Liposomes are the first and mostly explored nanocarriers for cancer drug delivery, which have shown great promise in clinical applications, but their limited accumulation and penetration into the ...tumor interstitial space, significantly reduce the therapeutic efficacy. Here, a γ‐glutamyltranspeptidase (GGT)‐triggered charge‐switchable approach is reported that can trigger the fast endocytosis and transcytosis of the liposome in tumor microenvironments to overcome the harsh biological barriers in tumor tissues. The active transporting liposomal nanocarrier (GCSDL) is prepared by surface modification with a glutathione (GSH) moiety and encapsulated with doxorubicin (DOX). When the GCSDL contacts with tumor vascular endothelial cells, the overexpressed GGT enzyme on cytomembrane catalyzes the hydrolysis of GSH to generate cationic primary amines. The cationic GCSDL triggers fast caveolae‐mediated endocytosis and vesicle‐mediated transcytosis, resulting in sequential transcytosis to augment its tumor accumulation and penetration. Along with continual intercellular transportation, GCSDL can release DOX throughout the tumor to induce cancer cell apoptosis, resulting in complete eradication of hepatocellular carcinoma and cessation of pancreatic ductal adenocarcinoma's progression. This study develops an efficient strategy to realize high tumor accumulation and deep penetration for the liposomal drug delivery system via active transcytosis.
An active transporting liposomal nanocarrier (GCSDL) is developed by surface modification of liposome with a glutathione moiety and encapsulation with doxorubicin. The GCSDL undergoes γ‐glutamyltranspeptidase‐triggered cationization in tumor microenvironments, initializes efficient transcytosis by endothelial cells and cancer cells, transports actively into deep tumors, and releases doxorubicin throughout tumor to induce cancer cell apoptosis.
This work presents an in-situ chemical vapor deposition (CVD) method to synthesis carbon nanotube (CNT) on Al powders in a vertical tube furnace. The carbon nanotube reinforced Al matrix composites ...(CNT/Al composites) were fabricated by a new powder metallurgy (PM) approach associated with vacuum induction melting technique. It was shown that CNT was homogenously distributed in the Al matrix, and an interfacial transiting layer of Al4C3 was formed between Al matrix and CNT in the bulk material. The tensile test showed that 1.5 vol% CNT/Al composites exhibited the largest tensile strength of 191 MPa as well as an excellent elongation of 32.6%. The strengthening efficiency of the 1.5 vol% CNT/Al composites improved by ~ 80% compared to the unreinforced pure Al. The strengthening mechanisms were mainly attributed to the load transfer of CNT, Al4C3 and dislocation strengthening. The Al4C3 transiting layer was beneficial to increase the interfacial shear strength and prolong the slide deformation of dislocation by forming an orientation relationship of Al4C3 // Al and CNT (002) // Al4C3 (001) according to the transmission electron microscope (TEM) observation. Besides, the thermocycling measurement enriched and deepened the understanding of the effect of Al4C3 on improving the interfacial bonding, degrading the interfacial thermal mismatch between CNT and the Al matrix and increasing the compactness of the CNT/Al composites.
The optimization of nanoparticle size for passing through glomerular filtration membrane, inefficient renal cellular uptake and rapid urinary excretion of nanoparticles are the major obstacles for ...renal disease treatment via a nanoparticle delivery system. Herein, we propose a concept of a two-step nanoparticular cascade of size control and enhancement of renal cellular uptake to overcome the renal delivery obstacles.
: We prepared kidney-targeted rhein (RH)-loaded liponanoparticles (KLPPR) with a yolk-shell structure composed by polycaprolactone-polyethyleneimine (PCL-PEI)-based cores and kidney targeting peptide (KTP)-modified lipid layers. The KLPPR size within the range of 30 ~ 80 nm allowed KLPPR distribute into kidney by passing through the glomerular filtration membrane and the KTP (sequence: CSAVPLC) decoration promoted the renal cellular uptake and endocytosis via a non-lysosomal pathway.
: The KLPPR had an average size of 59.5±6.2 nm and exhibited high RH loading, sustained release, good stability and biocompatibility, rapid cellular uptake in HK-2 cells. In addition, intravenous administration of KLPPR resulted in excellent kidney-targeted distribution and low urinary excretion in mice with streptozocin-induced diabetic nephropathy (DN), lowered the parameters of urea nitrogen, serum creatinine and kidney index, as well as facilitated the recovery of renal physiological function in improving the levels of urinary creatinine and the creatinine clearance rate by suppressing secretion and accumulation of fibronectin and TGF-β1.
