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AIMS: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodelling during the onset of PH. This study aimed to illustrate the role of Sirtuin 7 (SIRT7) in endothelial dysfunction during PH and explore the potential therapeutic strategy for PH. METHODS AND RESULTS: SIRT7 levels were measured in human and murine experimental PH samples. Bioinformatic analysis, immunoprecipitation, and deacetylation assay were used to identify the association between SIRT7 and Krüpple-like factor 4 (KLF4), a key transcription factor essential for endothelial cell (EC) homeostasis. Sugen5416 + hypoxia (SuHx)-induced PH mouse models and cell cultures were used for the study of the therapeutic effect of SIRT7 for PH. SIRT7 level was significantly reduced in lung tissues and PAECs from PH patients and the SuHx-induced PH mouse model as compared with healthy controls. Pulmonary endothelium-specific depletion of Sirt7 increased right ventricular systolic pressure and exacerbated right ventricular hypertrophy in the SuHx-induced PH model. At the molecular level, we identified KLF4 as a downstream target of SIRT7, which deacetylated KLF4 at K228 and inhibited the ubiquitination-proteasome degradation. Thus, the SIRT7/KLF4 axis maintained PAEC homeostasis by regulating proliferation, migration, and tube formation. PAEC dysfunction was reversed by adeno-associated virus type 1 vector-mediated endothelial overexpression of Sirt7 or supplementation with nicotinamide adenine dinucleotide (NAD)+ intermediate nicotinamide riboside which activated Sirt7; both approaches successfully reversed PH phenotypes. CONCLUSION: The SIRT7/KLF4 axis ensures PAEC homeostasis, and pulmonary endothelium-specific SIRT7 targeting might constitute a PH therapeutic strategy.

Background Tiaozhong Yiqi Soup was first used to treat gastrointestinal diseases caused by spleen deficiency and dampness stagnation. Years of experience in treating slow transit constipation (STC) in the elderly through the addition or subtraction of this formula has been found can treat elderly slow transit constipation. Objective To evaluate the clinical effect of Tiaozhong Yiqi Soup on elderly Qi deficiency type STC and intestinal motility. Methods A total of 100 cases of Qi deficiency type STC patients were selected from the Proctology Department and the Prevention and Treatment Center of Traditional Chinese Medicine Hospital of Yinchuan City from May 2022 to April 2023, and randomly divided into the observation group of 50 cases and control group of 50 cases using a 1∶1 randomized numerical table method. The observation group was orally treated with Tiaozhong Yiqi Soup decoction, the control group of 50 patients was orally treated with Prukapril Succinate Tablets, each group was treated for 4 weeks. The score of weekly Complete Spontaneous Bowel Movement (CSBM), traditional Chinese medicine (TCM) syndrome score, clinical symptom score, exclusion rates of markers at 48 and 72 hours before and after 4 weeks of treatment were recorded and compared, gastrointestinal hormone levels were detected and the occurrence of adverse reactions was observed. Follow up for 3 months to observe the recurrence of constipation in both groups of patients. Results After 4 weeks of treatment, the weekly CSBM score, TCM syndrome score, and clinical symptom score of the observation group were lower than those of the control group (P

The hippocampus is implicated in memory formation, and neurons in the hippocampus take part in replay sequences that have been proposed to reflect memory of explored space. By recording from large ensembles of hippocampal neurons as rats explored various tracks, we show that sustained replay appears after a single experience. Further, we found that with repeated experience in a novel environment, replay slows down, taking more time to traverse the same trajectory. This effect was dependent on experience, not passage of time, and was environment specific. By investigating the slow-gamma (25-50 Hz) hover-and-jump dynamics within replays, we show that replay slows by adding more hover locations, increasing the resolution of the behavioral trajectory. We provide evidence that inhibition and cortical engagement both increase as replay slows. Thus, replays can reflect single experiences and evolve with re-exposure, in a manner consistent with the encoding of greater detail into replay memories with experience.

Diverse functions such as decision-making and memory consolidation may depend upon communication between neurons in hippocampus (HP) and prefrontal cortex (PFC). HP replay is a candidate mechanism to facilitate this communication, however details remain largely unknown due to the technical challenges of recording sufficient numbers of HP neurons for replay while also recording PFC neurons. Here we implanted male rats with 40-tetrode drives, split between HP and PFC, during learning of a Y-maze spatial memory task. Surprisingly, we found that in contrast to their non-selectivity for maze arm during movement, a portion of PFC neurons were highly selective for HP replay of different arms. Moreover, PFC neurons' selectivity to HP non-local arm representation during running tended to match their replay arm selectivity and was predictive of future choice. Thus, PFC activity that is tuned to HP activity is best explained by non-local HP position representations rather than HP representation of actual position, providing a new potential mechanism of HP-PFC coordination during HP replay.SIGNIFICANCE STATEMENTThe hippocampus is implicated in spatial learning while the prefrontal cortex is implicated in decision-making. The question of how the two areas interact has been of great interest. A specific activity type in hippocampus called replay is particularly interesting because it resembles internal exploration of non-local experiences, but is technically challenging to study, requiring recordings from large numbers of hippocampus neurons simultaneously. Here we combined replay recordings from hippocampus with prefrontal recordings, to reveal a surprising degree of selectivity for replay, and a pattern of coordination that supports some conceptions of hippocampocortical interaction and challenges others.

Ligand-decorated metal surfaces play a pivotal role in various areas of chemistry, particularly in selective catalysis. Molecular dynamics simulations at the molecular mechanics level of theory are best adapted to gain complementary insights to experiments regarding the structure and dynamics of such organic films. However, standard force fields tend to capture only weak physisorption interactions. This is inadequate for ligands that are strongly adsorbed such as carboxylates on metal surfaces. To address this limitation, we employ the Gaussian Lennard-Jones (GLJ) potential, which incorporates an attractive Gaussian potential between the surface and ligand atoms. Here, we develop this approach for the interaction between cobalt surfaces and carboxylate ligands. The accuracy of the GLJ approach is validated through the analysis of the interaction of oxygen with two distinct cobalt surfaces. The accuracy of this method reaches a root mean square deviation (RMSD) of about 3 kcal/mol across all probed configurations, which corresponds to a percentage error of roughly 4%. Application of the GLJ force field to the dynamics of the organic layer on these surfaces reveals how the ligand concentration influences the film order, and highlights differing mobility in the x and y directions, attributable to surface corrugation on Co(11 2 ̄ 0). GLJ is versatile, suitable for a broad range of metal/ligand systems, and can, subsequently, be utilized to study the organic film on the adsorption/desorption of reactants and products during a catalytic process. [ABSTRACT FROM AUTHOR]