Glucose sensors based blood glucose detection are of great significance for the diagnosis and treatment of diabetes because diabetes has aroused wide concern in the world. In this study, bovine serum ...albumin (BSA) was used to cross-link glucose oxidase (GOD) on a glassy carbon electrode (GCE) modified by a composite of hydroxy fullerene (HFs) and multi-walled carbon nanotubes (MWCNTs) and protected with a glutaraldehyde (GLA)/Nafion (NF) composite membrane to prepare a novel glucose biosensor. The modified materials were analyzed by UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and cyclic voltammetry (CV). The prepared MWCNTs-HFs composite has excellent conductivity, the addition of BSA regulates MWCNTs-HFs hydrophobicity and biocompatibility, and better immobilizes GOD on MWCNTs-HFs. MWCNTs-BSA-HFs plays a synergistic role in the electrochemical response to glucose. The biosensor shows high sensitivity (167 μA·mM
·cm
), wide calibration range (0.01-3.5 mM), and low detection limit (17 μM). The apparent Michaelis-Menten constant Kmapp is 119 μM. Additionally, the proposed biosensor has good selectivity and excellent storage stability (120 days). The practicability of the biosensor was evaluated in real plasma samples, and the recovery rate was satisfactory.
Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases. Once the PDA is diagnosed, it needs to be dealt with in time. At present, main methods include pharmacological ...treatment, surgical closure, and interventional closure for treatment of PDA. However, the effect of different interventions in PDA management is still controversial. Thus, our study aims to assess the effectiveness of different interventions together and estimate the sequence of these therapies for PDA children. Meanwhile, it is necessary to conduct a Bayesian network meta-analysis to compare the safety of different interventions comprehensively.
To the best of our knowledge, this is the first Bayesian network meta-analysis comparing the efficacy and safety of different interventions for the treatment of PDA. PubMed, Embase, Cochrane Library, Web of Science, gray literature, and trial registry databases were searched from inception to December 2022. We will extract and report data according to methodological guidelines for Bayesian network meta-analysis by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Primary PDA closure, overall PDA closure, technical success, surgical success rate, mortality during hospital stay, operation time, intensive care unit stay, intraoperative radiation dose, radiation exposure time, total postoperative complication rate, and postoperative major complication rate will be defined as the outcomes. The quality of all random studies will be assessed using ROB, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
The results will be disseminated through peer-reviewed publication. Since no private and confidential patient data will be contained in the reporting, there are no ethical considerations associated with this protocol.
INPLASY2020110067.
The discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl ...groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O
as a green oxidant. The C-H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2'-deoxy-5-difluoromethyluridine (F
TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery.
Nanotechnology shows great potential for producing food with higher quality and better taste through including new additives, improving nutrient delivery, and using better packaging. However, lack of ...investigations on safety issues of nanofood has resulted in public fears. How to characterize engineered nanomaterials in food and assess the toxicity and health impact of nanofood remains a big challenge. Herein, a facile and highly reliable separation method of TiO2 particles from food products (focusing on sugar‐coated chewing gum) is reported, and the first comprehensive characterization study on food nanoparticles by multiple qualitative and quantitative methods is provided. The detailed information on nanoparticles in gum includes chemical composition, morphology, size distribution, crystalline phase, particle and mass concentration, surface charge, and aggregation state. Surprisingly, the results show that the number of food products containing nano‐TiO2 (<200 nm) is much larger than known, and consumers have already often been exposed to engineered nanoparticles in daily life. Over 93% of TiO2 in gum is nano‐TiO2, and it is unexpectedly easy to come out and be swallowed by a person who chews gum. Preliminary cytotoxicity assays show that the gum nano‐TiO2 particles are relatively safe for gastrointestinal cells within 24 h even at a concentration of 200 μg mL−1. This comprehensive study demonstrates accurate physicochemical property, exposure, and cytotoxicity information on engineered nanoparticles in food, which is a prerequisite for the successful safety assessment of nanofood products.
A facile method to separate nano‐TiO2 particles from chewing gum to achieve comprehensive characterization is reported. Over 93% of TiO2 in gum is smaller than 200 nm, and around 95% would enter the body of a person chewing the gum. These nano‐TiO2 particles are relatively safe for gastrointestinal cells.
