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1.
Cell Commun Signal ; 22(1): 78, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291510

RESUMO

BACKGROUND: Renal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis. METHODS: Male C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms. RESULTS: Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3ß/ß-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells. CONCLUSIONS: The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3ß/ß-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1.


Assuntos
Insuficiência Renal Crônica , beta Catenina , Masculino , Camundongos , Animais , beta Catenina/metabolismo , Ácido Succínico/metabolismo , Lipossomos/metabolismo , Ácido Clodrônico/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Insuficiência Renal Crônica/metabolismo , Fibrose , Macrófagos/metabolismo
2.
J Org Chem ; 89(4): 2431-2439, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38306607

RESUMO

The development of homogeneous metal catalysts for the efficient hydrogenation of carbon dioxide (CO2) into methanol (CH3OH) remains a significant challenge. In this study, a new cyclopentadienone diphosphine ligand (CPDDP ligand) was designed, which could coordinate with ruthenium to form a Ru-CPDDP complex to efficiently catalyze the CO2-to-methanol process using dihydrogen (H2) as the hydrogen resource based on density functional theory (DFT) mechanistic investigation. This process consists of three catalytic cycles, stage I (the hydrogenation of CO2 to HCOOH), stage II (the hydrogenation of HCOOH to HCHO), and stage III (the hydrogenation of HCHO to CH3OH). The calculated free energy barriers for the hydrogen transfer (HT) steps of stage I, stage II, and stage III are 7.5, 14.5, and 3.5 kcal/mol, respectively. The most favorable pathway of the dihydrogen activation (DA) steps of three stages to regenerate catalytic species is proposed to be the formate-assisted DA step with a free energy barrier of 10.4 kcal/mol. The calculated results indicate that the designed Ru-CPDDP and Ru-CPDDPEt complexes could catalyze hydrogenation of CO2 to CH3OH (HCM) under mild conditions and that the transition-metal owning designed CPDDP ligand framework be one kind of promising potential efficient catalysts for HCM.

3.
J Org Chem ; 89(19): 14408-14417, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39311017

RESUMO

Herein, the reaction mechanism for the GaCl3-catalyzed Knoevenagel condensation of 2-formylindacenodithieno[3,2-b]thiophene (ITIC-CHO) and active methylene compound 1,1-dicyanomethylene-3-indanone (IC) to synthesize ITIC in the presence of acetic anhydride was investigated using the density functional theory (DFT) method. The calculated results indicate that this reaction follows a bimolecular GaCl3 catalytic mechanism. The free energy span for the monomolecular GaCl3 catalytic mechanism is the highest (31.8 kcal/mol), followed by the trimolecular GaCl3 catalytic mechanism (26.4 kcal/mol) and the bimolecular GaCl3 catalytic mechanism (26.3 kcal/mol). The trimolecular GaCl3 path and bimolecular GaCl3 path are competitive, but the former path is limited by the concentration of GaCl3. The inclusion of GaCl3 could stabilize the transition states of C-H activation. Compared to the GaCl3-catalyzed Knoevenagel condensation, that catalyzed by pyridine is not advantageous, owning a high energy span of 31.7 kcal/mol. These agree well with experimental results. This work could provide a novel theoretical understanding of the Knoevenagel condensation, which could inspire the development of a synthesis strategy for electron acceptor materials.

