Self-shrinking supramolecular nanoparticles syndicate energy suppression and NIR-II mild photothermal amplification of mitochondrial oxidative stress for breast cancer therapy

Photothermal therapy(PTT)may lead to healthy tissue damage,tumor metastasis,and recurrence,which makes mild photothermal therapy(mild PTT)stand out.However,overcoming heat resistance,insufficient therapeutic effect,and poor photothermal conversion efficiency has become new challenge.Herein,we report a dynamic supramolecular nanocarrier formed from amide-sericin and aldehyde-polyhydroxy glucan(denoted as SDA),the loose cavity of which can be filled by using the pharmaceutical combination of lonidamine(LND)and NIR-II photothermal agent of IR-1061,producing SDLI with a tighter inner hole,smaller and uniform particle size and excellent stability due to multiple pulling forces.Moreover,the intricate internal network structure prevents the hydrophobic IR-1061 from forming aggregates in the small cavity,and the photothermal conversion efficiency(PCE)can reach 48.9%.At the acidic tumor microenvironment of pH 6.5,the controlled release of LND can solve the problem of heat resistance of NIR-II mild PTT and significantly improve the therapeutic effect of NIR-II mild PTT.Meanwhile,SDLI also shows a reasonable tumor inhibition rate,so the synergistic strategy of inhibiting tumor energy metabolism and NIR-II mild PTT to magnify mitochondrial oxidative stress,continuous cell stress state-induced immunogenic cell death to promote the induction of tumor apoptosis is proposed to achieve more effective cancer treatment.

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury

Background:Dysfunction of the gap junction channel protein connexin 43(Cx43)contributes to myocardial ischemia/reperfusion(I/R)-induced ventricular arrhythmias.Cx43 can be regulated by small ubiquitin-like modifier(SUMO)modification.Protein inhibitor of activated STAT Y(PIASy)is an E3 SUMO ligase for its target proteins.However,whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.Methods:Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid(shRNA)using recombinant adeno-associated virus subtype 9(rAAV9).Two weeks later,the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion.Electrocardiogram was recorded to assess arrhythmias.Rat ventricular tissues were collected for molecular biological measurements.Results:Following 45 min of ischemia,QRS duration and QTc intervals statistically significantly increased,but these values decreased after transfecting PIASy shRNA.PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R,as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation,and reduced arrythmia score.In addition,myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation,accompanied by reduced Cx43 phosphorylation and plakophilin 2(PKP2)expression.Moreover,PIASy downregulation remarkably reduced Cx43 SUMOylation,accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.Conclusion:PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression,thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

铁棍山药微型块茎遗传转化体系的建立

怀山药(Dioscorea opposita)遗传转化是对其进行基因功能分析和遗传改良的基础,但目前国内外尚未见相关报道。以怀山药优良品种铁棍山药(D. opposita cv.‘Tiegun’)的微型块茎为受体材料,对影响遗传转化的因素进行优化,建立了由根癌农杆菌介导的山药遗传转化体系。过表达质粒载体p CAMBIA1301-DoSERK2含GUS标记基因和潮霉素(Hyg)抗性筛选基因,沉默质粒载体pART27-DoSERK2含卡那霉素(Kan)抗性筛选基因。根癌农杆菌抑制剂特美汀(Tim)的最佳浓度为500mg·L^(–1);再生芽和生根时, Hyg的最佳浓度分别为15和20 mg·L^(–1), Kan的最佳浓度分别为120和160 mg·L^(–1)。对转化植株进行PCR和GUS组织化学检测,结果显示外源基因已整合到铁棍山药转基因株系的基因组中并在细胞中表达。该研究建立了一套取材便利的铁棍山药遗传转化方法,对其它品种山药的转化也具有参考价值。

Effect of nitrogen/phosphorus concentration on algal organic matter generation of the diatom Nitzschia palea:Total indicators and spectroscopic characterization

Critical algal blooms in great lakes increase the level of algal organic matters（AOMs）,significantly altering the composition of natural organic matters（NOMs） in freshwater of lake.This study examined the AOM＇s characteristics of Nitzschia palea（N.palea）,one kind of the predominant diatom and an important biomarker of water quality in the great lakes of China,to investigate the effect of AOMs on the variation of NOMs in lakes and the process of algal energy.Excitation–emission matrix fluorescence（EEM） spectroscopy,synchronous fluorescence（SF） spectroscopy and deconvolution UV–vis（D-UV） spectroscopy were utilized to characterize AOMs to study the effects of nutrient loading on the composition change of AOMs.From results,it was revealed that the phosphorus is the limiting factor for N.palea＇s growth and the generation of both total organic carbon and amino acids but the nitrogen is more important for the generation of carbohydrates and proteins.EEM spectra revealed differences in the composition of extracellular organic matter and intracellular organic matter.Regardless of the nitrogen and phosphorus concentrations,aromatic proteins and soluble microbial products were the main components,but the nitrogen concentration had a significant impact on their composition.The SF spectra were used to study the AOMs for the first time and identified that the protein-like substances were the major component of AOMs,creating as a result of aromatic group condensation.The D-UV spectra showed carboxylic acid and esters were the main functional groups in the EOMs,with –OCH_3,–SO_2NH_2,–CN,–NH_2,–O– and –COCH_3functional groups substituting into benzene rings.