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Spherical nucleic acids (SNAs) are nanostructures with the DNA arranged radially on the surface, thus allowing specific binding with cancer cells expressing high levels of scavenger receptor-A to enhance cellular uptake. However, conventional carriers for SNAs are cytotoxic, not degradable and difficult to deliver multiple payloads. In this study, we developed charge-reversible coordination-crosslinked SNAs to deliver dual anti-cancer genes and ferroptosis payload for anti-cancer purposes. To this end, we modified poly(lactic acid) (PLA) with functionalized side chains to allow its binding with antisense oligonucleotides (ASOs) and siRNA, annealed two single-stranded RNAs to obtain double-stranded RNA, and introduced a polyethylene glycol (PEG) shell to enhance the circulation time. Additionally, the ferroptosis payload imidazole was coordinated with iron ions as a core-crosslinked group to enhance the stability of SNAs and efficiency to kill cancer cells. We demonstrated that this novel nanocomplex efficiently internalized and killed CT-26 cells in vitro. In vivo data confirmed that the dual gene delivery system successfully targeted CT-26 tumors in tumor-bearing BALB/c mice, and exhibited strong tumor suppression ability, without inducing adverse toxic effects. Taken together, our dual gene therapy system offered an enhanced anti-tumor solution by simultaneously delivering dual anti-cancer genes and ferroptosis payload in tumor microenvironment.
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Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.
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We investigate the effect of a cavity on nonlinear two-photon transitions of a molecular system and we analyze how such an effect depends on the cavity quality factor, the field enhancement, and the possibility of dephasing. We find that the molecular response to strong light fields in a cavity with a variable quality factor can be understood as arising from a balance between (i) the ability of the cavity to enhance the field of an external probe and promote multiphoton transitions more easily and (ii) the fact that the strict selection rules on multiphoton transitions in a cavity support only one resonant frequency within the excitation range. Although our simulations use a classical level description of the radiation field (i.e., we solve Maxwell-Bloch or Maxwell-Liouville equations within the Ehrenfest approximation for the field-molecule interaction), based on experience with this level of approximation in the past studies of plasmonic and polaritonic systems, we believe that our results are valid over a wide range of external probing.
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The nature of catalysis has been hotly pursued for over a century, and current research is focused on understanding active centers and their electronic structures. Herein, the concept of conductive catalysis is proposed and verified by theoretical simulations and experimental observations. Metallic systems containing buried catalytically active transitional metals and exposed catalytically inert main group metals are constructed, and the electronic interaction between them via metallic bonding is disclosed. Through the electronic interaction, the catalytic properties of subsurface transitional metals (Pd or Rh) can be transferred to outermost main group metals (Al or Mg) for several important transformations like semi-hydrogenation, Suzuki-coupling and hydroformylation. The catalytic force is conductive, in analogy with the magnetic force and electrostatic force. The traditional definition of active centers is challenged by the concept of conductive catalysis and the electronic nature of catalysis is more easily understood. It might provide new opportunities for shielding traditional active centers against poisoning or leaching and allow for precise regulation of their catalytic properties by the conductive layer.
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Vegetation is vital to the ecosystem, contributing to the global carbon balance, but susceptible to the impacts of climate change. Monitoring vegetation drought remains challenging due to the lack of widely accepted drought indices. This study focused on vegetation, and simulated the vegetation suitable water demand and soil available water supply (calculated by Remote-sensing-based Water Balance Assessment Tool model). The standardized Vegetation Water deficit Index (SVWDI) was established by calculating the vegetation water deficit, which reflects the response of vegetation to drought. We examined the spatiotemporal evolution of vegetation drought on the Loess Plateau and evaluated the applicability of standardized vegetation water deficit index. Our findings revealed that the standardized vegetation water deficit index demonstrated an overall upward trend across different time scales from 1991 to 2020. Drought conditions were concentrated in the first 20 years of the study period, but vegetation drought on the Loess Plateau has been alleviated in the past decade. Moreover, as the time scale extended, the trend of SVWDI generally decreased, with approximately 49.50 % (1-month scale), 46.66 % (3-month scale), 47.08 % (12-month scale), and 32.16 % (24-month scale) of the grid areas experiencing increased SVWDI. The correlation between SVWDI and tree-ring width index (TRWI) performed well under all precipitation gradients, but the Palmer drought severity index (PDSI) was only highly correlated with TRWI in regions with low precipitation. In terms of the relationship with vegetation health, SVWDI demonstrated the highest correlation with the normalized difference vegetation index (NDVI) across different time scales, followed by PDSI and standardized precipitation evapotranspiration index (SPEI). This study provides insights into the evolution of vegetation drought in response to climate change. The findings can guide initiatives such as returning farmland to forest and grassland on the Loess Plateau to aid climate change adaptation strategies.
