Structural and dynamical studies of CH-πbonded CH4-C6H6dimer by ultrafast intermolecular Coulombic decay.

The inner-valence ionization and fragmentation dynamics of CH4-C6H6dimer induced by 200 eV electron impact is studied utilizing a multi-particle coincidence momentum spectroscopy. The three-dimensional momentum vectors and kinetic energy release (KER) of the CH4++C6H6+ion pairs are obtained by coincident momentum measurement. Our analysis on the absolute cross sections indicates that the intermediate dication CH4+-C6H6+is preferentially produced by the removal of an inner-valence electron from CH4or C6H6and subsequent relaxation of ultrafast intermolecular Coulombic decay followed by two-body Coulomb explosion. Combining withab initiomolecular dynamics (AIMD) simulations, the real-time fragmentation dynamics including translational, vibrational and rotational motions are presented as a function of propagation time. The revealed fragmentation dynamics are expected to have a potential implication for crystal structure imaging with various radiation sources.

Millet Bran Protein Hydrolysate Displays the Anti-non-alcoholic Fatty Liver Disease Effect via Activating Peroxisome Proliferator-Activated Receptor γ to Restrain Fatty Acid Uptake.

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem worldwide. Impeding fatty acid uptake may be an attractive therapeutic strategy for NAFLD. In the current study, we found that millet bran protein hydrolysate (MBPH) prepared by in vitro gastrointestinal bionic digestion exhibits the potential of anti-NAFLD in vitro and in vivo, characterized by the alleviation of hepatic steatosis and the reduction of lipid accumulation. Further, MBPH significantly decreased the expression levels of fatty acid uptake related genes (FABP1, FABP2, FABP4, CD36, and CPT-1α) of liver tissue in a NAFLD mice model through activating peroxisome proliferator-activated receptor γ (PPARγ) and efficiently restrained the fatty acid uptake of liver tissue, thus exerting anti-NAFLD activity. As expected, the anti-NAFLD effect induced by MBPH, characterized by the alleviation of hepatic vacuolar degeneration, hepatic steatosis, and fibrosis, was effectively abrogated with PPARγ inhibitor (GW9662) treatment. These results indicate that the retardant of fatty acid uptake induced by PPARγ activation may be the critical factor for the anti-NAFLD effect of MBPH. Collectively, MBPH has the potential as a next-generation dietary supplementation for the prevention and treatment of NAFLD.

Immediate effect in retina and choroid after 650 nm low-level red light therapy in children.

INTRODUCTION: To investigate the changes in the retina and choroid of children after 650 nm low-level red light therapy (LLRLT). METHODS: In this prospective study, 25 subjects in the Shanghai Eye and ENT Hospital of Fudan University were included from August 2021 to September 2021. One eye was randomly selected to receive LLRLT for 3 minutes. Swept-source optical coherence tomography (OCT) and OCT angiography (OCTA) were used to measure retinal fovea perfusion density (RFPD), retinal fovea thickness (RFT), choroidal fovea blood flow (CFBF), and choroidal fovea thickness (CFT) before LLRLT, 5 minutes and 1 hour after LLRLT. Baseline characteristics between LLRLT and non-LLRLT eyes were compared. Changes in the retinal and choroidal parameters were analyzed by ANCOVA models. SAS software was used for data analysis. The difference was considered statistically significant if p < 0.05. RESULTS: There was no difference in baseline characteristics between LLRLT eyes and non-LLRLT eyes. The RFPD in LLRLT eyes significantly increased 5 minutes after LLRLT and the increment was 1.70±0.83 % (p = 0.0389). The RFPD significantly decreased from 5 minutes to 1 hour after LLRLT with a mean of -2.62±0.86 % decrement (p = 0.0031). The RFPD levels returned to baseline at 1 hour after LLRLT (p = 0.8646). However, compared with insignificant RFPD changes in non-LLRLT eyes, there was no significant difference in RFPD changes at any sampling point. No significant changes in RFT, CFBF, and CFT were found in LLRLT eyes at each sampling point. CONCLUSION: Although LLRLT has no effect on the choroid, it may cause a short-term transient increase in RFPD. It will provide theoretical support for the role of LLRLT in myopia control.

A radical photochromic metal-organic framework for boosting NIR-II photothermal conversion and therapy.

This work demonstrates for the first time that a photochromic metal organic framework (pMOF) can be employed as a promising class of NIR-II photothermal material based on the photoinduced donor-acceptor intermolecular charge transfer process. After further surface-modification, such UV-activated pMOF-a nanoparticles allow the strong inhibition of 4T1 cancer cells under 1064 nm laser irradiation.

General characteristics, economic burden, causative drugs and medical errors associated with medical damage litigation involving severe cutaneous adverse drug reactions in China.

WHAT IS KNOWN AND OBJECTIVE: To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. METHODS: This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. RESULTS AND DISCUSSION: In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. WHAT IS NEW AND CONCLUSION: Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.

Phenylquinoline transient receptor potential vanilloid 1 antagonists for the treatment of pain: Discovery of 1-(2-phenylquinoline-4-carbonyl)-N-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide.

Reported herein is the design, synthesis, and pharmacologic characterization of a class of TRPV1 antagonists constructed on a phenylquinoline platform that evolved from Cinchophen lead. This design composes three sections: a phenylquinoline headgroup attached to an aliphatic carboxamides, which is tethered at a phenyl tail group. Optimization of this design led to the identification of 37, comprising a pyrrolidine linker and a trifluoromethyl-phenyl tail. In the TRPV1 functional assay, using cells expressed hTRPV1, 37 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 10.2 nM. In the complete mice analgesic model, 37 exhibited better antinociceptive activity than the positive control BCTC in diverse pain models. All of these results suggested that 37 could be considered as a lead candidate for the further development of antinociceptive drugs.