Tb^(3+)-nucleic acid probe-based label-free and rapid detection of mercury pollution in food

Mercury is a threatening pollutant in food,herein,we developed a Tb^(3+)-nucleic acid probe-based label-free assay for mix-and-read,rapid detection of mercury pollution.The assay utilized the feature of light-up fluorescence of terbium ions(Tb^(3+))via binding with single-strand DNA.Mercury ion,Hg^(2+)induced thymine(T)-rich DNA strand to form a double-strand structure(T-Hg^(2+)-T),thus leading to fluorescence reduction.Based on the principle,Hg^(2+)can be quantified based on the fluorescence of Tb^(3+),the limit of detection was 0.0689μmol/L and the linear range was 0.1-6.0μmol/L.Due to the specificity of T-Hg^(2+)-T artificial base pair,the assay could distinguish Hg^(2+)from other metal ions.The recovery rate was ranged in 98.71%-101.34%for detecting mercury pollution in three food samples.The assay is low-cost,separation-free and mix-to-read,thus was a competitive tool for detection of mercury pollution to ensure food safety.

Comparison of nutrition education policies and programs for children in China and other selected developed countries

A double burden of overweight/obesity and malnutrition during childhood is a major concern in China.Dietary intakes in this critical period affect children’s physical and cognitive development,and also have health consequences in later life.Therefore,establishing healthy eating habits that will endure is crucial for children.Nutrition education is an effective way in improving nutrition knowledge and attitudes,and healthy eating behaviors.Diverse forms of nutrition improvement programs that targeting children,family,teachers,and school settings have been conducted in many developed countries.However,due to the differences of genetic background,household environment as well as dietary patterns between Chinese children and children from other countries,the existing nutrition education programs for children abroad might not be appropriate for children in China.Thus,nutrition education programs that consider Chinese nutrition-related policies and food supply as well as the local educational resources are required for Chinese children.This review summarized nutrition-related policies and legislations in China and developed countries.A series of evidence-based nutrition education programs that combined educational strategies and environmental supports conducted in the Southwest China Childhood Nutrition and Growth Study were presented.These programs can serve as example models for adopting nutrition interventions to improve nutrition and health status of children in different regions of China.

Design, synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152):a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast-and platelet-derived growth factor receptors(VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics(PD)and pharmacokinetics(PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152,identified from a series of 4-oxyquinoline derivatives based on a structureeactivity relationship study,inhibited the proliferation of vascular endothelial cells(ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patientderived tumor xenograft(PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles.In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective tripleangiokinase inhibitor with clear PD and PK in tumor therapy.

Dietary protein sources, gut microbiome, and puberty timing in children: findings from a cohort study

Dear Editor,Developing countries are in a critical term of nutritional transition,marked by a sharp increase in the consumption of animal-source foods.In China,the intake of calories from animalsource foods in children tripled from 1990 to 2019,accompanied by a secular trend in early puberty.

Neuroprotective effect of hydroxy-α-sanshool against β-amyloid-induced damage in differentiated PC12 cells

To the Editor:Alzheimer’s disease(AD)is a chronic neurodegenerative disorder that accounts for approximately 70%of global dementia cases and leads to cognitive and behavioral impairments.[1]Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of AD and are related to the accumulation of b-amyloid(Ab)peptides in cerebral tissues and cytoskeletal changes,which arise from the hyperphosphorylation of microtubule-associated tau proteins in neurons.Oxidative stress is among the earliest events in AD pathogenesis.The accumulation of Ab could promote the production of reactive oxygen species(ROS)and consequently lipid peroxidation,protein oxidation,and tau hyperphosphorylation,exerting toxic effects on synapses and neurons.In turn,oxidative stress could increase Ab production.Therefore,antioxidant therapy is becoming a popular strategy for treating AD.

Identification of novel candidate genes in East Asian COPD patients by the functional summary-based imputation and the unified test for molecular signatures:a transcriptome-wide association study

To the Editor:Chronic obstructive pulmonary disease(COPD),a clinical syndrome encompassing a spectrum of chronic,progressive,and debilitating respiratory disorders,is increasingly recognized as a multisystemic heterogeneous disease.[1]Because the characteristics of East Asian COPD patients differ from those of Westerners,it would be practical to investigate whether variations in COPD genetic performance exist between East Asian and Western populations.

Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway

To the Editor:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are major causes of morbidity and mortality in older individuals,and their epidemiological link generates substantial challenges for the management of these devastating diseases.Abnormal glucose metabolism,accompanied by inhibition of the protein kinase B(Akt)/glycogen synthase kinase-3b(GSK-3b)signaling pathway,is a key factor in amyloid precursor protein(APP)accumulation and amyloid b(Ab)formation in neuronal cells.[1-3]Therefore,activation of the Akt/GSK-3b pathway may be a promising target for AD treatment.