4.
Phys Chem Chem Phys ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39412837

RESUMO

Methanol dehydrogenation (MD) is highly valuable in hydrogen energy production, and the introduction of nonmetals has received much attention to improve the activity and stability of the MD catalysts, but the understanding of the role of non-metallic elements in catalyzing the MD reaction is rather limited. Density functional theory (DFT) is employed to investigate the mechanism of methanol dehydrogenation on RuxPy surfaces. In this work, the P element is introduced into the Ru-based catalyst to obtain dispersed Ru sites and RuxPy (x/y = 2 : 1, 1 : 1, and 1 : 2) catalysts are designed. CH3OH adsorption, electronic structure of the catalyst, energy barriers for carbon accumulation reactions, and the mechanism of methanol decomposition are systematically calculated. The results of the effective reaction barrier (Eeffa) reveal that the order of the activity of the MD reaction is RuP(112) > Ru(0001) > Ru2P(210) > RuP2(110). The most preferable pathway on RuP(112) is pathway 1 (CH3OH* → CH3O* → CH2O* → CHO* → CO*). After the introduction of P, the weakened CO adsorption enhanced the resistance of catalysts to CO poisoning, and the activation energy of the carbon accumulation reaction increased, indicating that the anti-coking ability of the catalysts is improved. This theoretical study contributes to the design and modulation of highly active and stable metal catalysts for MD reactions.

5.
Cereb Cortex ; 33(10): 6366-6381, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36573440

RESUMO

Prior studies suggest that the cerebellum contributes to the prediction of action sequences as well as the detection of social violations. In this dynamic causal modeling study, we explored the effective connectivity of the cerebellum with the cerebrum in processing social action sequences. A first model aimed to explore functional cerebello-cerebral connectivity when learning trait/stereotype-implying action sequences. We found many significant bidirectional connectivities between mentalizing areas of the cerebellum and the cerebrum including the temporo-parietal junction (TPJ) and medial prefrontal cortex (mPFC). Within the cerebrum, we found significant connectivity between the right TPJ and the mPFC, and between the TPJ bilaterally. A second model aimed to investigate cerebello-cerebral connectivity when conflicting information arises. We found many significant closed loops between the cerebellum and cerebral mentalizing (e.g. dorsal mPFC) and executive control areas (e.g. medial and lateral prefrontal cortices). Additional closed loops were found within the cerebral mentalizing and executive networks. The current results confirm prior research on effective connectivity linking the cerebellum with mentalizing areas in the cerebrum for predicting social sequences, and extend it to cerebral executive areas for social violations. Overall, this study emphasizes the critical role of cerebello-cerebral connectivity in understanding social sequences.


Assuntos
Cérebro , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Mapeamento Encefálico
6.
Am J Physiol Cell Physiol ; 324(2): C467-C476, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36622070

RESUMO

Succinate has long been known to be only an intermediate product of the tricarboxylic acid cycle until identified as a natural ligand for SUCNR1 in 2004. SUCNR1 is widely expressed throughout the body, especially in the kidney. Abnormally elevated succinate is associated with many diseases, including obesity, type 2 diabetes, nonalcoholic fatty liver disease, and ischemia injury, but it is not known whether succinate can cause kidney damage. This study showed that succinate induced apparent renal injury after treatment for 12 wk, characterized by a reduction in 24 h urine and the significant detachment of the brush border of proximal tubular epithelial cells, tubular dilation, cast formation, and vacuolar degeneration of tubular cells in succinate-treated mice. Besides, succinate caused tubular epithelial cell apoptosis in kidneys and HK-2 cells. Mechanistically, succinate triggered cell apoptosis via SUCNR1 activation. In addition, succinate upregulated ERK by binding to SUCNR1, and inhibition of ERK using PD98059 abolished the proapoptotic effects of succinate in HK-2 cells. In summary, our study provides the first evidence that succinate acts as a risk factor and contributes to renal injury, and further research is required to discern the pathological effects of succinate on renal functions.


Assuntos
Diabetes Mellitus Tipo 2 , Ácido Succínico , Animais , Camundongos , Apoptose , Diabetes Mellitus Tipo 2/patologia , Células Epiteliais/metabolismo , Rim/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Succinatos , Ácido Succínico/metabolismo
7.
Cogn Affect Behav Neurosci ; 23(2): 323-339, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36788200

