Publications by authors named "Bo Zhong"

240 Publications

Impact of Concomitant Impairments of the Left and Right Ventricular Myocardial Strain on the Prognoses of Patients With ST-Elevation Myocardial Infarction.

Front Cardiovasc Med 2021 31;8:659364. Epub 2021 May 31.

Department of Cardiology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

The impact of concomitant impairments of left and right ventricular (LV and RV) strain on the long-term prognosis of acute ST-elevation myocardial infarction (STEMI) is not clear. We analyzed CMR images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12 h and CMR examination within 1 week (median, 5 days; range, 2-7 days) after infarction. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of both ventricles were measured based on CMR cine images. Conventional CMR indexes were also assessed. Primary clinical outcome was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. In addition, CMR data from 40 people without apparent heart disease were used as control group. Compared to controls, both LV and RV strains were remarkably reduced in STEMI patients. During follow-up (median: 52 months, interquartile range: 29-68 months), 80 patients experienced major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, heart failure, and stroke. LV-GCS > -11.20% was an independent predictor of MACCEs ( < 0.001). RV-GRS was the only RV strain index that could effectively predict the risk of MACCEs (AUC = 0.604, 95% CI [0.533, 0.674], = 0.004). Patient with RV-GRS ≤ 38.79% experienced more MACCEs than those with preserved RV-GRS (log rank < 0.001). Moreover, patients with the concomitant decrease of LV-GCS and RV-GRS were more likely to experience MACCEs than patients with decreased LV-GCS alone (log rank = 0.010). RV-GRS was incremental to LV-GCS for the predictive power of MACCEs (continuous NRI: 0.327; 95% CI: 0.095-0.558; = 0.006). Finally, tobacco use ( = 0.003), right coronary artery involvement ( = 0.002), and LV-GCS > -11.20% ( = 0.012) was correlated with lower RV-GRS. The concomitant decrease of LV and RV strain is associated with a worse long-term prognosis than impaired LV strain alone. Combination assessment of both LV and RV strain indexes could improve risk stratification of patients with STEMI. ClinicalTrials.gov, NCT03768453. Registered 7 December 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03768453.
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http://dx.doi.org/10.3389/fcvm.2021.659364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200389PMC
May 2021

Prevalence and spatial distribution patterns of human echinococcosis at the township level in Sichuan Province, China.

Infect Dis Poverty 2021 Jun 5;10(1):82. Epub 2021 Jun 5.

Department of Parasitic Diseases, Sichuan Provincial Center for Disease Control and Prevention, No.6 Zhongxue Road, Chengdu, 610041, People's Republic of China.

Background: Echinococcosis is a global zoonotic parasitic disease caused by Echinococcus larvae. This disease is highly endemic in Sichuan Province, China. This study investigates the prevalence and spatial distribution characteristics of human echinococcosis at the township level in Sichuan Province, geared towards providing a future reference for the development of precise prevention and control strategies.

Methods: Human prevalence of echinococcosis was evaluated using the B-ultrasonography diagnostic method in Sichuan Province between 2016 and 2019. All data were collected, collated, and analyzed. A spatial distribution map was drawn to intuitively analyze the spatial distribution features. Eventually, the spatial autocorrelation was specified and local indicators of spatial association (LISA) clustering map was drawn to investigate the spatial aggregation of echinococcosis at the township level in Sichuan Province.

Results: The prevalence of echinococcosis in humans of Sichuan Province was 0.462%, among which the occurrence of cystic echinococcosis (CE) was 0.221%, while that of alveolar echinococcosis (AE) was 0.244%. Based on the results of the spatial distribution map, a predominance of echinococcosis in humans decreased gradually from west to east and from north to south. The Global Moran's I index was 0.77 (Z = 32.07, P < 0.05), indicating that the prevalence of echinococcosis in humans was spatially clustered, exhibiting a significant spatial positive correlation. Further, the findings of local spatial autocorrelation analysis revealed that the "high-high" concentration areas were primarily located in some townships in the northwest of Sichuan Province. However, the "low-low" concentration areas were predominantly located in some townships in the southeast of Sichuan Province.

Conclusions: Our findings demonstrated that the prevalence of echinococcosis in humans of Sichuan Province follows a downward trend, suggesting that the current prevention and control work has achieved substantial outcomes. Nevertheless, the prevalence in humans at the township level is widely distributed and differs significantly, with a clear clustering in space. Therefore, precise prevention and control strategies should be formulated for clusters, specifically strengthening the "high-high" clusters at the township level.
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http://dx.doi.org/10.1186/s40249-021-00862-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180058PMC
June 2021

Transcription factor Ascl2 promotes germinal center B cell responses by directly regulating AID transcription.

Cell Rep 2021 Jun;35(9):109188

Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China; Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing 100084, China. Electronic address:

During germinal center (GC) reactions, activated B cells undergo clonal expansion and functional maturation to produce high-affinity antibodies and differentiate into plasma and memory cells, accompanied with class-switching recombination (CSR) and somatic hypermutation (SHM). Activation-induced cytidine deaminase (AID) is responsible for both CSR and SHM in GC B cells. Transcriptional mechanisms underlying AID regulation and GC B cell reactions are still not well understood. Here, we show that expression of Ascl2 transcription factor is upregulated in GC B cells. Ectopic expression of Ascl2 promotes GC B cell development and enhances antibody production and affinity maturation. Conversely, deletion of Ascl2 in B cells impairs the GC response. Genome-wide analysis reveals that Ascl2 directly regulates GC B cell-related genes, including AID; ectopic expression of AID in Ascl2-deficient B cells rescues their antibody defects. Thus, Ascl2 regulates AID transcription and promotes GC B cell responses.
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http://dx.doi.org/10.1016/j.celrep.2021.109188DOI Listing
June 2021

Low genetic variation in Echinococcus multilocularis from the Western Sichuan Plateau of China revealed by microsatellite and mitochondrial DNA markers.

