Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor

Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsive multifunctional nanoplatform(Bi2S3@Bi@PDA-HA/Art NRs)was presented for synergistic photothermal therapy(PTT),chemodynamic therapy(CDT),and photodynamic therapy(PDT)to achieve better therapeutic outcomes.The Z-scheme heterostructured bismuth sulfide@bismuth nanorods(Bi2S3@Bi NRs)guaranteed excellent photothermal performance of the nanoplatform.Moreover,its ability to produce O2 and reactive oxygen species(ROS)synchronously could relieve tumor hypoxia and improve PDT outcomes.The densely coated polydopamine/ammonium bicarbonate(PDA/ABC)and hyaluronic acid(HA)layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ“bomb-like”release of Art.The CDT treatment was achieved by activating the released Art through intracellular Fe2+ions in an H2O2-independent manner.Furthermore,decreasing the glutathione peroxidase 4(GPX4)levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs.Owing to the synergistic effect,this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo.Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.

Fluorescence Turn-On/Off Responses of In(Ⅲ)-MOF to Short-Chain Perfluorocarboxylic Acids

Short-chain perfluorocarboxylic acids(PFCAs) are a class of persistent organic pollutants that are widely used as substitutes for long-chain PFCAs. However, they also pose a non-negligible risk to ecosystems. In this study, we demonstrated that a fluorescent metal–organic framework(MOF)(named V-101) constructed from In^(3+)and an aromatic-rich tetratopic carboxylate ligand 5-[2,6-bis(4-carboxyphenyl) pyridin-4-yl] isophthalic acid(H4BCPIA) exhibited highly efficient turn-off and turn-on fluorescence responses toward five short-chain PFCAs in water and methanol, respectively. The limits of detection of V-101 toward five short-chain PFCAs are down to μg/L level, and it showed good anti-interference abilities toward short-chain PFCAs in the presence of common metal ions. The major mechanisms associated with fluorescence responses were molecular collisions and interactions between V-101 and short-chain PFCAs. This work demonstrates that the structure variety of MOFs imparts them with the potential of MOFs in the detection of short-chain PFCAs for pollution control.

A Scheduling Strategy of Light Supplement in Agricultural Greenhouse Based on the Displacement of Light Source Group

LED can effectively promote the growth of crops and improve the yield of crops. In order to make the crops grow evenly in the agricultural greenhouse, the uniformity of illumination is very important. Because of the importance of illumination uniformity to the growth of crops, this paper intends to establish the illuminance model of light source without considering the influence factors such as the difference of each light source group and air scattering. On this basis, the reasonable layout of each light source position in the light source group is considered. Therefore, a light replenishment scheduling strategy based on the displacement of light source group is proposed in this paper Improve the uniformity of illumination in agricultural greenhouse and reduce its operation cost. Experiments show that the strategy is effective.

鲍曼不动杆菌的耐药性检测及多重耐药菌株质粒图谱分析

目的本次研究探讨鲍曼不动杆菌的耐药性和菌株的质粒图谱分析,确定临床哪些药物治疗鲍曼不动杆菌效果最好,以为临床治疗提供新思路.方法收集2018年7月-2019年6月的临床患者标本,对分离培养出的100株鲍曼不动杆菌进行VITEK MS鉴定及VITEK2-COMPACT药敏实验.结果在分离培养出的100株鲍曼不动杆菌中,多重耐药耐药率达到了41.76%,对三代、四代头孢菌素耐药率为39.4%-56%.对氨基糖苷类药物妥布霉、庆大霉素耐药率为23.8%-52%.对喹诺酮类耐药率达到25.3%-60%.结论目前,绝大多数菌株对阿米卡星、头孢派酮/舒巴坦和替加环素、米诺环素保持敏感,有较好的治疗效果.

VEGF-C/VEGFR-3/iNOS Signaling in Osteosarcoma MG63 Cells Mediates Stimulatory Effects on Human Umbilical Vein Endothelial Cell Proliferation

