A series of homodinuclear β-diketone lanthanide(
iii
) complexes, formulated as (acac)
4
Ln
2
(L1) (Ln
3+
= Dy
3+
(
1
), Tb
3+
(
2
), and Gd
3+
(
3
), respectively) were first synthesized based on a ...closed-macrocyclic ligand (H
2
L1) derived from the 2 + 2 cyclocondensation of 4-
tert
-butyl-2,6-diformylphenol and
o
-phenylenediamine in the presence of lanthanide acetylacetonates. Subsequently, by using the above compounds as building blocks to assemble directly with another Schiff base ligand,
N
,
N
′-bis(5-chlorosalicylidene)-
o
-phenylenediamine (H
2
L2), three new homodinuclear sandwich-type lanthanide complexes with the general formula Ln
2
(L1)(L2)
2
(Ln
3+
= Dy
3+
(
4
), Tb
3+
(
5
), and Gd
3+
(
6
), respectively) were further designed and prepared. Single-crystal X-ray analyses show that the central Ln
3+
ion adopts a distorted square antiprism conformation with
D
4d
local symmetry. Magnetic studies reveal ferromagnetic interaction between Dy
3+
and Tb
3+
centres and zero-field slow relaxation of magnetization for Dy complexes
1
and
4
. The corresponding magneto-structural correlations of SMMs
1
and
4
were further discussed by theoretical calculations and with experimental outcomes.
Two series of homodinuclear lanthanide macrocyclic complexes with
D
4d
symmetry have been successively synthesized. Magnetic studies reveal ferromagnetic interactions between Dy
3+
or Tb
3+
centres and typical SMM behaviors for Dy complexes
1
and
4
.
Studying the influence of short chain branch (SCB) on the crystal properties and breakdown strength of low-density polyethylene (LDPE) plays an important role in improving the electrical and ...mechanical properties of LDPE by adjusting the molecular structure. In this work, the SCB and long chain branch (LCB) content of LDPE are quantitatively characterized. Grain size, crystallinity and breakdown strength of LDPE (including AC and DC) are calculated through related characterization experiments. The results show that the SCB content in LDPE is dozens of times that of LCB. Reducing the SCB content can reduce the grain size of 110 face in LDPE and improve the AC and DC breakdown strength. The trap distribution characteristics measured by the thermally stimulated depolarization current (TSDC) method show that the SCB inhibits the formation of deep cavity defects in the LDPE interface area and decreases the trap energy level of crystal defects. This inspired us to improve the breakdown strength by reducing the SCB content in LDPE.
Bacteria form a highly complex ecosystem in the gastrointestinal (GI) tract. In recent years, mounting evidence has shown that bacteria can release nanoscale phospholipid bilayer particles that ...encapsulate nucleic acids, proteins, lipids, and other molecules. Extracellular vesicles (EVs) are secreted by microorganisms and can transport a variety of important factors, such as virulence factors, antibiotics, HGT, and defensive factors produced by host eukaryotic cells. In addition, these EVs are vital in facilitating communication between microbiota and the host. Therefore, bacterial EVs play a crucial role in maintaining the GI tract's health and proper functioning. In this review, we outlined the structure and composition of bacterial EVs. Additionally, we highlighted the critical role that bacterial EVs play in immune regulation and in maintaining the balance of the gut microbiota. To further elucidate progress in the field of intestinal research and to provide a reference for future EV studies, we also discussed the clinical and pharmacological potential of bacterial EVs, as well as the necessary efforts required to understand the mechanisms of interaction between bacterial EVs and gut pathogenesis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Even in the antiretroviral treatment (ART) era, HIV-1-infected patients suffer from milder forms of HIV-1-associated neurocognitive disorders (HAND). While the viral proteins Tat and gp120 have been ...shown to individually inhibit the proliferation and neural differentiation of neural stem cells (NSCs), no studies have characterized the effects of all the combined viral proteins on adult neurogenesis.