Acta Trop 2021 Sep 28;221:105989. Epub 2021 May 28.

Institute of Parasitic Diseases, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, China.

The prevalence of E. multilocularis is a major public health problem in China. To better understand the molecular epidemiology and evolutionary patterns of E. multilocularis, an adequate dataset regarding the genetic variance of this parasite is necessary. However, for now, available genetic data of E. multilocularis is still insufficient. In the study, the EmsB microsatellite and the partial mitochondrial cox1 gene were combined to investigate the genetic diversity of 64 E. multilocularis samples from human, dogs and voles. These samples were collected in the Western Sichuan Plateau, where the highest village-based human prevalence of alveolar echinococcosis was recorded worldwide. The aim of the study is to gather more informative genetic data of E. multilocularis in the areas, especially those obtained using the EmsB marker. The microsatellite analysis revealed 7 different EmsB profiles, 1 of which was found in 90.63% of the total samples collected from all 3 hosts. This major profile was identical to the one detected in the same area 16 years ago. The rest of the 6 profiles, each represented by only 1 isolate, did not correspond to any of the profiles previously reported. All the profiles detected in the study belonged to the Asian cluster. Meanwhile, according to sequence analysis of the 758 bp cox1 region, 4 haplotypes all assigned to the Asian clade were detected among the isolates. A star-like haplotype network was exhibited with a centrally positioned haplotype found in 93.75% of the samples. The overall haplotype and nucleotide diversities were both low. These findings provided evidence for a founder event or bottleneck and subsequent population expansion in E. multilocularis. The EmsB profiles were not fully consistent with the cox1 haplotypes. The same correspondence relationship was mainly observed in samples with the major profile P5 and the main haplotype EmHa1. A total of 54 isolates assigned to profile P5 were classified to the EmHa1 haplotype. In conclusion, both the microsatellite and mtDNA markers showed low variability within the Tibetan population of E. multilocularis. An EmsB profile and a cox1 haplotype were found to be predominant in the study area, which appears to remain steady for over a decade. The results reinforce the higher potential of the microsatellite DNA marker with high discriminative power to identify the very low genetic polymorphism of E. multilocularis than that of the partial cox1 sequencing. The data obtained in the study would be helpful to enlarge the data pool to further probe the possible origins and dispersal of E. multilocularis in China.
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http://dx.doi.org/10.1016/j.actatropica.2021.105989DOI Listing
September 2021

Epidemiological analysis of cystic echinococcosis and alveolar echinococcosis in an extremely high prevalence region: Population-based survey and host animal monitoring in Shiqu County, China.

Acta Trop 2021 Sep 25;221:105982. Epub 2021 May 25.

Sichuan Center for Animal Disease Control and Prevention, Chengdu, China.

Echinococcosis is the most common parasitic disease in the Tibetan Plateau, placing a large disease burden on the local population. Shiqu County, located in western Sichuan Tibetan region, had a particularly high prevalence rate of cystic echinococcosis (CE) and alveolar echinococcosis (AE) in previous surveys. From 2015 to 2018, a population-based field survey was conducted to explore the epidemic situation. Epidemiological features were examined through demographic analysis and mapping. In addition, the infection prevalence of Echinococcus in dogs was also investigated and mapped by spatial autoregression. A total of 84,768 people were screened by abdominal ultrasound inspection, and 2,341 CE and 3,930 AE cases were detected, with a corresponding prevalence of 2.76% and 4.64%, respectively. This made Shiqu County one of the most severe echinococcosis endemic regions in the world, especially with regard to AE. The cases were not evenly distributed among towns: particularly, the AE rates in the northwest towns were very high and closely related to the infection rate of neighboring host animals. Simultaneously, a comprehensive prevention project including patient treatment and host management was conducted and achieved preliminary success in source control. According to feces monitoring findings, the infection rate of dogs declined from 26.38% in early 2016 to 3.71% in 2018. Combined with host animal distribution data at the town level, the predicted risk ranks were categorized by risk index and mapped to guide further control operations.
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http://dx.doi.org/10.1016/j.actatropica.2021.105982DOI Listing
September 2021

New insights on the tapeworm using molecular tools: age-based human definitive host prevalence and deliberation on parasite life span.

Pathog Glob Health 2021 May 24:1-8. Epub 2021 May 24.

Department of Parasitology, Asahikawa Medical University, Asahikawa, Japan.

