Design and Fabrication of Drug Delivery Devices with Complex Architectures Based on Three-dimensional Printing Technique

A new type of implantable drug delivery devices （ DDD ） with complicated architectures were fubricated by three-dimensional printing technique, employing levofloxacin （LVFX） as a model drug. Processing parameters were optimized in riew of the layer thickness, spucing between printed lines, flow rate of liquid binder and the fast axis speed. The prepared DDD prototype consists of a double-layer structure, of which the upper region is a reservoir system and the lower region is a matrix one. The in vitro release test revealed that LVFX was released in a dual-puse pattern. This DDD may present a new strategy for the prophylaxis and treatment of diseases such as bone infection in the near future.

Synthesis and Crystal Structure of a Three-dimensional (3D) Complex Mn(H_2O)_2(HNic)_2 (HNic=2-Hydroxynicotinic Acid)

The title complex Mn（H2O）2（HNic）2 （C22H12MnN2O8, Mr = 367.18） crystallizes in monoclinic, space group P21/c with a = 7.5735（8）, b = 12.5295（13）, c = 7.6466（8）A.β = 101.2790（10）°, Z = 2, V= 711.59（13） A^3, D, = 1.714 g/cm^3,μ（MoKa） = 0.974 mm^-1, F（000） = 374, R1 （1255 observed reflections （Ⅰ 〉 2σ（Ⅰ）） = 0.0250） and wR2 = 0.0662 （all data）. In this paper, we report the complexation of Mn（Ⅱ） by the bidentate ligand 2-hydroxynicotinic acid （HNic）. In the crystal the Mn（Ⅱ） ion exhibits a deformed octahedron structure. The title complex Mn（H2O）2（HNic）2 has a three-dimensional （3D） network structure extended by hydrogen bonds, which are formed by two typical eight-membered hydrogen-bonded rings.

Structure and Bonding in Some Gd(Ⅲ) Metal Complexes Studied by Three-Dimensional X-Ray Analysis and ^(155)Gd Mssbauer Spectroscopy

Some functional lanthanide metal complexes, such as acetylacetonato complexes, ethylenediaminetetraacetato complexes, were successfully applied for diagnostic technique. The authors are interested in investigating the structure and bonding in lanthanide and actinide metal complexes using 166Er, t55Gd, and 237Np Mtissbauer spectroscopies in connection with single-crystal and/or powder X-ray diffraction, making clear the differences on their structures as well as the differences in the participation of 4f and 5f orbitals in the chemical bonds. In this article, the crystal structures of two novel Gd（Ⅲ） acetylacetonato complexes, Gd（pta）3 · 2H2O （pta = 1,1,1 -trifluoro-5,5-dimethy 1-2,4-hexanedione） and Gd（bfa）3 · 2H2O （bfa = 1, 1, 1 -trifluoro-4-phenyl-2-4-butanedione） were reported. Though both of them were dihydrate and had distorted square antiprismatical structure, Gd（pta）3 · 2H2O crystallizes in the P 2 1/n （#14） monoclinic space group and its lattice parameters are a = 1.4141（6） nm, b = 1.0708（3） nm, c =2.2344（4） nm, β =952.4（2）°, and Gd（bfa）3· 2H2O crystallizes in P 212121 orthorhombic space group and its lattice parameters were a = 1.322 （1） nm, b = 2.295 （1） nm, c = 1. 0786（8） nm. In the meantime, the authors had finished a systematic investigation on the ^155Gd Mossbauer isomer shift （δ） of various Gd（Ⅲ） metal complexes having a different coordination number （C.N.） and different ratios coordinating oxygen to nitrogen. A tendency for the 6 value to decrease with an increase in the C.N, and the number of the nitrogen atom coordinating to Gd was confirmed. This indicated that the Gd-O and/or Gd-N bond in the investigated Gd（Ⅲ） metal complexes had a small covalent contribution, which was possible to be deduced from the O and/or N atoms of the lisands donating electrons to 6s, 5d, and 4f orbitals of Gd.

