A Mean-Field Game for a Forward-Backward Stochastic System With Partial Observation and Common Noise

This paper considers a linear-quadratic(LQ) meanfield game governed by a forward-backward stochastic system with partial observation and common noise,where a coupling structure enters state equations,cost functionals and observation equations.Firstly,to reduce the complexity of solving the meanfield game,a limiting control problem is introduced.By virtue of the decomposition approach,an admissible control set is proposed.Applying a filter technique and dimensional-expansion technique,a decentralized control strategy and a consistency condition system are derived,and the related solvability is also addressed.Secondly,we discuss an approximate Nash equilibrium property of the decentralized control strategy.Finally,we work out a financial problem with some numerical simulations.

Agrobacterium tumefaciens-mediated transformation of embryogenic callus and CRISPR/Cas9-mediated genome editing in‘Feizixiao'litchi

Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(such as hybridization)have limited ability to nurture new litchi cultivars.Here,an efficient and stable Agrobacterium tumefaciens-mediated genetic transformation of embryogenic callus was established in‘Feizixiao’litchi.Transgenic materials were verified using polymerase chain reaction(PCR)analysis,β-glucuronidase(GUS)assay,and green fluorescent protein(GFP)assay.To implement the technology of the Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/associated protein 9(CRISPR/Cas9)technology in‘Feizixiao’litchi and verify the validity of these transformation systems,the litchi polyphenol oxidase gene(LcPPO,JF926153)was knocked out.Various categories of mutations,covering base insertions,deletions,and substitutions,were found in transgenic materials via sequence analysis.The transformation system achieved high feasibility and efficiency,and the system of CRISPR/Cas9 was successfully employed to edit genes in‘Feizixiao’litchi.This work provides an essential foundation for investigating the functions of genes and accelerating litchi genetic improvement.

Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy

Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated lipid peroxidation.However,the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis.Herein,a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin(DOX),iron and unsaturated lipid for efficient ferroptosis.By leveraging the coordination effect between DOX and Fe3+,trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method.First,Fe3+could react with the overexpressed GSH in tumor cells,inducing the GSH depletion and Fe2+generation.Second,the cleavage of trisulfide bond could also consume GSH,and the released DOX induces the generation of H2O2,which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis.Third,the formed Fe3+/Fe2+couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis.This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion,ROS generation and lipid peroxidation,providing new sights for efficient cancer therapy.

Prodrugs incorporated into nanotechnology-based drug delivery systems for possible improvement in bioavailability of ocular drugs delivery

Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.

Succinylated whey protein isolate as a sustained-release excipient of puerarin derivative oral tablets:Preparation,optimization and pharmacokinetics

This work was done to investigate succinylated commercial whey protein isolate(S-WPI)as an oral sustained-release delivery carrier for puerarin 5(PR-5). The succinylation condi-tions were established for S-WPIs by optimization of single factor study and Box–Beehnkendesign. The effect of succinylation degree on S-WPIs solubility was evaluated. Physicochem-ical properties of S-WPIs dried by different three methods on their flow ability, particle size,morphology and in vitro release behavior were studied. After preparing PR-5 sustained re-lease protein tablets with S-WPIs as the carrier by direct powder compression method, thedrug release were studied in vitro and the oral pharmacokinetics and bioavailability wasevaluated using in vivo dog model. It was observed that concentration of substrate has asignificant effect on succinylation. Release behavior in vitro showed spry dried S-WPIs with100% succinylation rate and 30% drug loading would be applied to the preparation of PR-5 sustained-release protein tablets based on the swelling mechanism(protein loss). Comparedwith PR-5 conventional tablet with oral administration, T max value of PR-5 sustained-releaseprotein tablets was approximately 1.58 fold greater than those of the conventional tablets asfurther evidenced by the significantly prolonged MRT and T 1/2. The findings demonstratedthat spray-dried S-WPIs has potential as a promising functional excipient for the design of PR-5 oral sustained-release tablets which can fully improve sustained-release effect and oral bioavailability.

Targeted delivery of docetaxel to the metastatic lymph nodes:A comparison study between nanoliposomes and activated carbon nanoparticles

The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,we first prepared the DTX-loaded activated carbon nanoparticles(DTX-AC-NPs)by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon.We then prepared DTX-loaded nanoliposomes(DTX-LPs)by the proliposome method.The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro.The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites.The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies.DTX-AC-NPs significantly increased DTX-AUC_((0-24)) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo.This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.