Drug‐mediated or medical condition‐mediated disruption of hERG function accounts for the main cause of acquired long‐QT syndrome (acLQTs), which predisposes affected individuals to ventricular ...arrhythmias (VA) and sudden death. Many Chinese herbal medicines, especially alkaloids, have risks of arrhythmia in clinical application. The characterized mechanisms behind this adverse effect are frequently associated with inhibition of cardiac hERG channels. The present study aimed to assess the potent effect of Rutaecarpine (Rut) on hERG channels. hERG‐HEK293 cell was applied for evaluating the effect of Rut on hERG channels and the underlying mechanism. hERG current (IhERG) was measured by patch‐clamp technique. Protein levels were analysed by Western blot, and the phosphorylation of Sp1 was determined by immunoprecipitation. Optical mapping and programmed electrical stimulation were used to evaluate cardiac electrophysiological activities, such as APD, QT/QTc, occurrence of arrhythmia, phase singularities (PSs), and dominant frequency (DF). Our results demonstrated that Rut reduced the IhERG by binding to F656 and Y652 amino acid residues of hERG channel instantaneously, subsequently accelerating the channel inactivation, and being trapped in the channel. The level of hERG channels was reduced by incubating with Rut for 24 hours, and Sp1 in nucleus was inhibited simultaneously. Mechanismly, Rut reduced threonine (Thr)/ tyrosine (Tyr) phosphorylation of Sp1 through PI3K/Akt pathway to regulate hERG channels expression. Cell‐based model unables to fully reveal the pathological process of arrhythmia. In vivo study, we found that Rut prolonged QT/QTc intervals and increased induction rate of ventricular fibrillation (VF) in guinea pig heart after being dosed Rut for 2 weeks. The critical reasons led to increased incidence of arrhythmias eventually were prolonged APD90 and APD50 and the increase of DF, numbers of PSs, incidence of early after‐depolarizations (EADs). Collectively, the results of this study suggest that Rut could reduce the IhERG by binding to hERG channels through F656 and Y652 instantaneously. While, the PI3K/Akt/Sp1 axis may play an essential role in the regulation of hERG channels, from the perspective of the long‐term effects of Rut (incubating for 24 hours). Importantly, the changes of electrophysiological properties by Rut were the main cause of VA.
Combining immune checkpoint inhibitors with vascular endothelial growth factor/vascular endothelial growth factor receptor inhibitors is effective in treating a number of solid tumors; however, ...evidence in advanced gastric/gastroesophageal junction (G/GEJ) cancer is limited. This retrospective study included consecutive patients who received a programmed cell death protein 1 (PD‐1) inhibitor plus the vascular endothelial growth factor receptor 2 inhibitor apatinib, second‐line or later to treat unresectable advanced or metastatic, histologically proven, human epidermal growth factor receptor 2–negative G/GEJ cancer in a single center between November 1, 2018, and March 31, 2021. Treatment was continued until the disease progressed or the toxicity became intolerable. We examined data from 52 patients. The primary tumor site was the stomach in 29 patients and the GEJ in 23 patients. PD‐1 inhibitors administered included camrelizumab (n = 28), sintilimab (n = 18), pembrolizumab (n = 3), and tislelizumab (n = 1), and all patients were given 200 mg every 3 weeks, and toripalimab (240 mg every 3 weeks) and nivolumab (200 mg every 2 weeks) were given to 1 patient each. For 28 days, apatinib 250 mg was administered orally once a day. The objective response rate was 15.4% (95% confidence interval CI, 6.9‐28.1), and the disease control rate was 61.5% (95%CI, 47.0‐74.7). After 14.8 months of median follow‐up, the median progression‐free survival was 4.2 months (95%CI, 2.6‐4.8), and the overall survival was 9.3 months (95%CI, 7.9‐12.9). Twelve patients underwent grade 3‐4 treatment‐related adverse events (23.1%). There was no unexpected toxicity or death. This trial demonstrated combination therapy with an anti–PD‐1 antibody and apatinib was effective and safe in patients with previously treated unresectable advanced or metastatic G/GEJ cancer.
