Real-Time Monitoring of Multistep Batch and Flow Synthesis Processes of a Key Intermediate of Lifitegrast by a Combined Spectrometer System with Both Near-Infrared and Raman Spectroscopies Coupled to Partial Least-Squares.

Process analytical technology (PAT) has been successfully applied in numerous chemical synthesis cases and is an important tool in pharmaceutical process research and development. PAT brings new methods and opportunities for the real-time monitoring of chemical processes. In multistep synthesis, real-time monitoring of the complex reaction mixtures is a significant challenge but provides an opportunity to enhance reaction understanding and control. In this study, a combined multichannel spectrometer system with both near-infrared and Raman spectroscopy was built, and calibration models were developed to quantify the desired products, intermediates, and impurities in real-time at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating dynamic experiments in both batch and continuous-flow processes. It represents a significant step forward in data-driven, multistep pharmaceutical ingredient synthesis.

Identification and characterization of the CRK gene family in the wheat genome and analysis of their expression profile in response to high temperature-induced male sterility.

Cysteine-rich receptor-like kinases (CRKs) play many important roles during plant development, including defense responses under both biotic and abiotic stress, reactive oxygen species (ROS) homeostasis, callose deposition and programmed cell death (PCD). However, there are few studies on the involvement of the CRK family in male sterility due to heat stress in wheat (Triticum aestivum L.). In this study, a genome-wide characterization of the CRK family was performed to investigate the structural and functional attributes of the wheat CRKs in anther sterility caused by heat stress. A total of 95 CRK genes were unevenly distributed on 18 chromosomes, with the most genes distributed on chromosome 2B. Paralogous homologous genes with Ka/Ks ratios less than 1 may have undergone strong purifying selection during evolution and are more functionally conserved. The collinearity analysis results of CRK genes showed that wheat and Arabidopsis (A. thaliana), foxtail millet, Brachypodium distachyon (B. distachyon), and rice have three, 12, 15, and 11 pairs of orthologous genes, respectively. In addition, the results of the network interactions of genes and miRNAs showed that five miRNAs were in the hub of the interactions map, namely tae-miR9657b-5p, tae-miR9780, tae-miR9676-5p, tae-miR164, and tae-miR531. Furthermore, qRT-PCR validation of the six TaCRK genes showed that they play key roles in the development of the mononuclear stage anthers, as all six genes were expressed at highly significant levels in heat-stressed male sterile mononuclear stage anthers compared to normal anthers. We hypothesized that the TaCRK gene is significant in the process of high-temperature-induced sterility in wheat based on the combination of anther phenotypes, paraffin sections, and qRT-PCR data. These results improve our understanding of their relationship.

High AMH levels are associated with gestational hypertension in patients with PCOS who underwent IVF/ICSI-ET.

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) have a higher risk of obstetric complications. The association between anti-Müllerian hormone (AMH) and gestational hypertension in these patients is poorly understood. OBJECTIVE: To determine the association between serum AMH levels and gestational hypertension in patients with PCOS undergoing fresh embryo transfer. METHODS: This retrospective study included 649 patients with PCOS who had singleton live births after undergoing fresh embryo transfers. The association of AMH with gestational hypertension in these patients was estimated before and after propensity score matching (PSM). RESULTS: Patients with gestational hypertension had higher AMH levels than those without gestational hypertension. In single-factor logistic regression, the odds of gestational hypertension increased by 11.7% and 18.6% for every 1 ng/mL increase in AMH before and after adjusting for confounding factors [OR 1.117, 95% CI(1.025, 1.217), P = 0.012; adjusted OR 1.186, 95% CI(1.061, 1.327), adjusted P = 0.003], respectively. The odds of gestational hypertension increased more than 100% [adjusted OR 2.635, 95% CI(1.132, 6.137), adjusted P = 0.025] in the 75th percentile group (>9.30 ng/ml) and more than thrice [adjusted OR 4.75, 95% CI(1.672, 13.495), adjusted P = 0.003] in the 90th percentile group (>12.31 ng/ml) as compared to the without-gestational hypertension group. AMH level was still associated with gestational hypertension after PSM. The area under the curve of AMH predicting gestational hypertension was 0.654 [95% CI (0.532, 0.776), P = 0.011] with an optimal cutoff value of 11.975 ng/mL. CONCLUSIONS: High serum AMH level pre-pregnancy (especially at levels > 9.30 ng/mL) indicates a high odds of gestational hypertension in patients with PCOS undergoing fresh embryo transfer.

Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events, however, the effects of mechanical force on vesicular release has been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channel in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines release by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide a revealing insight on the regulatory effects of mechanical stimuli on vesicular exocytosis.

Interaction between Dietary Lactoferrin and Gut Microbiota in Host Health.

The gut microbiota are known to play an important role in host health and disease. Alterations in the gut microbiota composition can disrupt the stability of the gut ecosystem, which may result in noncommunicable chronic diseases (NCCDs). Remodeling the gut microbiota through personalized nutrition is a novel therapeutic avenue for both disease control and prevention. However, whether there are commonly used gut microbiota-targeted diets and how gut microbiota-diet interactions combat NCCDs and improve health remain questions to be addressed. Lactoferrin (LF), which is broadly used in dietary supplements, acts not only as an antimicrobial in the defense against enteropathogenic bacteria but also as a prebiotic to propagate certain probiotics. Thus, LF-induced gut microbiota alterations can be harnessed to induce changes in host physiology, and the underpinnings of their relationships and mechanisms are beginning to unravel in studies involving humans and animal models.

Experimental Demonstration of Controllable PT and Anti-PT Coupling in a Non-Hermitian Metamaterial.

Non-Hermiticity has recently emerged as a rapidly developing field due to its exotic characteristics related to open systems, where the dissipation plays a critical role. In the presence of balanced energy gain and loss with environment, the system exhibits parity-time (PT) symmetry, meanwhile as the conjugate counterpart, anti-PT symmetry can be achieved with dissipative coupling within the system. Here, we demonstrate the coherence of complex dissipative coupling can control the transition between PT and anti-PT symmetry in an electromagnetic metamaterial. Notably, the achievement of the anti-PT symmetric phase is independent of variations in dissipation. Furthermore, we observe phase transitions as the system crosses exceptional points in both anti-PT and PT symmetric metamaterial configurations, achieved by manipulating the frequency and dissipation of resonators. This work provides a promising metamaterial design for broader exploration of non-Hermitian physics and practical application with a controllable Hamiltonian.

Nanosensor detection of reactive oxygen and nitrogen species leakage in frustrated phagocytosis of nanofibres.

Exposure to widely used inert fibrous nanomaterials (for example, glass fibres or carbon nanotubes) may result in asbestos-like lung pathologies, becoming an important environmental and health concern. However, the origin of the pathogenesis of such fibres has not yet been clearly established. Here we report an electrochemical nanosensor that is used to monitor and quantitatively characterize the flux and dynamics of reactive species release during the frustrated phagocytosis of glass nanofibres by single macrophages. We show the existence of an intense prolonged release of reactive oxygen and nitrogen species by single macrophages near their phagocytic cups. This continued massive leakage of reactive oxygen and nitrogen species damages peripheral cells and eventually translates into chronic inflammation and lung injury, as seen during in vitro co-culture and in vivo experiments.

Green syntheses of silk fibroin/wool keratin-protected AuAg nanoclusters with enhanced fluorescence for multicolor and patterned anti-counterfeiting.