Information on age-based taeniasis prevalence is crucial for control of cysticercosis. taeniasis prevalence was determined for a village in Liangshan Prefecture, Sichuan Province, China that was co-endemic for , and . Individuals who were egg-positive by stool microscopy and/or expelled tapeworms or proglottids post-treatment were diagnosed as having taeniasis. Infecting species was identified via multiplex PCR on tapeworm specimens or coproPCR followed by sequencing. In addition, initial stool samples from 10 children with taeniasis suspected of having spontaneous expulsion of tapeworms within the period between diagnosis and treatment were subject to species confirmation via coproPCR and sequencing. Of the 389 study subjects, 194 (49.9%) were diagnosed with taeniasis. Children (< 16 years of age) had a higher taeniasis prevalence (8.8%) than older individuals (2.5%) (P = 0.0127). Molecular analysis of initial stool samples from 7 of 10 children suspected of spontaneously passing tapeworms indicated 6 infections due to and 1 infection due to . This study found that young children had a higher taeniasis prevalence than older individuals, providing additional support for the belief that adult likely has a relatively short lifespan compared to other species with human definitive hosts.
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http://dx.doi.org/10.1080/20477724.2021.1928869DOI Listing
May 2021

Unravelling the mechanism of amitriptyline removal from water by natural montmorillonite through batch adsorption, molecular simulation and adsorbent characterization studies.

J Colloid Interface Sci 2021 Sep 26;598:379-387. Epub 2021 Apr 26.

Environmental Contaminants Group, Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.

Amitriptyline (AMI) is one of the most common tricyclic antidepressant personal care medications. Due to its environmental persistence and bioaccumulation, release of AMI into the environment via wastewater streams in elevated levels could lead to significant ecological and human health impacts. In this study, the adsorption of AMI by montmorillonite (SWy-2), a naturally abundant smectite clay with sodium ions as the main interlayer cations, was investigated. Maximum AMI adsorption (276 mg/g) occurred at pH 7-8. After adsorption, examination of the adsorbent's X-ray diffraction pattern indicated that interlayer expansion had occurred, where chemical stoichiometry confirmed cation exchange as the principal adsorption mechanism. AMI adsorption reached equilibrium within 4 h, with kinetic data best fitting the pseudo-second order kinetic model (R = 0.98). AMI adsorption was unaffected by solution pH in the range 2-11, where adsorption was endothermic, and molecular simulations substantiated by Fourier transform infrared spectroscopy and thermogravimetric investigations indicated that the orientation of AMI molecules in the interlayer was via an amine group and a benzene ring. Overall this research shows that SWy-2 has significant potential as a low cost, effective, and geologically derived natural material for AMI removal in wastewater systems.
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http://dx.doi.org/10.1016/j.jcis.2021.04.033DOI Listing
September 2021

Radiometric Performance Evaluation of FY-4A/AGRI Based on Aqua/MODIS.

Sensors (Basel) 2021 Mar 7;21(5). Epub 2021 Mar 7.

State Key Laboratory of Remote Sensing Science, Aerospace information Research Institute, Chinese Academy of Sciences, Beijing 100101, China.

Fengyun-4A (FY-4A) is the first satellite of the Chinese second-generation geostationary orbit meteorological satellites (FY-4). The Advanced Geostationary Radiation Imager (AGRI), onboard FY-4A does not load with high-precision calibration facility in visible and near infrared (VNIR) channel. As a consequence, it is necessary to comprehensively evaluate its radiometric performance and quantitatively describe the attenuation while using its VNIR data. In this paper, the radiometric performance at VNIR channels of FY-4A/AGRI is evaluated based on Aqua/MODIS data using the deep convective cloud (DCC) target. In order to reduce the influence of view angle and spectral response difference, the bi-directional reflectance distribution function (BRDF) correction and spectral matching have been performed. The evaluation result shows the radiometric performance of FY-4A/AGRI: (1) is less stable and with obvious fluctuations; (2) has a lower radiation level because of 24.99% lower compared with Aqua/MODIS; 3) has a high attenuation with 9.11% total attenuation over 2 years and 4.0% average annual attenuation rate. After the evaluation, relative radiometric normalization between AGRI and MODIS in VNIR channel is performed and the procedure is proved effective. This paper proposed a more reliable reference for the quantitative applications of FY-4A data.
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http://dx.doi.org/10.3390/s21051859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962088PMC
March 2021

LUCAT1 as an oncogene in tongue squamous cell carcinoma by targeting miR-375 expression.

J Cell Mol Med 2021 May 30;25(10):4543-4550. Epub 2021 Mar 30.

Department of Endodontics, Jinan Stomatological Hospital, Shandong, China.

Emerging studies suggested that lncRNAs play a crucial molecular role in cancer development and progression. LncRNA LUCAT1 has been proved as oncogenic molecular in lung cancer, glioma, osteosarcoma, renal carcinoma and oesophageal squamous cell carcinoma. However, its roles and function mechanisms in tongue squamous cell carcinoma (TSCC) are still unknown. We showed that the expression of LUCAT1 was up-regulated in the TSCC cells and tissues and the higher LUCAT1 expression was associated with the poor overall survival (OS). Knockdown expression of LUCAT1 suppressed TSCC cell proliferation, cycle and migration. In addition, we demonstrated that miR-375 overexpression inhibited the luciferase activity of LUCAT1 wild-type and knockdown LUCAT1 promoted the miR-375 expression in TSCC cell. Furthermore, we indicated that miR-375 expression was down-regulated in the TSCC cell lines and tissues and the lower expression of miR-375 was associated with poor OS. The expression of miR-375 was inversely correlated with LUCAT1 expression in the TSCC tissues. Knockdown LUCAT1 promoted TSCC cell proliferation, cell cycle and migration partly through regulating miR-375 expression. In summary, this study suggested the tumorigenic effect of lncRNA LUCAT1 in TSCC cells by targeting miR-375 expression.
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http://dx.doi.org/10.1111/jcmm.15982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107098PMC
May 2021

Population genomic analyses of schistosome parasites highlight critical challenges facing endgame elimination efforts.

