Comparative Efficacy of Augmenting Escitalopram with Modified Electroconvulsive Therapy or High-Frequency Repetitive Transcranial Magnetic Stimulation on Depressive Symptoms, Quality of Life, and Cognitive Function in Treatment-Resistant Depression.

Treatment-resistant depression (TRD) poses significant therapeutic challenges despite available interventions. Escitalopram (ESC) is a highly selective antidepressant. This study aimed to compare ESC alone and ESC combined with modified electroconvulsive therapy (MECT) or high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in TRD patients. Ninety participants were randomized into ESC alone, ESC + MECT, and ESC + HF-rTMS groups. Notable differences were observed in Hamilton Depression Rating Scale (HDRS-17) scores at 12 weeks among ESC (14.37), ESC + MECT (10.27), and ESC + HF-rTMS (10.77) groups (P = 0.006). In terms of overall quality of life (QoL) evaluated using the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) at 12 weeks, the ESC, ESC + MECT, and ESC + HF-rTMS groups scored 2, 3, and 3.5, respectively. ESC + MECT/HF-rTMS groups showed reduced depressive symptoms compared to the ESC group, accompanied by higher overall QoL scores and increased satisfaction with health. Patients receiving ESC + MECT demonstrated no significant alterations in short-term memory and orientation, as measured by the Montreal Cognitive Assessment (MoCA), before and after treatment. Moreover, a decline in language was observed compared to baseline (12 weeks: median 2, IQR 2-3; baseline: median 1, IQR 1-3; P = 0.022). The positive impact of ESC with HF-rTMS on cognitive function was evidenced by improvements in all domines MoCA.Combining ESC with MECT or HF-rTMS exhibited enhanced effectiveness in alleviating depressive symptoms and enhancing QoL compared to ESC monotherapy. Specifically, the ESC + HF-rTMS combination displayed potential as a comprehensive treatment strategy for TRD, addressing both emotional and cognitive aspects.

Mechanistic photophysics of tellurium-substituted cytosine: Electronic structure calculations and nonadiabatic dynamics simulations.

Previously, the MS-CASPT2 method was performed to study the static and qualitative photophysics of tellurium-substituted cytosine (TeC). To get quantitative information, we used our recently developed QTMF-FSSH dynamics method to simulate the excited-state decay of TeC. The CASSCF method was adopted to reduce the calculation costs, which was confirmed to provide reliable structures and energies as those of MS-CASPT2. A detailed structural analysis showed that only 5% trajectories will hop to the lower triplet or singlet state via the twisted (S2 /S1 /T2 )T intersection, while 67% trajectories will choose the planar intersections of (S2 /S1 /T3 /T2 /T1 )P and (S2 /S1 /T2 /T1 )P but subsequently become twisted in other electronic states. By contrast, ~28% trajectories will maintain in a plane throughout dynamics. Electronic population revealed that the S2 population will ultrafast transfer to the lower triplet or singlet state. Later, the TeC system will populate in the spin-mixed electronic states composed of S1 , T1 and T2 . At the end of 300 fs, most trajectories (~74%) will decay to the ground state and only 17.4% will survive in the triplet states. Our dynamics simulation verified that tellurium substitution will enhance the intersystem crossings, but the very short triplet lifetime (ca. 125 fs) will make TeC a less effective photosensitizer.

Understanding the Excited-State Relaxation Mechanisms of Xanthophyll Lutein by Multi-configurational Electronic Structure Calculations.

The contradictory behaviors in light harvesting and non-photochemical quenching make xanthophyll lutein the most attractive functional molecule in photosynthesis. Despite several theoretical simulations on the spectral properties and excited-state dynamics, the atomic-level photophysical mechanisms need to be further studied and established, especially for an accurate description of geometric and electronic structures of conical intersections for the lowest several electronic states of lutein. In the present work, semiempirical OM2/MRCI and multi-configurational restricted active space self-consistent field methods were performed to optimize the minima and conical intersections in and between the 1Ag-, 2Ag-, 1Bu+, and 1Bu- states. Meanwhile, the relative energies were refined by MS-CASPT2(10,8)/6-31G*, which can reproduce correct electronic state properties as those in the spectroscopic experiments. Based on the above calculation results, we proposed a possible excited-state relaxation mechanism for lutein from its initially populated 1Bu+ state. Once excited to the optically bright 1Bu+ state, the system will propagate along the key reaction coordinate, i.e., the stretching vibration of the conjugated carbon chain. During this period of time, the 1Bu- state will participate in and forms a resonance state between the 1Bu- and 1Bu+ states. Later, the system will rapidly hop to the 2Ag- state via the 1Bu+/2Ag- conical intersection. Finally, the lutein molecule will survive in the 2Ag- state for a relatively long time before it internally converts to the ground state directly or via a twisted S1/S0 conical intersection. Notably, though the photophysical picture may be very different in solvents and proteins, the current theoretical study proposed a promising calculation protocol and also provided many valuable mechanistic insights for lutein and similar carotenoids.