Counterfeiting is a serious worldwide issue that threatens human health and economic security. How to apply anti-counterfeiting techniques to textile materials remains a great challenge. Herein, we report bimetallic AuAg nanoclusters (NCs) synthesized by one-step reduction of chloroauric acid (HAuCl4) and silver nitrate (AgNO3) with wool keratin (WK) as reducer and silk fibroin (SF) as stabilizer. The strongest orange-red fluorescence under ultraviolet light as well as the highest zeta potential absolute values of -27.97 mV were simultaneously realized in the optimal proportion Au-AgNCs2 (WK/SF is 3/2), which was further processed to a series of anti-counterfeiting films by blending with SF, silk sericin (SS), and polyvinyl alcohol (PVA). After successfully being numbered into fifteen colors, a dark blue-orange-dark red-dark blue cyclic fluorescent anti-counterfeiting color chart was designed. In addition, a two-Maxwell-unit model was constructed to assist with the microstructure analysis, which found that the formation of hydrogen bonds and the secondary structure transition from α-helices to ß-sheets during stretching were responsible for improving the mechanical properties and the two-staged fracture curves of films, respectively. Finally, a patterned and multicolor fluorescence anti-counterfeiting fabric application was demonstrated by combining the color chart and screen printing, indicating the great potential in textile anti-counterfeiting.

Radiofrequency ablation induces tumor cell dissemination in a mouse model of hepatocellular carcinoma.

BACKGROUND: We tested the hypothesis that radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) promotes tumor cell release and explored a method for reducing these effects. METHODS: A green fluorescent protein-transfected orthotopic HCC model was established in 99 nude mice. In vivo flow cytometry was used to monitor circulating tumor cell (CTC) dynamics. Pulmonary fluorescence imaging and pathology were performed to investigate lung metastases. First, the kinetics of CTCs during the periablation period and the survival rate of CTCs released during RFA were investigated. Next, mice were allocated to controls, sham ablation, or RFA with/without hepatic vessel blocking (ligation of the portal triads) for evaluating the postablation CTC level, lung metastases, and survival over time. Moreover, the kinetics of CTCs, lung metastases, and mice survival were evaluated for RFA with/without ethanol injection. Pathological changes in tumors and surrounding parenchyma after ethanol injection were noted. Statistical analysis included t-test, ANOVA, and Kaplan-Meier survival curves. RESULTS: CTC counts were 12.3-fold increased during RFA, and 73.7% of RFA-induced CTCs were viable. Pre-RFA hepatic vessel blocking prevented the increase of peripheral CTCs, reduced the number of lung metastases, and prolonged survival (all p ≤ 0.05). Similarly, pre-RFA ethanol injection remarkably decreased CTC release during RFA and further decreased lung metastases with extended survival (all p ≤ 0.05). Histopathology revealed thrombus formation in blood vessels after ethanol injection, which may clog tumor cell dissemination during RFA. CONCLUSION: RFA induces viable tumor cell dissemination, and pre-RFA ethanol injection may provide a prophylactic strategy to reduce this underestimated effect. RELEVANCE STATEMENT: RFA for HCC promotes viable tumor cell release during ablation, while ethanol injection can prevent RFA induced tumor cell release. KEY POINTS: • RFA induced the release of viable tumor cells during the ablation procedure in an animal model. • Hepatic vessel blocking can suppress tumor cells dissemination during RFA. • Ethanol injection can prevent RFA-induced tumor cell release, presumably because of the formation of thrombosis.

Effective protection: the embryonic development and clinical outcomes of emergency vitrification of 1246 oocytes and Day 0-Day 5 embryos in a natural disaster.

STUDY QUESTION: Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? SUMMARY ANSWER: Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. WHAT IS KNOWN ALREADY: When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. STUDY DESIGN, SIZE, DURATION: A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. PARTICIPANTS/MATERIALS, SETTING, METHODS: As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). LIMITATIONS, REASONS FOR CAUTION: The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER: N/A.

Applying a novel two-step deep learning network to improve the automatic delineation of esophagus in non-small cell lung cancer radiotherapy.