Sci Rep 2021 Mar 25;11(1):6884. Epub 2021 Mar 25.

Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

Schistosomiasis persists in Asian regions despite aggressive elimination measures. To identify factors enabling continued parasite transmission, we performed reduced representation genome sequencing on Schistosoma japonicum miracidia collected across multiple years from transmission hotspots in Sichuan, China. We discovered strong geographic structure, suggesting that local, rather than imported, reservoirs are key sources of persistent infections in the region. At the village level, parasites collected after referral for praziquantel treatment are closely related to local pre-treatment populations. Schistosomes within villages are also highly related, suggesting that only a few parasites from a limited number of hosts drive re-infection. The close familial relationships among miracidia from different human hosts also implicate short transmission routes among humans. At the individual host level, genetic evidence indicates that multiple humans retained infections following referral for treatment. Our findings suggest that end-game schistosomiasis control measures should focus on completely extirpating local parasite reservoirs and confirming successful treatment of infected human hosts.
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http://dx.doi.org/10.1038/s41598-021-86287-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994584PMC
March 2021

LC-MS/MS method for quantitation of gemcitabine and its metabolite 2',2'-difluoro-2'-deoxyuridine in mouse plasma and brain tissue: Application to a preclinical pharmacokinetic study.

J Pharm Biomed Anal 2021 May 13;198:114025. Epub 2021 Mar 13.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address:

A simple, sensitive, and relatively fast assay was developed and validated for the quantitation of gemcitabine (dFdC) and its major metabolite 2',2'-difluoro-2'-deoxyuridine (dFdU) in mouse plasma and brain tissue. The assay used a small sample (25 μL plasma and 5 mg brain) for extraction by protein precipitation. After dilution of the supernatant extract, 1 μL was injected into HPLC system for reverse phase chromatographic separation with a total run time of 8 min. Chromatographic resolution of dFdC and dFdU was achieved on a Gemini C18 column (50 × 4.6 mm, 3 μm) utilizing gradient elution. Multiple reaction monitoring (MRM) with positive/negative ion switching was performed for detection of dFdC and its internal standard (dFdC-IS) in positive ion mode and dFdU and its IS (dFdU-IS) in negative ion mode. Two calibration curves ranging from 5-2000 ng/mL and 250-50,000 ng/mL were generated for dFdC and dFdU in mouse plasma, respectively. For measurement of dFdC and dFdU in mouse brain tissue, another two curves were used ranging from 0.02 to 40 ng/mg and 1-40 ng/mg, respectively. This assay demonstrated excellent precision and accuracy within day and between days for simultaneous measurement of dFdC and dFdU at all the concentration levels in both matrices. The other parameters such as selectivity, sensitivity, matrix effects, recovery, and storage stability were also assessed for both analytes in each matrix. Compared to the previously reported methods, the sample extraction in the current assay was simplified significantly, and the analysis time was greatly shortened. We successfully applied the validated method to the analysis of dFdC and dFdU in mouse plasma, brain, and brain tumor tissue in a preclinical pharmacokinetic study.
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http://dx.doi.org/10.1016/j.jpba.2021.114025DOI Listing
May 2021

Frequency division combined machining method to improve polishing efficiency of continuous phase plate by bonnet polishing.

Opt Express 2021 Jan;29(2):1597-1612

Continuous phase plate (CPP), as a key diffractive optical element, is difficult to manufacture owing to its random and small features. In this paper, a novel frequency division combined machining (FDCM) method was proposed to improve polishing efficiency of CPP by optimizing the tool influence functions (TIFs) over targeted frequency bands. In addition, the convergence rate of power spectral density (CR-PSD) was proposed to evaluate the correct ability of TIF in different frequency bands, and to determine the division frequency for the combined processing. Through simulation verification, the combined processing with optimized TIFs by FDCM enabled high precision in less total time than that with single TIF processing. The experimental results verified that the method could imprint a 300 × 300 mm CPP with residual root-mean-square 24.7 nm after approximately 6-h bonnet polishing. Comparing the focal spots of designed and fabricated CPPs, the deviation of their energy concentration within 500 microns is only 0.22%. Hence, bonnet polishing using the FDCM is a new technical option for the production of large-aperture CPPs. Furthermore, the FDCM method shows a significant increase in efficiency, and it could be a generic method for CPP processing through other technologies, including magnetorheological and ion beam finishing.
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http://dx.doi.org/10.1364/OE.412678DOI Listing
January 2021

The PITX gene family as potential biomarkers and therapeutic targets in lung adenocarcinoma.

Medicine (Baltimore) 2021 Jan;100(4):e23936

Department of Respiratory Medicine, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Zhejiang China.