Background. Diabetic nephropathy (DN) is an important cause of end-stage renal disease and is recognized as a public health problem worldwide. However, there have been no nationwide surveys of DN ...prevalence in China. This study is aimed at estimating the pooled prevalence of DN among patients with type 2 diabetes in China. Methods. Published studies on the prevalence of DN among patients with type 2 diabetes published from January 1980 to October 2019 were systematically reviewed using PubMed, Embase, Google Scholar, Chinese Wanfang databases, and Chinese National Knowledge Infrastructure. The pooled prevalence of DN was estimated with the random effects model using R software. Prevalence estimates were also stratified by study design, methodological approach, and study population characteristics. Results. Thirty studies with a total of 79,364 participants were included in our study. The overall pooled prevalence of DN was 21.8% 95% confidence interval (CI): 18.5-25.4%. Subgroup analysis found that the prevalence of DN varied significantly according to different DM and DN diagnostic criteria (P<0.05); the pooling estimate was the highest in the west region of 41.3%, followed by that in the east region of China with 22.3%, northeast region with 20.7%, and central region with 15.6% (P<0.05), and was higher in the male-dominated studies 27.7%, compared with the female-dominated studies 17.6% (P<0.05). Conclusions. The prevalence of DN is high in Chinese patients with type 2 diabetes and shows geographic and gender variation. These data indicate that national strategies aimed at primary and secondary prevention of DN and screening programs for DN are urgently needed to reduce the risk and burden of DN in China.
As one of the fascinating high capacity cathodes, O3‐type layered oxides usually suffer from their intrinsic air sensitivity and sluggish kinetics originating from the spontaneous lattice Na ...extraction during air exposure and high tetrahedral site energy of Na+ diffusion transition state. What is worse, the improvement on the two handicaps is hard to simultaneously realize because of the contradiction between Na containment suggested in air stability mechanism and enhanced Na diffusion mentioned in kinetics strategy. Herein, it is shown that a simple strategy of introducing proper Na vacancies into lattice can simultaneously realize a dual performance improvement. Na vacancies decrease the charge density on transitional metal ions and enhance the antioxidative capability of material, ensuring a stable lattice Na containment for Na0.93Li0.12Ni0.25Fe0.15Mn0.48O2 when exposed to air. Additionally, more Na+ diffusional sites and enlarged Na layer spacing are obtained and result in a significantly decreased energy barrier from ≈1000 to 300 meV and a high rate capability of 70.8% retention at 2000 mA g−1. Remarkably, such a strategy can be easily realized by either pre‐ or post‐treating, which exhibits excellent universality for various O3 materials, implying its enormous potential to promote the commercial application of O3‐type cathodes.
A universal strategy of introducing proper Na vacancies into a crystal lattice is proposed to simultaneously improve air‐stability and kinetics of O3‐type layered oxide cathodes. The dual improvement benefits from the multiple effects of Na vacancies on crystalline and electronic structure, namely, decreased charge density on transition metal ions, enhanced antioxidative capability, decreased Na+ diffusion barrier, and optimized migration path.
To better understand the elevational pattern of phylogenetic structure shown by alpine taxa and the underlying causes, we analyzed the phylogenetic structure of each elevational belt of alpine plants ...in the Hengduan Mountains Region, measured by net related index (NRI) and net nearest taxon index (NTI). We found both the indices of phylogenetic diversity indicated that alpine plants tended to show phylogenetic overdispersion at low elevational belts, implying that the distribution of alpine plants in these belts was mainly determined by interspecific competition. Alpine plants at higher elevational belts tended to phylogenetic clustering indicated by NRI, and NTI revealed phylogenetic clustering at the belts between 4300 m and 5500 m, which presumably suggested environment filtering and rapid speciation. Above 5500 m, NTI indicated that the phylogenetic structure became random again, perhaps due to the low intensity of filtering and the large distances between plants at the top of the scree slopes. We concluded that phylogenetic structure was, indeed, influenced by the environmental filter, interspecies interaction, rapid speciation during the uplift of the Qinghai–Tibet Plateau, and distance between plants.
Environmental, social, and governance (ESG) performance has increasingly become the most pressing concern for governments, social organizations, companies, and other stakeholders. Understanding macro ...ESG behavior can assist governments in achieving their sustainable development goals (SDGs). In this paper, we investigate whether the macro ESG index of OPEC and non‐OPEC oil‐producing countries over the period 1990–2020 exhibits mean‐reversion behavior and whether the external shocks are transient or permanent. By conducting a series of advanced panel stationarity tests, we find that the macro ESG indices of the sample countries do not exhibit mean‐reversion and that an external shock has a permanent effect. We also identifies the yearly structural breaks that occur in the sample countries and attempts to explain why. Our research suggests that governments should use policy interventions to counteract external shocks to macro ESG behavior so as to achieve sustainable development and long‐term performance stability.
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