Purpose: To introduce a model for automatic segmentation of thoracic organs at risk (OARs), especially the esophagus, in non-small cell lung cancer radiotherapy, using a novel two-step deep learning network. Materials and methods: A total of 59 lung cancer patients' CT images were enrolled, of which 39 patients were randomly selected as the training set, 8 patients as the validation set, and 12 patients as the testing set. The automatic segmentations of the six OARs including the esophagus were carried out. In addition, two sets of treatment plans were made on the basis of the manually delineated tumor and OARs (Plan1) as well as the manually delineated tumor and the automatically delineated OARs (Plan2). The Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and average surface distance (ASD) of the proposed model were compared with those of U-Net as a benchmark. Next, two groups of plans were also compared according to the dose-volume histogram parameters. Results: The DSC, HD95, and ASD of the proposed model were better than those of U-Net, while the two groups of plans were almost the same. The highest mean DSC of the proposed method was 0.94 for the left lung, and the lowest HD95 and ASD were 3.78 and 1.16 mm for the trachea, respectively. Moreover, the DSC reached 0.73 for the esophagus. Conclusions: The two-step segmentation method can accurately segment the OARs of lung cancer. The mean DSC of the esophagus realized preliminary clinical significance (>0.70). Choosing different deep learning networks based on different characteristics of organs offers a new option for automatic segmentation in radiotherapy.

[Chromosomal aneuploidy and pregnancy outcomes for D5/D6 blastocysts from patients undergoing PGT-A treatment].

OBJECTIVE: To compare the prevalence of chromosomal aneuploidies and pregnancy outcomes of D5 and D6 blastocysts subjected to preimplantation genetic testing for aneuploidy (PGT-A). METHODS: Clinical and laboratory data of 268 couples who underwent PGT-A at the Reproductive Center of the First Affiliated Hospital of Zhengzhou University from September 2018 to September 2020 were collected. The prevalence of chromosomal aneuploidies and pregnancy outcomes of D5/D6 biopsied blastocysts were compared. RESULTS: Compared with D6 blastocysts, the euploidy rate of D5 blastocysts was significantly higher (49.1% vs. 41.1%, P = 0.001 1), whilst their aneuploidy rate was significantly lower (50.9% vs. 58.9%, P = 0.001 1). The rate of numerical abnormalities of D6 blastocysts was significantly higher than that of D5 blastocysts (27.9% vs. 20.2%, P = 0.000 5). For patients under 35 years old, the euploidy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (53.8% vs. 44.3%, P = 0.001), whilst the numerical abnormality rate was significantly lower (16.3% vs. 23.9%, P = 0.001). For both D5 and D6 blastocysts, the euploidy rates for patients <= 35 were significantly higher than those for > 35. The elder group had the lowest rates for aneuploidies and live births. Compared with those receiving D6 blastocysts transplantation, the pregnancy rate, implantation rate and live birth rate for those receiving thawed D5 blastocysts transplantation were significantly higher (60.2% vs.37.0%, P = 0.000 3; 59.1% vs.37.0%, P = 0.000 6; 47.7% vs. 28.3%, P = 0.002). CONCLUSION: For patients undergoing PGT-A, the chromosomal euploidy rate for D5 blastocysts is higher than that for D6 blastocysts, and the clinical outcome of D5 blastocysts with normal signal is better than that of D6 blastocysts. Elder patients have a higher rate of aneuploidies.

In vivo flow cytometry reveals an anti-metastatic effect of Rujifang in triple-negative breast cancer.

Breast cancer is the most common cancer, and triple-negative breast cancer (TNBC) has the highest metastasis and mortality rate among all breast cancer subtypes. Rujifang is a traditional Chinese medicine formula with many years of clinical application in breast cancer treatment. Here, we aim to investigate the effects of Rujifang on circulating tumor cell (CTC) dynamics and the tumor microenvironment in a ZsGreen/luciferase double-labeled TNBC orthotopic model. We report that the number of CTCs monitored by in vivo flow cytometry (IVFC) strongly correlates with disease progression. Rujifang treatment decreased the number of CTCs and suppressed the distant metastasis of TNBC. Moreover, immunofluorescence analysis revealed that Rujifang treatment could affect the tumor microenvironment by downregulating Kindlin-1, which has been reported to promote metastasis of TNBC. Our study provides evidence of the anti-metastatic effect of Rujifang against TNBC in an animal model using fluorescent cell lines. The results suggest the potential therapeutic value of Rujifang as an anti-metastatic drug, however, further clinical trials are needed to validate these findings in humans.