RESUMO

Humans read the minds of others to predict their actions and efficiently navigate social environments, a capacity called mentalizing. Accumulating evidence suggests that the cerebellum, especially Crus 1 and 2, and lobule IX are involved in identifying the sequence of others' actions. In the current study, we investigated the neural correlates that underly predicting others' intentions and how this plays out in the sequence of their actions. We developed a novel intention prediction task, which required participants to put protagonists' behaviors in the correct chronological order based on the protagonists' honest or deceitful intentions (i.e., inducing true or false beliefs in others). We found robust activation of cerebellar lobule IX and key mentalizing areas in the neocortex when participants ordered protagonists' intentional behaviors compared with not ordering behaviors or to ordering object scenarios. Unlike a previous task that involved prediction based on personality traits that recruited cerebellar Crus 1 and 2, and lobule IX (Haihambo et al., 2021), the present task recruited only the cerebellar lobule IX. These results suggest that cerebellar lobule IX may be generally involved in social action sequence prediction, and that different areas of the cerebellum are specialized for distinct mentalizing functions.


Assuntos
Mentalização , Neocórtex , Humanos , Intenção , Cerebelo/fisiologia , Mentalização/fisiologia , Imageamento por Ressonância Magnética
8.
Chemistry ; 29(35): e202300565, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37026372

RESUMO

In this paper the density functional theory (DFT) method was employed to investigate the cross-coupling of methanol with benzyl alcohol to afford methyl benzoate, catalysed by Mn-PNN pincer complex. The whole reaction process mainly includes three stages: the dehydrogenation of benzyl alcohol to benzaldehyde, the coupling of benzaldehyde with methanol to hemiacetal and the dehydrogenation of hemiacetal to methyl benzoate. The calculated results indicated that two dehydrogenation processes are influenced by two competitive mechanisms of inner and outer spheres. Dehydrogenation of benzyl alcohol to benzaldehyde is the rate-determining step of the whole reaction, with the energy barrier of 22.1 kcal/mol. In addition, the regeneration of catalyst is also extremely important. Compared with direct dehydrogenation, the dehydrogenation mode assisted by formic acid is more advantageous. This work might provide theoretical insights and shed light on the design of cheap transition-metal catalysts for the dehydrogenation reaction.


Assuntos
Manganês , Metanol , Álcool Benzílico , Benzaldeídos
9.
Cerebellum ; 22(4): 559-577, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35648333

RESUMO

Recent research has suggested that the posterior cerebellum encodes predictions and sequences of social actions, and also supports detecting inconsistent trait-implying actions of individuals as discussed by Pu et al. (2020, 2021). However, little is known about the role of the posterior cerebellum in detecting sequencing and inconsistencies by a group of individuals during social interaction. Therefore, the present study investigates these cerebellar functions during inconsistent trait-implying actions in a cooperative context. We presented scenarios in which two fictitious protagonists work together to accomplish a common (positive or negative) goal, followed by six sentences describing actions that implied a personality trait of the protagonists. Participants had to memorize the sequence of these actions. Crucially, the implied trait of the actions of the first protagonist contributed to achieving the goal, whereas the implied trait of the second protagonist was either consistent or inconsistent with that goal. As comparison, we added control conditions where participants had to memorize sequences of nonsocial events (implying the same characteristic of two objects), or simply read the social actions without memorizing their order. We found that the posterior cerebellum was activated while memorizing the sequence of social actions compared to simply reading these actions. More importantly, the cerebellar Crus was more strongly activated when detecting inconsistent (as opposed to consistent) actions, especially when inconsistent negative actions impeded a positive goal, relative to consistent negative actions that supported a negative goal. In conclusion, these findings confirm the crucial role of the posterior cerebellum in memorizing social action sequences and extend the cerebellar function in identifying inconsistencies in an individual's actions in a social collaborative context.