: Definitely, KLPPR were able to target the diseased kidney and improve the therapeutic effect of RH on DN by exploiting the two-step nanoparticular cascade of size control and enhancement of cellular uptake. This study offers a promising strategy for renal diseases treatment using liponanoparticle delivery system.
SLC7A11 has significant translational value in cancer treatment. However, there are few studies on whether SLC7A11 affects the immune status of lung adenocarcinoma (LUAD). Information on SLC7A11 ...expression and its impact on prognosis was obtained from the cancer genome atlas and gene expression omnibus databases. The differentially expressed genes (DEGs) were analysed by GO and KEGG. GSEA enrichment analysis was performed in the SLC7A11-high and SLC7A11-low groups. The relationship between SLC7A11 and tumour immunity, immune checkpoints, and immune cell infiltration was studied using R language. We analysed the correlation between SLC7A11 and chemotactic factors (CFs) and chemokine receptors using the TISIDB database. SLC7A11 is overexpressed in many tumours, including LUAD. The 5-year overall survival of patients in the SLC7A11-high group was lower than in the SLC7A11-low group. KEGG analysis found that the DEGs were enriched in ferroptosis signaling pathways. GSEA analysis found that the survival-related signaling pathways were enriched in the SLC7A11-low group. The SLC7A11-low group had higher immune scores and immune checkpoint expression. SLC7A11 was negatively correlated with many immune cells (CD8+ T cells, immature dendritic cells), CFs, chemokine receptors (such as CCL17/19/22/23, CXCL9/10/11/14, CCR4/6, CX3CR1, CXCR3) and MHCs (major histocompatibility complex). SLC7A11 may regulate tumour immunity and could be a potential therapeutic target for LUAD.
Ultrasound‐targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application ...of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon‐like peptide 1 (GLP‐1) in ultrasound‐induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP‐1 expression in macaque, which is characterized by ultrasound‐guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.
An efficient gene delivery system is constructed using plasmid encoding glucagon‐like peptide 1 (GLP‐1) in ultrasound‐induced microbubbles, toward treatment of type 2 diabetes (T2D). Such therapy is mediated by ultrasound‐targeted microbubble destruction (UTMD), affording 1) enhancement of cell membrane penetration and GLP‐1 expression, 2) improvement of pancreatic beta‐cell regeneration, and 3) regulation of plasma glucose in macaque with T2D.
Dysregulation of long non-coding RNAs has been implied to connect with cancer progression. This research was to decipher the mechanism of long non-coding RNA SDCBP2-AS1 in ovarian cancer (OC) through ...regulation of microRNA (miR)-100-5p and ependymin-related protein 1 (EPDR1).
LncRNA SDCBP2-AS1 and EPDR1 levels in OC were assessed by Gene Expression Profiling Interactive Analysis. lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 levels in OC tissues and cells were determined. SKOV3 and A2780 cells were transfected with lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1-related plasmids or sequences, and then their functions in cell viability, apoptosis, migration, and invasion were evaluated. The interplay of lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 was clarified.
LncRNA SDCBP2-AS1 and EPDR1 levels were suppressed whilst miR-100-5p level was elevated in OC. After upregulating lncRNA SDCBP2-AS1 or EPDR1, viability, migration, and invasion of OC cells were impaired, and apoptosis rate was increased. Downregulating EPDR1 or upregulating miR-100-5p partially mitigated upregulated lncRNA SDCBP2-AS1-induced impacts on the biological functions of OC cells. LncRNA SDCBP2-AS1 sponged miR-100-5p, and EPDR1 was targeted by miR-100-5p.
It is illustrated that lncRNA SDCBP2-AS1 regulates EPDR1 by sponge adsorption of miR-100-5p to inhibit the progression of OC.
Electrodeposition was employed to fabricate magnetite (Fe3O4) coated carbon fibers (MCCFs). Temperature and fiber surface pretreatment had a significant influence on the composition and morphology of ...Fe3O4 films. Uniform and compact Fe3O4 films were fabricated at 75 degree C on both nitric acid treated and untreated carbon fibers, while the films prepared at 60 degree C were continuous and rough. Microwave measurements of MCCF/paraffin composites (50wt.% of MCCFs, pretreated carbon fibers as deposition substrates) were carried out in the 2-18GHz frequency range. MCCFs prepared at 60 degree C obtained a much higher loss factor than that prepared at 75 degree C. However, the calculation results of reflection loss were very abnormal that MCCFs prepared at 60 degree C almost had no absorption property. While MCCFs prepared at 75 degree C exhibited a good absorption property and obtained -10dB and -20dB refection loss in wide matching thickness ranges (1.0-6.0mm and 1.7-6.0mm range, respectively). A secondary attenuation peak could also be observed when the thickness of MCCF/paraffin composite exceeded 4.0mm. The minimum reflection loss was lower.
