Search

Fengjiao Bu,1,2,* Yong-Soon Cho,3,4,* Qingfeng He,1 Xiaowen Wang,1 Saurav Howlader,3,4 Dong-Hyun Kim,3,4 Mingshe Zhu,5 Jae Gook Shin,3,4 Xiaoqiang Xiang1,6 1Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2Department of Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea; 4Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Busan, Republic of Korea; 5Department of DMPK, MassDefect Technologies, Princeton, NJ, USA; 6Department of Preclinical Evaluation, Quzhou Fudan Institute, Quzhou, Zhejiang Province, 324002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jae Gook Shin; Xiaoqiang Xiang, Email phshinjg@gmail.com; xiangxq@fudan.edu.cnBackground: Anlotinib was approved as a third line therapy for advanced non-small cell lung cancer in China. However, the impact of concurrent administration of various clinical drugs on the drug–drug interaction (DDI) potential of anlotinib remains undetermined. As such, this study aims to evaluate the DDI of anlotinib as a victim by establishing a physiologically based pharmacokinetic (PBPK) model.Methods: The PBPK model of anlotinib as a victim drug was constructed and validated in the Simcyp® incorporating parameters derived from in vitro studies, pre-clinical investigations, and clinical research encompassing patients with cancer. Subsequently, plasma exposure of anlotinib in cancer patients was predicted for single- and multi-dose co-administration with typical perpetrators mentioned in Food and Drug Administration (FDA) industrial guidance.Results: Based on predictions, the CYP3A potent inhibitor ketoconazole demonstrated the most significant DDI with anlotinib, regardless of whether anlotinib is administered as a single dose or multiple doses. Ketoconazole increased the area under the concentration-time curve (AUC) and maximum concentration (Cmax) of single-dose anlotinib to 1.41-fold and 1.08-fold, respectively. In contrast, rifampicin, a potent inducer of CYP3A enzymes, exhibited a relatively higher level of DDI, with AUCR and CmaxR values of 0.44 and 0.79, respectively.Conclusion: Based on the PBPK modeling, there is a low risk of DDI between anlotinib and potent CYP3A/1A2 inhibitors, but caution and enhanced monitoring for adverse reactions are advised. To mitigate the risk of anti-tumor treatment failure, it is recommended to avoid concurrent use of strong CYP3A inducers. In conclusion, our study enhances understanding of anlotinib’s interaction with medications, aiding scientists, prescribers, and drug labels in gauging the expected impact of CYP3A/1A2 modulators on anlotinib’s pharmacokinetics. Keywords: anlotinib, DDIs, CYP3A, CYP1A2, PBPK

Rong Wang,1,* Tuo Chen,2,* Qiong Wang,3 Xiao-Min Yuan,1 Zheng-Lan Duan,1 Ze-Yu Feng,1 Yang Ding,1 Fan Bu,1 Guo-Ping Shi,4 Yu-Gen Chen1 1Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of General Surgery, Affiliated hospital of Yangzhou university, Yangzhou, Jiangsu, 225000, People’s Republic of China; 3Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 4Collaborative Innovation Center for Cancer Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Gen Chen; Guo-Ping Shi Email chenyg666@126.com; 457569423@qq.comPurpose: Total flavone of Abelmoschus manihot (TFA), the effective constituents extracted from Flos Abelmoschus Manihot, has been reported to inhibit inflammation. However, the effect of TFA on ulcerative colitis (UC) progression in patients with depression is unknown. The purpose of our research was to explore the anti-UC effects of TFA in the context of depression in mice with UC by regulating the gut microbiota to drive the intestinal barrier.Methods: In this study, chronic stress (CS) and dextran sodium sulfate (DSS) were used to induce depression and UC, respectively, in C57BL/6J mice. Fecal microbiota transplantation (FMT) was used to evaluate how treating mice modeling UC and depression with TFA effected their gut microbiota.Results: Our results showed that TFA effectively improved UC aggravated by CS. In addition, TFA treatment improved the depression-like phenotype, the disturbed gut microbiota, and the intestinal barrier function in CS mice. It is worth noting that FMT from the CS mice to the receptor group further aggravated the damage of the intestinal barrier and the disturbance of the gut microbiota in the recipient DSS mice, thus further aggravating UC, however, treatment of the intervention of TFA in the CS fecal microbiota transplant with TFA also played its therapeutic outcome.Conclusion: Taken together, our results show that CS disrupts the gut microbiota, triggers intestinal barrier injury and aggravates DSS colitis, while TFA is a promising drug for the treatment of UC in patients with depression.Keywords: total flavone of Abelmoschus manihot, ulcerative colitis, depression, gut microbiota, intestinal barrier

