Publications by authors named "Qian Zhao"

1,237 Publications

  • Page 1 of 1

Evaluation of arsenic species in leukocytes and granulocytes of acute promyelocytic leukemia patients treated with arsenic trioxide.

J Pharm Biomed Anal 2021 Jun 8;203:114201. Epub 2021 Jun 8.

Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, 23 YouZheng Str, Nangang District, Harbin, China. Electronic address:

Concentrations of arsenic metabolites were important to clarify the sensitivity and resistance of APL (acute promyelocytic leukemia) patients to arsenic trioxide (AsO). Our purpose was to evaluate levels and distributions of arsenic species in leukocytes and granulocytes of APL patients. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured by high performance liquid chromatography coupled inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Leukocytes were collected from 21 patients treated with AsO during induction, consolidation, and drug-withdrawal period. The upregulation of granulocytes in induction period was closely related to the differentiation of promyelocytes. Therefore, granulocytes were collected during induction period from 4 APL patients and purified by flow cytometry sorting using a panel of monoclonal antibodies specific for CD45, CD3, CD14, and CD19. The developed HPLC-ICP-MS method was precise and accurate with the limit of quantification of 0.5 ng/mL. During induction, consolidation, and drug-withdrawal period, the general trend of arsenic species was iAs > MMA > DMA (P < 0.05) in leukocytes. iAs was predominant arsenic species with median concentration of 10.84 (6.03-14.62) ng/mL. MMA was major methylated metabolite with median concentration of 0.94 (0.60-2.50) ng/mL. Moreover, arsenicals were detected in leukocytes during drug-withdrawal. In granulocytes, iAs was found during induction period with median concentration of 1.08 ng/mL, while MMA and DMA were not detected. These results showed that iAs was the primary arsenic species in leukocytes and granulocytes from APL patients treated with AsO. This study suggested that iAs might play a dominant therapeutic role during the whole treatment process of APL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2021.114201DOI Listing
June 2021

68Ga-PSMA-11 PET/CT in Isolated Bilateral Adrenal Metastases From Prostate Adenocarcinoma.

Clin Nucl Med 2021 Jun 10. Epub 2021 Jun 10.

From the Department of Nuclear Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Departments of Urology Nuclear Medicine, Changhai Hospital, Navy Medical University, Shanghai, China.

Abstract: A 65-year-old man with treated prostate adenocarcinoma underwent 68Ga-PSMA-11 PET/CT scan for restaging due to significantly increased serum PSA levels. PET/CT showed bilateral adrenal masses with high 68Ga-PSMA-11 uptake. There was no other lesion suspicious for metastasis. The laboratory and imaging findings were consisted with isolated bilateral adrenal metastases from prostate adenocarcinoma. The patient received docetaxel chemotherapy in combination with androgen deprivation therapy. PSA levels gradually decreased during chemotherapy. Follow-up MRI showed the bilateral adrenal masses significantly decreased in size. This case demonstrates the usefulness of 68Ga-PSMA-11 PET/CT in identifying atypical metastasis from prostate adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0000000000003759DOI Listing
June 2021

Tissue- and stage-specific landscape of the mouse translatome.

Nucleic Acids Res 2021 Jun 9. Epub 2021 Jun 9.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

The current understanding of how overall principles of translational control govern the embryo-to-adult transition in mammals is still far from comprehensive. Herein we profiled the translatomes and transcriptomes of six tissues from the mice at embryonic and adult stages and presented the first report of tissue- and stage-specific translational landscape in mice. We quantified the extent of gene expression divergence among different expression layers, tissues and stages, detected significant changes in gene composition and function underlying these divergences and revealed the changing architecture of translational regulation. We further showed that dynamic translational regulation can be largely achieved via modulation of translational efficiency. Translational efficiency could be altered by alternative splicing (AS), upstream and downstream open reading frames (uORFs and dORFs). We revealed AS-mediated translational repression that was exerted in an event type-dependent manner. uORFs and dORFs exhibited mutually exclusive usage and the opposing effects of translational regulation. Furthermore, we discovered many novel microproteins encoded by long noncoding RNAs and demonstrated their regulatory potential and functional relevance. Our data and analyses will facilitate a better understanding of the complexity of translation and translational regulation across tissue and stage spectra and provide an important resource to the translatome research community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkab482DOI Listing
June 2021

Fluoride exposure and children's intelligence: Gene-environment interaction based on SNP-set, gene and pathway analysis, using a case-control design based on a cross-sectional study.

Environ Int 2021 Jun 4;155:106681. Epub 2021 Jun 4.

Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Background: Excessive fluoride exposure has been associated with intelligence loss, but little is known about gene-fluoride interactions on intelligence at SNP-set, gene and pathway level.

Objectives: Here we conducted a population-based study in Chinese school-aged children to estimate the associations of fluoride from internal and external exposures with intelligence as well as to explore the gene-fluoride interactions on intelligence at SNP-set, gene and neurodevelopmental pathway level.