Corrigendum: Genome-wide identification of genes encoding cystathionine beta synthase domain-containing proteins in wheat and its relationship with anther male sterility under heat stress.

[This corrects the article DOI: 10.3389/fpls.2022.1061472.].

Efficacy and safety of electroacupuncture for secondary sleep disorders: A meta-analysis and systematic review.

BACKGROUND: To explore the efficacy and safety of electroacupuncture (EA) for secondary insomnia through a meta-analysis and a systematic review. METHODS: The CNKI, Wanfang, VIP database, Web of Science, EMBASE, PubMed, and Cochrane Library were retrieved. The retrieval date was February 28, 2023. Two independent reviewers conducted literature screening, data extraction, and risk of bias (ROB) assessment. The revised Cochrane ROB tool was used to assess the ROB in included studies. Data analysis was performed using RevMan 5.4 software and Stata 15.0. RESULTS: Thirteen randomized controlled studies were included, involving 820 patients, including 414 patients in EA group and 406 patients in the control group. Compared with the control group, EA could improve secondary insomnia overall responses (relative risk = 3.90, 95% confidence interval [CI] [1.87, 8.13], P < .001), reduce Pittsburgh Sleep Quality Index score (mean difference [MD] = -2.26, 95% CI [-4.14, -0.37], P = .02), reduce Athens Insomnia Scale score (MD = -0.57, 95% CI [-2.70, 1.56], P = .60), prolonged total sleep time (MD = 2.63, 95% CI [-0.59, 5.86], P = .11), and not increase adverse events (relative risk = 0.50, 95% CI [0.18, 1.44], P = .20). CONCLUSION: EA may be a promising treatment for secondary sleep disorders; however, more high-quality studies are needed to confirm our findings.

Practical Synthesis of 5,7-Dichlorotetrahydroisoquinoline-6-carboxylic Acid-Key Intermediate of Lifitegrast (Xiidra).

In the present study, a practical method for synthesizing the key intermediate 5,7-dichlorotetrahydroisoquinoline-6-carboxylic acid (1) of Lifitegrast was proposed. First, an investigation was conducted into the utilization of the impurity and recrystallization method in the synthesis of 5,7-dichlorotetrahydroisoquinoline (5·HCl) via Friedel-Crafts cyclization. Through the screening of different protection groups, a previously unreported quaternary ammonium salt (13) was isolated with a 95.9% yield and 99.6% purity by simply adjusting the pH during the carboxylation reaction. Subsequently, free state 1 was obtained by controlling the pH to 4-5 with HCl(aq), thereby avoiding the need for a free operation in the synthesis of the API of Lifitegrast. Further, the triphenylmethanol (TrOH) was recycled to triphenylmethyl chloride (TrCl) using CaCl2/HCl(aq) with 93.0% yield and 98.0% purity.

Development of Child-Friendly Lisdexamfetamine Chewable Tablets Using Ion Exchange Resin as a Taste-Masking Carrier Based on the Concept of Quality by Design (QbD).

Taste masking is critical to improving the compliance of pediatric oral dosage forms. However, it is challenging for extremely bitter lisdexamfetamine dimesylate (LDX) with a long half-life and given in large dose. The present study aims to develop an immediate-release, taste-masked lisdexamfetamine chewable tablet. Lisdexamfetamine-resin complexes (LRCs) were prepared using the batch method. The molecular mechanism of taste masking was explored by PXRD, PLM, STA, and FT-IR. The results showed that taste masking was attributed to the ionic interaction between drug and the resin. The ion exchange process conformed to first-order kinetics. The rate-limiting step of drug release was the diffusion of ions inside the particles, and the concentration of H+ was the key factor for immediate release. The masking efficiency of the prepared LRCs in saliva exceeded 96%, and the drug could be completely released within 15 min in aqueous HCl (pH 1.2). Furthermore, the SeDeM expert system was used for the first time to comprehensively study the powder properties of LRCs and to quickly visualize their defects (compressibility, lubricity/stability, and lubricity/dosage). The selection of excipients was targeted rather than traditional screening, thus obtaining a robust chewable tablet formulation suitable for direct compression. Finally, the difference between chewable tablets containing LRCs and chewable tablets containing lisdexamfetamine dimesylate was compared by in vitro dissolution test, electronic tongue, and disintegration test. In conclusion, an immediate-released, child-friendly lisdexamfetamine chewable tablets without bitterness was successfully developed by the QbD approach, using the SeDeM system, which may help in further development of chewable tablets.