Fanqin Bu,1,2,* Xiaojian Zhu,3,* Jinfeng Zhu,1,2,* Zitao Liu,1,2 Ting Wu,4 Chen Luo,1,2 Kang Lin,1,2 Jun Huang1 1Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of China; 2Jiangxi Medical College of Nanchang University, Nanchang, People’s Republic of China; 3Research Center of The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China; 4Department of Infectious Diseases of Guixi Traditional Chinese Medicine Hospital, Yingtan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Huang Email huangjun0727@163.comBackground: Colorectal cancer (CRC) is one of the most lethal malignancies and the incidence of CRC has been on the rise. Herein, we aimed to identify effective biomarkers for early diagnosis and treatment of colorectal cancer via bioinformatic tools.Methods: To identify differentially expressed genes (DEGs) in CRC, we downloaded CRC gene expression data from GSE24514 and GSE110223 datasets in Gene Expression Omnibus (GEO) and employed R to analyze the data. We further performed functional enrichment analysis of the DEGs on the DAVID gene ontology analysis tool. STRING database and Cytoscape visualization tool were employed to construct a PPI (protein–protein interaction) network and establish intensive intervals in the network. Immunohistochemistry, qRT-PCR and Western blotting were performed to identify the expression level of GINS1 in CRC. In vitro and in vivo experiments were performed to assess the impact of GINS1 in the pathogenesis of CRC in terms of proliferation, migration and metastasis.Results: Among the two datasets, 389 DEGs were identified and used to construct a PPI network. These genes were mainly involved in cell proliferation and cell cycle. Among them, 15 genes including GINS1 were found to be strongly associated with the PPI network. We further performed immunohistochemistry, qRT-PCR and Western blotting to identify that GINS1 expression was higher in CRC than in paired normal tissues. Moreover, in vitro and in vivo experiments demonstrated GINS1 could promote the proliferation, invasion and migration of colorectal cancer cells.Conclusions: GINS1 could be considered as a potential biomarker for CRC patients.Keywords: GINS1, colorectal cancer, bioinformatics screening