Assuntos
Cerebelo , Idioma , Humanos
10.
Cerebellum ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608227

RESUMO

Although the human cerebellum has a surface that is about 80% of that of the cerebral cortex and has about four times as many neurons, its functional organization is still very much uncharted. Despite recent attempts to provide resting-state and task-based parcellations of the cerebellum, these two approaches lead to large discrepancies. This article describes a comprehensive task-based functional parcellation of the human cerebellum based on a large-scale functional database, NeuroSynth, involving an unprecedented diversity of tasks, which were reliably associated with ontological key terms referring to psychological functions. Involving over 44,500 participants from this database, we present a parcellation that exhibits replicability with earlier resting-state parcellations across cerebellar and neocortical structures. The functional parcellation of the cerebellum confirms the major networks revealed in prior work, including sensorimotor, directed (dorsal) attention, divided (ventral) attention, executive control, mentalizing (default mode) networks, tiny patches of a limbic network, and also a unilateral language network (but not the visual network), and the association of these networks with underlying ontological key terms confirms their major functionality. The networks are revealed at locations that are roughly similar to prior resting-state cerebellar parcellations, although they are less symmetric and more fragmented across the two hemispheres. This functional parcellation of the human cerebellum and associated key terms can provide a useful guide in designing studies to test specific functional hypotheses and provide a reference for interpreting the results.

11.
Inorg Chem ; 62(27): 10854-10864, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37365139

RESUMO

The synthesis of 1,1-diborylalkanes from readily available alkenes is an appealing method. The density functional theory (DFT) method was employed to investigate the reaction mechanism of 1,1-diborylalkanes, which was synthesized from alkenes and a borane, and the reaction was catalyzed by a zirconium complex Cp2ZrCl2. The entire reaction is divided into two cycles: dehydrogenative boration to form vinyl boronate esters (VBEs) and hydroboration of VBEs. This article focuses on the hydroboration cycle and elaborates on the role of the reducing reagents in the equilibrium of self-contradictory reactivity (dehydrogenative boration and hydroboration). The H2 and HBpin pathways were investigated as the reducing reagents in the hydroboration process. The calculated results showed that it is more advantageous to use H2 as a reducing agent (path A). Furthermore, the σ-bond metathesis is the rate-determining step (RDS) with an energetic span of 21.4 kcal/mol. This is consistent with the self-contradictory reactivity balance proposed in the experiment. The reaction modes of the hydroboration process were also discussed. These analyses revealed the origin of selectivity in this boration reaction, in which the σ-bond metathesis of HBpin needs to overcome the strong interaction between HBpin and the Zr metal. Meanwhile, the origin of the selectivity of different positions of H2 is the interaction between the σ(H1-H2) → σ*(Zr1-C1) overlap and these findings have implications for catalyst design and application.

12.
Phys Chem Chem Phys ; 25(28): 18983-18989, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37409650

RESUMO

In this work, high-performance two-dimensional (2D) graphene-based single-atom electrocatalysts (ZZ/ZA-MNxCy) for the oxygen reduction reaction (ORR) were screened out using machine learning (ML). A model was built for the fast prediction of electrocatalysts and two descriptors valence electron correction (VEc) and degree of construction differences (DC) were proposed to improve the accuracy of the model prediction. Two evaluation criteria, high-performance catalyst retention rate rR and high-performance catalyst occupancy rate rO, were proposed to evaluate the accuracy of ML models in high-performance catalyst screening. The addition of VEc and DC in the model could change the mean absolute error (MAEtest) of the test set, the coefficient of determination (R2test) of the test set, rO, and rR from 0.334 V, 0.683, 0.222, and 0.360 to 0.271 V, 0.774, 0.421, and 0.671, respectively. The partially screened potential high-performance ORR electrocatalysts such as ZZ-CoN4 and ZZ-CoN3C1 were also further investigated using a Density Functional Theory (DFT) method, which confirmed the accuracy of the ML model (MAE = 0.157 V, R2 = 0.821).