Objectives To assess the effects of vascular endothelial growth factor-C(VEGF-C)/vascular endothelial growth factor receptor-3(VEGFR-3)signaling on nitric oxide(NO)production and inducible nitric oxide synthase(iNOS)expression in human osteosarcoma MG63 cells and the subsequent impact on the proliferation of human umbilical vein endothelial cells(HUVECs).Methods MG63 cells were treated with VEGF-C alone(VEGF-C group),VEGF-C+iNOS inhibitor aminoguanidine(AG;AG group),and VEGF-C+VEGFR-3 inhibitor MAZ51(MAZ51 group);untreated MG63 cells were used as controls.NO production was evaluated by a colorimetric method involving nitrate reductase.Meanwhile,mRNA and protein levels of iNOS were examined by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.To explore the effect of VEGF-C/VEGFR-3/iNOS signaling of MG63 cells on proliferation of HUVECs,we set up six groups:HUVECs,HUVECs+MG63,HUVECs+VEGF-C,HUVECs+MG63+VEGF-C,HUVECs+MG63+VEGF-C+AG,and HUVECs+MG63+VEGF-C+MAZ51 groups.The proliferation of HUVEC cells was assessed by Cell Counting Kit-8(CCK-8),5-ethynyl-2'-deoxyuridine(EdU)incorporation assay,and proliferating cell nuclear antigen(PCNA)expression quantitation.Results VEGF-C treatment enhanced iNOS expression at both gene and protein levels(mRNA:LSD-t=4.152,P<0.01;protein:LSD-t=3.486,P<0.01)and increased NO release of MG63 cells(LSD-t=3.774,P<0.01);treatment with either AG or MAZ51 decreased these effects(mRNA:LSD-t=9.183,P<0.001;LSD-t=8.639,P<0.001;protein:LSD-t=5.170,P<0.001;LSD-t=7.25S,P<0.001;NO production:LSD-t=10.326,P<0.001;LSD-t=l0.540,P<0.001).Interestingly,co-incubation of HUVECs with MG63 cells and/or VEGF-C significantly promoted HUVEC proliferation(EdU:LSD-t=5.374,P<0.001;LSD-t=2.984,P<0.05;LSD-t=8.526,P<0.001;PCNA:LSD-t=9.267,P<0.001;LSD-t=5.515,P<0.001;LSD-t=14.873,P<0.001).The proliferation effects of HUVEC induced by MG63 cells and VEGF-C attenuated by the treatment of AG(EdU:LSD-t=10.770,P<0.001;PCNA:LSD-t=19.94O,P<0.001)or MAZ51(EdU:LSD-t=6.950,P<0.001;PCNA:LSD-t=14.001,P<0.001).Conclusion In human osteosarcoma MG63 cells,activation of VEGFR-3 by VEGF-C promotes iNOS expression and NO production,which subsequendy induces HUVEC proliferation.

MicroRNA-145-3p suppresses the malignant behaviors of T-cell acute lymphoblastic leukemia Jurkat cells via inhibiting the NF-kappaB signaling pathway

T-cell acute lymphoblastic leukemia(T-ALL)is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells.Emerging studies have stated that microRNAs(miRNAs)may play key roles in T-ALL progression.This study aimed to investigate the roles of miR-145-3p in T-ALL cell proliferation,invasion,and apoptosis with the involvement of the nuclear factor-kappaB(NF-κB)signaling pathway.T-ALL Jurkat cells were harvested,and the expression of miR-145-3p and NF-κB-p65 was measured.Gain-and loss-of-functions of miR-145-3p and NF-κB-p65 were performed to identify their roles in the biological behaviors of Jurkat cells,including proliferation,apoptosis,and invasion.Consequently,the current study demonstrated that miR-145-3p was down-regulated while NF-κB-p65 was up-regulated in Jurkat cells.miR-145-3p directly bound to the 3’untranslated region of NF-κB-p65.Over-expression of miR-145-3p inhibited Jurkat cell proliferation,invasion,and resistance to apoptosis,while over-expression of NF-κB-p65 presented opposite trends.Co-transfection of miR-145-3p and NF-κB-p65 promoted the malignant behaviors of Jurkat cells compared to miR-145-3p transfection alone,while it reduced these behaviors of Jurkat cells compared to NF-κB-p65 transfection alone.Taken together,this study provided evidence that miR-145-3p could suppress proliferation,invasion,and resistance to the death of T-ALL cells via inactivating the NF-κB signaling pathway.

