SeeThrough: a rationally designed skull clearing technique for in vivo brain imaging.

Light scattering in the skull limits optical access to the brain. Here we present SeeThrough, a skull-clearing technique that enables simple, high-resolution, and minimally-invasive brain imaging without skull removal. Through systematic screening of over 1600 chemicals, we rationally developed a refractive index-matching solution that combines water- and organic solvent-based components, achieving both high clearing efficiency and biocompatibility.

Sydnone Photochemistry: Formation of Nitrenes.

Photolysis of 3-phenyl- and 3-(3-pyridyl)-sydnones in Ar matrices is known to furnish Earl's bicyclic lactone (bicyclo[2.1.0]oxadiazolone) followed by the elimination of CO and the formation of carbodiimides .

Photoallylation Mechanism of Dicyanobenzenes with Allyltrimethylsilane in Solution Investigated by Cold UV and IR Spectroscopy in the Gas Phase.

The photoallylation of three structural isomers of dicyanobenzene (DCB), 1,4-DCB, 1,3-DCB, and 1,2-DCB, was investigated. Reactivity dependence on the relative position of the cyano groups is acknowledged; 1,3-DCB exhibits lower reactivity. The protonated reaction intermediates were identified at m/z 171 (CHN ) for all DCB isomers at comparable intensities.

Click Chemistry-Aided Synthesis of Triazole-Tethered Benzothiazoles as Novel Multifunctional Agents Against Alzheimer's Disease.

In the current medical era, Alzheimer's disease (AD) stands as a challenging multifaceted neurodegenerative disorder characterized by diverse pathological features that necessitate the development of multi-target directed ligands (MTDLs) as a promising therapeutic approach. This study reports the design and synthesis of triazole-tethered benzothiazole derivatives (10a-r and 11a-e) as MTDLs for AD. These molecules have been evaluated for their potential to inhibit cholinesterases, amyloid-β (Aβ) aggregation, and their reactive oxygen species (ROS) scavenging ability.

Triazole-functionalized benzofuran and benzothiophene semicarbazides as novel VEGFR-2-targeted anti-cancer agents.

Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, which makes it a prime target for anti-cancer therapies. Developing novel small molecules targeting VEGFR-2 and angiogenesis is essential to expand the therapeutic arsenal for cancer treatment. In this work, we designed, synthesized, and evaluated two series of triazole-based benzofuran and benzothiophene semicarbazides 9a-h and 12a-h, demonstrating their potential as promising VEGFR-2 inhibitors.

A Diverse Array of Catalytic Photoredox Reactions Based on Aluminum(III)-Salen Complexes: Understanding the Enhancement of Catalytic Activity via Amine Association.

Since aluminum is an earth-abundant and environmentally benign main-group metal, the development of aluminum-complex-based photoredox catalysts remains a significant issue. Herein, we report aluminum(III)-salen complexes (Al-salens) as versatile photoredox catalysts. The combination of an Al-salen catalyst with an amine under visible-light irradiation allowed the hydrodechlorinative transformations of aryl chlorides, the reductive coupling of carbonyl compounds, and the defluoroallylation of perfluoroalkylarenes.

Synthesis and Physical Properties of [n]Cycloparaphenylene Ketone (n = 6, 7, 8, and 10).

[n]Cycloparaphenylene ketone 4, [n]CPP-CO, in which a carbonyl group is inserted into [n]CPP framework, with n = 6, 7, 8, and 10, was synthesized by a coupling reaction between a CPP precursor and a ketone unit, followed by reductive aromatization. Single crystal X-ray diffraction analysis and density functional theory (DFT) calculations confirmed their Möbius topology and significant molecular strain as characterized by the deviations in bond angles at the carbonyl carbon. The strain was also evidenced by size-dependent 20-50 cm shifts in the carbonyl IR stretching bands.

KEAP1 retention in phase-separated p62 bodies drives liver damage under autophagy-deficient conditions.

Phase-separated p62 bodies activate NRF2, a key transcription factor for antioxidant response, by sequestering KEAP1, which targets NRF2 for degradation. Although p62 bodies containing KEAP1 are degraded by autophagy, they accumulate in various liver disorders. Their precise disease role remains unclear.

Fertilizable Rat Sperm Is Generated in Mice Using Blastocyst Complementation: An Efficient Method for Producing Rats With ES Cell Traits.

We developed a novel approach for generating rat offspring using rat embryonic stem (ES) cell-derived sperm produced in mice with the blastocyst complementation method. By optimizing culture conditions, we established naïve male rat ES cells from two transgenic rat strains expressing EGFP and Venus fluorescence, respectively. The pluripotency of these cells was confirmed by the formation of germline chimeras.

Discovery of 1-phenyl-1,2,3-triazole ureas as dual VEGFR-2/JNK-1 type II kinase inhibitors targeting pancreatic cancer.

In oncology, pancreatic cancer (PC) continues to be a problem that requires creative approaches to therapy. This research aims to create dual kinase inhibitors that target VEGFR-2 and JNK-1, two important factors in the angiogenesis and progression of PC. We found compounds with promising anticancer action using phenyltriazolyl piperazine/(piperidine) carboxamides (PTPCs) and phenyltriazolyl phenylureas (PTPUs).

Photochemical transformations of glycosyl bromides in the presence of amines.