13.
Phys Chem Chem Phys ; 25(40): 27829-27835, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37814900

RESUMO

Herein, a new series of bowl-shaped quadridentate ligands with a Si-N-Si-C-Si-C six-membered ring core and their manganese catalysts were designed using the density functional theory (DFT) method for the hydrogenation of unsaturated CX (XN, O) bonds. The frameworks of these ligands named by LYG (LYG = P(R1)2CH2Si(CH2)(CH3)NSi(CH3)(CH2Si(CH3)CH2P(R3)2)CH2P(R2)2) have a Si-N-Si-C-Si-C six-membered ring core at the bottom of the bowl structure and each Si atom links with one phosphorus arm (-CH2PR2). The Mn catalyst Mn(CO)-LYG was constructed to catalyze the hydrogenation of CO/CN bonds. The calculated results indicate that due to the bowl-shaped structure of LYG quadridentate ligands, these Mn catalysts could be advantageous not only in the tuneup of catalytic activity and stereoselectivity by modifying three phosphorus arms but also in the homogeneous catalyst immobilization by linking with the Si-N-Si-C-Si-C six-membered ring core using different supports. This work might provide theoretical insights to design new framework transition-metal catalysts for the hydrogenation of CX bonds.

14.
Phys Chem Chem Phys ; 25(20): 14232-14244, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37170792

RESUMO

Pt/CeO2 catalysts exhibit excellent catalytic performance for the methanol dehydrogenation (MD) reaction. In this work, MD reactions on three systems of Pt1/CeO2(110)), Pt7/CeO2(110), and Pt1/Ce1-xO2(110) are investigated via density functional theory (DFT) calculations. The CH3OH adsorption, electronic structure of the catalyst, and mechanism of methanol decomposition (MD) are systematically calculated. The results reveal that the d-band center of the Pt atom moves away from the Fermi level in the order of Pt1/CeO2(110) < Pt7/CeO2(110) < Pt1/Ce1-xO2(110), and the order of the activity of the MD reaction is Pt1/CeO2(110) < Pt7/CeO2(110) < Pt1/Ce1-xO2(110). The results of the microkinetic dynamics simulation verify that only Pt1/Ce1-xO2(110) is conducive to the decomposition of methanol at low temperatures (373 K), and the products CO and H2 are easily dissociated from the catalyst surface. This work uncovers that both the small size and the Ce vacancy substituted sites of Pt favor the performance of the Pt/CeO2 catalyst, and provides theoretical guidance for the construction and design of efficient metal-support catalysts for the MD reaction.

15.
Echocardiography ; 40(1): 37-44, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36522828

RESUMO

BACKGROUND: Most guidelines directing clinicians to manage valve disease are directed at single valve lesions. Limited data exists to direct our understanding of how concomitant valve disease impacts the left ventricle (LV). METHODS: We identified 2817 patients with aortic stenosis (AS) from the echocardiography laboratory database between September 2012 and June 2018 who had a LV ejection fraction (EF) ≥50%. LV mass, LV mass index, LV systolic pressure (systolic blood pressure + peak aortic gradient). Covariates were collected from the electronic medical record. Multi-variate analysis of covariance was used to generate adjusted comparisons. RESULTS: Our population was 66% female, 17% African-American with a mean age of 65 years. Of note, 7.3% were noted to have significant (moderate/severe) aortic regurgitation (AR), and 11% had significant (moderate/severe) mitral regurgitation (MR). Adjusting for covariates at different levels, significant MR had a much stronger association with heart failure compared to those with significant AR (p < .001 vs. p = .313, respectively) at all levels of adjustment. Both significant mitral and AR exhibited an association with increasing left ventricular mass, even with adjustment for baseline demographics and clinical features (p < .001 vs. p = .007, respectively). CONCLUSION: In patients with AS, 16% also experience at least moderate MR or AR. Further, significant MR has a stronger association with heart failure than significant AR, even though both increase left ventricular mass. Those with moderate AS and significant MR or AR experience similar or higher levels of heart failure compared to severe AS without regurgitation. Mixed valve disease merits further studies to direct longitudinal management.