Efficient small-molecule donor with improved structural order and molecular aggregation enabled by side-chain modification

Side-chain modification is a proven effective approach for morphology manipulation in organic solar cells(OSCs).However,in-depth analysis and investigation involving side-chain modification towards morphology improvement,including molecular microstructure,orientating packing and aggregation are urgent for all-small-molecule(ASM)systems.Herein,employing a fluorine-modified two-dimension benzodithiophene(BDT)as central unit,we contrastively synthesized two small-molecule donors,namely BDT-F-SR and BDT-F-R,each welding alkylthio side-chains on thienyl of central BDT unit and the other grafted non-sulfuric alkyl side-chains.As predicted,the synergetic side-chain modification of fluorination and alkyl changeover triggers diverse molecular dipole moments and orientations,resulting in different molecular energy levels,thermal stabilities,molecular planarity and order.Eventually,together with the preeminent small-molecule acceptor Y6,BDT-F-R-based ASM OSCs obtain enhanced power conversion efficiency(PCE)of 13.88%compared to BDT-F-SR-based devices(PCE of 12.75%)with more suitable phase-separation and balanced carrier mobilities.The contrast results reveal that alkyl sidechains seem to be a more satisfactory partner for fluorine-modified 2D BDT-based small-molecule donors compared to alkylthio pendants,and highlight the significance of subtle side-chain modification for molecular structural order fun-tuning and morphology control,laying the foundation for efficient ASM OSCs.

Case Report of Ectopic Pregnancy during Controlled Ovarian Stimulation without Oocytes Harvested and Late Ovarian Hyperstimulation Syndrome

Here we reported a rare case of misdiagnosed ectopic pregnancy (EP) due to unintended ovulation during controlled ovarian stimulation (COS) in GnRH agonist cycle, resulting in no oocytes harvested and late hyper-stimulation syndrome (OHSS). The patient was a 33-year old primary infertile woman due to male’s factors and underwent her second in vitro fertilization (IVF) cycle using GnRH agonist protocol, and no oocytes harvested on ovum picked-up (OPU) day. The start of gonadotropin usage was on day 8th of her period, and the P level increased rapidly and strangely high from day 8th after gonadotropin usage. The E2 level and follicles grew normally but finally no oocytes harvested. She was diagnosed as late ovarian hyper-stimulation syndrome (OHSS) 7 days after OPU. 20 days after OPU, no menstruation come and a positive urine test of hCG were reported. And the patient was diagnosed as EP by laparoscopy. In conclusion, rapidly increased P level, no oocyte retrieval and late onset of OHSS should be very important clues to diagnose this misdiagnosed EP.

N-Heterocyclic carbene catalyzed C-acylation reaction for access to linear aminoenones

An N-heterocyclic carbene(NHC)-catalyzed carbonyl nucleophilic substitution reaction between 1-cyclopropylcarbaldehydes and N-sulfonyl imines is developed for access to linearβ-aminoenone products.Theβ-aminoenones containing cyclopropyl fragments can be afforded in moderate to excellent yields under mild conditions.The reaction features excellent trans-diastereoselectivities and the desired aminoenone products are all afforded as Z-isomers.

Phase separation and domain crystallinity control enable open-air-printable highly efficient and sustainable organic photovoltaics

Organic solar cells(OSCs)have emerged as a promising solution for sustainable energy production,offering advantages such as a low carbon footprint,short energy payback period,and compatibility with eco-solvents.However,the use of hazardous solvents continues to dominate the best-performing OSCs,mainly because of the challenges of controlling phase separation and domain crystallinity in eco-solvents.In this study,we combined the solvent vapor treatment of CS2 and thermal annealing to precisely control the phase separation and domain crystallinity in PM6:M-Cl and PM6:O-Cl systems processed with the eco-solvent o-xylene.This method resulted in a maximum power conversion efficiency(PCE)of 18.4%,which is among the highest values reported for sustainable binary OSCs.Furthermore,the fabrication techniques were transferred from spin coating in a nitrogen environment to blade printing in ambient air,retaining a PCE of 16.0%,showing its potential for high-throughput and scalable production.In addition,a comparative analysis of OSCs processed with hazardous and green solvents was conducted to reveal the differences in phase aggregation.This work not only underscores the significance of sustainability in OSCs but also lays the groundwork for unlocking the full potential of open-air-printable sustainable OSCs for commercialization.

Jupiter system exploration trajectory design: Summary of the winning solution at CTOC10

This paper presents the methods and results submitted by the winning team from Harbin Institute of Technology of the 10th China Trajectory Optimization Competition(CTOC10).The problem posed by CTOC10 requires exploring the Jupiter system using a combined spacecraft.The exploration mission consists of the detection of Jupiter’s magnetic field and an exploration of the Galilean moons.The mission is completed through three steps:problem analysis,orbital design process,and data processing.The orbital design process is mainly divided into four parts,namely,repeating groundtrack orbit design,gravity-assisted orbit design,initial orbit parameter selection,and local optimization adjustment.The designed orbit is then evaluated using a heuristic optimization algorithm applied during the data processing.Finally,six full-coverage observations of Jupiter’s magnetic field are realized under the constraints of fuel and time.The final index of the submitted result is 357.8067.

