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Transition-metal-catalyzed C-Si/Ge cross-coupling offers promising avenues for the synthesis of organosilanes/organogermanes, yet it is fraught with long-standing challenges. A Ni/Ti-catalyzed strategy is reported here, allowing the use of disubstituted malononitriles as tertiary C(sp3) coupling partners to couple with chlorosilanes and chlorogermanes, respectively. This method enables the catalytic cleavage of the C(sp3)-CN bond of the quaternary carbon followed by the formation of C(sp3)-Si/C(sp3)-Ge bonds from ubiquitously available starting materials. The efficiency and generality are showcased by a broad scope for both of the coupling partners, therefore holding the potential to synthesize structurally diverse quaternary organosilanes and organogermanes that were difficult to access previously.
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RATIONALE: Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development. METHODS: The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology. RESULTS: A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism.
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Furocumarinas , Farmacologia em Rede , Psoralea , Ratos Sprague-Dawley , Animais , Furocumarinas/farmacologia , Furocumarinas/química , Psoralea/química , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Controle de Qualidade , Biomarcadores/análise , Biomarcadores/metabolismo , Biomarcadores/urina , Frutas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Espectrometria de Massas/métodos , Conservadores da Densidade Óssea/farmacologia , Metaboloma/efeitos dos fármacos , Metabolômica/métodosRESUMO
RATIONALE: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti-osteoporotic mechanism are still unclear, restricting its development and application. METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti-osteoporosis targets and mechanism were predicted using network pharmacology. RESULTS: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan-ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. CONCLUSIONS: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti-osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis.
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Lignanas , Farmacologia em Rede , Osteoporose , Ratos Sprague-Dawley , Animais , Lignanas/farmacologia , Lignanas/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/química , Metabolômica/métodos , Glucosídeos/farmacologia , Metaboloma/efeitos dos fármacos , Espectrometria de Massas/métodosRESUMO
In this paper, we present a comprehensive account of quantum dissipation theories with the quadratic environment couplings. The theoretical development includes the Brownian solvation mode embedded hierarchical quantum master equations, a core-system hierarchy construction that verifies the extended dissipaton equation of motion (DEOM) formalism [R. X. Xu et al., J. Chem. Phys. 148, 114103 (2018)]. Developed are also the quadratic imaginary-time DEOM for equilibrium and the λ(t)-DEOM for nonequilibrium thermodynamics problems. Both the celebrated Jarzynski equality and Crooks relation are accurately reproduced, which, in turn, confirms the rigorousness of the extended DEOM theories. While the extended DEOM is more numerically efficient, the core-system hierarchy quantum master equation is favorable for "visualizing" the correlated solvation dynamics.
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Simulating dynamics of open quantum systems is sometimes a significant challenge, despite the availability of various exact or approximate methods. Particularly when dealing with complex systems, the huge computational cost will largely limit the applicability of these methods. In this work, we investigate the usage of dynamic mode decomposition (DMD) to evaluate the rate kernels in quantum rate processes. DMD is a data-driven model reduction technique that characterizes the rate kernels using snapshots collected from a small time window, allowing us to predict the long-term behaviors with only a limited number of samples. Our investigations show that whether the external field is involved or not, the DMD can give accurate prediction of the result compared with the traditional propagations, and simultaneously reduce the required computational cost.
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In this paper, we present an extended dissipaton equation of motion for studying the dynamics of electronic impurity systems. Compared with the original theoretical formalism, the quadratic couplings are introduced into the Hamiltonian accounting for the interaction between the impurity and its surrounding environment. By exploiting the quadratic fermionic dissipaton algebra, the proposed extended dissipaton equation of motion offers a powerful tool for studying the dynamical behaviors of electronic impurity systems, particularly in situations where nonequilibrium and strongly correlated effects play significant roles. Numerical demonstrations are carried out to investigate the temperature dependence of the Kondo resonance in the Kondo impurity model.
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Dissipaton theory had been proposed as an exact, nonperturbative approach to deal with open quantum system dynamics, where the influence of the Gaussian environment is characterized by statistical quasi-particles, named dissipatons. In this work, we revisit the dissipaton equation of motion theory and establish an equivalent dissipaton-embedded quantum master equation (DQME) that gives rise to dissipatons as generalized Brownian particles. As explained in this work, the DQME supplies a direct approach to investigate the statistical characteristics of dissipatons and, thus, the physically supporting hybrid bath modes. Numerical demonstrations are carried out on the electron transfer model, exhibiting the transient statistical properties of the solvation coordinate.