Simona Hapca,1 Bruce Guthrie,1 Vera Cvoro,2 Feifei Bu,3 Alasdair C Rutherford,3 Emma Reynish,3 Peter T Donnan1 1Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK; 2NHS Fife, Kirkcaldy, Fife KY2 5AH, UK; 3Dementia and Ageing Research Group, Faculty of Social Science, University of Stirling, Stirling, FK9 4LA, UK Purpose: Cognitive impairment is common in older people admitted to hospital, but the outcomes are generally poorly understood, and previous research has shown inconsistent associations with mortality depending on the type of cognitive impairment examined and duration of follow-up. This study examines mortality in older people with any cognitive impairment during acute hospital admission.Patients and methods: Prospective cohort of 6,724 people aged ≥65 years with a structured cognitive assessment on acute admission were included in this study. Cognitive spectrum disorder (CSD) was defined as delirium alone, known dementia alone, delirium superimposed on known dementia, or unspecified cognitive impairment. Mortality associated with different types of CSD was examined using a non-proportional hazards model with 2-year follow-up.Results: On admission, 35.4% of patients had CSD, of which 52.6% died within 2 years. After adjustment for demographics and comorbidity, delirium alone was associated with increased mortality in the 6 months post-admission (HR =1.45, 95% CI 1.28–1.65) and again after 1 year (HR =1.44, 95% CI 1.17–1.77). Patients with known dementia (alone or with superimposed delirium) had increased mortality only after 3 months from admission (HR =1.85, 95% CI 1.56–2.18 and HR =1.80, 95% CI 1.52–2.14) compared with patients with unspecified cognitive impairment after 6 months (HR =1.55, 95% CI 1.21–1.99). Similar but partially attenuated associations were seen after adjustment for functional ability.Conclusion: Mortality post-admission is high in older people with CSD. Immediate risk is highest in those with delirium, while dementia or unspecified cognitive impairment is associated with medium- to long-term risk. These findings suggest that individuals without dementia who develop delirium are more seriously ill (have required a larger acute insult in order to precipitate delirium) than those with pre-existing brain pathology (dementia). Further research to explain the mortality patterns observed is required in order to translate the findings into clinical care. Keywords: acute admission, elderly, cognition, function, non-proportional hazards

Aims: This study aimed to examine potential heterogeneity in longitudinal changes in home-based arts engagement during the first national lockdown and following gradual easing of restrictions in the UK. Furthermore, it sought to explore factors that were associated with patterns of longitudinal changes in home-based arts engagement.Method: Data were from the UCL COVID-19 Social Study. The analytical sample consisted of 29,147 adults in the UK who were followed up for 22 weeks from 21 March to 21 August 2020. Data were analysed using growth mixture models.Results: Our analyses identified five classes of growth trajectories. There were two stable classes showing little change in arts engagement over time (64.4% in total), two classes showing initial increases in arts engagement followed by declines as restrictions were eased (29.8%), and one class showing slight declines during strict lockdown followed by an increase in arts engagement after the easing of restrictions (5.9%). A range of factors were found to be associated with class membership of these arts engagement trajectories, such as age, gender, education, income, employment status, and health.Conclusion: There is substantial heterogeneity in longitudinal changes in home-based arts engagement. For participants whose engagement changed over time, growth trajectories of arts engagement were related to changes in lockdown measures. These findings suggest that some individuals may have drawn on the arts when they needed them the most, such as during the strict lockdown period, even if they usually had lower levels of arts engagement before the pandemic. Overall, our results indicate the importance of promoting arts engagement during pandemics and periods of lockdown as part of public health campaigns. [ABSTRACT FROM AUTHOR]

There are concerns internationally that lockdown measures taken during the coronavirus disease 2019 (COVID-19) pandemic could lead to a rise in loneliness. As loneliness is recognised as a major public health concern, it is therefore vital that research considers the impact of the current COVID-19 pandemic on loneliness to provide necessary support. But it remains unclear, who is lonely in lockdown? This study compared sociodemographic predictors of loneliness before and during the COVID-19 pandemic using cross-cohort analyses of data from UK adults captured before the pandemic (UK Household Longitudinal Study, n = 31,064) and during the pandemic (UCL (University College London) COVID-19 Social Study, n = 60,341). Risk factors for loneliness were near identical before and during the pandemic. Young adults, women, people with lower education or income, the economically inactive, people living alone and urban residents had a higher risk of being lonely. Some people who were already at risk of being lonely (e.g. young adults aged 18–30 years, people with low household income and adults living alone) experienced a heightened risk during the COVID-19 pandemic compared with people living before COVID-19 emerged. Furthermore, being a student emerged as a higher risk factor during lockdown than usual. Findings suggest that interventions to reduce or prevent loneliness during COVID-19 should be targeted at those sociodemographic groups already identified as high risk in previous research. These groups are likely not just to experience loneliness during the pandemic but potentially to have an even higher risk than normal of experiencing loneliness relative to low-risk groups. • We compared data from 31,000 UK adults during 2017-2019 with 60,000 UK adults during the COVID-19 pandemic. • Some risk factors for loneliness were the same as in ordinary circumstances (e.g. women and people living alone). • Other groups experienced even greater risk of loneliness than usual (e.g. younger people and people of low income). • Some groups were at risk of loneliness who are not usually considered high risk (e.g. students). [ABSTRACT FROM AUTHOR]