Abstract: The PITX gene family of transcription factors have been reported to regulate the development of multiple organs. This study was designed to investigate the role of PITXs in lung adenocarcinoma (LUAD).In this study, the transcriptional levels of the 3 identified PITXs in patients with LUAD were examined using the gene expression profiling interactive analysis interactive web server. Meanwhile, the immunohistochemical data of the 3 PITXs were obtained in the Human Protein Atlas website, and western blotting was additionally conducted for further verification. Moreover, the association between the levels of PITXs and the stage plot as well as overall survival of patients with LUAD was analyzed.We found that the mRNA and protein levels of PITX1 and PITX2 were higher in LUAD tissues than those in normal lung tissues, while those of PITX3 displayed no significant differences. Additionally, PITX1 and PITX3 were found to be significantly associated with the stage of LUAD. The Kaplan-Meier Plot showed that the high level of PITX1 conferred a better overall survival of patients with LUAD while the high level of PITX3 was associated with poor prognosis.Our study implied that PITX1 and PITX3 are potential targets of precision therapy for patients with LUAD while PITX1 and PITX2 are regarded as novel biomarkers for the diagnosis of LUAD.
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http://dx.doi.org/10.1097/MD.0000000000023936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850728PMC
January 2021

Human Mobility Associated With Risk of Schistosoma japonicum Infection in Sichuan, China.

Am J Epidemiol 2021 Jul;190(7):1243-1252

Urbanization increases human mobility in ways that can alter the transmission of classically rural, vector-borne diseases like schistosomiasis. The impact of human mobility on individual-level Schistosoma risk is poorly characterized. Travel outside endemic areas may protect against infection by reducing exposure opportunities, whereas travel to other endemic regions may increase risk. Using detailed monthly travel- and water-contact surveys from 27 rural communities in Sichuan, China, in 2008, we aimed to describe human mobility and to identify mobility-related predictors of S. japonicum infection. Candidate predictors included timing, frequency, distance, duration, and purpose of recent travel as well as water-contact measures. Random forests machine learning was used to detect key predictors of individual infection status. Logistic regression was used to assess the strength and direction of associations. Key mobility-related predictors include frequent travel and travel during July-both associated with decreased probability of infection and less time engaged in risky water-contact behavior, suggesting travel may remove opportunities for schistosome exposure. The importance of July travel and July water contact suggests a high-risk window for cercarial exposure. The frequency and timing of human movement out of endemic areas should be considered when assessing potential drivers of rural infectious diseases.
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http://dx.doi.org/10.1093/aje/kwaa292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245870PMC
July 2021

Plasma Heat Shock Protein 90 Alpha: A Valuable Predictor of Early Chemotherapy Effectiveness in Advanced Non-Small-Cell Lung Cancer.

Med Sci Monit 2021 Jan 9;27:e924778. Epub 2021 Jan 9.

Department of Respiratory Medicine, Shaoxing People's Hospital, Shaoxing, Zhejiang, China (mainland).

BACKGROUND Heat shock protein-90 alpha (HSP90a) is more abundant in non-small-cell lung cancer (NSCLC) patients than in control individuals. However, whether it can reflect chemotherapy efficacy remains unknown. This study aimed to investigate the association of HSP90a with chemotherapy in advanced NSCLC. MATERIAL AND METHODS We retrospectively evaluated data from patients admitted to the Department of Respiratory Medicine, Shaoxing People's Hospital, from September 2016 to September 2018 with stage IIIB or IV NSCLC and administered 4 cycles of third-generation platinum-based combination chemotherapy (2 drugs simultaneously). Based on the RECIST1.1 criteria, complete remission (CR), partial response (PR), and stable disease (SD) in 60 cases were determined before and after chemotherapy. Before chemotherapy and after 1, 2, and 4 cycles of chemotherapy, plasma HSP90alpha levels were quantitated by ELISA. Chest CT was performed before and after 2 and 4 cycles of chemotherapy. RESULTS After 1-4 cycles of chemotherapy, plasma HSP90alpha levels were significantly lower than pre-chemotherapy levels (P<0.05). The sums of the longest tumor diameters after 2 and 4 cycles of chemotherapy were decreased compared with pre-chemotherapy values (P<0.05). Plasma HSP90alpha levels and tumor size showed no significant correlation before and after chemotherapy (r=0.244, P=0.06). CONCLUSIONS Plasma HSP90alpha can be considered a valuable predictor of early chemotherapy effectiveness in advanced NSCLC, and is positively correlated with tumor remission after chemotherapy. However, plasma HSP90alpha level is not correlated with tumor diameter and pathological type.
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http://dx.doi.org/10.12659/MSM.924778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805245PMC
January 2021

Patterns of relatedness and genetic diversity inferred from whole genome sequencing of archival blood fluke miracidia (Schistosoma japonicum).

PLoS Negl Trop Dis 2021 01 6;15(1):e0009020. Epub 2021 Jan 6.

Department of Biology, University of Texas at Arlington, Arlington, Texas, United States of America.

Genomic approaches hold great promise for resolving unanswered questions about transmission patterns and responses to control efforts for schistosomiasis and other neglected tropical diseases. However, the cost of generating genomic data and the challenges associated with obtaining sufficient DNA from individual schistosome larvae (miracidia) from mammalian hosts have limited the application of genomic data for studying schistosomes and other complex macroparasites. Here, we demonstrate the feasibility of utilizing whole genome amplification and sequencing (WGS) to analyze individual archival miracidia. As an example, we sequenced whole genomes of 22 miracidia from 11 human hosts representing two villages in rural Sichuan, China, and used these data to evaluate patterns of relatedness and genetic diversity. We also down-sampled our dataset to test how lower coverage sequencing could increase the cost effectiveness of WGS while maintaining power to accurately infer relatedness. Collectively, our results illustrate that population-level WGS datasets are attainable for individual miracidia and represent a powerful tool for ultimately providing insight into overall genetic diversity, parasite relatedness, and transmission patterns for better design and evaluation of disease control efforts.
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http://dx.doi.org/10.1371/journal.pntd.0009020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815185PMC
January 2021

CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer.