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Recent technological advancement in scanning tunneling microscopes has enabled the measurement of spin-field and spin-spin interactions in single atomic or molecular junctions with an unprecedentedly high resolution. Theoretically, although the fermionic hierarchical equations of motion (HEOM) method has been widely applied to investigate the strongly correlated Kondo states in these junctions, the existence of low-energy spin excitations presents new challenges to numerical simulations. These include the quest for a more accurate and efficient decomposition for the non-Markovian memory of low-temperature environments and a more careful handling of errors caused by the truncation of the hierarchy. In this work, we propose several new algorithms, which significantly enhance the performance of the HEOM method, as exemplified by the calculations on systems involving various types of low-energy spin excitations. Being able to characterize both the Kondo effect and spin excitation accurately, the HEOM method offers a sophisticated and versatile theoretical tool, which is valuable for the understanding and even prediction of the fascinating quantum phenomena explored in cutting-edge experiments.
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OBJECTIVE: The goal of this research was to determine whether or not there is a saturation effect and whether or not the visceral adiposity index (VAI) correlates with bone mineral density (BMD) in adult Americans. METHODS: This study used multivariate logistic regression models to examine the association between VAI and total femur BMD, drawing on the most up-to-date data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. Saturation levels and non-linear connections were calculated using a smooth curve-fitting algorithm and an investigation of saturation effects. Subgroup analyses and interaction tests were also conducted. RESULTS: This study ultimately recruited 6257 individuals aged 20 years or older. According to multivariate regression analysis, those with high VAI scores exhibited higher total femur BMD. Total femur BMD was greater in the highest VAI quartile (Q4: 0.060 g/cm2) after adjustment than in the lowest VAI quartile (Q1) (P < 0.05). After controlling for variables, subgroup analysis failed to reveal any significant interaction effects. Furthermore, the study determined that VAI and BMD exhibited a specific saturation effect through the investigation of the saturation effect and the fitting of smooth curves. Saturation effect investigation of total femur BMD using VAI revealed a saturation value of 3.3. CONCLUSION: The present study uncovered a non-linear relationship between VAI and total femur BMD, which exhibited a saturation effect.
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Adiposidade , Densidade Óssea , Adulto , Humanos , Estados Unidos , Inquéritos Nutricionais , Obesidade AbdominalRESUMO
An enantioselective nickel-catalyzed intramolecular reductive cross-coupling of C(sp2) electrophiles and cyano groups is reported. Enantioenriched CN-containing all-carbon quaternary stereocenters are assembled by desymmetrizing cyclization of aryl/alkenyl halide-tethered malononitriles. The use of an organic reductant, (EtO)2MeSiH, is crucial to the enantioselectivity and reactivity. Applications of the method are demonstrated through the synthesis of bioactive molecules and their cyanated analogues and the total synthesis of the natural product diomuscinone. This study exhibits the potential of desymmetrizing reductive coupling strategies to access structurally rigid and synthetically versatile molecules from readily available starting materials.
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Carbono , Níquel , Catálise , Ciclização , EstereoisomerismoRESUMO
Electron transfer (ET) processes are of broad interest in modern chemistry. With the advancements of experimental techniques, one may modulate the ET via such events as light-matter interactions. In this work, we study the ET under a Floquet modulation occurring in the donor-bridge-acceptor systems, with the rate kernels projected out from the exact dissipaton equation of motion formalism. This together with the Floquet theorem enables us to investigate the interplay between the intrinsic non-Markovianity and the driving periodicity. The observed rate kernel exhibits a Herzberg-Teller-like mechanism induced by the bridge fluctuation subject to effective modulation.
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For open quantum systems, the Gaussian environmental dissipative effect can be represented by statistical quasi-particles, namely, dissipatons. We exploit this fact to establish the dissipaton thermofield theory. The resulting generalized Langevin dynamics of absorptive and emissive thermofield operators are effectively noise-resolved. The system-bath entanglement theorem is then readily followed between an important class of nonequilibrium steady-state correlation functions. All these relations are validated numerically. A simple corollary is the transport current expression, which exactly recovers the result obtained from the nonequilibrium Green's function formalism.
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In this Communication, we propose the time-domain Prony fitting decomposition (t-PFD) as an accurate and efficient exponential series method, applicable to arbitrary bath correlation functions. The resulting numerical efficiency of hierarchical equations of motion (HEOM) formalism is greatly optimized, especially in low temperature regimes that would be inaccessible with other methods. For demonstration, we calibrate the present t-PFD against the celebrated Padé spectrum decomposition method, followed by converged HEOM evaluations on the single-impurity Anderson model system.