Effects of electrolyte thickness, chloride ion concentration, and an external direct current electric field (DCEF) on the corrosion behaviour of silver under a thin electrolyte layer (TEL) were investigated using electrochemical and surface techniques. The results indicate the corrosion rate of silver increases with the decrease of TEL thickness and the increase of chloride ion concentration. Moreover, an interesting conclusion was drawn that the corrosion rate of silver near the positive plate of DCEF first increases and then decreases with the increase of electric field intensity. In a DCEF, different polarisation behaviours of silver at different positions were attributed to the differences of the local corrosion environment. [ABSTRACT FROM AUTHOR]

Faults in CO2 storage reservoirs affect the migration and spatial distribution of injected CO2 in reservoir formations. Based on geological data from the Ordos CO2 geological storage demonstration project site, A 2D numerical model of the CO2 storage reservoir was constructed to study the influence of high-porosity and high-permeability faults within a low-porosity and low-permeability reservoir. The results show that the faults had a significant effect on CO2 migration and storage. If the permeability of the fault zone increased by 2-3 orders of magnitude (a common range of variation in fault zone) and porosity increased correspondingly compared to the base case (no fault in strata), the CO2 migration distance in the reservoir after 100 years was approximately 1.18 times larger than that of the base case without faults, and the total CO2 storage amount in the entire reservoir increased by 1.40-1.61 times. The faults weakened the sealing ability of the local interlayer caprocks (mudstone), which resulted in CO2 migrating through mudstone and entering in the neighboring interlayer storage stratum. When highly permeable faults existed, the CO2 migration distance and storage amount in the neighboring interlayer storage stratum were approximately two times and 19.41 times (maximum value) higher, respectively, compared with the case without a fault. Therefore, the faults distributed in strata should be given sufficient attention when selecting a CO2 sequestration site. [ABSTRACT FROM AUTHOR]

Faults in CO2 storage reservoirs affect the migration and spatial distribution of injected CO2 in reservoir formations. Based on geological data from the Ordos CO2 geological storage demonstration project site, A 2D numerical model of the CO2 storage reservoir was constructed to study the influence of high-porosity and high-permeability faults within a low-porosity and low-permeability reservoir. The results show that the faults had a significant effect on CO2 migration and storage. If the permeability of the fault zone increased by 2-3 orders of magnitude (a common range of variation in fault zone) and porosity increased correspondingly compared to the base case (no fault in strata), the CO2 migration distance in the reservoir after 100 years was approximately 1.18 times larger than that of the base case without faults, and the total CO2 storage amount in the entire reservoir increased by 1.40-1.61 times. The faults weakened the sealing ability of the local interlayer caprocks (mudstone), which resulted in CO2 migrating through mudstone and entering in the neighboring interlayer storage stratum. When highly permeable faults existed, the CO2 migration distance and storage amount in the neighboring interlayer storage stratum were approximately two times and 19.41 times (maximum value) higher, respectively, compared with the case without a fault. Therefore, the faults distributed in strata should be given sufficient attention when selecting a CO2 sequestration site. [ABSTRACT FROM AUTHOR]