Nat Commun 2020 11 30;11(1):6119. Epub 2020 Nov 30.

Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the KrasTp53 (KP) and the KrasLkb1 (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8 and CD4 T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC.
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http://dx.doi.org/10.1038/s41467-020-19973-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704643PMC
November 2020

Assessment of a 10-year dog deworming programme on the transmission of Echinococcus multilocularis in Tibetan communities in Sichuan Province, China.

Int J Parasitol 2021 Feb 19;51(2-3):159-166. Epub 2020 Nov 19.

University of Salford, Greater Manchester, UK.

Human alveolar echinococcosis (AE) is considered a neglected zoonotic disease by the World Health Organization (WHO). The causative pathogen, Echinococcus multilocularis, lives as an adult tapeworm in the intestinal tract of canines. AE was identified as an emerging public health issue in Tibetan communities of Shiqu County 20 years ago. On St. Lawrence Island, Alaska (USA), in the 1980s peri-domestic transmission of E. multilocularis was controlled by regular deworming of owned dogs over a 10-year period. In Tibetan communities, on the Tibetan Plateau, control of E. multilocularis transmission is challenging due to the continental setting, complex epidemiology, disease ecology, geography, and socio-cultural factors. However, a control programme based on deworming owned dogs using praziquental (PZQ) has been carried out since 2006. Assessment was conducted in townships where baseline data were available 10 years prior. Purging of dogs by oral administration of arecoline was used to measure E. multilocularis prevalence, trapping small mammals around communities was employed to assess the change in infection of pikas and voles, and analysis of human AE abdominal ultrasound-based data was used to understand the change in prevalence in the past decade. In all three evaluated townships, the E. multilocularis prevalence in owned dogs was significantly (P < 0.01) reduced from 7.23% (25/346) during 2000-2003 to 0.55% (1/181) in 2016. Human AE ultrasound-based prevalence (adjusted for age and sex) in five evaluated townships decreased significantly (P < 0.01) from 6.25% (200/3,198) during 2000-2002 to 3.67% (706/19,247) during 2015-2017. The 2016 prevalence of E. multilocularis metacestodes in small mammal intermediate hosts was not significantly different from the prevalence in 2008. The control programme was effective in reducing E. multilocularis infection in owned dogs and human AE prevalence, but did not significantly impact infection in wildlife intermediate hosts.
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http://dx.doi.org/10.1016/j.ijpara.2020.08.010DOI Listing
February 2021

The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response.

Cell Mol Immunol 2021 Aug 12;18(8):1981-1994. Epub 2020 Nov 12.

Department of Rheumatology and Immunology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.

Activation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications, including ubiquitination, SUMOylation, and phosphorylation; however, the underlying molecular mechanism is not fully understood. In this study, TRIM60 negatively regulated the formation and activation of the TAK1 signalosome. Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation, accompanied by elevated levels of proinflammatory cytokines but not IFN-I. Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination, resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways. The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562; substitution of these lysines with arginines abolished the SUMOylation of TAB2. In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock and L. monocytogenes infection. Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response, potentially paving the way for a new strategy to control antibacterial immune responses.
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http://dx.doi.org/10.1038/s41423-020-00564-wDOI Listing
August 2021

Should we remain hopeful? The key 8 weeks: spatiotemporal epidemic characteristics of COVID-19 in Sichuan Province and its comparative analysis with other provinces in China and global epidemic trends.

BMC Infect Dis 2020 Nov 5;20(1):807. Epub 2020 Nov 5.

Sichuan Center for Disease Control and Prevention, No. 6 Zhongxue Rd, Chengdu, 610041, China.

Background: The COVID-19 spread worldwide quickly. Exploring the epidemiological characteristics could provide a basis for responding to imported cases abroad and to formulate prevention and control strategies in areas where COVID-19 is still spreading rapidly.

Methods: The number of confirmed cases, daily growth, incidence and length of time from the first reported case to the end of the local cases (i.e., non-overseas imported cases) were compared by spatial (geographical) and temporal classification and visualization of the development and changes of the epidemic situation by layers through maps.

Results: In the first wave, a total of 539 cases were reported in Sichuan, with an incidence rate of 0.6462/100,000. The closer to Hubei the population centres were, the more pronounced the epidemic was. The peak in Sichuan Province occurred in the second week. Eight weeks after the Wuhan lockdown, the health crisis had eased. The longest epidemic length at the city level in China (except Wuhan, Taiwan, and Hong Kong) was 53 days, with a median of 23 days. Spatial autocorrelation analysis of China showed positive spatial correlation (Moran's Index > 0, p < 0.05). Most countries outside China began to experience a rapid rise in infection rates 4 weeks after their first case. Some European countries experienced that rise earlier than the USA. The pandemic in Germany, Spain, Italy, and China took 28, 29, 34, and 18 days, respectively, to reach the peak of daily infections, after their daily increase of up to 20 cases. During this time, countries in the African region and Southeast Asian region were at an early stage of infections, those in the Eastern Mediterranean region and region of the Americas were in a rapid growth phase.