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Excitation energy transfer (EET) and electron transfer (ET) are crucially involved in photosynthetic processes. In reality, the photosynthetic reaction center constitutes an open quantum system of EET and ET, which manifests interplay of pigments, solar light, and phonon baths. So far, theoretical studies have been mainly based on master equation approaches in the Markovian condition. The non-Markovian environmental effect, which may play a crucial role, has not been sufficiently considered. In this work, we propose a mixed dynamic approach to investigate this open system. The influence of phonon bath is treated via the exact dissipaton equation of motion (DEOM), while that of photon bath is via the Lindblad master equation. Specifically, we explore the effect of non-Markovian quantum phonon bath on the coherent transfer dynamics and its manipulation on the current-voltage behavior. Distinguished from the results of the completely Markovian-Lindblad equation and those adopting the classical environment description, the mixed DEOM-Lindblad simulations exhibit transfer coherence up to a few hundred femtoseconds and the related environmental manipulation effect on the current. These non-Markovian quantum coherent effects may be extended to more complex and realistic systems and be helpful in the design of organic photovoltaic devices.
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Complexo de Proteínas do Centro de Reação Fotossintética , Transferência de Energia , Modelos Teóricos , Fotossíntese , Teoria QuânticaRESUMO
An enantioselective Pd(II)-catalyzed amino-cyclization and desymmetrizing nitrile addition cascade reaction of alkyne-tethered malononitriles is reported. This reaction forms two rings and one quaternary carbon center in a single step and serves as an efficient strategy for the construction of α-quaternary carbazolones with high enantioselectivities (up to 98:2 er). The utility of this method is demonstrated by product derivatization into a diverse array of heterocycles and a nitrile-containing leucomidine A analog.
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Carbazóis/química , Nitrilas/química , Paládio/química , Alcinos/química , Carbazóis/síntese química , Carbono/química , Catálise , Ciclização , Conformação Molecular , EstereoisomerismoRESUMO
BACKGROUND AIMS: Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. METHODS: A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. RESULTS: Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. CONCLUSIONS: The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.
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Células-Tronco Mesenquimais , Traumatismos da Medula Espinal/terapia , Cordão Umbilical/citologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Espaço Subaracnóideo/fisiopatologia , Adulto JovemRESUMO
Excitation energy transfer is crucially involved in a variety of systems. During the process, the non-Condon vibronic coupling and the surrounding solvent interaction may synergetically play important roles. In this work, we study the correlated vibration-solvent influences on the non-Condon exciton spectroscopy. Statistical analysis is elaborated for the overall vibration-plus-solvent environmental effects. Analytic solutions are derived for the linear absorption of monomer systems. General simulations are accurately carried out via the dissipaton-equation-of-motion approach. The resulted spectra in either the linear absorption or strong field regime clearly demonstrate the coherence enhancement due to the synergetic vibration-solvent correlation.
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Accurate and efficient simulation on quantum dissipation with nonlinear environment couplings remains a challenging task nowadays. In this work, we propose to incorporate the stochastic fields, which resolve just the nonlinear environment coupling terms, into the dissipaton-equation-of-motion (DEOM) construction. The stochastic fields are introduced via the Hubbard-Stratonovich transformation. After the transformation, the resulted stochastic-fields-dressed (SFD) total Hamiltonian contains only linear environment coupling terms. On the basis of that, SFD-DEOM can then be constructed. The resultant SFD-DEOM, together with the ensemble average over the stochastic fields, constitutes an exact and nonperturbative approach to quantum dissipation under nonlinear environment couplings. It is also of relatively high efficiency and stability due to the fact that only nonlinear environment coupling terms are dealt with stochastic fields, while linear couplings are still treated as the usual DEOM. Numerical performance and demonstrations are presented with a two-state model system.
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Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD50) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application.
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Alcaloides , Extratos Vegetais , Animais , Camundongos , Etnofarmacologia , Extratos Vegetais/química , Medicina Tradicional Chinesa , Anti-Inflamatórios , Compostos FitoquímicosRESUMO
Two new aporphine-derived alkaloids, aporaloids C and D (1 and 2), along with eight known biogenetically related alkaloids (3-10) were isolated from the stems of Fissistigma maclurei Merr. Their structures were elucidated by detailed analysis of NMR, HRESIMS, MS, IR, UV and Optical rotations data. Compounds 1 and 2 represent a rare example of N-methylol aporphine-derived alkaloids from natural sources. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed potent inhibitory effect on the proliferation of synoviocytes with an IC50 value of 4.8 µM. Compounds 1, 2, 6-9 and 10 exhibited moderate inhibitory activity on synoviocytes, with IC50 values of 36.8, 37.1, 31.2 µM, 32.5, 36.3, 36.8 and 18.2 µM, respectively.