The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles ...exposure. It may be beneficial in some circumstances, yet autophagy‐mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo. This phenomenon is due to anomaly in the autophagy termination process named autophagic lysosome reformation (ALR). Phosphatidylinositol 4‐phosphate (PI(4)P) relocates onto autolysosome membrane, which is a key event of ALR. PI(4)P is then converted into phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P2) by phosphatidylinositol‐4‐phosphate 5‐kinase. Clathrin is subsequently recruited by PI(4,5)P2 and leads to tubule budding of ALR. Yet it is observed that PI(4)P cannot be converted in nanoparticle‐treated hepatocytes cells. Exogenous supplement of PI(4,5)P2 suppresses the enlarged autolysosomes in vitro. Abolishment of these enlarged autolysosomes by autophagy inhibitor relieves the hepatotoxicity of UCNs in vivo. The results provide evidence for disrupted ALR in nanoparticle‐treated hepatocytes, suggesting that the termination of nanoparticle‐induced autophagy is of equal importance as the initiation.
In hepatocytes treated with upconversion nanoparticles (UCN) or nano‐SiO2, loss of phosphatidylinositol‐4‐phosphate 5‐kinase causes the disrupted phospholipid transition from phosphatidylinositol 4‐phosphate to phosphatidylinositol 4,5‐bisphosphate on enlarged autolysosomal membrane and clathrin fails to be recruited to autolysosomes; autophagic lysosome reformation is blocked, leading to enlarged autolysosomes. In the UCN‐treated mice liver, manipulation of autophagy by 3‐methyladenine or trehalose affects liver damage.
Despite the excellent optoelectronic properties, organic‐inorganic hybrid perovskite solar cells (PSCs) still present significant challenges in terms of ambient stability. CsPbI2Br, a member of ...all‐inorganic perovskites, may respond to this challenge because of its inherent high stability against light, moisture, and heat, and therefore has gained tremendous attraction recently. However, the practical application of CsPbI2Br is still impeded by the notorious phenomenon of photoinduced halide segregation. Herein, by applying first‐principles calculations, the stability, electronic structure, defect properties, and ion‐diffusion properties of the stoichiometric CsPbI2Br (110) surface and that with the adsorption of KX (X = Cl, Br, I) are systematically investigated. It is found that the adsorbed KX can serve as an external substitute of the halogen vacancies on the surface, therefore inhibiting halogen segregation and improving the stability of the CsPbI2Br surface. The KX can also eliminate deep‐level defect states caused by antisites, thereby contributing to the promoted optoelectronic properties of CsPbI2Br. The mechanistic understanding of surface passivation in this work can lay the foundation for the future design of CsPbI2Br PSCs with optimized optoelectronic performance.
The adsorbed KX can serve as an external substitute of the halogen vacancies on the surface, therefore inhibiting halogen segregation and improving the stability of the CsPbI2Br surface. The KX can also eliminate deep‐level defect states caused by antisites, thereby contributing to the promoted optoelectronic properties of CsPbI2Br.
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•Novel metronidazole-indole-imine hybrids as antibacterial agents were developed.•Compound 6b with an MIC value of 0.5 µg/mL against E. coli had no obvious resistance.•Compound 6b ...possessed favorable antibiofilm activity and could destroy cell membranes.•Compound 6b could cause inactivation of LDH, metabolic arrest and the accumulation of ROS.•Compound 6b could form a supramolecular complex with DNA to obstruct DNA replication.
The dreadful bacterial resistance to clinical drugs calls for the development of novel antibacterials. This work developed a class of unique metronidazole-derived three-component hybrids as promising antibacterial therapeutic alternatives. Bioactive assay discovered that p-chlorophenylhydrazone derivative 6b possessed excellent ability to suppress the growth of drug-resistant E. coli (MIC = 0.5 µg/mL), being 16 folds more potent than norfloxacin (MIC = 8 µg/mL). The active molecule 6b with imperceptible hemolysis could effectively retard the development of bacterial drug resistance within 30 passages. Moreover, compound 6b displayed a favorable inhibitory effect on E. coli biofilms and could act rapidly in bactericidal efficacy. Subsequent exploration of mechanism revealed that 6b could destruct the bacterial cytoplasmic membrane, leading to the leakage of intracellular protein. The inactivation of lactate dehydrogenase, metabolic stagnation and the accumulation of reactive oxygen species caused by 6b were observed. Furthermore, molecule 6b could form a supramolecular complex with DNA to obstruct DNA replication. These results demonstrated that metronidazole-derived three-component hybrids provided a large potential for deep development as prospective antibacterial agents.