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies,on account of its good safety and long-term memory ability.Discouragingly,low patient response rates and potential immune-related side effects make it rather challenging to literally bring immunotherapy from bench to bedside.However,it has become evident that,although the immunosuppressive tumor microenvironment(TME)plays a pivotal role in facilitating tumor progression and metastasis,it also provides various potential targets for remodeling the immunosuppressive TME,which can consequently bolster the effectiveness of antitumor response and tumor suppression.Additionally,the particular characteristics of TME,in turn,can be exploited as avenues for designing diverse precise targeting nanomedicines.In general,it is of urgent necessity to deliver nanomedicines for remodeling the immunosuppressive TME,thus improving the therapeutic outcomes and clinical translation prospects of immunotherapy.Herein,we will illustrate several formation mechanisms of immunosuppressive TME.More importantly,a variety of strategies concerning remodeling immunosuppressive TME and strengthening patients'immune systems,will be reviewed.Ultimately,we will discuss the existing obstacles and future perspectives in the development of antitumor immunotherapy.Hopefully,the thriving bloom of immunotherapy will bring vibrancy to further exploration of comprehensive cancer treatment.

Assembly-enhanced triplet-triplet annihilation upconversion in the aggregation formed by Schiff-base Pt(Ⅱ) complex grafting-permethyl-β-CD and 9,10-diphenylanthracence dimer

Water-soluble triplet sensitizer with permethyl-β-cyclodextrin(PMCD)grafting on a Schiff-base Pt(II)complex(Pt-2),in which PMCD unit serves as a host for binding the acceptors and the Schiff-base Pt(II)complex serves as a triplet sensitizer,was synthesized to investigate the effect of supramolecular complexation and assembly on the triplet-triplet annihilation upconversion emission in water.9,10-Diphenylanthracence(DPA)carboxylate(A-1)and its dimer(A-2)in which two DPA carboxylate were covalently linked with an alkyl chain were synthesized as triplet acceptors which also play a role of guest molecules for PMCD.A-1 and A-2 showed high affinity with PMCD,and A-2 can readily aggregate in water and form micron sized assemblies due to the hydrophobic effect andπ-πstacking of anthracene core in A-2.The efficiency of TTA-UC was demonstrated to be enhanced by a synergistic effect of host-guest complexation of Pt-2 with A-2 and the self-aggregation of the acceptor A-2,which facilitated the energy transfer and energy fusion among donor and acceptor.

Bio-safety assessment of carbon quantum dots, N-doped and folic acid modified carbon quantum dots: A systemic comparison

The carbon quantum dots(CQDs)and their functionalized materials are promising in biomedical field because of their unique properties;meanwhile,a growing concern has been raised about the potential toxicity of these modified materials in biosystem.In this study,we synthesized original CQDs and two common functionalized CQDs including N-doped CQDs(NCQDs)and folic acid-modified CQDs(FACQDs),and compared the toxicity and biocompatibility with each other in vitro and in vivo.L929,C6 and normal cell MDCK were selected to detect the adverse reaction of these materials in vitro.No acute toxicity or obvious changes were noted from in vitro cytotoxicity studies with the dose of these CQD materials increasing to a high concentration at 1 mg/mL.Among these materials,the FA-CQDs show a much lower toxicity.Moreover,in vivo toxicity studies were performed on the nude mice for 15 days.The experimental animals in 10 or 15 mg/kg groups were similar with animals treated by phosphate buffer solution(PBS)after 15 days.The results of the multifa rious biochemical parameters also suggest that the functionalized products of CQDs do not influence the biological indicators at feasible concentration.Our findings in vitro and in vivo through toxicity tests demonstrate that CQDs and their modified materials are safe for future biological applications.

Pyrene-tiaraed pillar[5]arene:Strong intramolecular excimer emission applicable for photo-writing

A pyrene-tiaraed pillar[5]a re ne derivative was synthesized,which showed a concentration-independent intensive excimer emission.Photolysis of the pyrene-tiaraed pillar[5]arene led to a switch from excimer to monomer emission,applicable to photo-writing.

Temperature-driven braking of γ-cyclodextrin-curcubit[6]urilcowheeled [4]rotaxanes

Several cyclodextrin-cucurbit[6]uril-cowheeled [4]rotaxanes were synthesized through the cucurbit[6]uril-templated azide-alkyne 1,3-dipolar cycloaddition. The intramolecular interaction between the aromatic axle and the capping groups of cyclodextrin moieties was investigated by UV-vis, fluorescence,circular dichroism and NMR spectroscopic studies. The rotational kinetic of the wheel around the axle can be manipulated by adjusting the temperature. The capping group apparently slowed down the rotation of the wheel, playing a role of the brake, and lowering the temperature can stop the rotation of the wheel on the NMR timescale.

Bisindole [3]arenes—Indolyl Macrocyclic Arenes Having Significant Iodine Capture Capacity

Several novel macrocyclic arenes that are composed of six indole subunits,so-called bisindole[3]arenes(BID[3]s),were conveniently synthesized by the aluminum trichloride-catalyzed one-pot condensation of bisindole derivatives and paraformaldehyde in dichloromethane at room temperature.Their macrocyclic structures were demonstrated by X-ray single-crystal studies,and the presence of the macrocyclic cavities made it possible to accommodate specific small organic molecules.The BID[3]s have exceptionally high iodine adsorption ability due to the strong and synergic interaction of indole units toward iodine,exhibiting significant morphology changes upon adsorption and desorption of iodine.Iodine uptake capacity of up to 5.12 g·g^(−1) was found with MeBID[3],which is the highest value ever reported for macrocyclic arenes.