Nanotechnology has been extensively studied and exploited for cancer treatment as nanoparticles can play a significant role as a drug delivery system. Compared to conventional drugs, ...nanoparticle-based drug delivery has specific advantages, such as improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting. The application and development of hybrid nanoparticles, which incorporates the combined properties of different nanoparticles, has led this type of drug-carrier system to the next level. In addition, nanoparticle-based drug delivery systems have been shown to play a role in overcoming cancer-related drug resistance. The mechanisms of cancer drug resistance include overexpression of drug efflux transporters, defective apoptotic pathways, and hypoxic environment. Nanoparticles targeting these mechanisms can lead to an improvement in the reversal of multidrug resistance. Furthermore, as more tumor drug resistance mechanisms are revealed, nanoparticles are increasingly being developed to target these mechanisms. Moreover, scientists have recently started to investigate the role of nanoparticles in immunotherapy, which plays a more important role in cancer treatment. In this review, we discuss the roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy and describe the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance.
•Summary the underlying mechanism of ionizing radiation and possible choices of radioprotectant.•Hydrogen works as a scavenger of free radicals, exert anti-inflammation, and anti-apoptosis ...effect.•Hydrogen works as a signal modulator or through regulating gene expression.•Summary the main delivery methods of hydrogen.
In recent years, many studies have shown that hydrogen has therapeutic and preventive effects on various diseases. Its selective antioxidant properties were well noticed. Most of the ionizing radiation-induced damage is caused by hydroxyl radicals (OH) from radiolysis of H2O. Since hydrogen can mitigate such damage through multiple mechanisms, it presents noteworthy potential as a novel radio-protective agent. This review analyses possible mechanisms for hydrogen’s radioprotective properties and effective delivery methods. We also look into details of vitro and vivo studies for hydrogen’s radioprotective effects, and clinical practices. We conclude that hydrogen has good potential in radio-protection, with evidence that warrants greater research efforts in this field.
Three types of CeO2 were synthesized and through impregnation of Ag employing these CeO2 types as supports, three kinds of Ag/CeO2 were prepared. Their morphologies and structures were characterized ...by SEM, HRTEM, nitrogen adsorption–desorption isotherms, and H2‐TPR reduction, indicating that the effective soot‐catalyst contact and size distribution as well as the chemical state of Ag were identical. Surface oxygen vacancies (VO–s) and bulk oxygen vacancies (VO–b) were investigated by using XPS and Raman spectroscopy, respectively. The activities of the CeO2 catalysts are related to surface chemisorbed oxygen, while the activities of Ag/CeO2 are decided by VO–s near the Ag particles under oxygen‐rich conditions. When switching the atmosphere to oxygen‐poor conditions, the activities of Ag/CeO2 are controlled by VO–b instead. These results originate from the fact that the generation and delivery of active oxygen are affected by combinations of VO–s and VO–b rather than just one of them. The moderate concentration of VO–s and sufficient concentration of VO–b are favorable for increasing catalytic activity under oxygen‐poor conditions for Ag/CeO2. In this work, Ag loaded on CeO2, prepared at 50 °C, (defined as Ag/CeO2‐50) can be considered as a prospective catalyst for use in gasoline particulate filters.
Types of CeO2 were synthesized to catalyze soot from GID exhausts. After impregnation of Ag, the activity of the Ag/CeO2 types was decided by surface oxygen vacancies near the Ag particles under oxygen‐rich conditions. When switching the atmosphere to oxygen‐poor conditions, the activities of Ag/CeO2 were controlled by bulk oxygen vacancies instead.
Studies have found that RNA encoding proteins only account for a small part of the total number, most RNA is non-coding RNA, and non-coding RNA may affect the occurrence and development of human ...cancers by affecting gene expression, therefore play an important role in human pathology. At present, ncRNAs studied include miRNA, circRNA, lncRNA, piRNA, and snoRNA, etc. After decades of research, the basic role of these ncRNAs in many cancers has been clear. As far as we know, the role of miRNAs in cancer is one of the hottest research directions, however, it is also found that the imbalance of ncRNAs will affect the occurrence of gastric cancer, breast cancer, lung cancer, meanwhile, it may also affect the prognosis of these cancers. Therefore, the study of ncRNAs in cancers may help to find new cancer diagnostic and treatment methods. Here, we reviewed the biosynthesis and characteristics of miRNA, cricRNA, and lncRNA etc., their roles in human cancers, as well as the mechanism through which these ncRNAs affect human cancers.
