Brain-derived neurotrophic factor in the ventrolateral orbital cortex regulates spared nerve injury-induced neuropathic pain and related emotional disorders in mice.

Patients with neuropathic pain frequently experience comorbidity with anxiety and depression and lack of effective treatment. The ventrolateral orbital cortex (VLO) plays a pivotal role in regulating neuropathic pain, anxiety, and depression. Brain-derived neurotrophic factor (BDNF), abundant in the central nervous system, has increasingly been reported to play a crucial role in modulating pain, anxiety, and depression through the tyrosine kinase receptor B (TrkB).

m6A-modified circZNF548 regulates exosomal miR-7108-3p to activate CD3CD8 T cells and suppress NSCLC growth by JMY.

Background: Communication between cancer cells and tumor microenvironment (TME) plays a complicated role in cancer malignancy. Circular RNAs (circRNAs), known for their stability and conservation, contribute to TME remodeling in various cancers. This study aims to investigate the role of N6-methyladenosine (m6A)-modified circZNF548 in the proliferation and migration of non-small cell lung cancer (NSCLC) within the TME.

A copper-catalyzed tandem cyclization reaction of -acyl enamines and electron-deficient alkynes: direct synthesis of alkynyl substituted pyridines.

A copper-catalyzed coupling-cyclization reaction of -acyl enamides with electron-deficient alkynes is developed. This reaction tolerates a wide range of -acyl enamines and provides a simple and efficient method for the synthesis of 3-alkynyl-substituted pyridines in good to high yields from easily available acyclic starting materials with only water and hydrogen as the by-products in a single step.

Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals.

Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source-embryos from same-sex parents-aiming to establish a stable, maintainable imprinting pattern de novo in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate.

DNMT3a Downregulation Ttriggered Upregulation of GABA Receptor in the mPFC Promotes Paclitaxel-Induced Pain and Anxiety in Male Mice.

Chemotherapeutic agents, such as paclitaxel (PTX), induce neuroplastic changes and alter gene expression in the prefrontal cortex (PFC), which may be associated with chemotherapy-induced pain and negative emotions. Notably, DNA methylation undergoes adaptive changes in neurological disorders, emerging as a promising target for neuromodulation. In this study, systemic administration of PTX leads to a decrease in the expression of the DNA methyltransferase DNMT3a, while concurrently upregulating the expression of Gabrb1 mRNA and its encoded GABARβ1 protein in the medial PFC (mPFC) of male mice.

Dual Photoredox/Copper-Catalyzed Three-Component Alkylcyanation of Alkenes and 1,4-Alkylcyanation of 1,3-Enynes Employing Sulfoxonium Ylides as the Carbon Radical Precursors.

A novel dual photoredox/copper-catalyzed three-component alkylcyanation of alkenes and 1,4-alkylcyanation of 1,3-enynes have been developed. In this radical cyanoalkylation reaction, the photoredox induced alkyl radical from sulfoxonium ylides adds to the carbon-carbon double bonds of styrenes or 1,3-enynes, and the generated benzylic or allenyl radicals couple with a Cu(II) cyanide complex to achieve selective cyanation. The reaction exhibits high chemo- and regioselectivity and a wide substrate scope, providing an efficient method for the synthesis of alkyl nitriles and allenyl nitriles in a single step.

Activation of 5-HT Receptors in the Ventrolateral Orbital Cortex Produces Anti-Anxiodepressive Effects in a Rat Model of Neuropathic Pain.

The comorbidity of anxiety and depression frequently occurs in patients with neuropathic pain. The ventrolateral orbital cortex (VLO) plays a critical role in mediating neuropathic pain and anxiodepression in rodents. Previous studies suggested that 5-HT receptors in the VLO are involved in neuropathic pain.

Protein Profiles and Novel Molecular Biomarkers of Schizophrenia Based on 4D-DIA Proteomics.

Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology.

Visible light-promoted [3+2] cyclization reaction of vinyl azides with perfluoroalkyl-substituted-imidoyl sulfoxonium ylides.