The HIV-1 Tg26 transgenic mouse model was used due to its clinical relevance to ART-controlled HIV-1-infected patients who lack active viral replication but suffer from continuous stress from the viral proteins. Quantitative RT-PCR analysis was performed to validate the expression of viral genes in the neurogenic zones. In vitro stemness and lineage differentiation assays were performed in cultured NSCs from HIV-1 Tg26 transgenic mice and their wild-type littermates. Hippocampal neurogenic lineage analysis was performed to determine potential changes in initial and late differentiation of NSCs in the subgranular zone (SGZ). Finally, fluorescent retroviral labeling of mature dentate granule neurons was performed to assess dendritic complexity and dendritic spine densities.
Varying copy numbers of partial gag (p17), tat (unspliced and spliced variants), env (gp120), vpu, and nef transcripts were detected in the neurogenic zones of Tg26 mice. Significantly fewer primary neurospheres and a higher percentage of larger sized primary neurospheres were generated from Tg26 NSCs than from littermated wild-type mouse NSCs, implying that Tg26 mouse NSCs exhibit deficits in initial differentiation. In vitro differentiation assays revealed that Tg26 mouse NSCs have reduced neuronal differentiation and increased astrocytic differentiation. In the SGZs of Tg26 mice, significantly higher amounts of quiescent NSCs, as well as significantly lower levels of active NSCs, proliferating neural progenitor cells, and neuroblasts, were observed. Finally, newborn mature granule neurons in the dentate gyri of Tg26 mice had deficiencies in dendritic arborization, dendritic length, and dendritic spine density.
Both in vitro and in vivo studies demonstrate that HIV-1 Tg26 mice have early- and late-stage neurogenesis deficits, which could possibly contribute to the progression of HAND. Future therapies should be targeting this process to ameliorate, if not eliminate HAND-like symptoms in HIV-1-infected patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The objective of the present study was to develop a W/O/W nanoemulsion (NE) drug delivery system loaded with punicalagin (PGN) for oral delivery and evaluate its potential in antibacterial therapy. ...The W/O/W PGN-NE was prepared using a two-step process by combining ultrasonic with high-energy emulsification and subsequently characterized by its droplet size, zeta potential, and morphology. The PGN-NE was further evaluated for its pH, in vitro antibacterial activity, drug release property, and cytotoxicity. The results indicated the formation of spherical, nano-sized globules of PGN-NE had a mean particle size of 45.53 ± 2.2 nm, with a PDI value of 0.22 ± 0.028, zeta potential was −4.67 ± 0.88 mV, and pH value was 5.8. In vitro antibacterial activity studies showed a significantly higher antibacterial activity of PGN-NE in comparison to free PGN, suggesting that NE can effectively improve the antibacterial effect of natural pharmaceuticals. The drug release assay demonstrated that PGN was slowly released from the NE preparation and absorbed, helping to prolong the potency and improve the bioavailability of PGN. Cytotoxicity testing showed that PGN had reduced toxicity when encapsulated in NE. Thus, the developed NE formulation of PNG exhibited a greater potential for the slow-release effect delivery and in the treatment of microbial infections with favorable safety profile.
Graphical abstract
Micromorphology of W/O/W PGN nanoemulsion
The W/O/W PGN-NE are uniform in size and non-adhesive, with a size distribution of 28.214 to 141.772 nm and a mean size of 45.53 ± 2.2 nm, respectively, with a PDI value of 0.22 ± 0.028.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Fluorination in enhancing photoactivated antibacterial activity of Ru(
ii
) complexes with photo-labile ligands was studied. Ru(
ii
) polypyridine complexes containing a di-fluorinated dppz ...(dipyrido3,2-
a
:2′,3′-
c
phenazine) or mono-trifluoromethylated dppz bidentate ligand and four pyridine monodentate ligands (complexes
3
and
4
) were found to show potent photoactivated antibacterial activity against methicillin-resistant
Staphylococcus aureus
(MRSA), vancomycin-resistant
Enterococcus
(VRE), and
Escherichia coli
(
E. coli
) in both normoxic and hypoxic conditions. The bactericidal effect of complexes
3
and
4
under hypoxic conditions may stem from the fluorine-containing Ru(
ii
) aqua species after photo-induced pyridine dissociation, and DNA may be the potential antibacterial target. Photosensitized singlet oxygen may also account for their antibacterial activity under normoxic conditions. Moreover, negligible hemolysis rates as well as low dark- and photo-cytotoxicity toward human normal liver cells (L-O2) were also observed for both complexes. Our work may provide new insights into the development of novel and efficient Ru(
ii
) complex based photoactivatable antibacterial agents against antibiotic-resistant bacteria.
