摘要：Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering *** use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and ***,these sophisticated techniques can be timeconsuming,labor-intensive,and ***,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma *** this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a *** modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during *** proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or *** algorithm can generate both patient-specific and average bone ***,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or *** algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM *** and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.

摘要：Tissue engineering(TE)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue *** this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHEMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PEDOT)and polypyrrole(PPy)nanoparticles(NPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3D)*** presence of the NPs was critical as they altered the rheological properties during ***,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3D *** were 3D printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,*** observed that the NPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 *** conductivity of the printed hydrogels increased along with the NP concentration to(5.10±0.37)×10^(−7)S/*** vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHEMA-co-MAA NP hydrogels yielded high cellular viability and proliferation ***,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial *** together,these materials show promise for various TE strategies.

摘要：The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the *** between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological *** most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune ***,each pathway is intertwined with a complex *** the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative *** paper briefly retraces the possible communication pathways between the gut microbiome and the *** further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the *** diseases also decrease patients’quality of ***,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the *** of MGBA in the laboratory uses many molecular technologies and biomaterial *** and organoids provide a more realistic picture of the cell and tissue structure than *** them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between ***-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

摘要：The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid(PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z’ factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore,the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.

摘要：Sampling design(SD) plays a crucial role in providing reliable input for digital soil mapping(DSM) and increasing its *** design, with a predetermined sample size and consideration of budget and spatial variability, is a selection procedure for identifying a set of sample locations spread over a geographical space or with a good feature space coverage. A good feature space coverage ensures accurate estimation of regression parameters, while spatial coverage contributes to effective spatial ***, we review several statistical and geometric SDs that mainly optimize the sampling pattern in a geographical space and illustrate the strengths and weaknesses of these SDs by considering spatial coverage, simplicity, accuracy, and efficiency. Furthermore, Latin hypercube sampling, which obtains a full representation of multivariate distribution in geographical space, is described in detail for its development, improvement, and application. In addition, we discuss the fuzzy k-means sampling, response surface sampling, and Kennard-Stone sampling, which optimize sampling patterns in a feature space. We then discuss some practical applications that are mainly addressed by the conditioned Latin hypercube sampling with the flexibility and feasibility of adding multiple optimization criteria. We also discuss different methods of validation, an important stage of DSM, and conclude that an independent dataset selected from the probability sampling is superior for its free model assumptions. For future work, we recommend: 1) exploring SDs with both good spatial coverage and feature space coverage; 2) uncovering the real impacts of an SD on the integral DSM procedure;and 3) testing the feasibility and contribution of SDs in three-dimensional(3 D) DSM with variability for multiple layers.

摘要：A microwave-H202 process for sludge pretreatment exhibited high efticiencies of releasing organics, nitrogen, and phosphorus, but large quantifies of H202 residues were detected. A uniform design method was thus employed in this study to further optimize H202 dosage by investigating effects of pH and H202 dosage on the amount of 1-I202 residue and releases of organics, nitrogen, and phosphorus. A regression model was established with pH and H202 dosage as the independent variables, and H202 residue and releases of organics, nitrogen, and phosphorus as the dependent variables. In the optimized microwave-H202 process, the pH value of the sludge was firstly adjusted to 11.0, then the sludge was heated to 80~C and H202 was dosed at a H202 ：mixed liquor suspended solids （MLSS） ratio of 0.2, and the sludge was finally heated to 100~C by microwave irradiation. Compared to the microwave-H202 process without optimization, the H202 dosage and the utilization rate of H202 in the optimized microwave-H202 process were reduced by 80% and greatly improved by 3.87 times, respectively, when the H202：MLSS dosage ratio was decreased from 1.0 to 0.2, resulting in nearly the same release rate of soluble chemical oxygen demand in the microwave-H202 process without optimization at H202：MLSS ratio of 0.5.

摘要：In silico modeling and analysis of small molecules substantially accelerates the process of drug development. Representing and understanding molecules is the fundamental step for various in silico molecular analysis tasks. Traditionally, these molecular analysis tasks have been investigated individually and separately.

摘要：*** A geoengineering approach for removing atmospheric CO2is growing in the climate science literature and climate policy *** recent Fifth Assessment Report(AR5)of The Intergovernmental Panel on Climate Change(IPCC,2014)which provides a clear and up-to-date assessment of the current state of scientific knowledge relevant to climate change brings climate engineering from the fringes of the

摘要：目的:评估新型硫氧还蛋白还原酶抑制剂丁烷硒啉(BS)对小鼠免疫系统及肿瘤发生的影响,并初步探讨其作用机制。创新点:实验室自主设计的硫氧还蛋白还原酶抑制剂BS对免疫系统的调节作用及机制探究。方法:将24只体重为18~22g的正常雄性KM小鼠随机分为4组,分别为BS低、中、高剂量组和对照组,每组6只动物。于接种小鼠肝癌H22细胞(1×106个/只)后第2天开始给药,给药剂量分别为:空白对照组(5g/L羧甲基纤维素钠(CMC-Na),灌胃(i.g.),每日一次(q.d.));BS低剂量组(90mg/kg,i.g.,q.d.);BS中剂量组(180mg/kg,i.g.,q.d.);BS高剂量组(360 mg/kg,i.g.,q.d.)。每天观察小鼠状态,连续8天。结论:BS通过促进小鼠脾淋巴细胞的活化来抑制肿瘤增殖。BS能够通过下调体内肿瘤细胞表面的程序性死亡配体1(PD-L1)的表达,提高小鼠CD4^-CD8^+T淋巴细胞百分比和下游细胞因子的分泌。在HepG2和BEL-7402细胞中的进一步研究表明,通过抑制信号传导子及转录激活子3(STAT3)磷酸化,BS处理后PD-L1表达水平降低。综上所述,BS通过STAT3途径降低PD-L1表达,从而产生促进免疫应答的作用,抑制肿瘤发生。

摘要：鳙(花鲢)在自然环境中分布于中国南部流域至阿穆尔河,是重要的经济性鱼类,具江湖生殖洄游特性。大坝建设阻碍了其洄游产卵繁殖通道,导致自然环境中其繁殖力的下降,需要有效的过鱼设施帮助鳙通过大坝等水流屏障。为了设计高效的鱼道引导鳙通过,本文通过自制密封的鱼类游泳实验装置,研究了鳙幼鱼游泳能力。测定了5个温度(5、10、15、20和25℃)下鳙幼鱼的临界游泳速度。通过测定不同温度下,疲劳前后血清总蛋白(TP)、血糖(GLU)和甘油三酯(TG)含量,评价疲劳运动引起的生理胁迫。结果表明,在试验温度范围内,随着温度的升高,临界游泳速度显著提高(P<0.05)。25℃时临界游泳速度最大,为7.01 BL/s(1.19 m/s)。在疲劳运动后,血清总蛋白、血糖和甘油三酯含量显著升高(P<0.05)。水温低于15℃与高于15℃相比,鳙疲劳运动后血清总蛋白、血糖和甘油三酯含量显著升高。以鳙幼鱼为研究对象,研究了非适宜温度环境和疲劳运动胁迫下鱼类的生理反应。以期为鱼类生理学研究和渔业保护管理等领域提供理论依据,为制定有效的鱼道提供数据参考。