Photochemical transformations of glycosyl bromides are investigated in the presence of amines. The choice of amines such as N,N-diisopropylethylamine and triphenylamine was found to be critical for product selectivity. Alkylation and alkenylation of anomeric carbon with 1,1-diphenylethene could be realized.

Temperature-Dependent Photoreactivity of 2-Azidomethylbenzophenone: Insights into the Triplet Imine Biradical Pathway.

Photoenols, formed through photoinduced intramolecular H atom abstraction in -alkyl-substituted arylketones, typically have limited utility as reactive intermediates owing to fast reversion to the starting material. Herein, we introduced an azido group on the -alkyl substituent to render the photoreaction irreversible. Irradiation of 2-azidomethylbenzophenone () in methanol yielded 2-(hydroxy(phenyl)methyl)benzonitrile ().

Design, Synthesis, and Biological Evaluation of BODIPY-Caged Resiquimod as a Dual-Acting Phototherapeutic.

Resiquimod, an imidazoquinoline scaffold, exhibits potent immunotherapeutic activity but is associated with off-target effects, limiting its clinical utility. To address this limitation, we developed a novel BODIPY-caged resiquimod that is responsive to red light, combining photocaging and photodynamic therapy functionalities. Molecular docking studies guided identification of the optimal caging site for resiquimod, effectively masking its immune activity.

The microcephaly-associated transcriptional regulator AUTS2 cooperates with Polycomb complex PRC2 to produce upper-layer neurons in mice.

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

Central amygdala NPBWR1 neurons facilitate social novelty seeking and new social interactions.

The formation of new social interactions is vital for social animals, but the underlying neural mechanisms remain poorly understood. We identified CeA neurons, a population in central amygdala expressing neuropeptide B/W receptor-1 (NPBWR1), that play a critical role in these interactions. CeA neurons were activated during encounters with unfamiliar, but not with familiar, mice.

Influence of Curvature on the Physical Properties and Reactivity of Triplet Corannulene Nitrene.

Although nitrene chemistry is promising for the light-induced modification of organic compounds, the reactivity of large polycyclic aromatic compounds and the effects of their curvature remain unexplored. Irradiation of azidocorannulene () in methanol/acetonitrile followed by HCl addition produced diastereomers and . Azirine is apparently trapped by methanol to form diastereomeric acetal derivatives that are hydrolyzed with HCl to yield and '.

Impact of Transition-State Aromaticity on Selective Radical-Radical Coupling of Triarylimidazolyl Radicals.

Radical coupling reactions are generally known to have a low selectivity due to the high reactivity of radicals. In this study, high regio and substrate selectivity was discovered in the dimerization of triarylimidazolyl radicals (), a versatile photochromic reaction. When two different radicals, 2-(4-cyanophenyl)-4,5-diphenyl-1-imidazolyl radical () and 2-(4-methoxyphenyl)-4,5-diphenyl-1-imidazolyl radical (), were simultaneously generated in situ, a hexaarylbiimidazole, formed by selective coupling at the nitrogen atom at position 1 of and the carbon atom at position 2 of , was isolated with high selectivity as the main product among 24 possible radical dimer hexaarylbiimidazole derivatives.

Design and synthesis of a 2,5-Diarylthiophene chromophore for enhanced near-infrared two-photon uncaging efficiency of calcium ions.

The design and synthesis of two-photon-responsive chromophores have recently garnered significant attention owing to their potential applications in materials and life sciences. In this study, a novel π-conjugated system, 2-dimethylaminophenyl-5-nitrophenylthiophene derivatives, featuring a thiophene unit as the π-linker between the donor (NMeCH-) and acceptor (NOCH-) units was designed, synthesized, and applied for the development of two-photon-responsive chromophores as a photoremovable protecting group in the near-infrared region. Notably, the positional effect of the nitro group (NO), meta versus para position, was observed in the uncaging process of benzoic acid.

Generation of rat offspring from ovarian oocytes by xenotransplantation.

The idea of utilizing unused oocytes present in the ovaries has been tested in various ways to produce offspring. However, only a limited number of studies succeeded in offspring generation. They include transplantation of ovaries into autologous or allogeneic animals, and acquisition of pups from oocytes obtained by transplanting mouse ovaries into immunodeficient rats.

PCPE-1, a brown adipose tissue-derived cytokine, promotes obesity-induced liver fibrosis.

Metabolic dysfunction-associated steatohepatitis (MASH, previously termed non-alcoholic steatohepatitis (NASH)), is a major complication of obesity that promotes fatty liver disease. MASH is characterized by progressive tissue fibrosis and sterile liver inflammation that can lead to liver cirrhosis, cancer, and death. The molecular mechanisms of fibrosis in MASH and its systemic control remain poorly understood.

Organophotocatalytic access to -glycosides: multicomponent coupling reactions using glycosyl bromides.

Photochemical multi-component coupling reactions initiated by the activation of glycosyl bromides in the presence of 1,4-bis(diphenylamino)benzene (BDB) as an organic photocatalyst were developed. -glycosides accompanied by olefin (di)functionalization were obtained. This method allows us to access various -glycosides with alkene, carbonyl, alcohol, ether, and amide functionalities.

The role of CRMP4 in LPS-induced neuroinflammation.

Neuroinflammation has been gaining attention as one of the potential causes of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis in recent years. The suppression of excessive proinflammatory responses is expected to be a target for the treatment and prevention of neurodegenerative diseases. Collapsin response mediator protein 4 (CRMP4) is involved in cytoskeleton-associated axonal guidance in the developing brain.