Visible-light-induced [3+2] cyclization of vinyl azides with perfluoroalkyl-substituted imidoyl sulfoxonium ylides has been developed for the first time. In this transformation, perfluoroalkyl-substituted imidoyl sulfoxonium ylides are firstly employed as a carbon radical precursor under visible light irradiation, providing a new and efficient method for the construction of perfluoroalkyl-substituted 1-pyrrolines.

Activation of 5-HT receptor in the ventrolateral orbital cortex produces antinociceptive effects in rat models of neuropathic and inflammatory pain.

The ventrolateral orbital cortex (VLO) is identified as an integral component of the endogenous analgesic system comprising a spinal cord - thalamic nucleus submedius - VLO - periaqueductal gray (PAG) - spinal cord loop. The present study investigates the effects of 5-HT receptor activation in the VLO on allodynia induced by spared nerve injury and formalin-evoked flinching behavior and spinal c-Fos expression in male SD rats, and further examines whether GABAergic modulation is involved in the effects evoked by VLO 5-HT receptor activation. We found an upregulation of 5-HT receptor expression in the VLO during neuropathic and inflammatory pain states.

Effect of the Water Content on the Adsorption of CO and CH in Calcite Slit Nanopores: Insights from GCMC, MD, and DFT.

It is significant to understand the adsorption mechanisms of shale gas (CH) and CO in shale formations to enhance CH recovery rates and enable geological CO storage. This study provides a comprehensive investigation into the adsorption behaviors of CO and CH within dry and hydrous calcite nanopores, utilizing a combination of grand canonical Monte Carlo simulations, molecular dynamics simulations, and density functional theory calculations. In dry calcite slits, the calculated results for the adsorption capacity, density profile, and isosteric heat of CO and CH reveal that CO possesses a stronger adsorption affinity, making it preferentially adsorb on the pore surface compared to CH.

DBU-Promoted Tandem Cyclization of Ynones and Diazo Compounds: Direct Synthesis of Eight-Membered Cyclic Ethers.

A novel DBU-promoted tandem cyclization reaction of ynones with diazo compounds as the N-terminal electrophiles has been developed. The reaction provides a simple and efficient method for the synthesis of fused eight-membered oxocino[2,3-] pyrazoles from readily available acyclic starting materials in a single step. This reaction allows the formation of four new bonds and two rings in a highly regio- and diastereoselective manner, where two adjacent stereocenters are created simultaneously in an atom-economic manner.

Increased Microbial Translocation is a Prognostic Biomarker of Different Immune Responses to ART in People Living with HIV.

Background: Microbial translocation (MT) is a characteristic of human immunodeficiency virus (HIV) infection. Whether MT is also a biomarker of different immune responses to antiretroviral therapy (ART) received by people living with HIV (PLWH) is not known.

Methods: We examined the presence of MT in a cohort of 33 HIV-infected immunological responders (IRs) and 28 immunological non-responders (INRs) (≥500 and <200 cluster of differentiation (CD)4+ T-cell counts/µL after 2 years of HIV-1 suppression, respectively) with no comorbidities.

Lewis Acid Mediated Conjugate Addition of Isocyanides to β-Hydroxy-α-diazo Carbonyls: Synthesis of β-Carboxamido-α-diazo Carbonyl Compounds.

A Lewis acid mediated conjugate addition of isocyanides to β-hydroxy-α-diazo carbonyls has been developed for the first time. The reaction realizes the efficient construction of quaternary carbon centers and provides a novel and efficient strategy for the synthesis of β-carboxamido-α-diazo carbonyls that would be otherwise difficult to form in a single step. Further applications, including synthesis of methylenecyclohexane, spiro-β-lactam, and nitrogen-bridged tricyclic β-lactam, demonstrated the tremendous potential of the coupling reaction.

Visible Light-Induced Coupling Cyclization Reaction of α-Diazosulfonium Triflates with α-Oxocarboxylic Acids or Alkynes.