Characteristics of Sources and Sinks of Yugu 18

[Objectives] The study aimed to discuss the high-yield mechanism of Yugu 18.[Methods] The characteristics of sources and sinks of Yugu 18 with high quality, high yield, wide adaptability and multi-resistance to diseases were studied by using Jigu 18 as the control variety.[Results] Yugu 18 was superior in sink capability and the ability to fill sinks. In the filling period, its photosynthetic capacity was strong, and grain-leaf ratio was high. Photosynthetic products had a great contribution to grain filling after flowering, and the coordination between sources and sinks was good.[Conclusions] The research provides theoretical basis for the breeding and cultivation of high-yield foxtail millet.

Chemically derived graphene quantum dots for high-strain sensing

Graphene quantum dots(GQDs)refer to graphene fragments with a lateral dimension typically less than 100 nm,which possess unique electrical and optical properties due to the quantum confinement effect.In this study,we demonstrate that chemically derived graphene quantum dots show great potential for making highly stretchable and cost-effective strain sensors via an electron tunneling mechanism.Stretch-able strain sensors are critical devices for the field of flexible or wearable electronics which are expected to maintain function up to high strain values(>30%).However,strain sensors based on conventional materials(i.e.metal or semiconductors)or metal nanoparticles(e.g.gold or silver nanoparticles)only work within a small range of strain(i.e.the former have a working range<1%and the latter<3%).In this study,by simply dropcasting solution-processed GQDs between the interdigitated electrodes on polydimethylsiloxane,we obtained devices that can function in the range from 0.06%to over 50%ten-sile strain with both the sensitivity and working range conveniently adjustable by the concentration of GQDs applied.This study provides a new concept for practical applications of GQDs,revealing the poten-tial of this material for smart applications such as artificial skin,human-machine interfaces,and health monitoring.

辛夷散处方双提法提取工艺和挥发油包合工艺研究

目的筛选辛夷散处方双提法提取工艺和挥发油包合最佳工艺。方法以饮片粉碎粒度、提取次数、加水倍量和提取时间为考察因素,采用单因素试验优选辛夷散处方提取工艺;采用L9(34)正交试验优选辛夷散处方挥发油包合工艺。结果辛夷散双提法提取最佳工艺为饮片不粉碎,加10倍量水提取3 h;挥发油最佳包合工艺为β-环糊精∶水=1∶25,β-环糊精∶挥发油=6∶1,包合温度35℃,包合时间3 h。结论筛选的双提法提取工艺和挥发油包合工艺操作简单、稳定可行。

枯草芽孢杆菌fmb60菌株非核糖体肽类化合物对铜绿微囊藻生长的抑制作用

铜绿微囊藻是一种分布广泛的水华微藻,可对人类健康和生态环境造成严重危害,而枯草芽孢杆菌作为一种生防微生物可通过非核糖体肽合成酶合成多种生物活性物质。因此,枯草芽孢杆菌fmb60非核糖体肽(Non-ribosomal peptide,NRP)类产物对铜绿微囊藻生长抑制作用的研究在水华治理方面具有重要的意义。利用基因组挖掘技术从枯草芽孢杆菌fmb60中分离鉴定出bacillibactin、表面活性素(Surfactin)和芬芥素(Fengycin)3种NRP类产物,进而通过添加不同浓度的NRP类产物研究其对铜绿微囊藻生长的影响,结果显示其对铜绿微囊藻4 d的半效应浓度值EC50.4 d为26.5 mg/L,且随着样品浓度的增加,枯草芽孢杆菌fmb60的NRP类产物对铜绿微囊藻的抑制作用增强。当向其分别加入50 mg/L的样品时,培养4 d的铜绿微囊藻Fv/Fm、Fv/Fo、Yield参数分别比对照组降低了2.8%、1.7%、2.0%。表明枯草芽孢杆菌fmb60 NRP类产物能够显著抑制铜绿微囊藻的光合作用强度及代谢合成,从而为枯草芽孢杆菌抑藻剂的开发奠定理论基础。

