Dynamic proteomic and phosphoproteomic analysis reveals key pathways and targets in the early stages of high-altitude traumatic brain injury.

Traumatic brain injury (TBI), particularly at high altitudes (HA-TBI), is a leading cause of mortality and disability, yet clear diagnostic and treatment protocols are lacking. This study explores the early pathophysiological changes occurring within 24 h following HA-TBI, with a focus on differentially expressed proteins (DEPs) and phosphorylated proteins (DEPPs). Using a low-pressure hypoxic chamber to simulate high-altitude conditions combined with a controllable cortical impact (CCI) model, we established a rat model of HA-TBI.

Multi-omics landscape and molecular basis of radiation tolerance in a tardigrade.

Tardigrades are captivating organisms known for their resilience in extreme environments, including ultra-high-dose radiation, but the underlying mechanisms of this resilience remain largely unknown. Using genome, transcriptome, and proteome analysis of , we explored the molecular basis contributing to radiotolerance in this organism. A putatively horizontally transferred gene, DOPA dioxygenase 1 (), responds to radiation and confers radiotolerance by synthesizing betalains-a type of plant pigment with free radical-scavenging properties.

5-hydroxytryptamine 2C/1A receptors modulate the biphasic dose response of the head twitch response and locomotor activity induced by DOM in mice.

Rationale: The phenylalkylamine hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) exhibits an inverted U-shaped dose-response curve for both head twitch response (HTR) and locomotor activity in mice. Accumulated studies suggest that HTR and locomotor hyperactivity induced by DOM are mainly caused by the activation of serotonin 5-hydroxytryptamine 2 A receptor (5-HT receptor). However, the mechanisms underlying the biphasic dose response of HTR and locomotor activity induced by DOM, particularly at high doses, remain unclear.

Serine 3.39 and isoleucine 4.60 are key sites for 5-HTR-mediated G signaling.

Certain amino acid sites of 5-HTR play crucial roles in interacting with various G proteins. Hallucinogens and non-hallucinogens both act on 5-HTR but mediate different pharmacological effects, possibly due to the coupling of different G proteins. Therefore, this study identified the binding sites of hallucinogens and non-hallucinogens with 5-HTR through molecular docking.

Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice.

Background: Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified.

Aims: To investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity.

Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) via regulating the synaptic plasticity in hippocampus.

TSPO, translocator protein (18 kDa) ligands have demonstrated consistent antidepression and anxiolytic effects in several preclinical studies. This study aimed to examine whether YL-IPA08[N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl) -7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, could alleviate anxiety-related behaviors induced by electric shock (ES) and investigate its underlying mechanism. As expected, we showed that chronic treatment with YL-IPA08 significantly reversed anxiety-related behaviors induced by electrical stimulation (0.

Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity.

Background: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD.

Rearing behaviour in the mouse behavioural pattern monitor distinguishes the effects of psychedelics from those of lisuride and TBG.

Psychedelics alter consciousness and may have potential for drug development. As psychedelics are likely therapeutically active, it is important to study their effects and mechanisms using preclinical models. Here, we examined the effects of phenylalkylamine and indoleamine psychedelics on locomotor activity and exploratory behaviour using the mouse Behavioural Pattern Monitor (BPM).

Biocompatible hypocrellin A-Fe(III) nanoparticles exhibiting efficient photo-activated CDT and .

Chemodynamic therapy (CDT) is novel and promising for cancer treatment, however, the potential systematic toxicity of the used nanoparticles is still a big concern. In this work the biocompatible hypocrellin A-Fe(III) nanoparticles (HA-Fe(III) NPs) were synthesized and studied. The CDT effect of HA-Fe(III) NPs in the dark is negligible but can be photo-activated upon red light irradiation, which is meaningful to realize precise CDT treatment by selective light irradiation.

Selective and Efficient Photoinactivation of Intracellular and MRSA with Little Accumulation of Drug Resistance: Application of a Ru(II) Complex with Photolabile Ligands.

Novel antibacterial agents capable of efficiently sterilizing intracellular and methicillin-resistant (MRSA) but with low cytotoxicity and low resistance development are quite appealing. In this work, three Ru(II) complexes with photolabile ligands were explored to realize such a goal. Complex (5 μM) can inhibit more than 90% growth of /MRSA that has invaded in J774A.

UCNP@BSA@Ru nanoparticles with tumor-specific and NIR-triggered efficient PACT activity .

Ru(ii)-based photoactivated chemotherapy (PACT) agents are promising; however, their short wavelength absorption (generally <550 nm) and poor tumor accumulation ability limit their in vivo applications. Herein, bovine serum albumin (BSA) coated lanthanide-doped upconversion nanoparticles (NaYF4:Yb:Tm@NaYF4 (UCNPs)) were loaded with a Ru(ii) PACT agent, i.e.

A nuclear permeable Ru(ii)-based photoactivated chemotherapeutic agent towards a series of cancer cells: in vitro and in vivo studies.

Ru(ii) polypyridyl complexes which can undergo photo-induced ligand dissociation and DNA covalent binding are considered as potential photoactivated chemotherapeutic (PACT) agents. Herein four pyridine-2-sulfonate (py-SO3-) ligand based Ru(ii) complexes [Ru(N-N)2(py-SO3)]+ (1-4) were synthesized and studied. All the complexes can undergo fast py-SO3- ligand dissociation and DNA covalent binding upon visible light irradiation.

Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated.

Synthesis of N,O,B-Chelated Dipyrromethenes through an Unexpected Intramolecular Cyclisation: Enhanced Near-Infrared Emission in the Aggregate/Solid State.

The first example of the synthesis of mono-N,O-B-chelated dipyrromethene (BODIPY) derivatives through an unexpected intramolecular nucleophilic displacement of the fluorine by alkenols in the presence of boron trifluoride as Lewis acid is reported. The chlorine in the indacene core allowed for further structural modifications through nucleophilic substitutions or palladium-catalysed coupling reactions to afford new fluorophores with tuneable photophysical properties. Their expanded conjugation structure resulted in distinct red-shifted absorption and emission spectra in organic solutions.

Synthesis and biological evaluation of novel 10-substituted-7-ethyl-10-hydroxycamptothecin (SN-38) prodrugs.

In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. The synthesized compounds completely generated SN-38 in pH 7.4 buffer or in human plasma, while remaining stable under acidic conditions.

Coordination-driven hierarchical organization of pi-conjugated systems: from molecular to supramolecular pi-stacked assemblies.

The reaction of U-shaped, bimetallic, Cu(I) complexes, assembled from a heteroditopic pincer, with cyano-capped pi-conjugated linkers gives a straightforward access to pi-stacked metallocyclophanes in good yields. In these assemblies, the pi-walls have an almost face-to-face arrangement. The versatility of this rational supramolecular synthesis is demonstrated with the use of linkers that have nanoscale lengths (up to 27.