Metal-free base-mediated oxidative annulation cascades to 3-substituted-3-hydroxyoxindole and its 3-spirocyclic derivative

A simple and efficient method was developed for the construction of the medicinally important 3-substituted-3-hydroxyoxindoleand its 3-spirocyclic derivativeswith readily available aniline derivatives as starting materials. Thishighly atom-and step-economical one-pot protocolwas carried out undermetal-freebase-mediated conditions througha novel oxidative annulationstrategywith oxygen as the oxidant.The key intermediates were isolated and confirmed.A reasonablereaction pathway was proposed and supported by both the preliminary experiments and computational studies

Pre-Treatment with Melatonin Enhances Therapeutic Efficacy of Cardiac Progenitor Cells for Myocardial Infarction

Background/Aims: Melatonin possesses many biological activities such as antioxidant and anti-aging. Cardiac progenitor cells (CPCs) have emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the low survival of transplanted CPCs in infarcted myocardium limits the successful use in treating MI. In the present study, we aimed to investigate if melatonin protects against oxidative stress-induced CPCs damage and enhances its therapeutic efficacy for MI. Methods: TUNEL assay and EdU assay were used to detect the effects of melatonin and miR-98 on H2O2-induced apoptosis and proliferation. MI model was used to evaluate the potential cardioprotective effects of melatonin and miR-98. Results: Melatonin attenuated H2O2-induced the proliferation reduction and apoptosis of c-kit+ CPCs in vitro, and CPCs which pretreated with melatonin significantly improved the functions of post-infarct hearts compared with CPCs alone in vivo. Melatonin was capable to inhibit the increase of miR-98 level by H2O2 in CPCs. The proliferation reduction and apoptosis of CPCs induced by H2O2 was aggravated by miR-98. In vivo, transplantation of CPCs with miR-98 silencing caused the more significant improvement of cardiac functions in MI than CPCs. MiR-98 targets at the signal transducer and activator of the transcription 3 (STAT3), and thus aggravated H2O2-induced the reduction of Bcl-2 protein. Conclusions: Pre-treatment with melatonin protects c-kit+ CPCs against oxidative stress-induced damage via downregulation of miR-98 and thereby increasing STAT3, representing a potentially new strategy to improve CPC-based therapy for MI

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.Peer reviewe

Effects of norepinephrine on hemodynamics, vascular elasticity, cardiac pump function, and inflammatory factors in patients with septic shock

The effects of norepinephrine on hemodynamics, vascular elasticity, cardiac pump function, and inflammatory factors in patients with septic shock remained unknown. In this study, we included 124 cases of severe septic shock patients in our hospital. The patients were randomly divided into control group (treated with dopamine) and experimental group (treated with dopamine plus norepinephrine), while the hemodynamic index (heart rate (HR)), blood vessel elasticity index, heart pump function, and inflammatory factor index were recorded. After 12 h of treatment, both groups showed decreased HR, increased levels of cardiac index (CI), mean arterial pressure (MAP), central venous pressure (CVP), peripheral vascular resistance index (PVRI), and vascular elasticity ( P  < 0.05). To date, lower HR, higher levels of CI, MAP, CVP, and PVRI were observed in the experimental group ( P  < 0.05). Furthermore, the vascular elastic coefficient, stiffness index, arterial compliance, and the precursors of plasma amino-terminal brain natriuretic peptide were also significantly higher in the experimental group than those in the control group ( P  < 0.05). However, inflammatory cell tumor necrosis factor alpha factor test group (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) concentrations were significantly lower than the control group ( P  < 0.05), compared to experimental group ( P  < 0.05). This research indicates that phenylephrine could significantly improve hemodynamics in patients with severe septic shock, by maintaining blood vessel elasticity, improving heart pump function, and reducing the inflammatory factors’ activities, and this method could be used as a line of vascular tension of the medications used in patients with septic shock

Efficiency moderates the relationship between sleep-onset insomnia and resting-state electroencephalogram microstate