The First Three-dimensional Crown Ether Complex:{[Na(B18-C-6)]_(6)[Pt(SCN)_(6)]}[Pt(SCN)_(6)](SCN)_(2)with Covalent Bond

The novel benzo-18-crown-6(B18-C-6)complex;{[Na(Bl8-C-6)]_(6)[Pt(SCN)_(6)]}[Pt(SCN)_(6)](SCN)_(2)(1)was synthesized and characterized by elemental analysis,IR spectrum and x-ray diffraction analysis.Thr crystal structure belongs to rhomobohedral,space group R-3 with cell dimesions:a=6=1.9933(3),c=2.9760(6)nm,α=β=90,γ=120°,V=10.240(3)nm^(3),Z=3,A,aclcd=1.564 g/cm^(3),F(000)=4908.1 is composed of one{[Na(B18-C-6)]_(6)[Pt(SCN)_(6)]}4+complex cation,one[Pt(SCN)_(6)]^(2-)complex anion and two SCN~anions.{[Na(B18-C-6)]_(6)[Pt(SCN)_(6)3}4+complex cation shows a three-dimensional network structure bridged by Na-O interactions between adjacent[Na(B18-C-6)]+units.The function of[Pt(SCN)_(6)]^(2-)complex anion and two SCN'anions are balancing charge in crystal.

Two kinds of contact problems in three-dimensional icosahedral quasicrystals

Two kinds of contact problems, i.e., the frictional contact problem and the adhesive contact problem, in three-dimensional （3D） icosahedral quasicrystals are dis- cussed by a complex variable function method. For the frictional contact problem, the contact stress exhibits power singularities at the edge of the contact zone. For the adhe- sive contact problem, the contact stress exhibits oscillatory singularities at the edge of the contact zone. The numerical examples show that for the two kinds of contact problems, the contact stress exhibits singularities, and reaches the maximum value at the edge of the contact zone. The phonon-phason coupling constant has a significant effect on the contact stress intensity, while has little impact on the contact stress distribution regu- lation. The results are consistent with those of the classical elastic materials when the phonon-phason coupling constant is 0. For the adhesive contact problem, the indentation force has positive correlation with the contact displacement, but the phonon-phason cou- pling constant impact is barely perceptible. The validity of the conclusions is verified.

Three-dimensional imaging reconstruction of the kidney’s anatomy for a tailored minimally invasive partial nephrectomy:A pilot study

Objective:The aim of the study was to evaluate three-dimensional virtual models(3DVMs)usefulness in the intraoperative assistance of minimally-invasive partial nephrectomy in highly complex renal tumors.Methods:At our institution cT1-2N0M0 all renal masses with Preoperative Aspects and Dimensions Used for an Anatomical classification score≥10 treated with minimally-invasive partial nephrectomy were considered for the present study.For inclusion a baseline contrast-enhanced computed tomography in order to obtain 3DVMs,the baseline and postoperative serum creatinine as well as estimated glomerular filtration rate values were needed.These patients,in which 3DVMs were used to assist the surgeon in the planning and intraoperative guidance,were then compared with a control group of patients who underwent minimally-invasive partial nephrectomy with the same renal function assessments,but without 3DVMs.Multivariable logistic regression models were used to predict the margin,ischemia,and complication score achievement.Results:Overall,79 patients met the inclusion criteria and were compared with 143 complex renal masses without 3DVM assistance.The 3DVM group showed better postoperative outcomes in terms of baseline-weighted differential estimated glomerular filtration rate(-17.7%vs.-22.2%,p=0.03),postoperative complications(16.5%vs.23.1%,p=0.03),and major complications(Clavien Dindo>III,2.5%vs.5.6%,p=0.03).At multivariable logistic regression 3DVM assistance independently predicted higher rates of successful partial nephrectomy(odds ratio:1.42,p=0.03).Conclusion:3DVMs represent a useful tool to plan a tailored surgical approach in case of surgically complex masses.They can be used in different ways,matching the surgeon's needs from the planning phase to the demolitive and reconstructive phase,leading towards maximum safety and efficacy outcomes.

Modeling time-dependent mechanical behavior of hard rock considering excavation-induced damage and complex 3D stress states

To investigate the long-term stability of deep rocks,a three-dimensional(3D)time-dependent model that accounts for excavation-induced damage and complex stress state is developed.This model comprises three main components:a 3D viscoplastic isotropic constitutive relation that considers excavation damage and complex stress state,a quantitative relationship between critical irreversible deformation and complex stress state,and evolution characteristics of strength parameters.The proposed model is implemented in a self-developed numerical code,i.e.CASRock.The reliability of the model is validated through experiments.It is indicated that the time-dependent fracturing potential index(xTFPI)at a given time during the attenuation creep stage shows a negative correlation with the extent of excavationinduced damage.The time-dependent fracturing process of rock demonstrates a distinct interval effect of the intermediate principal stress,thereby highlighting the 3D stress-dependent characteristic of the model.Finally,the influence of excavation-induced damage and intermediate principal stress on the time-dependent fracturing characteristics of the surrounding rocks around the tunnel is discussed.