Randomized controlled trial for time-restricted eating in overweight and obese young adults.

Time-restricted eating (TRE) is known to improve metabolic health, whereas very few studies have compared the effects of early and late TRE (eTRE and lTRE) on metabolic health. Overweight and obese young adults were randomized to 6-h eTRE (eating from 7 a.m. to 1 p.m.) (n = 21), 6-h lTRE (eating from 12 p.m. to 6 p.m.) (n = 20), or a control group (ad libitum intake in a day) (n = 19). After 8 weeks, 6-h eTRE and lTRE produced comparable body weight loss compared with controls. Compared with control, 6-h eTRE reduced systolic blood pressure, mean glucose, fasting insulin, insulin resistance, leptin, and thyroid axis activity, whereas lTRE only reduced leptin. These findings shed light on the promise of 6-h eTRE and lTRE for weight loss. Larger studies are needed to assess the promise of eTRE to yield better thyroid axis modulation and overall cardiometabolic health improvement.

Sesamin attenuates PM2.5-induced cardiovascular injury by inhibiting ferroptosis in rats.

Objective: This study aimed to elucidate the pharmacological effects of sesamin (Ses) and its mechanism of action towards PM2.5-induced cardiovascular injuries. Method: Forty Sprague Dawley (SD) rats were randomly divided into five groups: a saline control group; a PM2.5 exposure group; and low-, middle-, and high-dose Ses pretreatment groups. The SD rats were pretreated with different concentrations of Ses for 21 days. Afterward, the rats were exposed to ambient PM2.5 by intratracheal instillation every other day for a total of three times. The levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6), and indicators related to oxidative responses, such as total superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), were measured in the blood and heart. The expression of ferroptosis-related proteins in heart tissues was determined via western blot and immunohistochemistry. Results: Ses pretreatment substantially ameliorated cardiovascular injuries in rats as evidenced by the decrease in the pathological score and collagen area. The decreased levels of SOD, GSH, and GSH-Px in the heart and serum were inhibited by Ses. In addition, Ses not only notably increased the activity of antioxidant enzymes but also reduced the levels of MDA, CK, LDH, CK-MB, IL-6, TNF-α, IL-1ß, and IL-6. Furthermore, Ses pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Conclusion: Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Therefore, Ses pretreatment may be a novel strategy for the prevention and treatment of PM2.5-induced cardiovascular injury.

BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder.

AIM: This study aimed to determine the correlation between B-lymphoid tyrosine kinase (BLK) polymorphism, mRNA gene expression of BLK, and NMOSD in a Chinese Han population. BACKGROUND: B-lymphoid tyrosine kinase gene expressed mainly in B cells plays a key role in various autoimmune disorders. However, no studies have investigated the association of BLK polymorphisms with neuromyelitis optica spectrum disorder (NMOSD). METHODS: Han Chinese population of 310 subjects were recruited to analyze three single nucleotide polymorphisms (rs13277113, rs4840568, and rs2248932) under allele, genotype, and haplotype frequencies, followed by clinical characteristics stratified analysis. Real-time PCR was used to analyze mRNA expression levels of BLK in the peripheral blood mononuclear cells of 64 subjects. RESULTS: Patients with NMOSD showed lower frequencies of the minor allele G of rs2248932 than healthy controls (odds ratio (OR) =0.57, 95% confidence intervals (CI) 0.39-0.83, p = 0.003). The association between minor allele G of rs2248932 and reduced NMOSD susceptibility was found by applying genetic models of inheritance (codominant, dominant, and recessive) and haplotypes analysis. Subsequently, by stratification analysis for AQP4-positivity, the minor allele G frequencies of rs2248932 in AQP4-positive subgroup were significantly lower than in the healthy controls (OR =0.46, 95% CI 0.30-0.72, p = 0.001). Notably, the genotype GG of rs2248932 was more frequent in AQP4-negative subgroup (n = 14) than in AQP4-positive subgroup (n = 93) (p = 0.003, OR =0.05, 95% CI =0.01-0.57). BLK mRNA expression levels in the NMOSD patients (n = 36) were lower than in healthy controls (n = 28) (p < 0.05). However, the acute non-treatment (n = 7), who were untreated patients in the acute phase from the NMOSD group, showed BLK mRNA expression levels 1.8-fold higher than healthy controls (n = 8) (p < 0.05). CONCLUSION: This study evaluated that the minor allele G of rs2248932 in BLK is associated with reduced susceptibility to NMOSD and protected the risk of AQP4-positive. BLK mRNA expression in NMOSD was lower as compared to healthy controls while significantly increased in acute-untreated patients.