Methods: A total of 952 resident children aged 7 to 13 were included in the current study. The fluoride contents in drinking water, urine, hair and nail were measured using the ion-selective electrode method. LASSO Binomial regression was conducted to screen the intelligence-related SNP-set. The gene-fluoride interactions at gene and pathway levels were detected by the Adaptive Rank Truncated Product method.

Results: The probability of high intelligence was inversely correlated with fluoride contents in water, urine, hair and nail (all P < 0.001). The SNP-set based on rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 was related to high intelligence (P = 0.001) alone and by interaction with water, urinary and hair fluoride (P = 0.030, 0.040, 0.010), separately. In gene level, CLU and TOMM40 interacted with hair fluoride (both P = 0.017) on intelligence. In pathway level, Alzheimer disease pathway, metabolic pathway, signal transduction pathway, sphingolipid signaling pathway and PI3K-AKT signaling pathway interacted with fluoride on intelligence in men.

Conclusions: Our study suggests that fluoride is inversely associated with intelligence. Moreover, the interactions of fluoride with mitochondrial function-related SNP-set, genes and pathways may also be involved in high intelligence loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2021.106681DOI Listing
June 2021

Combustion-derived particulate organic matter associated with hemodynamic abnormality and metabolic dysfunction in healthy adults.

J Hazard Mater 2021 May 29;418:126261. Epub 2021 May 29.

Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, and Peking University Institute of Environmental Medicine, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Health Science Center, Peking University, Beijing, China. Electronic address:

Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6-2.9% in diastolic blood pressure, 6.6-8.1% in soluble ST2, 10.5-14.5% in insulin, 40.9-45.7% in osteoprotegerin, and 36.3-48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.126261DOI Listing
May 2021

Childhood Clear Cell Sarcoma of Kidney: Incidence and Survival.

Front Pediatr 2021 20;9:675373. Epub 2021 May 20.

Anhui Provincial Cancer Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

This study is to describe current incidence of childhood clear cell sarcoma of kidney (CCSK) and to investigate the present survival of this cancer. Surveillance, Epidemiology, and End Result (SEER) data was used to identify children with CCSK and Wilms tumor (WT) aged 0-19 years in the US. Age-adjusted incidences were estimated over the decades. Age- and sex-specific epidemiology was also presented. Propensity score matching was used to balance features of CCSK and WT cases. Log rank test was used to compare survivals and Cox regression was used to evaluate independent effects of factors. The present age-adjusted incidence of childhood CCSK was 0.205 per million, which remained stable for years and ranked third in all pediatric renal tumors. The incidence rate ratios for boy and age under 4 were 3 and 21, respectively. The current 5-year overall survival (OS) rate for CCSK was 87%, which is not evidently inferior to that for WT (90%); however the outcome of CCSK was significantly poorer if both groups were well-balanced (OS rate was 86 vs. 95%). Early year of diagnosis and distant metastasis were independent survival factors. In conclusion, occurrence of CCSK remains stable over the years, with an age-adjusted incidence of 0.205 per million. Boy and age under 4 are risk factors for tumor development. CCSK currently has a favorable outcome but its nature may be more aggressive than common kidney tumor, which in turn proves efficacy of modern treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.675373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173214PMC
May 2021

Fluorescent probes for and quantification of hydrogen peroxide.

Chem Sci 2020 Oct 27;11(44):11989-11997. Epub 2020 Oct 27.

Department of Chemistry, Morningside Laboratory for Chemical Biology, The University of Hong Kong Shenzhen Institute of Research and Innovation (HKU-SIRI), The University of Hong Kong Pokfulam Road Hong Kong P. R. China

Hydrogen peroxide (HO) plays essential roles in redox signaling and oxidative stress, and its dynamic concentration is critical to human health and diseases. Here we report the design, syntheses, and biological applications of and for quantitative measurement of HO. Both probes were successfully applied to detect endogenous HO fluxes in living cells or zebrafish, and biological effects of multiple stress inducers including rotenone, arsenic trioxide, and starvation were investigated. As HO is a common by-product for oxidase oxidation, a general assay was developed for ultrasensitive detection of various metabolites (glucose, uric acid, and sarcosine). Moreover, cellular HO measurements were achieved for the first time by combining flow cytometry with live cell calibration. This study provides a pair of unique molecular tools for advanced HO bio-imaging and assay development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sc04888gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162884PMC
October 2020

Sex differences in factors associated with quality of life in patients with epilepsy in Northeast China.

Epilepsy Behav 2021 May 31;121(Pt A):108076. Epub 2021 May 31.

Department of Neurology, The First Hospital of Jilin University, Changchun, China. Electronic address:

Objective: We aimed to investigate sex differences in factors associated with poor quality of life (QOL) in a cohort of patients with epilepsy (PWE) in Northeast China.

Methods: A consecutive cohort of 221 PWE from the First Hospital of Jilin University was recruited. The Chinese versions of the Patient Health Questionnaire-9 (PHQ-9), the Beck Anxiety Inventory (BAI), and the Quality of Life in Epilepsy Inventory (QOLIE-31) were used to measure depressive symptoms, anxiety symptoms, and the QOL.