To clarify the risk of tuberculosis (TB) infection in patients with Takayasu arteritis (TAK). In this study, we conducted a comprehensive search across multiple databases, including PubMed, Web of ...Science, Embase, Cochrane, and Medline, from the inception of the Literature Library to May 16, 2023. Using a specific set of keywords, including "Takayasu Arteritis", "Tuberculosis", and "Mycobacterium tuberculosis", the main objective of this search was to identify all relevant observational studies, including case-control studies, cohort studies, and cross-sectional studies, that report the prevalence of TB in individuals diagnosed with TAK. Two independent evaluators rigorously screened the studies, extracted data, and assessed the study quality using the Joanna Briggs Institute (JBI) critical appraisal tools. Statistical analyses were conducted using R software version 4.3.0, which allowed for the synthesis of prevalence and subgroup analyses. Subgroup analyses were stratified based on quality scores, World Health Organization regional categorizations, and TB categories. Assessment of publication bias was performed using a funnel plot. The study included a total of 30 studies with 5548 participants. The findings showed that individuals with TAK exhibited an average prevalence of TB infection at 31.27% (95% CI 20.48-43.11%). Significantly, the prevalence of TB infection demonstrated notable regional disparities, ranging from 16.93% (95% CI 7.71-28.76%) in the Western Pacific Region to 63.58% (95% CI 35.70-87.66%) in the African Region. Moreover, the study revealed that patients with TAK displayed a high prevalence of latent TB infection (LTBI) at 50.01% (95% CI 31.25-68.77%) and active TB at 14.40% (95% CI 9.03-20.68%). The high heterogeneity observed in the data highlights significant variability in TB infection rates among the populations studied, with the African Region exhibiting the highest rates. The study concludes that there is a high prevalence of TB infection in the TAK population, with regional variations. Consideration should be given to implementing rigorous TB screening measures and preventive interventions specifically tailored for the TAK population.
The exopolysaccharides (EPS) excreted by the unicellular red alga,
Porphyridium
, have potential applications in medicine, cosmetics, and health care products. In the present study, two different
...Porphyridium
stains, i.e.,
Porphyridium cruentum
CCALA 415 and
Porphyridium purpureum
FACHB 806, were selected and their EPS productivity, chemical characteristics, and antioxidant activities were compared to determine the potential
Porphyridium
strain with high productivity and antioxidant activity for large-scale EPS production. The EPS productivity of
P
.
cruentum
CCALA 415 (EPS-C) and
P
.
purpureum
FACHB 806 (EPS-P) were 20.81 mg·L
−1
·day
−1
and 63.24 mg·L
−1
·day
−1
, respectively. The sulfate contents of EPS-C and EPS-P were 20.58% and 21.63%, respectively. The monosaccharide of these two EPS consisted of xylose, glucose, and galactose. EPS-C had a higher galactose content (40.16%), whereas EPS-P had a higher xylose content (36.62%), but the glucose content was less for both EPS. Compared with the scavenging superoxide anions and ABTS free radicals, the scavenging hydroxyl free radicals contributed to the antioxidant activity of
Porphyridium
EPS. The scavenging activities of EPS-C and EPS-P were 74.1% and 59.5% (1 mg·mL
−1
), respectively. In conclusion, the EPS of
P
.
purpureum
FACHB 806 exhibited higher potential for application than those of
P
.
cruentum
CCALA 415 due to its high EPS productivity and antioxidant activity.
Six benzophenone derivatives, carneusones A-F (
-
), along with seven known compounds (
-
) were isolated from a strain of sponge-derived marine fungus
GXIMD00543. Their chemical structures were ...elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds
,
, and
exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC
values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 μM, while
showed potent effect with an EC
value of 2.9 ± 0.1 μM.
How low should the layer-to-layer contact resistance be for super-conducting tapes to form a good stack? With the purpose of answering this question, a 3-D finite element model was established based ...on the idea that a superconducting stack with an anisotropic resistivity could macroscopically behave just like a stack of coated conductor tapes with interlayer resistance. The model was first carefully compared with common sense under several conditions and then used for obtaining the quantitative relation between the current redistribution distance and the interlayer resistivity. As a short conclusion, average perpendicular resistivity as low as 4 × 10 −7 Ω·m is necessary, if one wants the current redistribution to be done in 5 cm characteristic length.
Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies including neuroblastoma. ...Small molecule inhibitors of AURKA have shown potential, but still not as good as expected effects in clinical trials. Little is known about this underlying mechanism. Here, we evaluated the inhibitory effects of AURKA inhibitor MLN8237 on neuroblastoma cells to understand the potential mechanisms responsible for tumor therapy.