Specific sensing of antibiotics with metal-organic frameworks based dual sensor system

The illegal usage of antibiotics as veterinary drugs is an increasing threat for human health.The specific sensing of antibiotics with different toxicity levels is of high challenge,and mainly relies on expensive,time-consuming,and complex instruments.To realize specific sensing by rapid and handy optical sensors,a metal-organic framework(MOF)based dual sensor system is herein developed using two MOF materials BUT-128 and BUT-129 with high sensing selectivity and sensitivity.BUT-128 and BUT-129 exhibit the lowest limit of detection(LOD)towards chloramphenicol and furazolidone among reported MOF sensors.The corresponding dual sensor system with enriched signal readouts realized specific sensing of the strictly forbidden antibiotics(chloramphenicol and nitrofurans)from other regulated veterinary drugs including thiamphenicol,a structural analog of chloramphenicol.Besides,the strategy of this work is expected to flourish the development of optical sensors with high specificity for environment and food safety purposes.

Carbene-catalyzed activation of cyclopropylcarbaldehydes for mannich reaction andδ-lactam formation:remote enantioselecitvity control and dynamic kinetic asymmetric transformation

An N-heterocyclic carbene(NHC)-catalyzed enantioselective Mannich reaction of the remoteγ-carbon of cyclopropylcarbaldehydes is disclosed for the first time.Diastereo-and enantiomerically enriched multicyclicδ-lactam compound is afforded as the main product from 8 possible stereo-specific isomers through dynamic kinetic asymmetric transformation(DYKAT)processes.Multiple chiral functional molecules can be afforded from the lactam products through simple protocols with retentions of the optical purities.

Administrative division adjustments and stock price comovement:Evidence from the city–county mergers in China

Under the background of Chinese market segmentation,whether governmentled administrative division adjustments can promote regional economic integration is a practical issue.Taking interregional firms’stock price comovement as a micro measurement of regional integration,this paper investigates the regional integration effect of administrative division adjustments,i.e.,city–county mergers.We find that stock price comovement between county-level and municipal district-level firms in the merged counties and municipal districts significantly improve after city–county mergers,particularly in regions with a higher degree of market segmentation and lower degree of marketization.We further find that the increase in stock price comovement caused by city–county mergers emerges from the increase in comovement of real activities between firms in the merged counties and municipal districts.Taken together,our results suggest that government-led administrative division adjustments effectively promote regional integration.

MACMIC Reveals A Dual Role of CTCF in Epigenetic Regulation of Cell Identity Genes

Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome,likely because such relationship can be easily identified by many established methods for correlation analysis.However,two features with little correlation may still colocalize at many genomic sites to implement important functions.There is no bioinformatic tool for researchers to specifically identify such feature pairs.Here,we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation(MACMIC)across the genome.By MACMIC analysis of 3306 feature pairs in 16 human cell types,we reveal a dual role of CCCTC-binding factor(CTCF)in epigenetic regulation of cell identity genes.Although super-enhancers are associated with activation of target genes,only a subset of super-enhancers colocalized with CTCF regulate cell identity genes.At super-enhancers colocalized with CTCF,CTCF is required for the active marker H3 K27 ac in cell types requiring the activation,and also required for the repressive marker H3 K27 me3 in other cell types requiring repression.Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity.The code for MACMIC is available at https://github.com/bxia888/MACMIC.

Broad H3K4me3 as A Novel Epigenetic Signature for Normal Development and Disease

The breadth of the enrichment site for post-translational trimethylation of histone H3 at lysine 4 （H3K4me3） on chromatin has attracted great attention recently. H3K4me3, an extensively-studied histone modification, is reported to promote gene transcription by directing preinitiation complex assembly through interaction with effector proteins, e.g.,

Cell-cell contact-induced gene editing/activation in mammalian cells using a synNotch-CRISPR/Cas9 system

Dear Editor,The CRISPR system has been widely used for genome manipulation in various cells,tissues and whole organisms.Although an increasing variety of inducible CRISPR systems have been exploited for a variety of applications,such as chemical switch(Zetsche et al.,2015),photo switch(Shao et al.,2018)and solution ligand switch(Baeumler et al.,2017;Kipniss et al.,2017;Schwarz et al.,2017)systems,a cell-cell interaction inducible system is absent.The synthetic Notch(synNotch)receptor is a recently developed cell-cell contact sensing platform,which contains a customized extracellular sensor module,a transmembrane core domain of native Notch,and a customized intracellular responder module(Morsut et al.,2016).