Partner and localizer of BRCA2 (PALB2) is vital for homologous recombination (HR) repair in response to DNA double-strand breaks (DSBs). PALB2 functions as a tumor suppressor and participates in the ...maintenance of genome integrity. In this review, we summarize the current knowledge of the biological roles of the multifaceted PALB2 protein and of its regulation. Moreover, we describe the link between
pathogenic variants (PVs) and breast cancer predisposition, aggressive clinicopathological features, and adverse clinical prognosis. We also refer to both the opportunities and challenges that the identification of
PVs provides in breast cancer genetic counseling and precision medicine.
Researchers have investigated the causal effect between serum uric acid (SUA) concentrations and kidney function for decades, but studies produced inconsistent results. This study aimed to clarify ...the bidirectional causal effects between SUA concentrations and kidney function and to explore the potential ethnic disparities by conducting a trans-ethnic Mendelian randomization study in European, African, and Asian ancestries.
The summary-level data for this study were obtained from the Global Urate Genetics Consortium, CKDGen Consortium, UK Biobank, and Japan Biobank for different outcomes and exposures, respectively. The traits of kidney function were estimated glomerular filtration rate from serum creatinine (eGFRcr), estimated glomerular filtration rate from cystatin C (eGFRcys), and blood urea nitrogen (BUN). Using the multiplicative random-effects inverse variance weighting mode, our primary analysis produced robust results despite heterogeneity. Additionally, we performed the Mendelian randomization pleiotropy residual sum and outlier test to eliminate the horizontal pleiotropy and obtain accurate results.
Our findings revealed that elevated SUA concentrations had causal effects on declined eGFRcys, BUN, and a diagnosis of chronic kidney disease in European ancestries and eGFRcr in Asian ancestries. Additionally, the causal effects of declined eGFRcr and elevated BUN concentrations on elevated SUA concentrations were observed in both European and Asian ancestries. However, no bidirectional causal effect was found between SUA concentrations and eGFRcr among African ancestries.
This trans-ethnic Mendelian randomization study confirmed the bidirectional causal effects between SUA concentrations and kidney function and highlighted the importance of considering ethnic disparities in clinical treatments.
Using a two‐stage light gas gun, we obtained new shock wave Hugoniot data for an iron‐sulfur alloy (Fe‐11.8wt%S) over the pressure range of 94–204 GPa. A least‐squares fit to the Hugoniot data yields ...a linear relationship between shock velocity DS and particle velocity u, DS (km/s) =3.60(0.14) +1.57(0.05) u. The measured Hugoniot data for Fe‐11.8wt%S agree well with the calculated results based on the thermodynamic parameters of Fe and FeS using the additive law. By comparing the calculated densities along the adiabatic core temperature with the PREM density profile, an iron core with 10 wt.% sulfur (S) provides the best solution for the composition of the Earth's outer core.
Key Points
New equation of state for Fe‐11.8wt%S at high pressure
The experimental data show the ideal mixing relative to Fe and FeS
Fe‐10S provides the best fit to the density profile of the Earth's outer core.
At the present time, one of the most relevant challenges in marine and ocean engineering and practice is the development of a mathematical modeling that can accurately replicate the interaction of ...water waves with porous coastal structures. Over the last 60 years, multiple techniques and solutions have been identified, from linearized solutions based on wave theories and constant friction coefficients to very sophisticated Eulerian or Lagrangian solvers of the Navier-Stokes (NS) equations. In order to explore the flow field interior and exterior of the porous media under different working conditions, the Smooth Particle Hydrodynamics (SPH) numerical simulation method was used to simulate the flow distribution inside and outside a porous media applied to interact with the wave propagation. The flow behavior is described avoiding Euler’s description of the interface problem between the Euler mesh and the material selected. Considering the velocity boundary conditions and the cyclical circulation boundary conditions at the junction of the porous media and the water flow, the SPH numerical simulation is used to analyze the flow field characteristics, as well as the longitudinal and vertical velocity distribution of the back vortex flow field and the law of eddy current motion. This study provides innovative insights on the mathematical modelling of the interaction between porous structures and flow propagation. Furthermore, there is a good agreement (within 10%) between the numerical results and the experimental ones collected for scenarios with porosity of 0.349 and 0.475, demonstrating that SPH can simulate the flow patterns of the porous media, the flow through the inner and outer areas of the porous media, and the flow field of the back vortex region. Results obtained and the new mathematical approach used can help to effectively simulate with high-precision the changes along the water depth, for a better design of marine and ocean engineering solutions adopted to protect coastal areas.