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Sequías , Ecosistema , Agua , Suelo , Bosques , Plantas , Árboles , Cambio Climático , ChinaRESUMEN
With the rapid economic development of coastal cities, the discharge of substantial amounts of heavy metal pollutants poses a serious hazard to mangroves; however, the potential sources of heavy metals and the resulting health risks are not fully understood. In this study, we analyzed the contents, sources, and ecological and health risks of heavy metal contamination in mangrove sediments from the northern margin of China. The accumulation of heavy metals in mangroves was primarily driven by five potential sources, namely agricultural (33.5 %), natural sources (21.3 %), industrial (19.1 %), aquaculture (14.3 %), and traffic (11.8 %). The assessment of health risks using a probabilistic approach demonstrated that noncarcinogenic risks were within acceptable limits for all populations. It was worth noting that both noncarcinogenic and carcinogenic risks were greater in children than in adults. Analysis of source-oriented health risks revealed that agricultural sources and As and Cd were priority sources and elements of pollution requiring attention.
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Metales Pesados , Contaminantes del Suelo , Adulto , Niño , Humanos , Monitoreo del Ambiente , Suelo , Contaminantes del Suelo/análisis , Medición de Riesgo , China , Metales Pesados/análisis , CadmioRESUMEN
The Ketogenic Diet (KD) improves memory and longevity in aged C57BL/6 mice. We tested 7 months KD vs. control diet (CD) in the mouse Alzheimer's Disease (AD) model APP/PS1. KD significantly rescued Long-Term-Potentiation (LTP) to wild-type levels, not by changing Amyloid-ß (Aß) levels. KD's 'main actor' is thought to be Beta-Hydroxy-butyrate (BHB) whose levels rose significantly in KD vs. CD mice, and BHB itself significantly rescued LTP in APP/PS1 hippocampi. KD's 6 most significant pathways induced in brains by RNAseq all related to Synaptic Plasticity. KD induced significant increases in synaptic plasticity enzymes p-ERK and p-CREB in both sexes, and of brain-derived neurotrophic factor (BDNF) in APP/PS1 females. We suggest KD rescues LTP through BHB's enhancement of synaptic plasticity. LTP falls in Mild-Cognitive Impairment (MCI) of human AD. KD and BHB, because they are an approved diet and supplement respectively, may be most therapeutically and translationally relevant to the MCI phase of Alzheimer's Disease.
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Enfermedad de Alzheimer , Dieta Cetogénica , Humanos , Ratones , Animales , Anciano , Potenciación a Largo Plazo , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Ratones Transgénicos , Ratones Endogámicos C57BL , Plasticidad NeuronalRESUMEN
Alfalfa (Medicago sativa L.) is a leguminous forage widely grown worldwide. Saline and alkaline stress can affect its development and yield. To elucidate the physiological mechanisms of alfalfa in response to saline and alkaline stress, we investigated the growth and physiological and metabolomic changes in alfalfa under saline (100 mM NaCl) and alkaline (100 mM Na2CO3, NaHCO3) stress. At the same Na+ concentration, alkaline stress caused more damage than that caused by saline stress. A total of 65 and 124 metabolites were identified in response to saline and alkaline stress, respectively. Determination of gene expression, enzyme activity, substance content, and KEGG enrichment analysis in key pathways revealed that alfalfa responded to saline stress primarily by osmoregulation and TCA cycle enhancement. Flavonoid synthesis, TCA cycle, glutamate anabolism, jasmonate synthesis, and cell wall component synthesis increased as responses to alkaline stress. This study provides important resources for breeding saline-alkaline-resistant alfalfa.
