Can semipermeable membranes coating materials influence in vivo performance for paliperidone tri-layer ascending release osmotic pump tablet:In vitro evaluation and in vivo pharmacokinetics study

One purpose of this study was to develop a paliperidone(PAL)tri-layer ascending release pushepull osmotic pump(TA-PPOP)tablet which could meet the needs of clinical applications.And another purpose was to investigate whether different coating materials influenced in vivo performance of TA-PPOP.The ascending release mechanism of this trilayer delivery system on theory was elaborated.TA-PPOP was prepared by means of coating with cellulose acetate(CA)or ethyl cellulose(EC).Several important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated.The optimization of formulation and process was conducted by comparing different in vitro release behaviors of PAL.In vitro dissolution studies indicated that both the two formulations of different coating materials were able to deliver PAL at an ascending release rate during the whole 24 h test.The in vivo pharmacokinetics study showed that both self-made PPOP tablets with different coating had a good in vitro-in vivo correlation(IVIVC)and were bioequivalent with the brand product,which demonstrated no significant influence of the coating materials on the in vivo release acceleration of TA-PPOP.

Development and validation of a rapid and sensitive UHPLCeMS/MS method for the determination of paliperidone in beagle dog plasma

In order to evaluate the pharmacokinetic profile of paliperidone extended-release tablets in vivo,a simple and rapid ultra-high performance liquid chromatographyetandem mass spectrometry(UHPLCeMS/MS)method was developed and validated for the determination of paliperidone in beagle dog plasma.Paliperidone and diazepam(internal standard)were extracted from plasma samples with diethyl ether,and then separated on a C_(18) column(2.1×50 mm,2.6 mm)under gradient elution with methanol-0.1%formic acid at a flow rate of 0.3 ml/min.The compounds were detected using a triple-quadrupole mass spectrometer equipped with an electrospray ionization(ESI)source.The validated method was linear over the concentration range of 1.00-1000.00 ng/ml and the lower limit of quantitation was 1.00 ng/ml.The intra-day and inter-day precision values were not more than 15%(relative standard deviation<20%at low levels),while the accuracy was within±10%of nominal values.The validated UHPLC-MS/MS method was successfully applied to an oral pharmacokinetic study of paliperidone extended-release tablets in a beagle dog.

Pharmacokinetic performance of the nitrendipine intravenous submicron emulsion in rats

To compare pharmacokinetic behaviors of nitrendipine submicron emulsion with nitrendipine solution following intravenous administration in rats.The plasma concentrations were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry detection(UPLC-MS/MS)through a new validated method.The pharmacokinetic parameters of the nitrendipine submicron emulsion and nitrendipine solution were as follows:AUC_(0-t) 900.76±186.59 versus 687.08±66.24 ng h/ml,C_(max) 854.54±159.48 versus 610.59±235.99 ng/ml,t_(1/2)2.37±1.99 versus 2.80±2.69 h.The relative bioavailability of nitrendipine submicron emulsion to nitrendipine solution was 131.4±11.3%.The developed methods could meet the requirements of bioanalysis.Compared to the solution injection,intravenous submicron emulsion presents higher systematic exposure which can help to improve the therapeutic efficacy.

Preliminary Study on Quality Analysis of Root of Griffith Streptocaulon

[Objectives]To make a preliminary study on quality analysis of Root of Griffith Streptocaulon.[Methods]The moisture,ash and extract of Root of Griffith Streptocaulon were tested in accordance with the requirements of 2015 Chinese Pharmacopoeia(Volume 4).[Results]The moisture content of Root of Griffith Streptocaulon was not higher than 12.74%,not lower than 6.26%,total ash content was not higher than 15.36%,not lower than 6.17%,acid-insoluble ash content was not higher than 0.55%,not lower than 0.17%,and extract was not higher than 11.83%,not lower than 5.23%.[Conclusions]This experiment made a preliminary study on the quality analysis of the Root of Griffith Streptocaulon,in the hope of providing a scientific basis for its quality control and formulation of the quality standard.

