articaine hydrochloride + epinephrine (Septocaine)

Regarding emergency medical services activation after epinephrine for anaphylaxis.

Bahna Sami L SL

D-Amino Acid Prodrug DLMEH Activates mTORC1 via Sestrin2 to Restore Muscle Protein Synthesis in Sarcopenia.

Shim Jae Ho JH, Lee Ji Yeon JY, Ahn Byung Kook BK, Woo Sang Woo SW et al.

Sarcopenia, the age-related loss of skeletal muscle mass and function, lacks FDA-approved pharmacotherapy. The mechanistic target of rapamycin complex 1 (mTORC1), activated by leucine via Sestrin2, is the master regulator of muscle protein synthesis, but L-leucine suffers from rapid catabolism and poor bioavailability. Here, we report D-leucine methyl ester hydrochloride (DLMEH), a metabolically stabilized prodrug incorporating D-stereoisomer conversion, methyl esterification, and hydrochloride salt formation. Three orthogonal biophysical methods demonstrate that DLMEH directly binds Sestrin2 (Kd 28.3 μM), equivalent to L-leucine. Sestrin2 siRNA knockdown and rapamycin co-treatment confirm Sestrin2-dependent, mTORC1-specific activation. In human primary myotubes, DLMEH (100 μM) restores dexamethasone-suppressed protein synthesis by 58.2%, significantly exceeding L-leucine (800 μM, 28.5%). In a rat dexamethasone-induced atrophy model, intravenous DLMEH (100 mg/kg/day, 14 days) preserves gastrocnemius mass (19.3% rescue), grip strength (90% of normal), and treadmill endurance (85% of normal), all superior to oral L-leucine. RNA-seq reveals 41.7% reversal of dexamethasone-induced transcriptomic changes with enrichment in mTOR signaling, ribosome biogenesis, and oxidative phosphorylation. Safety profiling establishes NOAEL at 2000 mg/kg with therapeutic index greater than 30. DLMEH represents a first-in-class Sestrin2-targeting mTORC1 activator for sarcopenia.

Neuroprotective effects of chrysin in a rat model of Parkinson's disease.

Moradi Sana S, Rajaei Farzad F, Darabi Shahram S

Chrysin, or 5,7-dihydroxyflavone, is a flavonoid with antioxidant, anti-inflammatory, and anti-apoptotic effects, which are significant in Parkinson's disease. The objective of the study is to investigate the protective effects of chrysin in Parkinson's disease. Wistar strain rats were divided into three groups: treatment (receiving chrysin before and after OHDA-6 injection), control (injected with 0.9% normal saline into the left striatum), and lesion (injected with 0.9% normal saline and OHDA-6 into the left striatum). Behavioral testing with apomorphine hydrochloride was conducted 1 week before and 4 weeks after surgery. For histological examination, black blocks of tissue were prepared, and Nissl staining was used for neuron counting. Microscopic studies were performed by capturing images of the slides. In the behavioral test conducted after apomorphine injection and before surgery, there was no significant difference in the number of rotations among the control, lesion, and treatment groups. However, after surgery, this difference was significant between the lesion and treatment groups (P ≤ 0.05). In Nissl staining, a significant difference in the number of neurons in the substantia nigra was observed between the treatment and lesion groups. According to the results obtained from this study, chrysin prevented the neurodegeneration caused by OHDA-6, leading to a lower rate of mortality in the neurons of the midbrain substantia nigra.

Synergistic non-metal doping and heterojunction engineering in B-doped Bi2MoO6/MIL-88B(Fe) for efficient photocatalytic tetracycline degradation under visible light.

Song Linjie L, Chigan Tonglin T, Ma Jingfang J, Hui Yaguang Y et al.

Among diverse photocatalytic materials, Bi2MoO6 (BMO) has attracted significant attention by virtue of its unique layered structure, narrow bandgap, and tunable energy band configuration. However, its practical application was hindered by inefficient separation of photogenerated carriers and inadequate visible-light utilization. To overcome these limitations, synergistic modification through elemental doping and heterojunction construction was implemented in this study. Herein, boron-doped Bi2MoO6 (B-BMO)/MIL-88B(Fe) composites with Z-scheme heterojunctions were fabricated via a facile solvothermal method. Boron doping effectively modulated the energy band structure, reduced the bandgap, enhanced the light absorption capacity, and induced lattice distortion. Meanwhile, the staggered energy band alignment between MIL-88B(Fe) and B-BMO facilitated Z-scheme heterojunction formation, which strengthened charge carrier separation while maintaining a strong redox capability. Under visible-light irradiation, the B-BMO/MIL-88B(Fe) composite achieved 91.26% degradation efficiency for tetracycline hydrochloride (TCH) within 120 min, with a reaction rate constant of 0.0129 min-1. Compared to pristine B-BMO, the degradation rate improved by 10.2%. The composite maintained over 80% degradation efficiency after three consecutive cycles and retained favorable activity after five successive cycles. Sacrificial agent experiments identified superoxide anion radicals (˙O2-) as the dominant reactive species during the degradation process. Liquid chromatography-mass spectrometry (LC-MS) analysis enabled identification of degradation intermediates, leading to the proposal of a plausible TCH degradation pathway. This study provides insights into subsequent non-metallic element doping and heterojunction engineering strategies for BMO-based photocatalysts.