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Medicago sativa , Fitomejoramiento , Medicago sativa/genética , Cloruro de Sodio/farmacología , Cloruro de Sodio/metabolismo , Sodio/metabolismo , Metabolómica , Estrés Fisiológico , Regulación de la Expresión Génica de las PlantasRESUMEN
The first asymmetric total synthesis of the monoterpenoid indole alkaloid arboduridine has been accomplished. The tricyclic A/B/D ring system was constructed by an enantioselective Michael reaction followed by intramolecular nucleophilic addition. Intramolecular α-amination of a ketone forged the piperidine ring, while a Horner-Wadsworth-Emmons (HWE) reaction was used to form the pyrrolidine ring. A reduction cyclization cascade led to formation of the tetrahydrofuran ring.
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Background: As one of the most frequent complications of type 2 diabetes mellitus (T2DM), diabetic peripheral neuropathy (DPN) shows a profound impact on 50% of patients with symptoms of neuropathic pain, numbness and other paresthesia. No valid serum biomarkers for the prediction of DPN have been identified in the clinic so far. This study is to investigate the potential serum biomarkers for DPN firstly based on 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomics technique. Methods: Thirty-six patients enrolled in this study were divided into two groups: 18 T2DM patients without DPN (T2DM group) and 18 T2DM patients with DPN (DPN group). Serum metabolites were measured via 1H-NMR spectroscopy. Bioinformatic approaches including principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), independent sample t-test, Fisher's test, Pearson and Spearman correlation analysis, Stepwise multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the potential altered serum biomarkers. Results: A total of 20 metabolites were obtained and further analyzed. Formate was identified as the only potential biomarker that decreased in the DPN group with statistical significance after multiple comparisons (p<0.05). Formate also displayed a negative relationship with some elevated clinical markers in DPN. ROC curve analysis showed a good discriminative ability for formate in DPN with an area under the curve (AUC) value of 0.981. Conclusion: Formate could be considered a potential serum metabolic biomarker for DPN. The reduced level of formate in DPN may be associated with mitochondrial dysfunction and gut microbiota alteration. Monitoring the level of serum formate would be an important strategy for the early diagnosis of DPN and a supplement of formate may be a promising treatment for DPN in the future.
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Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid-gestational age-the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case-control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.
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Cardiopatías Congénitas , Proteoma , Embarazo , Humanos , Femenino , Estudios de Casos y Controles , Proteómica , Cardiopatías Congénitas/diagnóstico , Biomarcadores , Cisplatino , CiclofosfamidaRESUMEN
PURPOSE: To show that the acoustic noise of spiral MRI can be reduced by derating the gradients with minimal penalty to image quality and scan time, and to illustrate an algorithm for optimal choice of derating parameters. THEORY AND METHODS: Acoustic noise level was measured and compared for various values of maximum gradient amplitude and slew rate for T1 -weighted spin-echo spiral scans while maintaining image contrast, FOV and resolution, and readout time. A full gradient trajectory and a derated gradient (undersampled) trajectory were chosen for a volunteer scan followed by parallel imaging-aided reconstruction to illustrate comparable image SNR. Two auto-derating methods, which prioritize slew rate and gradient amplitude, respectively, were derived using analytical results from the WHIRLED PEAS variant of spiral waveforms and compared in their acoustic noise level under test use cases. RESULTS: Derating the gradients made the scan quieter by 16.6 dB(A) on average than a full gradient trajectory and required an undersampling factor R = 2 in order to maintain scan time, with no appreciable penalty in image SNR. Prioritizing reduced slew rate resulted in maximal loudness reduction. CONCLUSION: Scanner gradients can often be derated to reduce the acoustic noise for spiral MRI with minimal penalty in scan time and image quality with the help of parallel imaging. An automatic slew-priority derating method that maximizes loudness reduction is given.
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Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Relación Señal-Ruido , Algoritmos , AcústicaRESUMEN
Oxidative carbonylation of methane is an appealing approach to the synthesis of acetic acid but is limited by the demand for additional reagents. Here, we report a direct synthesis of CH3COOH solely from CH4 via photochemical conversion without additional reagents. This is made possible through the construction of the PdO/Pd-WO3 heterointerface nanocomposite containing active sites for CH4 activation and C-C coupling. In situ characterizations reveal that CH4 is dissociated into methyl groups on Pd sites while oxygen from PdO is the responsible for carbonyl formation. The cascade reaction between the methyl and carbonyl groups generates an acetyl precursor which is subsequently converted to CH3COOH. Remarkably, a production rate of 1.5 mmol gPd-1 h-1 and selectivity of 91.6% toward CH3COOH is achieved in a photochemical flow reactor. This work provides insights into intermediate control via material design, and opens an avenue to conversion of CH4 to oxygenates.