Complex formulations, simple techniques: Can 3D printing technology be the Midas touch in pharmaceutical industry?

3 D printing is a method of rapid prototyping and manufacturing in which materials are deposited onto one another in layers to produce a three-dimensional object. Although 3 D printing was developed in the 1980 s and the technology has found widespread industrial applications for production from automotive parts to machine tools,its application in pharmaceutical area is still limited. However,the potential of 3 D printing in the pharmaceutical industry is now being recognized. The ability of 3 D printing to produce medications to exact specifications tailored to the needs of individual patients has indicated the possibility of developing personalized medicines. The technology allows dosage forms to be precisely printed in various shapes,sizes and textures that are difficult to produce using traditional techniques. However,there are various challenges associated with the proper application of3 D printing in the pharmaceutical sector which should be overcome to exploit the scope of this technology. In this review,an overview is provided on the various 3 D printing technologies used in fabrication of complex dosage forms along with their feasibility and limitations.

Towards dynamic structure of biological complexes at atomic resolution by cryo-EM

Cryo-electron microscopy makes use of transmission electron microscopy to image vitrified biological samples and reconstruct their three-dimensional structures from two-dimensional projections via computational approaches. After over40 years of development, this technique is now reaching its zenith and reforming the research paradigm of modern structural biology. It has been gradually taking over X-ray crystallography as the mainstream method. In this review, we briefly introduce the history of cryo-EM, recent technical development and its potential power to reveal dynamic structures. The technical barriers and possible approaches to tackle the upcoming challenges are discussed.

Crystal Structure of Organometallic Complex[Zn (pom)_2I_2]

The title complex [Zn (pom)_2I_2] (pom = 3-Methyl-4-Nitropyridine-1Oxide), C_(12)H_(12)N_4O_6I_2Zn, M_r= 627. 43, triclinic, space group P1, a= 11. 301 (2), b=13. 561(2) , c=6. 792(1) A, α=101. 29(1), β=96. 87(2), γ= 107. 13(1)°, V=957. 80(62) A￣3, Z=2, D_c=2. 175 g/cm￣3, λ(MoKa)=0. 71069 A, μ=45. 4 cm(-1),F (000) = 592, T= 296K, R(R_w) is 0. 068 (0. 078) for 2556 observed unique reflections. The structure of the complex is isolated and three-dimensional.

Precise 3D shape measurement of three-dimensional digital image correlation for complex surfaces

Three dimensional-digital image correlation （3D-DIC） is a widely used optical metrology in the experimental mechanics community because of its reliability, practicality, and flexibility. Although the precision of digital image correlation （DIC） has been thoroughly studied theoretically and numerically, verification experiments have seldom been performed, especially fbr complex surfaces with a small field of view （FOV）. In this work, the shape of a 1-yuan coin was measured using 3D-DIC; the shape was complex due to the presence of many fine details, and the FOV was relatively small because the coin diameter was only 25 mm. During the experiment, a novel strategy for speckle production was developed： white paint was simply sprayed onto the surface. Black paint was not used; instead, taking advantage of the reflective nature of the coin surface, polarized light and a Polaroid filter were introduced, and the polarization direction was carefully adjusted, ensuring that the spray pattern was extremely thin and that high-quality speckle images with significant contrast were captured. The three-dimensional coin shape was also successfully determined for comparison using a stylus profiler. The results demonstrate that 3D-DIC provides high precision in shape measurement even for complex surfaces with small FOV. The precision of 3D-DIC can reach 1/7000 of the field of view, corresponding to about 6 ~tm in this experiment.

