Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.

SeDeM Expert System: A review and new perspectives

The SeDeM Expert System was first known as a galenic pre-formulation system, which was based on the experimental research and quantitative determination of powdered substances. And the mathematical formula provided by the SeDeM Expert System has plays an important role in the study of powder properties. The system can be used not only to evaluate the powder direct compression (DC) of excipients and active pharmaceutical ingredients (API’s), but also to predict the possible formulations, so it can reduce unnecessary research and trials, and shorten the time of development. In this paper, the research development and application of SeDeM Expert System in DC was summarized, and the results showed that with a few exceptions, the system was skilled in predicting acceptable tablet formulations. Finally, the new application prospect of the system is presented, including the application of the Internet traffic and content management (iTCM) database and the new co-processed excipients.

Drawing on the Development Experiences of Infectious Disease Surveillance Systems Around the World

High-quality infectious disease surveillance systems are foundational to infectious disease prevention and control.Current major infectious disease surveillance systems globally can be categorized as either indicatorbased,which are more specific,or event-based,which are more timely.Modern surveillance systems commonly utilize multi-source data,strengthened information sharing,advanced technology,and improved early warning accuracy and sensitivity.International experience may provide valuable insights for China.China’s existing infectious disease surveillance systems require urgent enhancements to monitor emerging infectious diseases and improve the integration and learning capabilities of early warning models.Methods such as establishing multi-stage surveillance systems,promoting cross-sectoral and cross-provincial data sharing,applying advanced technologies like artificial intelligence,and cultivating professional talent should be adopted to enhance the development of intelligent and multipoint-triggered infectious disease surveillance systems in China.

应用生物技术降解木质纤维素水解液中呋喃醛

木质纤维素是地球上储量最为丰富的可再生有机碳资源,但由于其结构的复杂性,必须经过一系列预处理过程才能被微生物高效利用,这就不可避免地带来了呋喃醛等典型抑制物,严重阻碍了微生物的生长和后续发酵过程。认知微生物的呋喃醛代谢途径,并基于此开发耐受性和转化能力强的微生物菌株是生物炼制领域的重要研究内容。文中综述了呋喃醛抑制物的来源、呋喃醛对微生物的抑制机理以及微生物降解呋喃醛的代谢途径,并重点讨论了基于生物法降解呋喃醛抑制物的研究进展,涉及的主要技术手段包括传统的适应性进化工程和代谢工程,以及近年来新兴的微生物共培养系统和功能化材料辅助微生物脱除呋喃醛等。

Metal-organic frameworks for advanced drug delivery

Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and easy surface functionalization make this large family more and more popular for drug delivery.There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications.This article presents an overall review and perspectives of MOFs-based drug delivery systems(DDSs),starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands.Then,the synthesis and characterization of MOFs for DDSs are developed,followed by the drug loading strategies,applications,biopharmaceutics and quality control.Importantly,a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics,diseases therapy and advanced DDSs.In particular,the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed.Finally,challenges in MOFs development for DDSs are discussed,such as biostability,biosafety,biopharmaceutics and nomenclature.

病毒功能性受体的筛选新策略及其应用

病毒通过与靶细胞表面的特异性受体结合,进而吸附、入侵靶细胞,劫持细胞的复制机器完成自身的复制周期。细胞受体作为病毒入侵宿主的门户,细胞受体的结构与功能及其介导病毒入侵的机制一直是病毒学研究的热点之一。对细胞受体的研究有助于了解病毒的致病机制并为病毒性疾病的防控提供科学依据。近年来,利用功能缺失性基因组学筛选病毒功能性受体的进展极大地拓展了人类对病毒入侵机制的认识和理解。目前,应用较为广泛的病毒功能性受体筛选策略包括RNA干扰技术、利用单倍体细胞系随机插入逆转录病毒致突变技术以及基于CRISPR/Cas9系统的新型编辑技术。本文系统介绍并比较了这三种病毒功能性受体筛选新策略,同时对其应用及优缺点进行了归纳总结,可为相关研究者提供一定的参考。

Topological insula tor: Spintronics and quantum computations

Topological insulators are emergent states of quantum matter that are gapped in the bulk with timereversal symmetry-pteserved gapless edge/surface states, adiabatically distinct from conventional mat erials. By proximity to various magnets and superconductors, to pological insula tors show novel physics at the interfaces, which give rise to two new areas named topological spintronics and topological quantum compu tat ion. Effects in the former such as the spin to rques, spin-charge conversion, to pological antiferromagnetic spintronics, and skyrmions realized in topological systems will be addressed. In the latter, a superconducting pairing gap leads to a state that supports Majorana fermions states, which may provide a new path for realizing to pological quantum comp ut at ion. Various signa tu res of Majorana zero modes/edge mode in topological superconductors will be discussed. The review ends by outlooks and potential applications of topological insulators. Topological superconductors that are fabricated using topological insulators with superconductors have a full pairing gap in the bulk and gapless surface states consisting of Majorana fermions. The theory of topological superconductors is reviewed, in close analogy to the theory of topological insulators.

