L-Selenocystine induce HepG2 cells apoptosis through ROS-mediated signaling pathways

At present,Hepatocarcinoma is one of the main causes of tumor related death all over the world.However,there are still many clinical restrictions on the treatment of liver cancer.Recently,L-Selenocystine has been shown to be a novel treatment for tumors,especially human glioma cells.But,the mechanism of L-Selenocystine against hepatocellular carcinoma remains unclear.Therefore,the main objective of this study was to investigate the effects of L-Selenocystine on HepG2 cell proliferation and activation of reactive oxygen species(ROS)mediated signaling pathway.L-Selenocystine can significantly inhibit HepG2 cell proliferation by activating caspase-3 and cleaving PARP to induce apoptosis.Moreover,the excessive production of ROS and the influence of Bax signaling pathway which can promote cell apoptosis are key factors for L-Selenocystine to induce HepG2 cell apoptosis.Therefore,the date of this study suggest that ROS mediated signal transduction mechanism may provide certain reference significance for L-Selenocystine induced HepG2 cell apoptosis.

Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.

Risk factors for prolonged intensive care unit stays in patients after cardiac surgery with cardiopulmonary bypass:A retrospective observational study

Objectives:Patients after cardiac surgery with cardiopulmonary bypass(CPB)require a stay in the ICU postoperatively.This study aimed to investigate the incidence of prolonged length of stay(LOS)in the ICU after cardiac surgery with CPB and identify associated risk factors.Methods:The current investigation was an observational,retrospective study that included 395 ICU patients who underwent cardiac surgery with CPB at a tertiary hospital in Guangzhou from June 2015 to June 2017.Data were obtained from the hospital database.Binary logistic regression modeling was used to analyze risk factors for prolonged ICU LOS.Results:Of 395 patients,137(34.7%)had a prolonged ICU LOS(>72.0 h),and the median ICU LOS was 50.9 h.Several variables were found associated with prolonged ICU LOS:duration of CPB,prolonged mechanical ventilation and non-invasive assisted ventilation use,PaO2/FiO2 ratios within 6 h after surgery,type of surgery,red blood cell infusion during surgery,postoperative atrial arrhythmia,postoperative ventricular arrhythmia(all P<0.05).Conclusions:These findings are clinically relevant for identifying patients with an estimated prolonged ICU LOS,enabling clinicians to facilitate earlier intervention to reduce the risk and prevent resulting delayed recovery.

Photochemical production of carbonyl sulfide,carbon disulfide and dimethyl sulfide in a lake water

Photochemical production of carbonyl sulfide（COS）,carbon disulfide（CS_2） and dimethyl sulfide（DMS） was intensively studied in the water from the Aohai Lake of Beijing city.The lake water was found to be highly supersaturated with COS,CS_2 and DMS,with their initial concentrations of 0.91 ± 0.073 nmol/L,0.55 ± 0.071 nmol/L and 0.37 ± 0.062 nmol/L,respectively.The evident photochemical production of COS and CS_2 in the lake water under irradiation of 365 nm and 302 nm indicated that photochemical production of them might be the reason for their supersaturation.The similar dependence of wavelength and oxygen for photochemical production of COS,CS_2 and DMS implied that they might be from the same precursors.The water cage effect was found to favor COS production but inhibit CS_2and DMS formation,indicating that COS photochemical production was mainly from direct degradation of the precursors and the formation of CS_2 and DMS needed intermediates via combination of carbon-centered radicals and sulfur-centered radicals.The above assumptions were further confirmed by simulation experiments with addition of carbonyls and amino acids（cysteine and methionine）,and the photochemical formation mechanisms for COS,CS_2 and DMS in water were derived from the investigations.

CEPC Technical Design Report

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.

N掺杂ZnO的缺陷识别与物性调控

ZnO由于其室温下激子稳定存在,因此是一种具备高效发光性能的宽禁带半导体材料.然而,由于ZnO材料本征缺陷种类繁多、性质复杂,且缺乏合适的p型掺杂剂,其出色的光电性能一直未得到应用.近年来,越来越多的研究工作指出,ZnO的材料性质极大程度依赖于其中杂质缺陷的组成,因此对ZnO中缺陷的种类识别和调控手段的研究成为ZnO材料走向应用前待解决的重要问题.本文结合近年来的研究进展,介绍了ZnO中各类本征缺陷的性质和调控手段,指出了N掺杂ZnO体系中受主的主要来源,获得了抑制补偿施主和诱导浅受主的一系列有效方法.在此基础上,提出了等价元素-受主共掺技术,实现了ZnO纳米材料的p型掺杂及同质结LED,并进一步拓展了ZnO纳米材料应用于存储器和宽频光探测器.

Label-free fiber nanograting sensor for real-time in situ early monitoring of cellular apoptosis

The achievement of functional nanomodules for subcellular label-free measurement has long been pursued in order to fully understand cellular functions.Here,a compact label-free nanosensor based on a fiber taper and zinc oxide nanogratings is designed and applied for the early monitoring of apoptosis in individual living cells.Because of its nanoscale dimensions,mechanical flexibility,and minimal cytotoxicity to cells,the sensing module can be loaded in cells for long term in situ tracking with high sensitivity.A gradual increase in the nuclear refractive index during the apoptosis process is observed,revealing the increase in molecular density and the decrease in cell volume.The strategy used in our study not only contributes to the understanding of internal environmental variations during cellular apoptosis but also provides a new platform for nonfluorescent fiber devices for investigation of cellular events and understanding fundamental cell biochemical engineering.