MLN8237 treatment on neuroblastoma cell line IMR32 was done and in vivo inhibitory effects were investigated using tumor xenograft model. Cellular senescence was evaluated by senescence-associated β-gal Staining assay. Flow cytometry was used to tested cell cycle arrest and cell apoptosis. Senescence-associated signal pathways were detected by western blot. CD133 microbeads and microsphere formation were used to separate and enrich CD133
cells. AURKA small interfering RNA transfection was carried to downregulate AURKA level. Finally, the combination of MLN8237 treatment with AURKA small interfering RNA transfection were adopted to evaluate the inhibitory effect on neuroblastoma cells.
We demonstrate that MLN8237, an inhibitor of AURKA, induces the neuroblastoma cell line IMR32 into cellular senescence and G2/M cell phase arrest. Inactivation of AURKA results in MYCN destabilization and inhibits cell growth in vitro and in a mouse model. Although MLN8237 inhibits AURKA kinase activity, it has almost no inhibitory effect on the AURKA protein level. By contrast, MLN8237 treatment leads to abnormal high expression of AURKA in vitro and in vivo. Knockdown of AURKA reduces cell survival. The combination of MLN8237 with AURKA small interfering RNA results in more profound inhibitory effects on neuroblastoma cell growth. Moreover, MLN8237 treatment followed by AURKA siRNA forces senescent cells into apoptosis via suppression of the Akt/Stat3 pathway.
The effect of AURKA-targeted inhibition of tumor growth plays roles in both the inactivation of AURKA activity and the decrease in the AURKA protein expression level.
In this study, two kinds of carboxyl-terminated hyperbranched polyesters (HBPs) with special three-dimensional structure were proposed to act as the substrates to synthesize two new kinds of acyl ...chloride-terminated hyperbranched polyesters (HBPACs) that were used as the key functional materials to participate in the interfacial polymerization reaction to fabricate the novel thin film composite membranes (TFC) with high water flux and monovalent salt rejection. First, the two HBPACs were synthesized from two HBPs with different molecule weights (Mn ≈ 3289 g/mol and 1964 g/mol) through acylation reaction with thionyl chloride. Then, the resultant HBPACs were used to modify the conventional reverse osmosis (RO) membrane by a new twice-crosslinked interfacial polymerization method. That is, the m-phenylenediamine (MPD) coated on the polysulfone supporting was successively reacted with HBPAC and trimesoyl chloride (TMC) which were solved in different organic solutions, respectively. The resultant HBPAC-based TFC membranes presented smoother surface and showed few change in surface hydrophilicity. Especially, one of the HBPAC-based membrane fabricated with the mixture of two HPBACs (a mass ratio of 1:1), showed a ~50% increase in water flux without sacrificing the salt rejection and exhibited excellent long-term stability compared with the conventional TFC RO membrane. Obviously, the HBPAC-based composite PA layer showed a certain cross-linking network, which not only maintained the salt retention rate but also enhanced the compatibility of HBPAC in PA main body, and as a result promoted the membrane stability. Furthermore, the residual carboxyl groups of HBPAC can act as hydrophilic sites between polyamide chains, which contribute to the rapid diffusion of water molecules through the PA layer of the membrane. Thus, this work provides a new approach to enhance the flux and stability of the membrane via the incorporation of new acyl chloride-terminated hyperbranched polymer.
•Two kinds of HBPACs were successfully synthesized based on two carboxyl-terminated hyperbranched polyesters with different molecule weights.•Two HBPACs were used to fabricate the high flux RO membranes via a new twice-crosslinked interfacial polymerization method.•The resultant HBPAC-based reverse osmosis membranes presented smoother surface and few change in surface hydrophilicity.•The HBPAC-based RO membrane had a ~50% increase in water flux without sacrificing the salt rejection and excellent long-term operational stability.
In order to investigate the formability of Ti-6Al-4V titanium alloy sheet in high speed forming process, electromagnetic forming (EMF) namely magnetic pulse forming with an Al driver sheet is ...performed experimentally. Formability under EMF is compared with that in quasi static condition. Fracture analysis for the titanium alloy Ti-6Al-4V is then carried out to study the fracture mechanism and material response. Results indicate that the formability undergoing EMF process with a driver sheet is increased beyond that exhibited in quasi-static tests. In electromagnetic free bulging, the forming limit of Ti-6Al-4V increases by 24.37%, which is more optimistic than AA5052-O. Fractography analysis using SEM determines that the Ti-6Al-4V titanium alloy sheet fails in a combination of ductile fracture and shear fracture when subjected to the electromagnetic bulging process while only ductile fracture develops in quasi-static condition.
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