基于信号子空间和信息复杂度的语音端点检测

针对染有加性噪声的语音信号,提出了一种基于信号子空间和信息复杂度相结合的语音端点检测方法。该方法先利用信号子空间法去除加性噪声,再对增强后的语音利用信息复杂度进行端点检测。实验仿真表明,该方法相对传统的语音端点检测方法,能提高语音端点检测准确率,特别在低信噪比条件下具有较高的端点检测准确率。

Grover量子搜索算法的一般化多相位匹配

一个量子系统将不可避免地受到不可预知的微扰影响,据此断定文献中的Grover量子搜索算法的实验实现是在三维复子空间中完成的.同时证明在二维复子空间中,对任意给定的初始态|γ0〉=cosβ0|α〉+sinβ0 eiζ|β〉(β0是较小的正实数,ζ是任意的一个实数),存在解集Fj={(θj,θj-1,…,θ1),(φj,φj-1,…,φ1)}(整数j≥2)使得目标态能以100%的最大成功概率找到,其中相位旋转角θl和φl是不为2k'π的实数(1≤l≤j,k'为任意整数).如果只要求目标态以较高的成功概率找到,那么当一个无序数据库中目标态和非目标态的总个数足够大时,对于相对较小的正整数j,解集Fj可表示为Σji=1θl=Σji=1φl的形式.

Overcoming Debye length limitations:Three-dimensional wrinkled graphene field-effect transistor for ultra-sensitive adenosine triphosphate detection

Adenosine triphosphate(ATP)is closely related to the pathogenesis of certain diseases,so the detection of trace ATP is of great significance to disease diagnosis and drug development.Graphene field-effect transistors(GFETs)have been proven to be a promising platform for the rapid and accurate detection of small molecules,while the Debye shielding limits the sensitive detection in real samples.Here,a three-dimensional wrinkled graphene field-effect transistor(3D WG-FET)biosensor for ultra-sensitive detection of ATP is demonstrated.The lowest detection limit of 3D WG-FET for analyzing ATP is down to 3.01 aM,which is much lower than the reported results.In addition,the 3D WG-FET biosensor shows a good linear electrical response to ATP concentrations in a broad range of detection from 10 aM to 10 pM.Meanwhile,we achieved ultra-sensitive(LOD:10 aM)and quantitative(range from 10 aM to 100 fM)measurements of ATP in human serum.The 3D WG-FET also exhibits high specificity.This work may provide a novel approach to improve the sensitivity for the detection of ATP in complex biological matrix,showing a broad application value for early clinical diagnosis and food health monitoring.

Efficient Approach for 3D Stationary Optical Solitons in Dissipative Systems

We feature the stationary solutions of the 3D complex cubic-quintic Ginzburg-Landau equation (CGLE). Our approach is based on collective variables approach which helps to obtain a system of variational equations, giving the evolution of the light pulses parameters as a function of the propagation distance. The collective variables approach permits us to obtain, efficiently, a global mapping of the 3D stationary dissipative solitons. In addition it allows describing the influence of the parameters of the equation on the various physical parameters of the pulse and their dynamics. Thus it helps to show the impact of dispersion and nonlinear gain on the stationary dynamic.

Modeling tuberous sclerosis complex with human induced pluripotent stem cells

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and skin.Importantly,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum disorder.Mutations in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling pathway.Animal models have been widely used to study the effect of TSCl/2 genes on the development and function of the brain.Despite considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human neurodevelopment.Data sources Literature reviews and research articles were published in PubMed-indexed journals.Results Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human brain.Conclusions In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

Crystal structures and thermal decomposition mechanism of four lanthanide complexes with halogen-benzoic acid and 1,10-phenanthroline

This paper describes syntheses and structure determination of four lanthanide complexes [Nd(2-Cl-4-FBA) 3 phen] 2 (1, 2-Cl-4-FBA = 2-chloro-4-fluorobenzoate, phen = 1,10-phenanthroline), [Ln(2,5-DClBA) 3 phen] 2 (Ln = Sm(2) and Tb(3), 2,5-DClBA = 2,5-dichlorobenzoate) and [Sm(2-Cl-4,5-DFBA) 3 (phen)(H 2 O)] 2 (4, (2-Cl-4,5-DFBA = 2-chloro-4,5-difluorobenzo- ate). The complexes were characterized by elemental analysis, infrared and ultraviolet spectra, and X-ray single-crystal diffraction. In the molecular structures of 1 4, two Ln 3+ ions are linked by four carboxyl groups, with two of them in a bridging bidentate mode and the other two in a bridging-chelating tridentate mode, forming four binuclear molecules. In addition, each Ln 3+ ion is also chelated to one phen molecule and one carboxyl group in the complexes, except each Sm 3+ ion in 4 which is bonded to one carboxyl group by unidentate mode and one H 2 O molecule. There are two different coordination polyhedrons for each Nd 3+ ion in the two similar molecular structures of 1 and they are a distorted monocapped square antiprismatic and a distorted tricapped triangular prism conformation, respectively. The coordination polyhedron for each Ln 3+ ion in 2 4 is a nine-coordinated distorted mono-capped square antiprismatic conformation. The complex 3 exhibits green luminescence under the radiation of UV light. The thermal decomposition behaviors of the complexes have been discussed by simultaneous TG/DSC-FTIR technique. The 3D surface graphs for the FTIR spectra of the evolved gases were recorded and the gaseous products were identified by the typical IR spectra obtained at different temperatures from the 3D surface graphs. Meanwhile, we discussed the nonisothermal kinetics of 1 4 by the integral isoconversional non-linear (NL-INT) method.