Conclusions: After the closure of the outbreak city, appropriate isolation and control measures in the next 8 weeks were key to control the outbreak, which reduced the peak value and length of the outbreak. Some countries with improved epidemic situations need to develop a continuous "local strategy at entry checkpoints" to to fend off imported COVID-19.
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http://dx.doi.org/10.1186/s12879-020-05494-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642853PMC
November 2020

RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.

Nat Commun 2020 11 2;11(1):5536. Epub 2020 Nov 2.

Department of Virology, College of Life Sciences, Zhongnan Hospital of Wuhan University, 430071, Wuhan, China.

MAVS and MITA are essential adaptor proteins mediating innate antiviral immune responses against RNA and DNA viruses, respectively. Here we show that RNF115 plays dual roles in response to RNA or DNA virus infections by catalyzing distinct types of ubiquitination of MAVS and MITA at different phases of viral infection. RNF115 constitutively interacts with and induces K48-linked ubiquitination and proteasomal degradation of homeostatic MAVS in uninfected cells, whereas associates with and catalyzes K63-linked ubiquitination of MITA after HSV-1 infection. Consistently, the protein levels of MAVS are substantially increased in Rnf115 organs or cells without viral infection, and HSV-1-induced aggregation of MITA is impaired in Rnf115 cells compared to the wild-type counterparts. Consequently, the Rnf115 mice exhibit hypo- and hyper-sensitivity to EMCV and HSV-1 infection, respectively. These findings highlight dual regulation of cellular antiviral responses by RNF115-mediated ubiquitination of MAVS and MITA and contribute to our understanding of innate immune signaling.
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http://dx.doi.org/10.1038/s41467-020-19318-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606512PMC
November 2020

Site-specific contacts enable distinct modes of TRPV1 regulation by the potassium channel Kvβ1 subunit.

J Biol Chem 2020 12 15;295(50):17337-17348. Epub 2020 Oct 15.

State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, Hubei, China. Electronic address:

Transient receptor potential vanilloid 1 (TRPV1) channel is a multimodal receptor that is responsible for nociceptive, thermal, and mechanical sensations. However, which biomolecular partners specifically interact with TRPV1 remains to be elucidated. Here, we used cDNA library screening of genes from mouse dorsal root ganglia combined with patch-clamp electrophysiology to identify the voltage-gated potassium channel auxiliary subunit Kvβ1 physically interacting with TRPV1 channel and regulating its function. The interaction was validated using endogenous dorsal root ganglia neurons, as well as a recombinant expression model in HEK 293T cells. The presence of Kvβ1 enhanced the expression stability of TRPV1 channels on the plasma membrane and the nociceptive current density. Surprisingly, Kvβ1 interaction also shifted the temperature threshold for TRPV1 thermal activation. Using site-specific mapping, we further revealed that Kvβ1 interacted with the membrane-distal domain and membrane-proximal domain of TRPV1 to regulate its membrane expression and temperature-activation threshold, respectively. Our data therefore suggest that Kvβ1 is a key element in the TRPV1 signaling complex and exerts dual regulatory effects in a site-specific manner.
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http://dx.doi.org/10.1074/jbc.RA120.015605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863878PMC
December 2020

Evaluation and compensation of a kinematic error to enhance prepolishing accuracy for large aspheric surfaces by robotic bonnet technology.

Opt Express 2020 Aug;28(17):25085-25100

To obtain an economical uniform polishing method, it is effective to combine robot technology with bonnet polishing technology and apply it to the precision processing of large aspheric surfaces. However, the large robotic kinematic error causes significant deterioration to the surface shape of aspheric optics during robotic bonnet polishing (R-BP). To address this problem, research on the evaluation and compensation of the kinematic error was conducted to enhance the prepolishing accuracy on large aspheric surfaces by R-BP. Firstly, a precession control model of R-BP applied to the polishing of large aspheric surfaces was proposed. Then, an evaluation and compensation method of a robot kinematic error was presented based on machining errors. At last, it had been verified by experiments that at the removal depth of 2.5 μm, the variation of surface shape was reduced from 0.42 μm to 0.11 μm after compensation. Meanwhile, the change rate was reduced from 16.8% to 4.4%. Hence, the effectiveness of evaluation and compensation method to improve the prepolishing accuracy was verified, which is beneficial to implement mass production of high-precision large aspheric surfaces with low cost.
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http://dx.doi.org/10.1364/OE.400753DOI Listing
August 2020

Visit-to-visit blood pressure variability and risk of adverse birth outcomes in pregnancies in East China.

Hypertens Res 2021 Feb 7;44(2):239-249. Epub 2020 Sep 7.

Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Suzhou, China.

To investigate the potential associations between visit-to-visit blood pressure variability (VVV) and adverse birth outcomes in pregnancies, 48,209 pregnant women without proteinuria or chronic hypertension before 20 weeks of gestation who delivered live singletons between January 2014 and November 2019 in Taizhou or Taicang cities were recruited. VVV was estimated as the standard deviation and coefficient of variation of blood pressure [i.e., systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)] measured from 20 weeks of gestation onwards. Pregnant women were classified into four groups according to the corresponding quartiles for each VVV index. It was found that VVV was significantly higher in women with small for gestational age (SGA) or low birth weight (LBW) infants than in their counterparts. Graded associations between VVV categories and poor birth outcomes were observed. In particular, when comparing the women with the highest to the lowest quartiles of standard deviation and coefficient variation of DBP, the odds ratios (95% confidence interval) for SGA was 1.15 (1.06-1.26) and 1.14 (1.05-1.25), respectively. Interestingly, the addition of DBP-VVV to established risk factors improved risk prediction of SGA; DBP-VVV demonstrated modestly superior predictive performance to VVV obtained from SBP or MAP. Similar results were found even among normotensive pregnancies. Our findings indicated that VVV during pregnancy, especially DBP-VVV, was independently associated with poor birth outcomes of pregnancies in East China. The inclusion of DBP-VVV with established risk factors may help in identifying pregnancies at high risk of SGA. Validations are needed.
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http://dx.doi.org/10.1038/s41440-020-00544-7DOI Listing
February 2021

SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation.