农杆菌介导转化莱茵衣藻体系的优化

为建立根癌农杆菌介导的莱茵衣藻快速简便高效的遗传转化体系,本研究以模式生物莱茵衣藻为受体材料,从转化方法和转化子快速鉴定两个方面进行了优化。[方法]比较了固体培养基共培养转化方法和液体培养基共培养转化方法对根癌农杆菌LBA 4404介导的莱茵衣藻CC425转化效率的影响;研究并比较了(1)首先经过TE裂解再进行PCR(两步法)和(2)不经TE裂解直接进行PCR(一步法)的两种转化子鉴定方法的最佳反应条件和扩增效率。[结果]农杆菌LBA 4404和莱茵衣藻CC425液体培养基共培养5 d后的转化效果最好,转化率达43.33±1.67个转化子/10^(6)个藻细胞。PCR最佳反应条件为:使用高保真DNA聚合酶Taq 1进行扩增;参加PCR反应的细胞密度为5×10^(3)-5×10^(6)个/mL;TE裂解缓冲液沸水浴20 min(两步直接PCR方法),或者预变性15 min(一步直接PCR方法)。两步法直接PCR的扩增效率优于一步法,但后者反应步骤更简洁。[结论]本研究建立并优化了农杆菌液体介导莱茵衣藻遗传转化体系,该体系可快速获得遗传转化子,减少转化工作量。

Laser-MIG Arc Hybrid Brazing-Fusion Welding of Al Alloy to Galvanized Steel with Different Filler Metals

Aluminum alloy plates were joined to galvanized steel sheets with lap joint by laser-MIG arc hybrid brazingfusion welding with AlSiS, AlSi12, AlMg5 filler wires, respectively. The influences of Si and Mg on the microstructure and mechanical properties of the brazed-fusion welded joint were studied. The increase of Si element in the fusion weld can make the grain refined, and increase the microhardness of the fusion weld. Therefore, the microhardness in fusion weld made from AlSi12 and AlSi5 filler wires can be up to 98.4 HV0.01 and 96.8 HV0.01, which is higher than that from AlMg5 filler wire of 70.4 HV0.01. The highest tensile strength can reach 178.9 MPa made with AlMg5 filler wire. The tensile strength is 172.43 MPa made with AlSi5 filler wire. However, the lowest tensile strength is 144 MPa made with AlSi12 filler wire. The average thicknesses of the intermetallic compounds （IMCs） layer with AlSiS, AlSi12, AlMg5 filler wires are 1.49-2.64 #m. The IMCs layer made from AlSi5, AlSi12 filler wires are identified as FeAl2, Fe2Als, Fe4Al13 and Al0.sFesSio.5, that from AlMg5 filler wire are identified as FeAl2, Fe2Al5 and Fe4Al13.

Fibrinolytic Evaluation of Compounds Isolated from a Marine Fungus Stachybotrys Iongispora FG216

As a part of our continuing work to discover bioactive leading molecules from marine microorganism, ethyl acetate fraction of organic extract of the train Stachybotrys longispora FG216 showed fibrinolytic activity in our primary screen. The bioassay-guided purification of the active fractions resulted in isolation of a new isoindolone, FGFC2 （1） （FGFC2, Fungi fibrinolytic compound 2）, together with two known compounds, LL-Zl272β （2） and ergosterol （3）. The structure of compound 1 was elucidated by the spectral analysis of 1D （^1H, ^13C） NMR, 2D （COSY, HSQC, and HMBC） and ESI-MS. Three compounds were evaluated for fibrinolytic activities in vitro. Compared to FGFC1 （EC50=47 μmol/L） as a reference drug, compound 1 and ergosterol （3） showed moderate fibrinolytic activities in vitro with EC50 values of 108.16 and 156.30 μmol/L, respectively. LL-Z127213 （2） had no fibrinolytic activity.

Long-term exposure to decabrominated diphenyl ether mpairs CD8 T-cell function in adult mice

Polybrominated diphenyl ethers （PBDEs） are ubiquitous environmental pollutants that accumulate to high levels in human populations that are subject to occupational or regional industry exposure. PBDEs have been shown to affect human neuronal, endocrine and reproductive systems, but their effect on the immune system is not well understood. In this study, experimental adult mice were intragastrically administered 2,2＇,3,3＇,4,4＇,5,5＇,6,6＇-decabromodiphenyl ether （BDE-209） at doses of 8, 80 or 800 mg/kg of body weight （bw） at 2-day intervals. Our results showed that continuous exposure to BDE-209 resulted in high levels of BDE-209 in the plasma that approached the levels found in people who work in professions with high risks of PDBE exposure. Reduced leukocytes, decreased cytokine （IFN-7, IL-2 and TNF-a） production and lower CD8 T-cell proliferation were observed in the mice exposed to BDE-209. Additionally, mice with long-term BDE-209 exposure had lower numbers of antigen-specific CD8 T cells after immunization with recombinant Listeria monocytogenesexpressing ovalbumin （rLm-OVA） and the OVA-specific CD8 T cells had reduced functionality. Taken together, our study demonstrates that continuous BDE-209 exposure causes adverse effects on the number and functionality of immune cells in adult mice.