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The growing demand for efficient healthcare delivery has intensified the need for technological innovations that facilitate medical professionals' decision-making processes. In this study, we investigate ChatGPT (OpenAI Incorporated, Mission District, San Francisco, United States), a state-of-the-art language model based on the GPT-4 architecture, as an effective tool for assisting healthcare professionals in writing medical reports based on real patient laboratory results. By leveraging ChatGPT's extraordinary performance across multiple medical domains, including lab result diagnostics and medical literature analysis, we aimed to streamline and enhance the medical report generation process. The generated case report presents a 31-year-old male patient with no significant past medical history who visited a clinic to establish care and seek evaluation for abdominal pain. Following routine laboratory tests, including a complete blood count, comprehensive metabolic panel, and a Helicobacter pylori breath test, ChatGPT provided tailored recommendations addressing identified concerns and abnormalities. These included lifestyle modifications, such as dietary changes, weight management, and avoiding trigger foods or behaviors; alongside medical treatment options, the patient was advised to consult a gastroenterologist for further evaluation and potential advanced treatment options. The organization and structure of this case study are derived from ChatGPT's output, using patient's actual physical information and lab results as input, without any prior knowledge. Ultimately, we will compare the generated report with suggestions from an online doctor consultation system to demonstrate the precision and reliability of ChatGPT's recommendations. Through this comparison, we aim to show that ChatGPT can produce coherent, comprehensive, and clinically relevant medical reports with a relatively high degree of accuracy and consistency.
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OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groupsï¼ with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structureï¼ the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.
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Aloinjertos , Electroacupuntura , Ganglios Espinales , Traumatismos de los Nervios Periféricos , Nervio Ciático , Animales , Masculino , Ratas , Aloinjertos/metabolismo , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Factor de Crecimiento Nervioso/genética , Factor de Crecimiento Nervioso/metabolismo , Traumatismos de los Nervios Periféricos/terapia , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Nervio Ciático/lesionesRESUMEN
Studies have shown ketogenic diets (KD) started from early middle-age improved health span and longevity in mice. KDs started later in life or administered intermittently may be more feasible and promote compliance. Therefore, this study sought to test if continuous or intermittent KDs started in late-middle-aged mice would improve cognition and motor function at advanced age. Eighteen-month-old male C57BL/6JN mice were assigned to an isocaloric control (CD), KD, or intermittent ketogenic (IKD, 3-day KD/week) diet. A panel of behavior tests were performed to assess cognitive and motor functions with aging. Y-maze alternation rate was higher for both IKD and KD mice at 23 months of age and for KD mice at 26 months indicating an improved spatial working memory. Twenty-six-month-old KD mice also showed better spatial learning memory in Barnes maze when compared to the CD. Improved grid wire hang performance was observed in aged IKD and KD versus CD mice indicating better muscle endurance under isometric contraction. A reduced level of circulating proinflammatory cytokines in aged KD (IL-6 and TNF-α) and IKD (IL-6) mice may contribute to the phenotypic improvements observed with these interventions. This study demonstrates that when initiated at late-middle age, the KD improved measures of spatial memory and grid wire hang performance in aged male mice, with IKD showing results intermediate to the CD and KD groups.
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Dieta Cetogénica , Ratones , Masculino , Animales , Dieta Cetogénica/métodos , Memoria Espacial , Interleucina-6 , Ratones Endogámicos C57BL , DietaRESUMEN
Dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring with an unknown mechanism, and the effect of folic acid fortification in preventing CHD is controversial. Using gas chromatography coupled to either a flame ionization detector or mass spectrometer (GC-FID/MS) analysis, we find that the palmitic acid (PA) concentration increases significantly in serum samples of pregnant women bearing children with CHD. Feeding pregnant mice with PA increased CHD risk in offspring and cannot be rescued by folic acid supplementation. We further find that PA promotes methionyl-tRNA synthetase (MARS) expression and protein lysine homocysteinylation (K-Hcy) of GATA4 and results in GATA4 inhibition and abnormal heart development. Targeting K-Hcy modification by either genetic ablation of Mars or using N-acetyl-L-cysteine (NAC) decreases CHD onset in high-PA-diet-fed mice. In summary, our work links maternal malnutrition and MARS/K-Hcy with the onset of CHD and provides a potential strategy in preventing CHD by targeting K-Hcy other than folic acid supplementation.