Efficient and Fast X-Ray Luminescence in Organic Phosphors Through High-Level Triplet-Singlet Reverse Intersystem Crossing

Organic scintillators that efficiently generate bright triplet excitons are of critical importance for highperformance X-ray-excited luminescence in radiation detection.However,the nature of triplet-singlet spinforbidden transitions in these materials often result in long-lived phosphorescence,which is undesirable for ultrafast X-ray detection and imaging.Here we demonstrate that the effect of hybridized local and charge-transfer(HLCT)excited states enables organic scintillators to exhibit highly efficient and fast radioluminescence(RL)in response to X-ray irradiation.Our experimental and theoretical investigation shows that the oxidized 1,8-naphthalimide-phenothiazine dyad(OMNI-PTZ 2)with HLCT-excited states has an enhanced overlap integral of the highest occupied molecular orbital(HOMO)and lowest unoccupied molecular orbital(LUMO)on MNIπ-orbitals,and moderate donor–acceptor electron interactions.As a result,the RL of these crystals exhibits a 61-fold increase and its monoexponential decay lifetime is three orders of magnitude faster compared to its corresponding thermally activated delayed fluorescence(TADF)molecule MNI-PTZ 1.We further demonstrate the practical utility of the OMNI-PTZ 2(G)in high-performance X-ray detection and imaging,achieving an X-ray dose sensitivity of 97 nGy s−1 and an exceptional spatial resolution of 20 lp/mm.Our study provides a promising molecular design principle for utilizing triplet excitons to develop high-efficiency and fast X-ray scintillators for the development of next-generation flexible and stretchable X-ray imaging detectors.

用于X射线成像的联萘酚二酰亚胺闪烁体

稠环二酰亚胺是一类具有突出光学性能和光电应用潜力的有机染料.本文聚焦本课题组新近开发的1,1′-双(2-萘酚-4,5-二酰亚胺)(BiND-OH)及其苯基/甲基衍生物BiND-OPh和BiND-OMe,详细研究其晶体堆积与X射线发光性能之间的构效关系,并对其X射线成像进行研究.单晶X射线衍射结果表明,BiND-OH通过分子间氢键形成两个互锁的紧密结构,导致其辐射发光性能差.相反,BiND-OPh和BiND-OMe的辐射发光强度则提高了约73倍和537倍,这主要是因为两者对分子间氢键的破坏以及以π-π作用诱导的J聚集堆积.其中,BiND-OMe具有最优异的X射线发光性能还与其较大的π-π平面距离、更长的滑移距离以及较小的π平面重叠区域等因素有关;将其用于X射线成像,检测限低至70.68 nGys^(-1),衰减时间短至4.37ns,可实现11.0 lpmm^(-1);的空间分辨率.这一发现为了解分子结构和聚集状态对有机闪烁特性的内在影响提供了宝贵的见解.

Enhancing Generic Reaction Yield Prediction through Reaction Condition-Based Contrastive Learning

Deep learning(DL)-driven efficient synthesis planning may profoundly transform the paradigm for designing novel pharmaceuticals and materials.However,the progress of many DL-assisted synthesis planning(DASP)algorithms has suffered from the lack of reliable automated pathway evaluation tools.As a critical metric for evaluating chemical reactions,accurate prediction of reaction yields helps improve the practicality of DASP algorithms in the real-world scenarios.Currently,accurately predicting yields of interesting reactions still faces numerous challenges,mainly including the absence of high-quality generic reaction yield datasets and robust generic yield predictors.To compensate for the limitations of high-throughput yield datasets,we curated a generic reaction yield dataset containing 12 reaction categories and rich reaction condition information.Subsequently,by utilizing 2 pretraining tasks based on chemical reaction masked language modeling and contrastive learning,we proposed a powerful bidirectional encoder representations from transformers(BERT)-based reaction yield predictor named Egret.It achieved comparable or even superior performance to the best previous models on 4 benchmark datasets and established state-of-the-art performance on the newly curated dataset.We found that reaction-condition-based contrastive learning enhances the model’s sensitivity to reaction conditions,and Egret is capable of capturing subtle differences between reactions involving identical reactants and products but different reaction conditions.Furthermore,we proposed a new scoring function that incorporated Egret into the evaluation of multistep synthesis routes.Test results showed that yield-incorporated scoring facilitated the prioritization of literature-supported high-yield reaction pathways for target molecules.In addition,through meta-learning strategy,we further improved the reliability of the model’s prediction for reaction types with limited data and lower data quality.Our results suggest that Egret holds the potential to become an essential component of the next-generation DASP tools.

