pH-Responsive Charge Convertible Hyperbranched Poly(ionic liquid) Nanoassembly with High Biocompatibility for Resistance-Free Antimicrobial Applications.

As a potential alternative to antibiotics, hyperbranched poly(ionic liquid)s (HPILs) have demonstrated significant potential in combating bacterial biofilms. However, their high cation density poses a high risk of toxicity, greatly limiting their in vivo applications. In this study, we constructed a biocompatible HPIL (HPIL-Glu) from a hyperbranched polyurea core with modified terminals featuring charge-convertible ionic liquids. These ionic liquid moieties consist of an ammonium-based cation and a gluconate (Glu) organic counter. HPIL-Glu could form a homogeneous nanoassembly in water and exhibited a pH-responsive charge conversion property. Under neutral conditions, Glu shielded the positively charged surface, minimizing the toxicity. In a mildly acidic environment, Glu protonation exposes cationic moieties to biofilm eradication. Comprehensive antimicrobial assessments demonstrate that HPIL-Glu effectively kills bacteria and promotes the healing of bacteria-infected chronic wounds. Furthermore, prolonged exposure to HPIL-Glu does not induce antimicrobial resistance.

Chronic Alcohol Exposure Alters the Levels and Assembly of the Actin Cytoskeleton and Microtubules in the Adult Mouse Hippocampus.

BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.

Hsa_circ_0010729 is Involved in Oxygen-Glucose Deprivation/Reoxygenation-Induced Human Microvascular Endothelial Cell Deprivation by Targeting miR-665/ING5.

Ischemic stroke is a disease with high mortality. Circular RNA_0010729 (hsa_circ_0010729) has been reported to be involved in ischemic heart disease. However, it is not clear whether hsa_circ_0010729 is involved in the regulation of ischemic stroke. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R) to stimulate human brain microvascular endothelial cells (HBMECs) model to investigate the potential role of hsa_circ_0010729 in stroke in vitro. The expression levels of hsa_circ_0010729, miR-665, and ING5 in ischemic stroke were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HBMECs proliferation was detected by CCK-8. Cell apoptosis was detected by flow cytometry. The levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the related protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to examine the target relationship between miR-665 and hsa_circ_0010729 or ING5. Compared with the control group, hsa_circ_0010729 and ING5 were highly expressed in OGD/R-induced HBMECs, while miR-665 was lowly expressed. Hsa_circ_0010729 silencing promoted OGD/R-induced cell proliferation and inhibited apoptosis. However, the effect of hsa_circ_0010729 down-regulation on OGD/R-induced cell was partially restored after co-transfection with miR-665 inhibitor. Overexpression of miR-665 can promote the proliferation and inhibit apoptosis of OGD/R-induced HBMECs by inhibiting ING5 expression. In OGD/R-induced HBMECs, hsa_circ_0010729 silencing decreased ING5 expression by upregulating miR-665. Hsa_circ_0010729 regulated miR-665/ING5 axis in OGD/R-induced HBMECs. Therefore, hsa_circ_0010729 may be a new therapeutic target for ischemic stroke.

The binding pattern of ferric iron and iron-binding protein in Botrytis cinerea.

Iron-binding protein (Ibp) has protective effect on pathogen exposed to H2O2 in defense response of plants. Ibp in Botrytis cinerea (BcIbp) is related to its virulence. Bcibp mutation lead to virulence deficiencies in B. cinerea. BcIbp is involved in the Fe3+ homeostasis regulation. Recognition the binding site and binding pattern of ferric iron and iron-binding protein in B. cinerea are vital to understand its function. In this study, molecular dynamics (MD) simulations, gaussian accelerated molecular dynamics (GaMD) simulations, dynamic cross correlation analysis and quantum chemical energy calculation were used to explore binding pattern of ferric iron. MD results showed that the C-terminal region had little effect on the stability of residues in the Fe3+-binding pocket. Energy calculations suggested the most likely coordination pattern for ferric iron in iron-binding protein. These results will help to understand the binding of ferric iron to iron-binding protein and provide new ideas for regulating the virulence of B. cinerea.

A Rare Case of a Primary Cutaneous Collision Tumor Comprising Malignant Melanoma and Rhabdomyosarcoma.

