixed or random effects model. Result Sixteen studies were included in this meta-analysis. The results showed that pooled relative ratio for CAEs was 1.69 (95% CI: 1.39–2.06, p <0.001) for anthracyclines, and that risk factors for CAEs caused by anthracyclines included hypertension (RR = 2.15, 95% CI: 1.53–3.01, p  < 0.001), radiation therapy (RR = 1.71, 95% CI: 1.19–2.47, p  < 0.001), diabetes (RR = 1.57, 95% CI: 1.20–2.06, p <0.001), smoking (RR = 1.35, 95% CI: 0.96–1.88, p  < 0.05), and age (RR = 1.16, 95% CI: 1.07–1.26, p  < 0.001). In addition, BMI > 25 kg/m 2 (RR = 1.34, 95% CI: 1.08–1.67, p  = 0.470), gender (RR = 1.17, 95% CI: 1.06–1.2, p  = 0.350), and hyperlipidemia (RR = 1.10, 95% CI: 0.91–1.34, p  = 0.327) was not significantly associated with CAEs caused by anthracyclines. Conclusions Our research findings indicate that patients with a history of hypertension, radiation therapy, diabetes, smoking, and elderly individuals are at an elevated risk of cardiovascular disease in the process of administration of anthracycline drugs. Consequently, careful case selection and condition monitoring are important in the treatment process. Graphical Abstract Patients with comorbidities are more prone to suffering from CAEs with anthracycline based chemotherapy, and the risk factors are arranged clockwise in a descending order: hypertension, radiation therapy, diabetes, smoking, age. BMI>25 kg/m 2 , gender, and hyperlipidemia are not significant associated with CAEs with anthracycline based chemotherapy.

Background Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects. Methods An extensive PubMed search was conducted until February 26, 2023, with the search term “prostate”, “whole-mount”, “large format histology”, which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding. Results WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region. Conclusions WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.

Background Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. Methods The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) ( n  = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) ( n  = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) ( n  = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. Results The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p  = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p  = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p  = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p  = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p  = 0.516). Conclusions RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.

Background GDSL esterases/lipases are a large protein subfamily defined by the distinct GDSL motif, and play important roles in plant development and stress responses. However, few studies have reported on the role of GDSLs in the growth and development of axillary buds. This work aims to identify the GDSL family members in tobacco and explore whether the NtGDSL gene contributes to development of the axillary bud in tobacco. Results One hundred fifty-nine GDSL esterase/lipase genes from cultivated tobacco ( Nicotiana tabacum ) were identified, and the dynamic changes in the expression levels of 93 of these genes in response to topping, as assessed using transcriptome data of topping-induced axillary shoots, were analysed. In total, 13 GDSL esterase/lipase genes responded with changes in expression level. To identify genes and promoters that drive the tissue-specific expression in tobacco apical and axillary buds, the expression patterns of these 13 genes were verified using qRT-PCR. GUS activity and a lethal gene expression pattern driven by the NtGDSL127 promoter in transgenic tobacco demonstrated that NtGDSL127 is specifically expressed in apical buds, axillary buds, and flowers. Three separate deletions in the NtGDSL127 promoter demonstrated that a minimum upstream segment of 235 bp from the translation start site can drive the tissue-specific expression in the apical meristem. Additionally, NtGDSL127 responded to phytohormones, providing strategies for improving tobacco breeding and growth. Conclusion We propose that in tobacco, the NtGDSL127 promoter directs expression specifically in the apical meristem and that expression is closely correlated with axillary bud development.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia‐inducible factor 1α (HIF‐1α) and glucose transporter 1 (Glut‐1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of 18F‐fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K/Akt/mTOR pathway. Inhibition of PI3K/Akt/mTOR activity abolished hypoxia‐induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF‐1α and Glut‐1. Moreover, the PI3K/Akt/mTOR pathway was a positive mediator of HIF‐1α and/or Glut‐1 in the presence of irradiation. HIF‐1α and/or Glut‐1 knockout significantly reduced cell viability, glucose uptake and PI3K/Akt/mTOR activity, all of which were induced by hypoxia in the presence of irradiation. In vivo analysis showed that knockout of HIF‐1α and/or Glut‐1 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF‐1α and Glut‐1. HIF‐1α and/or Glut‐1 knockout also abrogated PI3K/Akt/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF‐1α and/or Glut‐1 knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K/Akt/mTOR pathway.