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Cardiopatías Congénitas , Infarto del Miocardio , Animales , Femenino , Humanos , Ratones , Embarazo , Ácido Fólico/farmacología , Cardiopatías Congénitas/genética , Ácido Palmítico , Transducción de SeñalRESUMEN
Nonadiabatic chemical reactions involving continuous circularly polarized light (cw CPL) have not attracted as much attention as dynamics in unpolarized/linearly polarized light. However, including circularly (in contrast to linearly) polarized light allows one to effectively introduce a complex-valued time-dependent Hamiltonian, which offers a new path for control or exploration through the introduction of Berry forces. Here, we investigate several inexpensive semiclassical approaches for modeling such nonadiabatic dynamics in the presence of a time-dependent complex-valued Hamiltonian, beginning with a straightforward instantaneous adiabatic fewest-switches surface hopping (IA-FSSH) approach (where the electronic states depend on position and time), continuing to a standard Floquet fewest switches surface hopping (F-FSSH) approach (where the electronic states depend on position and frequency), and ending with an exotic Floquet phase-space surface hopping (F-PSSH) approach (where the electronic states depend on position, frequency, and momentum). Using a set of model systems with time-dependent complex-valued Hamiltonians, we show that the Floquet phase-space adiabats are the optimal choice of basis as far as accounting for Berry phase effects and delivering accuracy. Thus, the F-PSSH algorithm sets the stage for future modeling of nonadiabatic dynamics under strong externally pumped circular polarization.
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The effect of a ketogenic diet (KD) on middle aged female mice is poorly understood as most of this work have been conducted in young female mice or diseased models. We have previously shown that an isocaloric KD started at middle age in male mice results in enhanced mitochondrial mass and function after 2 months on diet and improved cognitive behavior after being on diet for 14 months when compared with their control diet (CD) fed counterparts. Here, we aimed to investigate the effect of an isocaloric 2-month KD or CD on healthy 14-month-old female mice. At 16 months of age cognitive behavior tests were performed and then serum, skeletal muscle, cortex, and hippocampal tissues were collected for biochemical analysis. Two months on a KD resulted in enhanced cognitive behavior associated with anxiety, memory, and willingness to explore. The improved neurocognitive function was associated with increased PGC1α protein in the gastrocnemius (GTN) muscle and nuclear fraction. The KD resulted in a tissue specific increase in mitochondrial mass and kynurenine aminotransferase (KAT) levels in the GTN and soleus muscles, with a corresponding decrease in kynurenine and increase in kynurenic acid levels in serum. With KAT proteins being responsible for converting kynurenine into kynurenic acid, which is unable to cross the blood brain barrier and be turned into quinolinic acid-a potent neurotoxin, this study provides a potential mechanism of crosstalk between muscle and brain in mice on a KD that may contribute to improved cognitive function in middle-aged female mice.
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Dieta Cetogénica , Animales , Cognición , Femenino , Ácido Quinurénico/metabolismo , Ácido Quinurénico/farmacología , Quinurenina/metabolismo , Quinurenina/farmacología , Masculino , Ratones , Músculo Esquelético/metabolismo , Neurotoxinas , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Ácido Quinolínico/farmacologíaRESUMEN
We present an efficient set of methods for propagating excited-state dynamics involving a large number of configuration interaction singles (CIS) or Tamm-Dancoff approximation (TDA) single-reference excited states. Specifically, (i) following Head-Gordon et al., we implement an exact evaluation of the overlap of singly-excited CIS/TDA electronic states at different nuclear geometries using a biorthogonal basis and (ii) we employ a unified protocol for choosing the correct phase for each adiabat at each geometry. For many-electron systems, the combination of these techniques significantly reduces the computational cost of integrating the electronic Schrodinger equation and imposes minimal overhead on top of the underlying electronic structure calculation. As a demonstration, we calculate the electronic excited-state dynamics for a hydrogen molecule scattering off a silver metal cluster, focusing on high-lying excited states, where many electrons can be excited collectively and crossings are plentiful. Interestingly, we find that the high-lying, plasmon-like collective excitation spectrum changes with nuclear dynamics, highlighting the need to simulate non-adiabatic nuclear dynamics and plasmonic excitations simultaneously. In the future, the combination of methods presented here should help theorists build a mechanistic understanding of plasmon-assisted charge transfer and excitation energy relaxation processes near a nanoparticle or metal surface.