A 30-day growth trial was conducted to investigate the individual variations in feeding rate, growth rate, spontaneous activity, and their possible interrelationships in hybrid tilapia ( Oreochromis niloticus × O. aureus) reared individually at feeding frequencies of one and two meals daily. Results show that the feeding rate in energy ( FRe), specific growth rate in energy ( SGRe), and food conversion efficiency ( FCE) of fish fed twice a day were significantly higher than that of fish fed only once. However, no significant differences in distance or in time spent swimming were observed between the groups. SGRe was positively correlated with FRe in fish fed only once daily, and SGRe was positively correlated with food conversion efficiency in energy ( FCEe) between the two groups. SGRe was only inversely correlated with the distance that fish swam when fed once daily. The results suggest that the individual growth differences of hybrid tilapia could be attributed mainly to variations in FRe, and that the energy costs of spontaneous activity play an important role in the differences at feeding frequency of one meal a day. However, at feeding frequencies of two meals a day, individual growth differences in fish may be caused by variations in FCEe, and energy costs of spontaneous activity have only marginal effects on the differences. [ABSTRACT FROM AUTHOR]

A novel solvent induced fabrication technique is developed for the preparation of the sulfonated poly (ether ether ketone) (sPEEK) based water electrolysis membrane electrode assembly (MEA). The solvent, dimethyl formamide (DMF), instead of the high pressure and temperature, is used to induce the softening of the membrane and better integration of the MEA with excellent interface compatibility. The influence of hot pressing period, the amount of polymer used in the electrode, and the temperature are investigated to optimize the performance of the MEA. The single cell performance for the water electrolysis is evaluated to optimize the fabrication parameters. It is found out that all three factors have great influences on the final cell performance and the tradeoff effects are observed due to the various states of the catalyst efficiency, TPBs, the conductivity, and cell resistance. As a result, the cell performance is optimized with the MEA fabricated at 120 °C, using the catalysts to polymer weight ratio of 5:1 and a 60s hot pressing period. [ABSTRACT FROM AUTHOR]

Wood fiber reinforced thermoplastic composites are usually manufactured by the extrusion method. However, the size of the extruded board and bio-fibers are limited. The objective of this study was to manufacture large size straw— polymer composite panels by hot-pressing method, focusing on the forms of raw materials and heating method. Wheat straw was reduced to particles and high density polyethylene (HDPE) was processed into fibers or powders. After mixing, preheating, hot-pressing, and cooling, the resulted panels were tested for mechanical and water resistance properties. The data indicated that HDPE in the form of fiber presented better properties than those in powders and preheating treatment before hot-pressing was an effective way to improve the mechanical properties of the straw— PE composite. Coupling agent helped to improve the bonding strength. [ABSTRACT FROM PUBLISHER]

The relative virulence of strains of Acidovorax avenae to their reported hosts was investigated. Strains of A. avenae subsp. avenae were more virulent to sweet com than to maize or sugarcane, and only weakly virulent or avirulent to oat. Passage of weakly virulent strains of subsp. avenae through sweet com did not affect strain virulence. A. avenae subsp. cattleyae was not shown to cause symptoms in Cattleya sp. Strains of A. avenae subsp. citrulli were more virulent to cucumber than to melon. Conditions which favoured the expression of symptoms by subspecies of A. avenae were established. A. avenae subsp. avenae and A. avenae subsp. citrulli were most virulent in the young tissue of their respective hosts (sweet com and cucumber) at 27-30°C, with expression at higher temperatures being limited by the thermal tolerance of the plants. A general equation relating symptom expression to inoculum concentration was developed. This simple linear equation related the logarithm of lesion number to the logarithm of inoculum concentration. The intercept values in the equation for each strain can be considered to be an expression of the heterogeneity of pathogenicity of inoculum, whereas the gradient gives an expression of the relative virulence of infective cells. [ABSTRACT FROM AUTHOR]

The temporal appearance of antibodies to guinea pig cytomegalovirus (CMV) proteins was examined in pregnant and non-pregnant guinea pigs by immunoblotting. Antibodies to 12 guinea pig CMV proteins appeared in a defined time course during primary infection and were detected at a later time and in lower concentrations in pregnant than in non-pregnant guinea pigs. [ABSTRACT FROM AUTHOR]