Science 2020 08;369(6506):984-988

Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P. R. China.

Germinal center (GC) responses potentiate the generation of follicular regulatory T (T) cells. However, the molecular cues driving T cell formation remain unknown. Here, we show that sclerostin domain-containing protein 1 (SOSTDC1), secreted by a subpopulation of follicular helper T (T) cells and T-B cell border-enriched fibroblastic reticular cells, is developmentally required for T cell generation. Fate tracking and transcriptome assessment in reporter mice establishes SOSTDC1-expressing T cells as a distinct T cell population that develops after SOSTDC1 T cells and loses the ability to help B cells for antibody production. Notably, ablation in T cells results in substantially reduced T cell numbers and consequently elevated GC responses. Mechanistically, SOSTDC1 blocks the WNT-β-catenin axis and facilitates T cell differentiation.
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http://dx.doi.org/10.1126/science.aba6652DOI Listing
August 2020

Three-dimensional network-like structure formed by silicon coated carbon nanotubes for enhanced microwave absorption.

J Colloid Interface Sci 2021 Jan 7;582(Pt A):177-186. Epub 2020 Aug 7.

School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001, People's Republic of China.

The rapid development of electronic technology generates a great deal of electromagnetic wave (EMW) that is tremendously hazardous to environment and human health. Correspondingly, the high efficient EMW absorption materials with lightweight, high capacity and broad bandwidth are highly required. Herein, a series of three-dimensional (3D) network-like structure formed by silicon coated carbon nanotubes ([email protected]) are massively prepared through an improved sol-gel process. The as-obtained 3D [email protected] exhibit low densities of about 1.6 ± 0.2 g/cm. The formation of this special 3D structure can provide high dielectric loss and good impedance matching for EMW absorption. As expected, a minimum reflection loss (RL) of -54.076 dB is obtained when uses the sample prepared by 0.1 g of CNTs and 0.2 mL of tetraethoxysilane as absorbent with a low loading rate of 10 wt% and thin absorber thickness of 1.08 mm. This specific minimum RL value exceeds many other CNT based EMW absorbers reported in previous literature. These findings featured with a green and scalable preparation process provides a facile strategy to design and fabricate high-performance EMW absorption materials, which can be applied to other materials such as carbon fibers and graphene.
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http://dx.doi.org/10.1016/j.jcis.2020.08.024DOI Listing
January 2021

Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1.

Protein Cell 2021 Apr 9;12(4):261-278. Epub 2020 Aug 9.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.
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http://dx.doi.org/10.1007/s13238-020-00751-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018997PMC
April 2021

Author Correction: USP29 maintains the stability of cGAS and promotes cellular antiviral responses and autoimmunity.

Cell Res 2020 Sep;30(9):821-822

Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41422-020-0368-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608391PMC
September 2020

LC-MS/MS method for quantitation of the CK2 inhibitor silmitasertib (CX-4945) in human plasma, CSF, and brain tissue, and application to a clinical pharmacokinetic study in children with brain tumors.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Sep 23;1152:122254. Epub 2020 Jun 23.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, United States. Electronic address:

Silmitasertib (CX-4945) as a potent and selective inhibitor of CK2 exhibited promising in vitro and in vivo anti-cancer activity. An assay employing cation-exchange solid phase extraction (SPE) followed by LC-MS/MS analysis was successfully developed and validated for the quantitation of silmitasertib in human plasma, brain tissue, and human cerebrospinal fluid (CSF). Reverse phase chromatographic separation was achieved using Synergi™ hydro-RP column (4 μm, 75 × 2.0 mm) and gradient elution with 5 mM ammonium formate aqueous solution (pH 6.5) as mobile phase A and 0.1% formic acid in acetonitrile as mobile phase B. Multiple reaction monitoring (MRM) transition of m/z 350.2 → 223.2 and m/z 316.2 → 223.2 were chosen for detection of silmitasertib and internal standard (CX-4786) respectively. Since silmitasertib concentration in patient plasma is expected to be in a wide range due to the study design, two calibration curves with range 0.2-125 ng/ml and 32-20,000 ng/ml were established. A different curve ranging from 2 to 40 ng/g was used for measurement of silmitasertib in brain tissue, while another calibration curve ranging from 0.2 to 20 ng/ml was established for CSF. All these calibration curves corresponding to different matrices showed good linearity (R > 0.99) over the concentration range. This assay demonstrated excellent precision below 15% and accuracies between 85% and 115% within-day and between-day for all the concentration levels in each matrix. This assay was also validated for each matrix for selectivity, sensitivity, matrix effects, recovery, and stability. We applied the validated method to the analysis of plasma silmitasertib for a clinical study.
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http://dx.doi.org/10.1016/j.jchromb.2020.122254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484447PMC
September 2020
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