Explainable deep learning and biomechanical modeling for TMJ disorder morphological risk factors.

Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis, development of targeted prevention, and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analyses of disease data sets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context.

Viable Vitreous Grafts of Whole Porcine Menisci for Transplant in the Knee and Temporomandibular Joints.

The shortage of suitable donor meniscus grafts from the knee and temporomandibular joint (TMJ) impedes treatments for millions of patients. Vitrification offers a promising solution by transitioning these tissues into a vitreous state at cryogenic temperatures, protecting them from ice crystal damage using high concentrations of cryoprotectant agents (CPAs). However, vitrification's success is hindered for larger tissues (>3 mL) due to challenges in CPA penetration.

Lgr5-expressing secretory cells form a Wnt inhibitory niche in cartilage critical for chondrocyte identity.

Osteoarthritis is a degenerative joint disease that causes pain, degradation, and dysfunction. Excessive canonical Wnt signaling in osteoarthritis contributes to chondrocyte phenotypic instability and loss of cartilage homeostasis; however, the regulatory niche is unknown. Using the temporomandibular joint as a model in multiple species, we identify Lgr5-expressing secretory cells as forming a Wnt inhibitory niche that instruct Wnt-inactive chondroprogenitors to form the nascent synovial joint and regulate chondrocyte lineage and identity.

Structure-function relationships of TMJ lateral capsule-ligament complex.

The human temporomandibular joint (TMJ) lateral capsule ligament (LCL) complex is debated as a fibrous capsule with distinct ligaments or ligamentous thickening, necessitating further evaluation of the complex and its role in TMJ anatomy and mechanics. This study explores the ultrastructural arrangement, biomechanical tensile properties, and biochemical composition of the human LCL complex including region-specific differences to explore the presence of a distinct temporomandibular ligament and sex-specific differences to inform evaluations of potential etiological mechanisms. LCL complex ultrastructural arrangement, biomechanical properties, and biochemical composition were determined using cadaveric samples.

Modulation of Reduction Potentials of Bis(pyridinium)alkane Dications through Encapsulation within Cucurbit[7]uril.

Supramolecular modulation of reduction potentials of two series of bis(pyridinium)alkane salts is described. Study of the encapsulation of bis(pyridinium)alkane guests within the CB[7] cavity revealed the critical influence of the linker length and the position of the heteroatom on the reduction potentials of encapsulated guests. CB[7] complexation of pyridinium salts induced reduction potential changes ranging between +50 and -430 mV.

Aerobic Oxidation of in Situ Generated Cyanine Dyes Leading to DNA Damage.

DNA damage induced by noncatalytic aerobic oxidation of pyridinocyanine dyes is described. The dyes are generated in situ during spontaneous oxidations of tetrakis- and bis( N-methylpyridin-4-ium)alkane salts. The mechanism of aerobic oxidation of the latter compound is proposed, and a rare direct catalyst-free transition from saturated alkane to a gem-diol is demonstrated.

Spontaneous Aerobic Oxidation of 1,1,2,2-Tetrakis(N-methylpyridin- 4-ium)ethane Iodide to the Alkene and the Epoxide.

The tetrapyridinium salt 1 was found to undergo quantitative air oxidation upon dissolving it in water. The corresponding alkene and the epoxide were found as the only products of the oxidation. A mechanism that involves an alkyl hydroperoxide intermediate 1″ undergoing a transformation that yields both products is proposed.

Mechanism of Formation of Copper(II) Chloro Complexes Revealed by Transient Absorption Spectroscopy and DFT/TDDFT Calculations.

Copper(II) complexes are extremely labile with typical ligand exchange rate constants on the order of 10(6)-10(9) M(-1) s(-1). As a result, it is often difficult to identify the actual formation mechanism of these complexes. In this work, using UV-vis transient absorption when probing in a broad time range (20 ps to 8 μs) in conjunction with DFT/TDDFT calculations, we studied the dynamics and underlying reaction mechanisms of the formation of extremely labile copper(II) CuCl4(2-) chloro complexes from copper(II) CuCl3(-) trichloro complexes and chloride ions.