Synthesis and Crystal Structure of a New Diamine Complex CuCl_4(H_2tn)

In an attempt to synthesize a new pyrimidine complex of copper(II) in a solution reaction of CuBr2 with 2,2'-bis(hexahydropyrimidine) and hydro-chloric acid, we unexpectedly obtained a bright yellow chip-like crystal of CuCl4(H2tn) [H2tn=(H3NCH2CH2CH2NH3)2+]. Its structure was determined by single-crystal X-ray diffraction analysis. The crystal belongs to orthorhombic system, space group Pnma, with cell parameters: a=0.7216(2) nm, b=1.8308(6) nm, c=0.7553(3) nm, V=0.9953(6) nm3, Z=4, F(000)=564, Mr=281.49, Dc=1.879 g/cm3. (Mo Ka)=3.204 mm-1, R1=0.0248, wR2=0.0575. The analysis of the crystal structure indicates that the complex has a three-dimensional network structure, which is formed by hydrogen bonds and electrostatic interaction.

Synthesis and crystal structure of heteronuclear La(Ⅲ)-Cu(Ⅱ) complex {[LaCu_2(NTA)_2(4,4'-bpy)(H_2O)_3]NO_3·5H_2O}_n

A novel La(Ⅲ)-Cu(Ⅱ)heterometallic coordination polymer {[LaCu2(NTA)2(4,4'-bpy)(H2O)3]NO3 5H2O}n,where H3NTA denotes nitrilotriacetic acid and 4,4'-bpy denotes 4,4'-bipyridine,was synthesized and characterized by IR spectrum,elemental analysis and X-ray diffraction.The complex crystallizes in the triclnic space group PT with cell parameters a=1.33710(10)nm,b=1.44530(10)nm,c=1.0949(2)nm,α=71.905(7),β=74.327(7),γ=64.427(9),V=1.7912(4)nm3 and Z=2.It consists of heterometallic units,in which each La(Ⅲ)ion is coordinated in a distorted mono-capped square antiprism by three oxygen atoms from water molecules and six carboxyl oxygen atoms from five NTA3-ions,and each Cu(Ⅱ)ion is coordinated by one nitrogen atom from 4,4'-bpy and one nitrogen atom,three oxygen atoms from NTA3-.In the title complex,La(Ⅲ)ions and Cu(Ⅱ)ions are connected by the heterometallic bridging of NTA3-,constructing a two-dimensional network structure along the [110].And it is extended into an infinite three-dimensional network structure by the formation of homometallic bridging of Cu-4,4'-bpy-Cu,exhibiting a certain inclusion ability.

Numerical study of successive CMEs during November 4―5, 1998

We present the solar-terrestrial transit process of three successive coronal mass ejections (CMEs) of November 4―5, 1998 originating from active region 8375 by using a time-dependent three-dimensional magnetohydrodynamics (MHD) simula-tion. These CMEs interacted with each other while they were propagating in inter-planetary space and finally formed a "complex ejecta". A newly developed SIP-CESE MHD model was applied to solve MHD equations numerically. The quiet solar wind was started from Parker-like 1D solar wind solution and the magnetic field map was calculated from the solar photospheric magnetic field data. In our simulation, the ejections were initiated using pulse in the real active region 8375. The interplanetary disturbance parameters, such as speed, direction and angular size of the expanding CME, were determined from the SOHO/LASCO data with the cone-model. We discussed the three-dimensional aspects of the propagation, in-teraction and merging of the three ejections. The simulated interplanetary shocks were compared with the nearby-Earth measurement. The results showed that our simulation could reproduce and explain some of the general features observed by satellite for the "complex ejecta".