This case reports a 35-year-old man who presented with a painful erythematous nodule on his right posterior calf. He first noticed this nodule several years ago and it often bled upon contact with clothing. An excisional biopsy of the skin lesion revealed two distinct populations of cells. One population of epithelioid cells stained positive for Mart-1, HMB45, and SOX-10, confirming the diagnosis of malignant melanoma. The second population of cells stained positive for desmin and calponin, confirming the diagnosis of sarcoma with muscular differentiation. Subsequently, these unusual findings led to the diagnosis of a collision tumor comprising malignant melanoma and rhabdomyosarcoma. Follow-up PET/CT and brain MRI revealed no metastasis from the primary skin lesion. This case highlights a rare combination of cell types found within a collision tumor in addition to providing details on how to diagnose this skin lesion.

Memantine alleviates cognitive impairment and hippocampal morphology injury in a mouse model of chronic alcohol exposure.

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI.

Sialic acid-targeting multi-functionalized silicon quantum dots for synergistic photodynamic and photothermal cancer therapy.

To explore the potential of silicon quantum dots (SiQDs) in combined photodynamic therapy (PDT) and photothermal therapy (PTT), we engineered the surface of SiQDs with the photosensitizer Ce6 and the tumor-cell-targeting ligand phenylboronic acid (PBA) via polydopamine-mediated chemistry. Upon irradiation with light of specific wavelengths, SiQDs@Ce6/PBA could generate high levels of reactive oxygen species (ROS) and trigger effective photo-to-thermal conversion. PBA-conjugation could not only increase the cellular uptake and transcellular transport capability of nanoparticles, but also enhance their tumor accumulation. In the presence of a 635 nm laser, SiQDs@Ce6/PBA was able to trigger intracellular ROS production, which further altered the mitochondrial membrane potential and promoted apoptosis of tumor cells. Finally, combined PDT/PTT treatments led to synergistically enhanced cancer cell killing and tumor-growth inhibition effects. This study demonstrates the surface engineering of silicon quantum dots for synergistic PDT/PTT cancer therapy.

Flow-induced aggregation of colloidal particles in viscoelastic fluids.

The flow-induced aggregation of dilute colloidal polystyrene nanoparticles suspended in Newtonian and viscoelastic solutions is reported. A rheo-optical method has been used to detect real-time aggregation processes via measuring optical absorption or scattering in a quartz Couette cell. The observed absorbance decreases over time are attributed to the flow-induced coagulation. Numerical simulations show that the aggregation processes still follow the Smoluchowski coagulation equation in a revised version. Suspensions in a series of media are studied to evaluate the effect of the media rheological properties on the particle aggregation. The data shows that elasticity reduces the aggregation while the solution viscosity enhances the aggregation processes.

Alignment of Red Poly[dodecadyin-1,12-diol-bis(4-butoxycarbonyl-methyl-urethane)] in Couette Flow.

The flow-induced alignment of red poly[dodecadyin-1,12-diol-bis(4-butoxycarbonyl-methyl-urethane)] (poly-4BCMU) in chloroform/toluene solution is reported. Absorption spectra have been measured over a range of shear rates in an optically transparent quartz Couette cell. The measured spectra show that the poly-4BCMU structure stays the same in flow, while the measured absorbance anisotropy is attributed to the flow-induced particle alignment in the red form poly-4BCMU solutions. A limiting orientation at shear rates >50 s(-1) is observed. Numerical simulations show that the spectral changes are consistent with the rodlike poly-4BCMU particle having an aspect ratio of 2.9. The dichroic ratio of 1.9 interpreted from the data indicates that the individual poly-4BCMU chains do not aggregate amorphously in the rodlike conformation, rather they show a preferred orientation along the long axis of the prolate aggregates.

Shear Induced Alignment of Low Aspect Ratio Gold Nanorods in Newtonian Fluids.

The flow-induced alignment of small gold nanorods ranging in aspect ratio from 2.4 to 4.2 in aqueous sucrose solutions is reported. Optical absorption spectra have been measured over a range of shear rates using polarized incident light in an optically transparent quartz Couette cell. The measured spectral changes are directly attributed to the shear-induced anisotropy in the suspension due to particle alignment that saturates at Péclet number of around 200. The measured optical changes are reversible, indicating that the nanorods do not undergo aggregation during measurement. Numerical simulations show that the spectral shifts are consistent with the rods flipping between extreme orientations of the Jeffery's orbits and that the effect of the Brownian motion on the gold nanorods cannot be ignored even at large Péclet number.