Causal relationship between circulating vitamin C and 25-hydroxyvitamin D concentrations and common mental disorders-a Mendelian randomization study

Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.

Progress in Research on Propagation Technology of Machilus Nees

Machilus spp.are mostly valuable timber and economic tree species,widely used in many fields such as artificial afforestation,landscaping,furniture and building materials,chemicals and medicine.In this article,the distribution,uses and domestic resources of Machilus Nees are summarized.Focus is placed on the analysis of propagation methods,including seed propagation,cutting propagation and tissue culture propagation.The research status and existing problems are summarized,and the future research focus on the propagation technology of Machilus Nees is prospected,with a view to provide theoretical references for the efficient breeding of high-quality seedlings and comprehensive promotion and application of Machilus spp.and contribute to the conservation and sustainable use of wild resources.

DFM:“Design for Manufacturing”or“Design Friendly Manufacturing”

As the IC manufacturing enter sub 20nm tech nodes,DFM become more and more important to make sure more stable yield and lower cost.However,by introducing newly designed hardware(1980i etc.)process chemical(NTD)and Control Algorithm(Focus APC)into the mature tech nodes such as 14nm/12nm,more process window and less process variations are expected for latecomer wafer fabs(Tier-2/3 companies)who just started the competition with Tier-1 companies.With improved weapons,latecomer companies are able to review their DFM strategy one more time to see whether the benefit from hardware/process/control algorithm improvement can be shared with designers.In this paper,we use OPC simulation tools from different EDA suppliers to see the feasibility of transferring the benefits of hardware/process/control algorithm improvement to more relaxed design limitation through source mask optimization(SMO):1)Better hardware:scanner(better focus/exposure variation),CMP(intrafield topo),Mask CD variation(relaxed MEEF spec),etc.2) New process:from positive tone development to negative tone development.3)Better control schemes:holistic focus feedback,feedback/forward overlay control,high order CD uniformity improvement.Simulations show all those gains in hardware and process can be transferred into more relaxed design such as sub design rule structure process window include forbidden pitches(1D)and smaller E2E gaps(2D weak points).

GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy

Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them.The purpose of this work is to construct a self-assembled glutathione(GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription(RCT) method. GSH-responsive cationic polymer polyethyleneimine(pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid(DHA), a targeting molecule, which is a substrate of glucose transporter 1(GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.

Clinically applicable artificial intelligence algorithm for the diagnosis,evaluation,and monitoring of acute retinal necrosis

The prompt detection and proper evaluation of necrotic retinal region are especially important for the diagnosis and treatment of acute retinal necrosis(ARN).The potential application of artificial intelligence(AI)algorithms in these areas of clinical research has not been reported previously.The present study aims to create a computational algorithm for the automated detection and evaluation of retinal necrosis from retinal fundus photographs.A total of 149 wide-angle fundus photographs from40 eyes of 32 ARN patients were collected,and the U-Net method was used to construct the AI algorithm.Thereby,a novel algorithm based on deep machine learning in detection and evaluation of retinal necrosis was constructed for the first time.This algorithm had an area under the receiver operating curve of 0.92,with 86%sensitivity and 88%specificity in the detection of retinal necrosis.For the purpose of retinal necrosis evaluation,necrotic areas calculated by the AI algorithm were significantly positively correlated with viral load in aqueous humor samples(R2=0.7444,P<0.0001)and therapeutic response of ARN(R2=0.999,P<0.0001).Therefore,our AI algorithm has a potential application in the clinical aided diagnosis of ARN,evaluation of ARN severity,and treatment response monitoring.

A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

Background:Multidrug-resistant(MDR)gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality.Moreover,the formation of biofilms makes these bacteria difficult to control.Therefore,developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed.The purpose of this study was to develop a multifunctional nanoassembly(IRNB)based on IR-780 and N,N-di-sec-butyl-N,N-dinitroso-1,4-phenylenediamine(BNN6)for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.Methods:The characterization and bacteria-targeting ability of IRNB were investigated.The bac-tericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay,plate counting method and live/dead staining in vitro.The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo.A cell counting kit-8 assay,Calcein/PI cytotoxicity assay,hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo.Results:Herein,we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy(PTT),photodynamic therapy(PDT)and nitric oxide(NO)effect triggered by an 808 nm laser.This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect.Upon irradiation with an 808 nm laser,IRNB was activated and produced both reactive oxygen species(ROS)and hyperthermia.The local hyperthermia could induce NO generation,which further reacted with ROS to generate ONOO−,leading to the enhancement of bactericidal efficacy.Furthermore,NO and ONOO−could disrupt the cell membrane,which converts bacteria to an extremely susceptible state and further enhances the photothermal effect.In this study,IRNB showed a superior photothermal-photodynamic-chemo(NO)synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.This resulted in effective control of associated infections,relief of inflammation,promotion of re-epithelization and collagen deposition,and regulation of angiogenesis during wound healing.Moreover,IRNB exhibited excellent biocompatibility,both in vitro and in vivo.Conclusions:The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.

