Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase.

In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50=19.4±2.5µM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury.

[Expression of CD163 in children with Epstein-Barr virus infection].

OBJECTIVE: To study the clinical significance of CD163 in the diagnosis and the evaluation of severity and prognosis of childhood hemophagocytic lymphohistiocytosis (HLH). METHODS: Ninety-four children were classified into Epstein-Barr virus (EBV)-positive (n=55) and EBV-negative groups (n=39; control group). The EBV-positive group was subgrouped into infectious mononucleosis (IM; n=47) and HLH (n=8). Serum levels of soluble CD163 were measured using ELISA. Expression of CD163 on mononuclear cells was detected by flow cytometry. RESULTS: The serum levels of soluble CD163 were>10 000 ng/mL in all eight HLH patients (>30 000 ng/mL in 3 cases). The mean serum levels of soluble CD163 in the HLH group were significantly higher than in the control and IM groups (P<0.05). The serum levels of soluble CD163 in EBV-positive children were positively correlated with EBV-DNA copies and serum levels of ferritin and LDH, but were negatively correlated with white blood cell count, neutrophil count, hemoglobin and platelet count. The follow-up after treatment for three HLH patients showed that serum levels of soluble CD163 were significantly reduced, but the soluble CD163 levels rebounded in one patient who was complicated by fungal pneumonia infection. CONCLUSIONS: The levels of serum soluble CD163 may be related to the severity in children with HLH. The EBV-positive children with soluble CD163 levels >10 000 ng/mL should be considered the possibility of HLH.

Ligand Engineering of Inorganic Lead Halide Perovskite Quantum Dots toward High and Stable Photoluminescence.

The ligand engineering of inorganic lead halide perovskite quantum dots (PQDs) is an indispensable strategy to boost their photoluminescence stability, which is pivotal for optoelectronics applications. CsPbX3 (X = Cl, Br, I) PQDs exhibit exceptional optical properties, including high color purity and tunable bandgaps. Despite their promising characteristics, environmental sensitivity poses a challenge to their stability. This article reviews the solution-based synthesis methods with ligand engineering. It introduces the impact of factors like humidity, temperature, and light exposure on PQD's instability, as well as in situ and post-synthesis ligand engineering strategies. The use of various ligands, including X- and L-type ligands, is reviewed for their effectiveness in enhancing stability and luminescence performance. Finally, the significant potential of ligand engineering for the broader application of PQDs in optoelectronic devices is also discussed.

Highly Efficient Nonfullerene Acceptor with Sulfonyl-Based Ending Groups.

Ending groups play a vital role in regulating the band gap and energy level of low-band gap nonfullerene acceptors (NFAs). In this work, a novel NFA, BTP-IS, is synthesized by adopting sulfonyl-based ending groups. Compared to the ketone counterpart BTP-IC, BTP-IS exhibits a red-shift in absorption spectra with lower lowest unoccupied molecular orbital level. More importantly, the BTP-IS-based organic solar cells with PM6 as donor present a high power conversion efficiency (PCE) of 12.79%, which is much higher than that of the BTP-IC device (PCE of 7.54%). The efficient charge transfer between the polymer donor and NFA acceptor, the balance charge transport, and the fine photoactive morphology bear on the effective exciton dissociation and charge collection in the BTP-IS device, which induces high short circuit current (JSC) and fill factor (FF) values. This research has shed light on designing novel NFAs from the perspective of ending groups.

Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice.

Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice were investigated. Twenty-five neonatal CD1 mice aged 1 week were selected and randomly divided into sham-operation group (n=8) and newborn hypoxia ischemia encephalopathy (NHIE) model group (n=17). The messenger ribonucleic acid (mRNA) expression levels of caspase-3 and Fas ligand (FasL) in brain tissues of mice in both groups were detected via reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of caspase-3 and FasL in mice in both groups were detected via western blotting. Moreover, apoptosis of brain tissues was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and caspase-3 protein expression level in brain tissues was detected using immunohistochemical methods. Results of RT-PCR and western blotting revealed that compared with those in sham-operation group, caspase-3 and FasL expression levels in model group were significantly increased. Results of TUNEL showed that the number of apoptotic neurons in model group was significantly increased. Besides, results of immunohistochemical detection manifested that the caspase-3 protein expression level in model group was obviously increased. Hypoxia ischemia can lead to significant increase of caspase-3 expression and increase of neuronal apoptosis in the brain of neonatal mice.

[Optimization of culture of fetal rat cardiomyocytes in vitro].

Objective To explore the optimal method for in vitro cultivation of SD fetal rat cardiomyocytes. Methods Cardiomyocytes of SD fetal rats from pregnant rats on gestational day 19 were obtained by digesting cardiac tissues with 0.8 g/L trypsin and 0.4 g/L collagenase II. With differential centrifugation and different animal serums (bovine fetal serum or horse serum), we tried to look for the optimal culture conditions. The morphology and beat frequency of cardiomyocytes were observed under an inverted phase-contrast microscope. In addition, the expressions of alpha-sarcomeric actinin (α-SA) and cardiac troponin I (cTnI) in the cultured cardiomyocytes were detected by immunofluorescence staining to identify cardiomyocytes and the purity of these cells after 24, 48, 72 and 96 hours of cultivation. Results After 24 hours of cultivation, we had seen a majority of adherent cells and a few of suspension cells, and also seen some pulsating cardiomyocytes. The positive rates of α-SA and cTnI in the cardiomyocytes of the horse serum-cultured group were obviously higher than those in the bovine fetal serum-cultured group after 48, 72 and 96 hours of cultivation. Conclusion Co-digestion with trypsin and collagenaseII in combination with horse serum cultivation are easier to cultivate fetal rat cardiomyocytes.