A time-released osmotic pump fabricated by compression-coated method: Formulation screen, mechanism research and pharmacokinetic study

In this investigation,time-released monolithic osmotic pump(TMOP)tablets containing diltiazem hydrochloride(DIL)were prepared on the basis of osmotic pumping mechanism.The developed dosage forms were coated by Kollidon®SR-Polyethylene Glycol(PEG)mixtures via compression-coated technology instead of spray-coating method to form the outer membrane.For more efficient formulation screening,a three-factor five-level central composite design(CCD)was introduced to explore the optimal TMOP formulation during the experiments.The in vitro tests showed that the optimized formulation of DIL-loaded TMOP had a lag time of 4 h and a following 20-h drug release at an approximate zero-order rate.Moreover,the releasemechanismwas proven based on osmotic pressure and its profile could be well simulated by a dynamic equation.After oral administration by beagle dogs,the comparison of parameters with the TMOP tablets and reference preparations show no significant differences for C_(max)(111.56±20.42,128.38±29.46 ng/ml)and AUC_(0-48 h)(1654.97±283.77,1625.10±313.58 ng h/ml)but show significant differences for T_(max)(13.00±1.16,4.00±0.82 h).These pharmacokinetic parameters were consistent with the dissolution tests that the TMOP tablets had turned out to prolong the lag time of DIL release.

Petrogenesis and tectonic significance of the early Paleozoic Delenuoer ophiolite in the Central Qilian Shan, northeastern Tibetan Plateau

The newly discovered early Paleozoic Delenuoer ophiolite,in the western margin of the Central Qilian Shan,is composed of serpentinized peridotite,cumulate gabbro,diabase,massive basalt,and pillow basalt.This study presents geochronological and geochemical data for the cumulate gabbro and basalt.LA-ICP-MS U-Pb dating of zircons from the cumulate gabbro yielded a magmatic crystallization age of 472±4 Ma.The basalts have normal mid-ocean ridge basalt(N-MORB)compositions and a narrow range ofεNd(t)values(+4.5 to+5.3),which indicates they were derived from a depleted mantle source.On the basis of regional geological constraints,it is proposed that the Delenuoer ophiolite is a westward extension of the South Ophiolite Belt(Yushigou-Youhulugou-Donggou-Dongcaohe Ophiolite Belt)in the North Qilian Shan.The Delenuoer ophiolite,along with the Gulangxia-Delenuoer fault,defines the westernmost part of the tectonic boundary between the North and Central Qilian Shan.This ophiolite may have formed during southward subduction of the Qilian Ocean slab during the early Paleozoic.

A systematic in vitro investigation on poly-arginine modified nanostructured lipid carrier: Pharmaceutical characteristics, cellular uptake, mechanisms and cytotoxicity

The aim of the present study was to develop a poly-arginine modified nanostructured lipid carrier(R-NLC) by fusion-emulsification method and to test its pharmaceutical characteristics. The influence of R-NLC on A549 cells like cellular uptake and cytotoxicity was also appraised using unmodified NLC as the controlled group. As the results revealed, R-NLC had an average diameter of about 40 nm and a positive zeta potential of about +17 mv, the entrapment efficiency decreased apparently, and no significant difference on the in vitro drug release was found after R8-modification. The cellular uptake and cytotoxicity increased obviously compared with unmodified NLC. The cellular uptake mechanisms of R-NLC involved energy, macropinocytosis, clathrin-mediated endocytosis, and caveolin-mediated endocytosis. The outcomes of the present study strongly support the theory that cell penetrating peptides have the ability of enhancing the cellular uptake of nanocarriers.

Nanopore sequencing:flourishing in its teenage years

Over the past decade,nanopore sequencing has experienced significant advancements and changes,transitioning from an initially emerging technology to a significant instrument in the field of genomic sequencing.However,as advancements in next-generation sequencing technology persist,nanopore sequencing also improves.This paper reviews the developments,applications,and outlook on nanopore sequencing technology.Currently,nanopore sequencing supports both DNA and RNA sequencing,making it widely applicable in areas such as telomere-to-telomere(T2T)genome assembly,direct RNA sequencing(DRS),and metagenomics.The openness and versatility of nanopore sequencing have established it as a preferred option for an increasing number of research teams,signaling a transformative influence on life science research.As the nanopore sequencing technology advances,it provides a faster,more costeffective approach with extended read lengths,demonstrating the significant potential for complex genome assembly,pathogen detection,environmental monitoring,and human disease research,offering a fresh perspective in sequencing technologies.

Microbiome research outlook:past,present,and future

With its critical role in human health and disease,the microbiome has transformed modern biology.Over the past few years,microbiome research has evolved rapidly,with microbiologists gradually shifting their focus from cataloging microorganisms in the human microbiome to understanding their functional roles and how they interact with the host.Here,we present the global trends in microbiome research and summarize the past and current work on microbiome published in Protein&Cell.