Random skin flaps have many applications in plastic and reconstructive surgeries. However, distal flap necrosis restricts wider clinical utility. Mitophagy, a vital form of autophagy for damaged ...mitochondria, is excessively activated in flap ischemia/reperfusion (I/R) injury, thus inducing cell death. Aldehyde dehydrogenase-2 (ALDH2), an allosteric tetrameric enzyme, plays an important role in regulating mitophagy. We explored whether ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) could reduce the risk of ischemic random skin flap necrosis, and the possible mechanism of action.
Modified McFarlane flap models were established in 36 male Sprague-Dawley rats assigned randomly to three groups: a low-dose Alda-1 group (10 mg/kg/day), a high-dose Alda-1 group (20 mg/kg/day) and a control group. The percentage surviving skin flap area, neutrophil density and microvessel density (MVD) were evaluated on day 7. Oxidative stress was quantitated by measuring the superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Blood perfusion and skin flap angiogenesis were assessed
laser Doppler flow imaging and lead oxide-gelatin angiography, respectively. The expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), vascular endothelial growth factor (VEGF), ALDH2, PTEN-induced kinase 1 (PINK1), and E3 ubiquitin ligase (Parkin) were immunohistochemically detected. Indicators of mitophagy such as Beclin-1, p62, and microtubule-associated protein light chain 3 (LC3) were evaluated by immunofluorescence.
Alda-1 significantly enhanced the survival area of random skin flaps. The SOD activity increased and the MDA level decreased, suggesting that Alda-1 reduced oxidative stress. ALDH2 was upregulated, and mitophagy-related proteins (PINK1, Parkin, Beclin-1, p62, and LC3) were downregulated, indicating that ALDH2 inhibited mitophagy through the PINK1/Parkin signaling pathway. Treatment with Alda-1 reduced neutrophil infiltration and expressions of inflammatory cytokines. Alda-1 significantly upregulated VEGF expression, increased the MVD, promoted angiogenesis, and enhanced blood perfusion.
ALDH2 activation can effectively enhance random skin flap viability
inhibiting PINK1/Parkin-dependent mitophagy. Moreover, enhancement of ALDH2 activity also exerts anti-inflammatory and angiogenic properties.
Maxwell-Wagner-Sillars (MWS) dynamics and electromagnetic radio-frequency (RF) actuation of the volumetric phase change are investigated in a hybrid polymer composite consisting of hydrogel suspended ...with high-k nanoparticles. Poly(N-isopropylacrylamide) (PNIPAm) hydrogels were combined with 10% KF-doped barium titanate (Ba
0.9
K
0.1
TiO
2.9
F
0.1
, KBT) nanoparticles with highly anisotropic dielectric properties using poly(vinyl alcohol) (PVA) to form a nanoparticle-hydrogel composite. Whereas the addition of PVA to the synthesis maintains a strong volumetric phase transition with polarization and relaxation features similar to standard bulk PNIPAm, the addition of KBT nanoparticles results in reduced volumetric phase transition and MWS polarization due to charge screening of intramolecular interactions. The added nanoparticles and modified synthesis process enhanced the dielectric permittivity of bulk PNIPAm, increased RF conductivity up to 7×, and decreased the specific heat while still maintaining a discontinuous volumetric phase transition. An RF antenna emitting at 544 kHz was only able to actuate a phase change in the composites with modified synthesis versus bulk PNIPAm. Measured heating rates were 3× greater than that of un-modified PNIPAm.
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