Generic Interpretable Reaction Condition Predictions with Open Reaction Condition Datasets and Unsupervised Learning of Reaction Center

Effective synthesis planning powered by deep learning(DL)can significantly accelerate the discovery of new drugs and materials.However,most DL-assisted synthesis planning methods offer either none or very limited capability to recommend suitable reaction conditions(RCs)for their reaction predictions.Currently,the prediction of RCs with a DL framework is hindered by several factors,including:(a)lack of a standardized dataset for benchmarking,(b)lack of a general prediction model with powerful representation,and(c)lack of interpretability.To address these issues,we first created 2 standardized RC datasets covering a broad range of reaction classes and then proposed a powerful and interpretable Transformer-based RC predictor named Parrot.Through careful design of the model architecture,pretraining method,and training strategy,Parrot improved the overall top-3 prediction accuracy on catalysis,solvents,and other reagents by as much as 13.44%,compared to the best previous model on a newly curated dataset.Additionally,the mean absolute error of the predicted temperatures was reduced by about 4℃.Furthermore,Parrot manifests strong generalization capacity with superior cross-chemical-space prediction accuracy.Attention analysis indicates that Parrot effectively captures crucial chemical information and exhibits a high level of interpretability in the prediction of RCs.The proposed model Parrot exemplifies how modern neural network architecture when appropriately pretrained can be versatile in making reliable,generalizable,and interpretable recommendation for RCs even when the underlying training dataset may still be limited in diversity.

外伤性颈动脉海绵窦瘘致眼外肌麻痹1例

患者,女,40岁,因"双眼复视2周"于2020年12月21日至嘉兴市中医医院眼科就诊。患者1个月前骑电瓶车摔伤,左肩部着地受伤,未伤及头面部,就诊于外院,诊断为:左侧锁骨断裂,予以左侧锁骨整复手术。查体:一般情况可。眼科检查:裸眼视力(UCVA)右眼0.6,左眼0.4,双眼矫正视力均为1.0。眼压右眼28.8 mmHg(1 mmHg=0.133 kPa),左眼18.4 mmHg。眼球突出度:右眼19 mm,左眼12 mm,眶距104 mm。

Recent advances in metal-organic frameworks for X-ray detection

Metal-organic frameworks(MOFs)are a class of fascinating supramolecular crystalline materials that have been widely developed for catalysis,gas storage,illumination,drug delivery/cytoprotection,and so on.Recently,MOFs have been found to have potential applications in X-ray detection due to their high sensitivity,fast response time,high absorption coefficient,and radiation stability.In this review,we present an overview on the fundamental mechanism of using MOFs for X-ray scintillation.We further discuss the recent developments in X-ray detection based on indirect X-ray scintillation and direct X-ray conversion.Finally,we provide a summary and a perspective on the future of this promising research field.

1,1’-Binaphthol annulated perylene diimides: Aggregation-induced emission enhancement and chirality inversion

Aggregation-induced emission enhancement and aggregation-induced chirality inversion are two individ-ual phenomena for the enantiomerically pure organic dyes in the aggregates.Herein we reported for the first time that these two interesting phenomena could be observed simultaneously in the aggregated states of enantiomerically pure S/R-1,1?-binaphthol annulated perylene diimides,in which two perylene diimides moieties were bridged by S/R-1,1?-binaphthol(BINOL)at the bay positions.Owing to the rotat-able C2 axes between two naphthol annulated perylene diimides moieties,both of them display intrinsic behaviors of aggregation-induced emission enhancements.At the same time,due to the steric hindrances in the imide and methoxy positions,the neighboring twoπ-systems of these two unique polycyclic aro-matic imides in poor solvents are preferable to adopt a cross-stacking mode and thus form helical X-aggregates of opposite chirality(M/P)with chirality inversion characteristics in their circular dichroism and circularly polarized luminescence spectroscopic studies.