Surface coal mining in semi-arid regions has detrimental impacts on the structure and function of surface ecosystems, thereby impeding the attainment of regional sustainable development goals. ...Moreover, the impact of climate change on ecological restoration in semi-arid mining areas is an inevitable consideration. To elucidate the response of ecosystem services in mining areas to regional climate change, topography, soil, vegetation and socioeconomic development, this study selected six large-scale surface coal mines located in semi-arid regions of China as research objects. In this study, we aimed to assess the main ecosystem services (carbon sequestration, soil conservation, and flow regulation) provided by these mines. In addition, we analysed the spatial and temporal evolution and interrelationships of these ecosystem services. Furthermore, we explored the underlying mechanisms between ecosystem services and environmental factors. The results showed the following: (1) Geospatially, there was a gradual decrease in carbon sequestration and flow regulation from northeast to southwest in the mining areas. However, the soil conservation exhibited an upward trend. Throughout the research period, the carbon sequestration change rate in the six mining areas displayed an initial downward and subsequent upward trend, the rate of soil conservation exhibited a gradual upward trend, and the flow regulation decline rate followed a downward trend. (2) Change rate of carbon sequestration and soil conservation in the six mining areas showed a significant positive correlation (r = 0.51, p < 0.001), with the strongest correlation observed in the Shengli Mining Area (r = 0.64, p < 0.001). (3) Ecosystem service changes in the mining areas were primarily driven by initial conditions (95.0%), followed by meteorological factors (4.2%). Three ecological restoration models were proposed for the different regions based on driver analyses. The findings of this study offer scientific evidence that can be used to inform ecological management, enhance ecological security, and promote regional sustainable development in mining areas.
The aim of this study was to identify the applicability of an ultrasound-guided attenuation parameter (UGAP) for the noninvasive assessment of hepatic steatosis in clinical practice and to compare ...its correlation with B-mode ultrasound (US). From May to July 2021, 63 subjects with different body mass index (BMI) grades were included in the prospective study. All of them performed UGAP measurements, under different breathing manipulations, positions, diet statuses, and operators. After that, the UGAP values were compared with the visual grades of hepatic steatosis on B-mode US using a 4-point scale method. The intraclass correlation (ICC) of the UGAP values between the two radiologists was 0.862 (p < 0.001), and the ICCs of the UGAP values on the same day and different days by radiologist A were 0.899 (p < 0.001) and 0.910 (p < 0.001), respectively. There were no significant differences in UGAP values under different breathing manipulations (p > 0.05), positions (p > 0.05), or diet statuses (p = 0.300). The UGAP values in the fasting (supine position, segment V, 1) condition among the lean (BMI < 24 kg/m
), overweight (24 kg/m
≤ BMI < 28 kg/m
) and obese groups (BMI ≥ 28 kg/m
) were 0.60 ± 0.12, 0.66 ± 0.14, and 0.71 ± 0.11 dB/cm/MHz, respectively, with a significant difference (p = 0.006). The correlation coefficients (Rho) between the UGAP values and the visual grades of hepatic steatosis by the two reviewers were 0.845 (p < 0.001) and 0.850 (p < 0.001), corresponding to a strong relationship. Steatosis grades by reviewer 1 (p = 0.036) and reviewer 2 (p = 0.003) were significant factors determining the UGAP values according to the multivariate linear regression analysis. UGAP demonstrated excellent intraobserver and interobserver reproducibility in the assessment of hepatic steatosis. UGAP may be a promising tool in clinical practice to predict hepatic steatosis.
Ultrasound (US), as a safe and non-invasive tool, has drawn researchers' attention to treat pancreatic ductal adenocarcinoma (PDAC). Piezo1, a mechanosensitive channel, can be activated by various ...mechanical stimuli. In this study, we tested the expression of Piezo1 in PDAC cell lines and tissues, and cell apoptosis in vitro and in vivo with siRNA, a lentivirus system, and a subcutaneous xenograft tumor-bearing model under the condition of US with microbubbles (MBs). We found that Piezo1 was highly expressed in PDAC cells; it was activated by US with MBs and was closely related to the apoptosis of PDAC cell lines and tumors. This study highlighted the idea of utilizing the high expression of Piezo1 in PDAC and US with MBs to provide a non-invasive strategy for the treatment of PDAC from the aspect of mechanotransduction.
Display omitted
•Mechanosensitive channel Piezo1 is highly expressed in pancreatic cancer cells•Ultrasound with microbubbles induces apoptosis of pancreatic cancer cells•Piezo1 is activated by ultrasound with microbubbles and mediates calcium influx
Molecular biology; Cell biology; Cancer
PDF