Background: Overactivation of the salience network (SN) causes hyperarousal in insomnia patients and is associated with sleep-onset insomnia (SOI). Resting-state microstate 3 (RS-MS3) duration is closely related to SN overactivation. However, whether RS-MS3 duration is a biomarker for SOI has not yet been reported in the literature. In addition, SN activity is also associated with efficiency. However, it is not clear whether there are individual differences in the neural mechanisms of SOI in different efficiency groups. Methods: Considering that RS-MS3 duration characterizes the stability and persistent activation of the SN in the resting state, the current study investigated the link between SOI measured by sleep latency of Pittsburg Sleep Quality Index (PSQI), efficiency measured by Kirton Adaption-Innovation Inventory (KAI), and RS-MS3 in a Chinese healthy (subclinical) student population, using electroencephalography (EEG) microstate analysis. Results: We found that RS-MS3 duration was positively correlated with sleep latency and efficiency. The interaction between sleep latency and efficiency was significant. Simple slope analysis showed that high sleep latency was positively correlated with longer RS-MS3 duration in participants with higher efficiency scores. This correlation did not exist in participants with low efficiency scores. Conclusions: RS-MS3 duration may serve as a biomarker for SOI. There is heterogeneity in the relationship between SOI and RS-MS3 duration between individuals with high and low efficiency

Synthesis of Functionalized Biaryls and Poly(hetero)aryl Containing Medium-Sized Lactones with Cyclic Diaryliodonium Salts

A novel one-pot procedure is described for the transition-metal catalyzed sequential difunctionalization of diaryliodonium reagents. Reaction of commercially available anthranilic acid derivatives with readily available cyclic diaryliodonium salts followed by a Sonogashira coupling afforded various alkyne substituted biaryls in good to excellent yields. The functionalized biaryls were then utilized for the rapid and efficient one-pot synthesis of novel poly­(hetero)­aryl containing 10-membered lactones which are potential G-quadruplex binders and telomerase inhibitors

Enantiospecific electrochemical rearrangement for the synthesis of hindered triazolopyridinone derivatives

Chiral and hindered triazolopyridinone derivatives are an underexplored area of chemical space mainly due to their challenging synthesis via classical methods. Here, the authors report an electrochemical rearrangement for the synthesis of triazolopyridinones using diverse, available alkyl carboxylic acids as starting materials

Attenuation of Low Ambient Temperature-Induced Myocardial Hypertrophy by Atorvastatin via Promoting Bcl-2 Expression

Background/Aims: It is well documented that myocardial hypertrophy is associated with low ambient temperature. Atorvastatin (Atv) has been shown to protect against atherosclerosis, cardiac fibrosis, ischemia/reperfusion injury, etc. In this study, we aim to determine whether atorvastatin is effective in the treatment of myocardial hypertrophy induced by cold exposure and to shed light on underlying mechanism. Methods: The mice aged 4-week were randomized to Control (Ctl) group (raised at room temperature), Cold group (raised at 3-5ºC) and Atv treatment group (raised at 3-5ºC followed by 10mg/kg/day Atv infusion). Echocardiography (ECG), HE, TUNEL and Masson’s trichrome staining, and Transmission electronic microscopy were performed to analyze cardiac function, myocardial hypertrophy, cardiac fibrosis, apoptosis and cardiomyocyte ultrastructure, respectively. Western blot was carried out to determine the involvement of MAPK and apoptosis pathways. Results: Exposure of mice to low temperature induced myocardial hypertrophic growth characterized by the elevation of heart/body weight index and heart weight /tibia length index, compared with control mice. Atv treatment attenuated cardiac hypertrophy induced by cold exposure; Atv also attenuated the increase of cross-sectional area of cardiomyocytes and cardiac collagen content fraction in mice exposed to cold. ECG showed that the decline of cardiac functions including the elevated left ventricular systolic/diastolic internal dimension (LVIDs/d) and fractional shortening (FS) in mice with cold exposure was also inhibited by Atv treatment. Transmission electronic microscopy uncovered that Atv attenuated mitochondrial injury induced by cold exposure in mice. In addition, systolic blood pressure was gradually increased in mice exposed to cold temperature, and Atv treatment significantly inhibited the elevation of blood pressure in cold-treated mice. Mechanistically, mitogen-activated protein kinase (MAPK) signal was not altered in mice exposed to cold, and Atv did not affect MAPK signal in cold-treated mice. But Atv mitigated the reduction of Bcl-2/Bax level in heart of cold-treated mice. Conclusion: Atv attenuated myocardial hypertrophy induced by cold exposure through inhibiting the downregulation of Bcl-2 in heart. It may provide a novel strategy for low temperature-induced myocardial hypertrophy treatment