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Insuficiência Cardíaca , Insuficiência da Valva Mitral , Humanos , Feminino , Idoso , Masculino , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/epidemiologia , Prevalência , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/epidemiologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Insuficiência Cardíaca/complicações
16.
Am J Physiol Renal Physiol ; 322(4): F437-F448, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35073210

RESUMO

Calcineurin inhibitors such as cyclosporin A (CsA) have been widely used to improve graft survival following solid-organ transplantation. However, the clinical use of CsA is often limited by its nephrotoxicity. The present study tested the hypothesis that activation of the (pro)renin receptor (PRR) contributes to CsA-induced nephropathy by activating the renin-angiotensin system (RAS). Renal injury in male Sprague-Dawley rats was induced by a low-salt diet combined with CsA as evidenced by elevated plasma creatinine and blood urea nitrogen levels, decreased creatinine clearance and induced renal inflammation, apoptosis and interstitial fibrosis, and elevated urinary N-acetyl-ß-d-glucosaminidase activity and urinary kidney injury molecule-1 content. Each index of renal injury was attenuated following 2 wk of treatment with the PRR decoy inhibitor PRO20. Although CsA-treated rats with kidney injury displayed increased renal soluble (s)PRR abundance, plasma sPRR, renin activity, angiotensin II, and heightened urinary total prorenin/renin content, RAS activation was attenuated by PRO20. Exposure of cultured human renal proximal tubular HK-2 cells to CsA induced expression of fibronectin and sPRR production, but the fibrotic response was attenuated by PRO20 and siRNA-mediated PRR knockdown. These findings support the hypothesis that activation of PRR contributes to CsA-induced nephropathy by activating the RAS in rats. Of importance, we provide strong proof of concept that targeting PRR offers a novel therapeutic strategy to limit nephrotoxic effects of immunosuppressant drugs.NEW & NOTEWORTHY The present study reports, for the first time, that activation of the (pro)renin receptor drives the renin-angiotensin system to induce renal injury during cyclosporin A administration. More importantly, our study has identified that antagonism with PRO20 offers a novel intervention in the management of side effects of cyclosporin A.


Assuntos
Nefropatias , Renina , Animais , Creatinina/metabolismo , Ciclosporina/toxicidade , Feminino , Humanos , Rim/metabolismo , Nefropatias/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/metabolismo , Renina/metabolismo , Sistema Renina-Angiotensina
17.
Cogn Affect Behav Neurosci ; 22(3): 467-491, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34811709

RESUMO

This study tests the hypothesis that the posterior cerebellum is involved in social cognition by identifying and automatizing sequences of social actions. We applied a belief serial reaction time task (Belief SRT task), which requires mentalizing about two protagonists' beliefs about how many flowers they receive. The protagonists' beliefs could either be true or false depending on their orientation (true belief: oriented towards and directly observing the flowers; or false belief: oriented away and knowing only prior information about flowers). A Control SRT task was created by replacing protagonists and their beliefs with shapes and colors. Participants were explicitly told that there was a standard sequence related to the two protagonists' belief orientations (Belief SRT task) or the shapes' colors (Control SRT task). Both tasks included a Training phase where the standard sequence was repeated and a Test phase where this standard sequence was interrupted by random sequences. As hypothesized, compared with the Control SRT task, the Belief SRT task recruited the posterior cerebellar Crus II and the temporoparietal junction (TPJ) more. Faster response times were correlated with less Crus II activation and with more TPJ activation, suggesting that the Crus II supported automatizing the belief sequence while the TPJ supported inferring the protagonists' beliefs. Also as hypothesized, compared with an implicit version of the Belief SRT task (i.e., participants did not know about the existence of sequences; Ma, Pu, et al., 2021b), the cerebellar Crus I &II was engaged less during initial training and automatic application of the sequence, and the cortical TPJ was activated more in processing random sequences.