浙江种子植物物种编目

生物多样性的编目和分类以及生物多样性监测是全球生物多样性研究的两个核心内容。物种编目是了解物种多样性的基础,只有掌握物种分布格局及物种与环境的关系,才能为物种监测和科学管理提供依据。作为浙江种子植物研究的“家底”,本文在《浙江植物志(新编)》编研的基础上,系统整理了浙江种子植物的物种名录。结果显示,浙江共有种子植物212科1,469属4,430种,其中野生植物有190科1,085属3,347种。所含种数多于100种的科有禾本科(285种)、莎草科(216种)、菊科(186种)、蔷薇科(153种)、兰科(126种)、蝶形花科(109种)和唇形科(108种);含20种以上的属有15属,包括薹草属(Carex,126种)、刚竹属(Phyllostachys,44种)、悬钩子属(Rubus,44种)、冬青属(Ilex,35种)、蓼属(Polygonum,34种)、珍珠菜属(Lysimachia,32种)、铁线莲属(Clematis,31种)、景天属(Sedum,28种)、槭属(Acer,26种)、荚蒾属(Viburnum,26种)、飘拂草属(Fimbristylis,26种)、蒿属(Artemisia,25种)、堇菜属(Viola,22种)、葡萄属(Vitis,21种)和山矾属(Symplocos,21种)。其区系特点主要反映在:物种丰富,其科属组成多样;保存了较多古老孑遗植物;地理成分多样,联系广泛,由热带向温带过渡;中国特有科2科、中国特有属45属、浙江(准)特有种近500种(含亚种和变种),珍稀濒危植物丰富,96种为国家重点保护植物;外来植物多,入侵风险大,有些种已形成明显的危害。

Substance P-modified human serum albumin nanoparticles loaded with paclitaxel for targeted therapy of glioma

The blood–brain barrier(BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme(GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel(PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles(NPs). Here we characterize PTX-loaded human serum albumin(HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P(SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content(7.89%) and entrapment efficiency(85.7%) with a spherical structure(about 150 nm) and zeta potential of -12.0 mV. The in vitro drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells(BCECs) and U87 cells was greatly improved.The low IC_(50), prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.

Bone marrow mesenchymal stem cells-derived exosomes for penetrating and targeted chemotherapy of pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix(ECM). Based on the theory that bone marrow mesenchymal stem cells(BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes(Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel(PTX) and gemcitabine monophosphate(GEMP)-an intermediate product of gemcitabine metabolismd-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy in vivo and in vitro, plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance(Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.

Construction of heparin-based hydrogel incorporated with Cu_(5.4)O ultrasmall nanozymes for wound healing and inflammation inhibition

Excessive production of inflammatory chemokines and reactive oxygen species(ROS)can cause a feedback cycle of inflammation response that has a negative effect on cutaneous wound healing.The use of wound-dressing materials that simultaneously absorb chemokines and scavenge ROS constitutes a novel‘weeding and uprooting’treatment strategy for inflammatory conditions.In the present study,a composite hydrogel comprising an amine-functionalized star-shaped polyethylene glycol(starPEG)and heparin for chemokine sequestration as well as Cu_(5.4)O ultrasmall nanozymes for ROS scavenging(Cu_(5.4)O@Hep-PEG)was developed.The material effectively adsorbs the inflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8,decreasing the migratory activity of macrophages and neutrophils.Furthermore,it scavenges the ROS in wound fluids to mitigate oxidative stress,and the sustained release of Cu_(5.4)O promotes angiogenesis.In acute wounds and impaired-healing wounds(diabetic wounds),Cu_(5.4)O@Hep-PEG hydrogels outperform the standard-of-care product Promogram®in terms of inflammation reduction,increased epidermis regeneration,vascularization,and wound closure.

A ROS-responsive,self-immolative and self-reporting hydrogen sulfide donor with multiple biological activities for the treatment of myocardial infarction

Myocardial infarction(MI),as one of the leading causes of global death,urgently needs effective therapies.Recently,hydrogen sulfide(H2S)has been regarded as a promising therapeutic agent for MI,while its spatiotemporally controlled delivery remains a major issue limiting clinical translation.To address this limitation,we designed and synthesized a novel H2S donor(HSD-R)that can produce H2S and emit fluorescence in response to reactive oxygen species(ROS)highly expressed at diseased sites.HSD-R can specifically target mitochondria and provide red fluorescence to visualize and quantify H2S release in vitro and in vivo.Therapeutically,HSD-R significantly promoted the reconstruction of cardiac structure and function in a rat MI model.Mechanistically,myocardial protection is achieved by reducing cardiomyocyte apoptosis,attenuating local inflammation,and promoting angiogenesis.Furthermore,inhibition of typical pro-apoptotic genes(Bid,Apaf-1,and p53)played an important role in the anti-apoptotic effect of HSD-R to achieve cardioprotection,which were identified as new therapeutic targets of H2S against myocardial ischemia injury.This ROS-responsive,self-immolative,and fluorescent H2S donor can serve as a new theranostic agent for MI and other ischemic diseases.

SED：An SDN-Based Explicit-Deadline-Aware TCP for Cloud Data Center Networks

Cloud data centers now provide a plethora of rich online applications such as web search, social networking, and cloud computing. A key challenge for such applications, however, is to meet soft real-time constraints. Due to the deadline-agnostic congestion control in Transmission Control Protocol（TCP）, many deadline-sensitive flows cannot finish transmission before their deadlines. In this paper, we propose an SDNbased Explicit-Deadline-aware TCP（SED） for cloud Data Center Networks（DCN）. SED assigns a base rate for non-deadline flows first and gives spare bandwidth to the deadline flows as much as possible. Subsequently,a Retransmission-enhanced SED（RSED） is introduced to solve the packet-loss timeout problem. Through our experiments, we show that SED can make flows meet deadlines effectively, and that it significantly outperforms previous protocols in the cloud data center environment.