Backward-forward linear-quadratic mean-field games with major and minor agents

This paper studies the backward-forward linear-quadratic-Gaussian(LQG)games with major and minor agents(players).The state of major agent follows a linear backward stochastic differential equation(BSDE)and the states of minor agents are governed by linear forward stochastic differential equations(SDEs).The major agent is dominating as its state enters those of minor agents.On the other hand,all minor agents are individually negligible but their state-average affects the cost functional of major agent.The mean-field game in such backward-major and forward-minor setup is formulated to analyze the decentralized strategies.We first derive the consistency condition via an auxiliary mean-field SDEs and a 3×2 mixed backward-forward stochastic differential equation(BFSDE)system.Next,we discuss the wellposedness of such BFSDE system by virtue of the monotonicity method.Consequently,we obtain the decentralized strategies for major and minor agents which are proved to satisfy the-Nash equilibrium property.

Burden of Acute Viral Hepatitis--China,1990−2019

What is already known about this topic?The World Health Organization’s(WHO)Global Health Estimates(GHE)reported that acute hepatitis caused 9,213 deaths and 307,720 person years of disability-adjusted life years(DALYs)in 2016,and acute hepatitis B accounted for 85.81%of all DALYs among acute hepatitis types A,B,C,and E in China.What is added by this report?In China,the percent changes in years lived with disability(YLDs)due to acute hepatitis A,B,and E in groups aged 50–69 years and 70 years or more and in all age groups for acute hepatitis C were increased from 2000 to 2019.What are the implications for public health practices?Effective vaccines,interventions,and treatments are key approaches to achieve the WHO’s goal of reducing new hepatitis infections by 90%and deaths by 65%between 2016 and 2030.

Development of environmentally friendly biological algicide and biochemical analysis of inhibitory effect of diatom Skeletonema costatum

Skeletonema costatum is a diatom widely distributed in red tide microalgae blooms and as one of the main algae causing harmful algal blooms,because of their rapid reproduction and production of toxic and harmful substances,often play a negative role in aquatic ecosystems,and human health and wellbeing.Bacillomycin D is a nonribosomal cyclic antifungal lipopeptide in the iturins family.In this study,Bacillomycin D was tested for its ability to inhibit the growth of S.costatum.The EC_(50 24h) of Bacillomycin D on S.costatum was 24.70μg/mL.The chlorophyll fluorescence parameters F_(v)/F_(m),F_(v)/F_(o),and yield of the diatoms decreased significantly with increasing concentrations of Bacillomycin D.Study of the mechanism showed that Bacillomycin D induced cell death by changing cell membrane permeability,promoting the release of cellular contents.In this study,transcriptomic analysis showed Bacillomycin D significantly inhibited the photosynthesis and metabolism of S.costatum.These findings investigated the inhibitory effect of Bacillomycin D on the growth of S.costatum and provided a theoretical foundation for the development of new environmentally friendly biological algicide.

北京市某三甲医院急诊成人烧烫伤的流行病学特征

目的:了解解放军总医院第四医学中心急诊成人烧烫伤患者流行病学特征,以期为北京地区烧烫伤预防与自救处置科普工作提供参考。方法:收集2018年1月至2021年12月在解放军总医院第四医学中心烧伤整形科急诊就诊的5374例成人烧烫伤患者的病历资料。统计患者性别、致伤原因、受伤时间、受伤部位、烧伤程度等数据,并采用Excel 2019和SPSS 22.0软件进行统计学分析。结果:热液烫伤是最常见的致伤原因,占总数的73.45%。其他致伤原因包括火焰烧伤(15.17%)、化学烧伤(4.37%)、电烧伤(3.11%)、低温烫伤(2.44%)及其他原因(1.47%)。男性患者2692例,女性患者2682例,男女比例接近(1.004∶1)。在中度以上烧伤患者中,男性比例明显高于女性(2.839∶1)。上肢是最容易受到烧烫伤的部位,占受伤部位的44.08%。结论:北京地区成人烧烫伤的流行病学特征与其他地区有一定的差异,这与北京地区生产生活特点密切相关。烧烫伤预防和自救处理很重要。