Assuntos
Aprendizagem , Mentalização , Cerebelo , Humanos , Tempo de Reação , Cognição Social
18.
Cogn Affect Behav Neurosci ; 22(5): 1090-1107, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35411417

RESUMO

Recent research has indicated that the posterior cerebellum plays a crucial role in social cognition by encoding sequences of social actions. This study investigates its role in learning sequences of stereotype-implying actions by group members. We presented a set of five sentences that each described a group member who performed either stereotype-consistent or inconsistent actions. Participants were instructed to memorize the temporal order of the sentences and infer a common stereotype of the group. As a comparison, we included control conditions where participants had to memorize sequences of nonsocial consistent events or simply read stereotype-consistent sentences without memorizing their order. The results showed that the posterior cerebellum was strongly activated when participants were memorizing the order of the social actions, as opposed to simply reading these social actions. More importantly, when the social actions were inconsistent as opposed to consistent with the stereotype of the group, the posterior cerebellum was activated more strongly. This activation occurred together with cortical recruitment of the mentalizing network involving the dorsomedial prefrontal cortex (dmPFC) during social actions, and additionally the conflict monitoring network involving the lateral prefrontal cortex (PFC) and posterior medial frontal cortex (pmFC) during stereotype-inconsistent actions. These findings suggest that the cerebellum supports not only learning of low-level action sequences, but also of their high-level social implications.


Assuntos
Imageamento por Ressonância Magnética , Mentalização , Cerebelo/fisiologia , Humanos , Mentalização/fisiologia , Córtex Pré-Frontal/fisiologia , Leitura
19.
Cerebellum ; 21(5): 733-741, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34694590

RESUMO

Recent advances in social neuroscience have highlighted the critical role of the cerebellum and especially the posterior cerebellar Crus in social mentalizing (i.e., theory of mind). Research in the past 5 years has provided growing evidence supporting the view that the posterior cerebellum builds internal action models of our social interactions to predict how other people's actions will be executed, and what our most likely responses to these actions will be. This paper presents an overview of a series of fMRI experiments on novel tasks involving a combination of (a) the learning or generation of chronological sequences of social actions either in an explicit or implicit manner, which (b) require social mentalizing on another person's mental state such as goals, beliefs, and implied traits. Together, the results strongly confirm the central role of the posterior cerebellar Crus in identifying and automatizing action sequencing during social mentalizing, and in predicting future action sequences based on social mentalizing inferences about others. This research program has important implications: It provides for the first time (a) fruitful starting points for diagnosing and investigating social sequencing dysfunctions in a variety of mental disorders which have also been related to cerebellar dysfunctions, (b) provides the necessary tools for testing whether non-invasive neurostimulation targeting the posterior cerebellum has a causal effect on social functioning, and (c) whether these stimulation techniques and training programs guided by novel cerebellar social sequencing insights, can be exploited to increase posterior cerebellar plasticity in order to alleviate social impairments in mental disorders.


Assuntos
Cerebelo , Mentalização , Cerebelo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Mentalização/fisiologia
20.
J Org Chem ; 87(24): 16632-16643, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36446027

RESUMO

For the synthesis of vinyl boronate esters, the direct catalytic H2-acceptorless dehydrogenative boration of alkenes is one of the promising strategies. In this paper, the density functional theory method was employed to investigate the reaction mechanism of dehydrogenative boration and transfer boration of alkenes catalyzed by a zirconium complex (Cp2ZrH2). There are two possible pathways for this reaction: the alkene insertion followed by the dehydrogenative boration (path A) and the alkene insertion after the dehydrogenative boration (path B). The calculated results showed that path A is more favorable than path B, and that the rate-determining step is the C-B coupling step with an energy barrier of 18.7 kcal/mol. The reaction modes of the C-B coupling assisted dehydrogenative boration and the alkene insertion were also discussed. These analyses reveal a novel hydrogen release behavior in dehydrogenative boration and the alkene insertion modes and sequences were proposed to be of importance in the chemoselectivity of this reaction. In addition, the X ligand effect (X = H, Cl) on the catalytic activity of the zirconium complex was explored, indicating that the H ligand could enhance the catalytic activity of the complex for styrene dehydrogenative boration.


Assuntos
Alcenos , Zircônio , Ligantes , Teoria da Densidade Funcional , Catálise
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