A photocatalyst-free radical cleavage of α-diazo sulfonium salts has been developed for the first time. The reaction provides an efficient method for the generation of diazomethyl radicals from α-diazosulfonium triflates under photochemical conditions. Utilizing the in situ generated diazomethyl radicals as key intermediate, the coupling cyclization reaction of α-diazosulfonium triflates with α-oxocarboxylic acids or alkynes has been achieved.

Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession.

PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a "pseudokinase", contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear.

Spinal 5-HT receptor is involved in electroacupuncture inhibition of chronic pain.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, and it is a typical disease which can develop chronic pain. Our previous study has proved that endocannabinoid (2-AG)-CB1R-GABA-5-HT pathway is involved in electroacupuncture (EA) mediated inhibition of chronic pain. However, it is still unclear which among the 5-HT receptor subtype is involved in EA evoked 5-HT mediated inhibition of chronic pain in the dorsal spinal cord.

NaN(SiMe)/CsTFA Copromoted Aminobenzylation/Cyclization of 2-Isocyanobenzaldehydes with Toluene Derivatives or Benzyl Compounds: One-Pot Access to Dihydroquinazolines and Quinazolines.

A NaN(SiMe)/CsTFA copromoted aminobenzylation/cyclization reaction of 2-isocyanobenzaldehydes with toluene derivatives or benzyl compounds has been developed. The reaction works with a broad range of toluene derivatives and benzyl compounds, and provides a simple and efficient strategy for the synthesis of 4-benzyl-substitued dihydroquinazoline and quinazoline derivatives from easily available acyclic starting materials in a single step. Further applications, including synthesis of quinazoline, dihydroindolo[1,2-]quinazoline, and dihydro-8-isoquinolino[2,3-]quinazoline, demonstrated the tremendous potential of the tandem reaction.

MiR-205-5p promotes lung cancer progression and is valuable for the diagnosis of lung cancer.

Background: MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR-205-5p in lung cancer progression and diagnosis.

Materials And Methods: MiR-205-5p was detected by quantitative real-time PCR.

5-HT Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord.

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT, 5-HT, and 5-HT receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT receptor plays antinociceptive role in the spinal cord.

Silver-Catalyzed Cascade Cyclization Reaction of Isocyanides with Sulfoxonium Ylides: Synthesis of 3-Aminofurans and 4-Aminoquinolines.

A silver-catalyzed cascade cyclization reaction of isocyanides with sulfoxonium ylides has been developed for the first time. This reaction provides a new and efficient method for the construction of highly functionalized 3-aminofurans and 4-aminoquinolines from readily available starting materials in a single step.

Copper-catalyzed cascade cyclization reaction of 3-aminocyclobutenones with electron-deficient internal alkynes: synthesis of fully substituted indoles.

A novel copper-catalyzed cascade cyclization reaction of 3-aminocyclobutenones with electron-deficient internal alkynes has been developed for the first time. This reaction provides a new and highly efficient method for the synthesis of fully substituted indoles by formation of four new bonds and two rings from readily available starting materials in a single step.

Synthesis of pyrazolo[1,5-c]quinazoline derivatives through the copper-catalyzed domino reaction of o-alkenyl aromatic isocyanides with diazo compounds.

A novel copper-catalyzed domino reaction between o-alkenyl aromatic isocyanides and diazo compounds has been developed under mild reaction conditions. Various o-alkenyl aromatic isocyanides were prepared from readily available reactants. The reaction provides a general and efficient method for the synthesis of pyrazolo[1,5-c]quinazolines by the formation of two rings and three new bonds in a single step from readily available acyclic starting materials.

Copper-Catalyzed Cascade Cyclization Reaction of Enamines and Electron-Deficient Terminal Alkynes: Synthesis of Polysubstituted Pyrido[1,2-]indoles.

A novel copper-catalyzed cascade cyclization reaction between enamines and electron-deficient terminal alkynes has been developed. The reaction provides a new and efficient strategy for the construction of polysubstituted pyrido[1,2-]indoles by the formation of two rings, three C-C bonds, and one C-N bond in a single step from readily available acyclic starting materials.