Fluorination in the dppz ligand efficiently enhanced the photoactivated antibacterial activity of Ru(
ii
) complexes with photo-labile ligands against antibiotic-resistant bacteria both under normoxic and hypoxic conditions.
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IJS, KILJ, NUK, UL, UM, UPUK
Cancer represents a profound challenge to healthcare systems and individuals worldwide. The development of multiple drug resistance is a major problem in cancer therapy and can result in progression ...of the disease. In our previous studies, we developed small-molecule inhibitors targeting ubiquitin-specific peptidase 24 (USP24) to combat drug-resistant lung cancer. Recently, we found that the USP24 inhibitor NCI677397 induced ferroptosis, a type of programmed cell death, in drug-resistant cancer cells by increasing lipid reactive oxygen species (ROS) levels. In the present study, we investigated the molecular mechanisms and found that the targeting of USP24 by NCI677397 increased gene expression of most lipogenesis-related genes, such as acyl-CoA synthetase long-chain family member 4 (ACSL4), and activated autophagy. In addition, the activity of several antioxidant enzymes, such as glutathione peroxidase 4 (GPX4) and dihydrofolate reductase (DHFR), was inhibited by NCI677397 treatment via an increase in protein degradation, thereby inducing lipid ROS production and lipid peroxidation. In summary, we demonstrated that NCI677397 induced a marked increase in lipid ROS levels, subsequently causing lipid peroxidation and leading to the ferroptotic death of drug-resistant cancer cells. Our study provides new insights into the clinical use of USP24 inhibitors as ferroptosis inducers (FINs) to block drug resistance during chemotherapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Under the high stress of a 300-m dam, the particle breakage patterns of rockfill material may differ from those under low-stress levels. The existing studies on the particle breakage of rockfill ...material under ultra-high dams are relatively rare. In this study, by performing a series of large-scale triaxial shear tests under different relative densities and confining pressures, the stress–strain relationships and particle breakage characteristics of a sandstone rockfill material were investigated. The development of four particle breakage indexes before and after the triaxial test, the evolution of the gradation curves, and the applicability of three gradation formulas to the data of this study were analyzed. Based on the distribution of one relative breakage index, its relationship with strength and compressibility was established. Finally, three failure modes for the sandstone rockfill material after the triaxial test were given. And the relationships among failure modes and confining pressure, and particle size were discussed.
Graphical Abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•We provide the first proteomic analysis of DIV1.•Thirty viral structural proteins are identified by one-dimension electrophoresis coupled with LC-MS/MS.•Twenty-three of the structural proteins are ...confirmed by Western blotting.
Decapod iridescent virus 1 (DIV1) is one of the major pathogens of farmed shrimp. In this study, the structural proteins of DIV1 were analyzed by mass spectrometry. DIV1 virions were purified from the hemolymph of artificially infected Cherax quadricarinatus. The viral proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a total of 28 protein bands were obtained. These protein bands were in-gel digested with trypsin and the resulting tryptic peptide mixtures were subjected to liquid chromatography with tandem mass spectrometry analysis. Thirty virus-encoded proteins were identified. Among them, 6 proteins were predicted to contain transmembrane domains, 3 proteins were predicted to contain an Arg-Gly-Asp motif. Nine proteins showed significant homology with functionally characterized proteins. Antibodies were produced for these candidate proteins and 23 of them were confirmed to be the components of DIV1 virions by Western blotting. This study provides the first proteomic analysis of DIV1, which establishes a foundation for further investigation of viral infection and replication.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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