Intrinsic Descriptor Guided Noble Metal Cathode Design for Li-CO2 Battery.

To date, the effect of noble metal (NM) electronic structures on CO2 reaction activity remains unknown, and explicit screening criteria are still lacking for designing highly efficient catalysts in CO2 -breathing batteries. Herein, by preferentially considering the decomposition of key intermediate Li2 CO3 , an intrinsic descriptor constituted of the d x 2 - y 2 ${{\rm{d}}}_{{x}^2 - {y}^2}$ orbital states and the electronegativity for predicting high-performance cathode material are discovered. As a demonstration, a series of graphene-supported noble metals (NM@G) as cathodes are fabricated via a fast laser scribing technique. Consistent with the preliminary prediction, Pd@G exhibits an ultralow overpotential (0.41 V), along with superior cycling performance up to 1400 h. Moreover, the overall thermodynamic reaction pathways on NM@G confirm the reliability of the established intrinsic descriptor. This basic finding of the relationship between the electronic properties of noble metal cathodes and the performance of Li-CO2 batteries provides a novel avenue for designing remarkably efficient cathode materials for metal-CO2 batteries.

Nanoelectrochemistry reveals how soluble Aß42 oligomers alter vesicular storage and release of glutamate.

Glutamate (Glu) is the major excitatory transmitter in the nervous system. Impairment of its vesicular release by ß-amyloid (Aß) oligomers is thought to participate in pathological processes leading to Alzheimer's disease. However, it remains unclear whether soluble Aß42 oligomers affect intravesicular amounts of Glu or their release in the brain, or both. Measurements made in this work on single Glu varicosities with an amperometric nanowire Glu biosensor revealed that soluble Aß42 oligomers first caused a dramatic increase in vesicular Glu storage and stimulation-induced release, accompanied by a high level of parallel spontaneous exocytosis, ultimately resulting in the depletion of intravesicular Glu content and greatly reduced release. Molecular biology tools and mouse models of Aß amyloidosis have further established that the transient hyperexcitation observed during the primary pathological stage is mediated by an altered behavior of VGLUT1 responsible for transporting Glu into synaptic vesicles. Thereafter, an overexpression of Vps10p-tail-interactor-1a, a protein that maintains spontaneous release of neurotransmitters by selective interaction with t-SNAREs, resulted in a depletion of intravesicular Glu content, triggering advanced-stage neuronal malfunction. These findings are expected to open perspectives for remediating Aß42-induced neuronal hyperactivity and neuronal degeneration.

Analysis of influencing factors on gas film characteristics for hemispherical dynamic pressure motors.

The hemispherical dynamic pressure motor (HDPM) has the advantages of high speed, wear resistance and stability, which is widely used in inertial instruments to produce the gyroscopic effect. The ultra-thin gas film between the stator and rotor of the motor provides dynamic pressure lubrication and bearing capacity, whose dynamic characteristics determine the motor performance. However, the influence mechanism of some key factors such as ball center distance on the film characteristics is not clear, which has become the bottleneck restricting the performance improvement of HDPMs. Therefore, in this paper, a series of gas film similarity models were solved under different geometric and working parameters, and the influence law of the ball center distance, rotor displacement and stopping process on the aerodynamic characteristics was obtained, the results show that these primary parameters have significant effects on the pressure distribution, resistance moment and frictional heat of the ultra-thin gas film. This work can not only provide a theoretical basis for the aerodynamic performance optimization of HDPMs, but also serve as a reference for the design of other aerodynamic instruments.