5-Azido-2-aminopyridine, a new nitrene/nitrenium ion photoaffinity labeling agent that exhibits reversible intersystem crossing between singlet and triplet nitrenes.

The photochemistry of a new photoaffinity labeling (PAL) agent, 5-azido-2-(N,N-diethylamino)pyridine, was studied in aprotic and protic solvents using femtosecond-to-microsecond transient absorption and product analysis, in conjunction with ab initio multiconfigurational and multireference quantum chemical calculations. The excited singlet S1 state is spectroscopically dark, whereas photoexcitation to higher-lying singlet excited S2 and S3 states drives the photochemical reaction toward a barrierless ultrafast relaxation path via two conical intersections to S1, where N2 elimination leads to the formation of the closed-shell singlet nitrene. The singlet nitrene undergoes intersystem crossing (ISC) to the triplet nitrene in aprotic and protic solvents as well as protonation to form the nitrenium ion.

Oxidation of adenosine and inosine: the chemistry of 8-oxo-7,8-dihydropurines, purine iminoquinones, and purine quinones as observed by ultrafast spectroscopy.

Oxidative damage to purine nucleic acid bases proceeds through quinoidal intermediates derived from their corresponding 8-oxo-7,8-dihydropurine bases. Oxidation studies of 8-oxo-7,8-dihyroadenosine and 8-oxo-7,8-dihydroinosine indicate that these quinoidal species can produce stable cross-links with a wide variety of nucleophiles in the 2-positions of the purines. An azide precursor for the adenosine iminoquinone has been synthesized and applied in ultrafast transient absorption spectroscopic studies.

Photoaffinity labeling via nitrenium ion chemistry: protonation of the nitrene derived from 4-amino-3-nitrophenyl azide to afford reactive nitrenium ion pairs.

Phenyl azides with powerful electron-donating substituents are known to deviate from the usual photochemical behavior of other phenyl azides. They do not undergo ring expansion but form basic nitrenes that protonate to form nitrenium ions. The photochemistry of the widely used photoaffinity labeling system 4-amino-3-nitrophenyl azide, 5, has been studied by transient absorption spectroscopy from femtosecond to microsecond time domains and from a theoretical perspective.

Photoaffinity labeling with 8-azidoadenosine and its derivatives: chemistry of closed and opened adenosine diazaquinodimethanes.

The reactive intermediate produced upon photolysis of 8-azidoadenosine was studied by chemical trapping studies, laser flash photolysis with UV-vis and IR detection, and modern computational chemistry. It is concluded that photolysis of 8-azidoadenosine in aqueous solution releases the corresponding singlet nitrene which rapidly tautomerizes to form a closed adenosine diazaquinodimethane in less than 400 fs. A perbenzoylated derivative of 8-azidoadenosine cannot undergo this tautomerization, and instead, it fragments upon photolysis to form an opened adenosine diazaquinodimethane.

DNA photocleavage and biological activity of a pyrene dihydrodioxin.

A pyrene dihydrodioxin has been synthesized, shown to bind to duplex DNA by intercalation, and cleave the phiX 174 supercoiled plasmid upon irradiation with UV light. This compound also exhibits cytotoxic activity at the micromolar range in a number of human cancer cell lines.

Thermal and photochemistry of a pyrene dihydrodioxin (PDHD) and its radical cation: a photoactivated masking group for ortho-quinones.

Pyrene dihydrodioxins (1 and 2) have been synthesized and shown to be effective photochemical blocking groups for pyrene-4,5-dione (3). The mechanism of quinone release proceeds through the formation of a remarkably stable radical cation. Direct evidence is provided that this radical cation is not only thermally labile but also photochemically labile, and that both pathways lead to quinone extrusion.