Impact of molecular weight on the mechanism of cellular uptake of polyethylene glycols(PEGs) with particular reference to P-glycoprotein

Polyethylene glycols(PEGs)in general use are polydisperse molecules with molecular weight(MW)distributed around an average value applied in their designation e.g.,PEG 4000.Previous research has shown that PEGs can act as P-glycoprotein(P-gp)inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs.However,questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed.In this study,we examined the mechanism of uptake of PEGs by MDCK-mock cells,in particular,the effect of MW and interaction with P-gp by MDCK-hMDRl and A549 cells.The results show that:(a)the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors;(b)PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil;and(c)uptake of PEGs of low MW(<2000 Da)occurs by passive diffusion whereas uptake of PEGs of hish MW(>5000 Da)occurs by a combination of passive diffusion and caveolae-mediated endocytosis.These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.

High-capacity organic electrode material calix[4] quinone/CMK-3 nanocomposite for lithium batteries

Organic lithium-ion batteries（OLIBs） represent a new generation of power storage approach for their environmental benignity and high theoretical specific capacities.However, it has the disadvantage with regard to the dissolution of active materials in organic electrolyte. In this study, we encapsulated high capacity material calix[4]quinone（C4Q） in the nanochannels of ordered mesoporous carbon（OMC）CMK-3 with various mass ratios ranging from 1：3 to 3：1, and then systematically investigated their morphology and electrochemical properties. The nanocomposites characterizations confirmed that C4Q is almost entirely capsulated in the nanosized pores of the CMK-3 while the mass ratio is less than2：1. As cathodes in lithium-ion batteries, the C4Q/CMK-3（1：2） nanocomposite exhibits optimal initial discharge capacity of 427 mA h g^（-1） with 58.7% cycling retention after 100 cycles. Meanwhile, the rate performance is also optimized with a capacity of 170.4 mA h g^（-1） at 1 C. This method paves a new way to apply organic cathodes for lithium-ion batteries.

HBXIP blocks myosin-ⅡA assembly by phosphorylating and interacting with NMHC-ⅡA in breast cancer metastasis

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton.As a key component of actomyosin filaments,non-muscle myosin-ⅡA disassembly contributes to tumor cell spreading and migration.However,its regulatory mechanism in tumor migration and invasion is poorly understood.Here,we found that oncoprotein hepatitis B X-interacting protein(HBXIP) blocked the myosin-ⅡA assemble state promoting breast cancer cell migration.Mechanistically,mass spectrometry analysis,co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain(ACD) of non-muscle heavy chain myosin-ⅡA(NMHC-ⅡA).The interaction was enhanced by NMHC-ⅡA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβⅡ.Moreover,HBXIP induced the transcription of PRKCB,encoding PKCβⅡ,by coactivating Sp1,and triggered PKCβⅡ kinase activity.Interestingly,RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate(BZF) suppressed breast cancer metastasis via inhibiting PKCβⅡ-mediated NMHC-ⅡA phosphorylation in vitro and in vivo.We reveal a novel mechanism by which HBXIP promotes myosin-ⅡA disassembly via interacting and phosphorylating NMHC-ⅡA,and BZF can serve as an effective anti-metastatic drug in breast cancer.

Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats

Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.

腹部无辅助切口经直肠切口取标本的腹腔镜右半结肠癌根治术(CRC-NOSES-Ⅷ式B法)近期疗效分析

目的探讨经直肠取标本的腹腔镜右半结肠癌根治术(CRC-NOSES-Ⅷ式B法)的安全性、可行性和近期疗效。方法收集2018年1月至2021年4月在中国医学科学院肿瘤医院行腹部无辅助切口经直肠取标本的腹腔镜右半结肠癌根治术和腹腔镜辅助下右半结肠癌根治术患者的临床资料,回顾性分析两种术式对患者术后恢复情况、并发症及病理结果的影响。结果共有15例患者行腹部无辅助切口经直肠取标本的腹腔镜右半结肠癌根治手术(研究组),随机抽取同期符合入组条件的腹腔镜辅助下右半结肠癌根治术男性患者45例设为对照组。研究组和对照组性别、年龄、ASA分级、实验室检查、术前肿瘤大小、部位及TNM分期等差异无统计学意义(P>0.05),BMI指数研究组和对照组之间差异有统计学意义(t=-2.401,P=0.022)。研究组和对照组患者均顺利完成手术,无中转开腹病例,手术时间、术中出血量、肠道功能恢复时间、术后住院天数、术后病理肿瘤最大径、淋巴结检出及阳性个数、肿瘤病理类型、分化程度和肿瘤的术后TNM分期等差异均无统计学意义(P>0.05),术后第一天疼痛评分、第三天疼痛评分研究组与对照组差异有统计学意义(t=-6.477,10.160;P<0.05)。研究组术后均未出现肠梗阻、腹腔出血、腹腔感染、吻合口漏、吻合口出血、吻合口狭窄、直肠切口出血、直肠切口漏等并发症,全组患者控粪功能未受明显影响。结论BMI指数在CRC-NOSES-Ⅷ式B法与腹腔镜辅助右半结肠癌根治术术式选择方面有重要价值和参考意义。在经选择适合入组的右半结肠癌患者行CRC-NOSES-Ⅷ式B法与传统腹腔镜辅助右半结肠癌根治术的近期疗效类似,手术技术安全可行,患者的疼痛感明显减轻。