Chemogenetic activation of PVN CRH neurons disrupts the estrous cycle and LH dynamics in female mice.

Introduction: The impact of stress on reproductive function is significant. Hypothalamic paraventricular nucleus (PVN) corticotrophin-releasing hormone (CRH) plays a major role in regulating the stress response. Understanding how the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis interact is crucial for comprehending how stress can lead to reproductive dysfunction.

Maternal High-Fat Diet Multigenerationally Impairs Hippocampal Synaptic Plasticity and Memory in Male Rat Offspring.

As advances are made in the field of developmental origins of health and disease, there is an emphasis on long-term influence of maternal environmental factors on offspring health. Maternal high-fat diet (HFD) consumption has been suggested to exert detrimental effects on cognitive function in offspring, but whether HFD-dependent brain remodeling can be transmitted to the next generations is still unclear. This study tested the hypothesis that HFD consumption during rat pregnancy and lactation multigenerationally influences male offspring hippocampal synaptic plasticity and cognitive function.

Impact of hyperglycaemia on complications in patients who had a stroke after thrombolysis.

Background: We sought to investigate whether admission hyperglycaemia is associated with complications in patients who had an acute ischaemic stroke (AIS) treated with intravenous recombinant tissue plasminogen activator and, if so, whether complications during hospitalisation modify the effect of hyperglycaemia on 3-month poor outcome after thrombolysis.

Methods: Patients who were diagnosed with AIS after thrombolysis between July 2016 and January 2019 were enrolled in this study. Five prespecified complications, including infections, brain oedema, deep vein thrombosis (DVT), haemorrhagic transformation (HT) and gastrointestinal bleeding, were recorded during hospitalisation.

Neutrophil-to-lymphocyte ratio, hyperglycemia, and outcomes in ischemic stroke patients treated with intravenous thrombolysis.

Introduction: Increased neutrophil-to-lymphocyte ratio (NLR) and hyperglycemia on admission are associated with poor outcomes in acute ischemic stroke (AIS) patients. We sought to evaluate the combined effect of increased NLR and hyperglycemia on the prognosis of ischemia stroke treated with intravenous thrombolysis (IVT).

Methods: Patients with acute ischemic stroke receiving IVT treatment were prospectively enrolled.

Dynamic increase in neutrophil levels predicts parenchymal hemorrhage and function outcome of ischemic stroke with r-tPA thrombolysis.

Background: The higher level of neutrophil on admission has been reported to predict worse 3-month outcomes in ischemic stroke patients. Our study was to explore the dynamic changes of neutrophil and lymphocyte after r-tPA thrombolysis of ischemic stroke and the relationship with parenchymal hemorrhage (PH) and 3-month function outcome.

Methods: A total of 208 acute ischemic stroke (AIS) patients with intravenous thrombolysis were included and then received 3-month follow-up in the present study.

Photophysical Switching between Aggregation-Induced Phosphorescence and Dual-State Emission by Isomeric Substitution.

It is attractive but highly challenging to achieve controllable regulation of photophysical properties of pure organic luminogens, due to distinct work mechanisms and molecular structures. Here, a strategy to regulate in a controllable way the emission behavior of luminogens is reported, according to which long-lived aggregation-induced emission (AIE) can be switched to short-lived dual-state emission (DSE) by an isomer-based substitution reaction. Three luminogens with sharply different photophysical behaviors, including aggregation-induced phosphorescence and dual-state fluorescence emission, were obtained through a substitution reaction with three isomers.

Rational Design of Dual-State Emission Luminogens with Solvatochromism by Combining a Partially Shared Donor-Acceptor Pattern and Twisted Structures.

We report a general design strategy for a new class of luminogens with dual-state emission (DSEgens) that are brightly emissive in both the solution and solid state, with solvatochromism properties, by constructing a partially shared donor-acceptor pattern based on a twisted molecule. The DSEgens with bright fluorescence emission in both the solid and solution state demonstrate a unique solvatochromism behaviour depending on solvent polarity and thus may have applications in anti-counterfeiting.

Engineering TiO supported Pt sub-nanoclusters via introducing variable valence Co ion in high-temperature flame for CO oxidation.

As a typical catalytic reaction model, CO catalytic oxidation has many practical applications in gas purification. TiO2 supported Pt sub-nanoclusters have been prepared by introducing variable valence Co ions into a one step flame spray pyrolysis process. Co2+ was oxidized to Co3+ in the high-temperature flame, and the released electrons were transferred to the surface of Pt and suppressed the aggregation of Pt nanoclusters supported on TiO2.

Nuclear Localizing Peptide-Conjugated, Redox-Sensitive Polymersomes for Delivering Curcumin and Doxorubicin to Pancreatic Cancer Microtumors.

Improving the therapeutic index of anticancer agents is an enormous challenge. Targeting decreases the side effects of the therapeutic agents by delivering the drugs to the intended destination. Nanocarriers containing the nuclear localizing peptide sequences (NLS) translocate to the cell nuclei.

Real-time monitoring of conformational transitions of single-molecule histone deacetylase 8 with nanocircuits.

Using single-molecule approaches, we directly observed the dynamic interaction between HDAC8 and various ligands as well as conformational interconversions during the catalytic reaction. Statistical analysis identified key kinetic parameters, demonstrating that the enzymatic activity is highly sensitive to both minor variations in the ligand structures and small synthetic molecules.

Role of the Substrate Specificity-Defining Residues of Human SIRT5 in Modulating the Structural Stability and Inhibitory Features of the Enzyme.

Sirtuins are emerging as the key regulators of metabolism and aging, and their potential activators and inhibitors are being explored as therapeutics for improving health and treating associated diseases. Despite the global structural similarity among all seven isoforms of sirtuins (of which most of them catalyze the deacetylation reaction), SIRT5 is the only isoform that catalyzes the cleavage of negatively charged acylated substrates, and the latter feature appears to be encoded by the presence of Tyr102 and Arg105 residues at the active site pocket of the enzyme. To determine the contributions of the above residues in SIRT5 (vis a vis the corresponding residues of SIRT1) on substrate selectivity, inhibition by EX527 and nicotinamide, secondary structural features and thermal stability of the enzymes, we created single and double mutations (viz.

Mechanism of N-Acylthiourea-mediated activation of human histone deacetylase 8 (HDAC8) at molecular and cellular levels.

We reported previously that an N-acylthiourea derivative (TM-2-51) serves as a potent and isozyme-selective activator for human histone deacetylase 8 (HDAC8). To probe the molecular mechanism of the enzyme activation, we performed a detailed account of the steady-state kinetics, thermodynamics, molecular modeling, and cell biology studies. The steady-state kinetic data revealed that TM-2-51 binds to HDAC8 at two sites in a positive cooperative manner.