Results: A total of 221 adult PWE participated in this study. In the multivariate regression model, three independent factors were found to be significantly associated with the total QOLIE-31 score in men: epilepsy duration (p = 0.007), the PHQ-9 score (p < 0.001), and the BAI score (p < 0.001). As for the subscale domain of QOL, marital status showed a relationship with cognitive function (p = 0.047), and residence was related with medication effects (p = 0.034). Two independent factors were found to be significantly associated with the total QOLIE-31 score in women: the PHQ-9 score (p < 0.001) and the BAI score (p < 0.001). The education level of women was positively associated with three subdomain scores of QOL, including overall QOL (p < 0.001), emotional well-being (p = 0.028), and energy/fatigue (p = 0.025).

Conclusion: We found that high levels of depressive and anxiety symptoms are strong predictors of a poor QOL in both men and women. Sex differences also occur in several demographic and clinical factors influencing the overall QOL or subscale domain scores such as epilepsy duration, marital status, and educational level. Timely diagnosis and treatment of psychiatric comorbidities might be crucial for improving the QOL in both men and women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.108076DOI Listing
May 2021

A CDR-based approach to generate covalent inhibitory antibody for human rhinovirus protease.

Bioorg Med Chem 2021 May 19;42:116219. Epub 2021 May 19.

School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Outer Ring Road, Guangzhou 510006, China. Electronic address:

Covalent target modulation with small molecules has been emerging as a promising strategy for drug discovery. However, covalent inhibitory antibody remains unexplored due to the lack of efficient strategies to engineer antibody with desired bioactivity. Herein, we developed an intracellular selection method to generate covalent inhibitory antibody against human rhinovirus 14 (HRV14) 3C protease through unnatural amino acid mutagenesis along the heavy chain complementarity-determining region 3 (CDR-H3). A library of antibody mutants was thus constructed and screened in vivo through co-expression with the target protease. Using this screening strategy, six covalent antibodies with proximity-enabled bioactivity were identified, which were shown to covalently target HRV14-3C protease with high inhibitory potency and exquisite selectivity. Compared to structure-based rational design, this library-based screening method provides a simple and efficient way for the discovery and engineering of covalent antibody for enzyme inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2021.116219DOI Listing
May 2021

Cold Plasma Preparation of Pd/Graphene Catalyst for Reduction of p-Nitrophenol.

Nanomaterials (Basel) 2021 May 20;11(5). Epub 2021 May 20.

College of Physical Science and Technology, Dalian University, Dalian 116622, China.

Supported metal nanoparticles with small size and high dispersion can improve the performance of heterogeneous catalysts. To prepare graphene-supported Pd catalysts, graphene and PdCl were used as support and Pd precursors, respectively. Pd/G-P and Pd/G-H catalysts were prepared by cold plasma and conventional thermal reduction, respectively, for the catalytic reduction of p-nitrophenol (4-NP). The reaction followed quasi-first-order kinetics, and the apparent rate constant of Pd/G-P and Pd/G-H was 0.0111 and 0.0042 s, respectively. The graphene support was exfoliated by thermal reduction and cold plasma, which benefits the 4-NP adsorption. Pd/G-P presented a higher performance because cold plasma promoted the migration of Pd species to the support outer surface. The Pd/C atomic ratio for Pd/G-P and Pd/G-H was 0.014 and 0.010, respectively. In addition, the Pd nanoparticles in Pd/G-P were smaller than those in Pd/G-H, which was beneficial for the catalytic reduction. The Pd/G-P sample presented abundant oxygen-containing functional groups, which anchored the metal nanoparticles and enhanced the metal-support interaction. This was further confirmed by the shift in the binding energy to a high value for Pd3d in Pd/G-P. The cold plasma method operated under atmospheric pressure is effective for the preparation of Pd/G catalysts with enhanced catalytic activity for 4-NP reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano11051341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160827PMC
May 2021

Classical swine fever virus infection suppresses claudin-1 expression to facilitate its replication in PK-15 cells.

Microb Pathog 2021 May 29;157:105012. Epub 2021 May 29.

College of Animal Veterinary Medicine, Yunnan Agricultural University, Kunming, 650201, Yunnan, China. Electronic address:

Classical swine fever (CSF) is one of the most epidemic viral diseases in swine industry. The causative pathogen is CSF virus (CSFV), a small enveloped RNA virus of Flaviviridae family. Claudin-1 was reported to be involved in the infections of a number of viruses, including many from Flaviviridae family, but no studies have investigated the role of porcine claudin-1 during CSFV infection in PK-15 cells. In this study, on the one hand, we demonstrated that CSFV infection reduced the claudin-1 expression at both mRNA and protein levels; on the other hand, CSFV infection was enhanced after claudin-1 knockdown, but inhibited by claudin-1 overexpression in a dose-dependent manner. Furthermore, negative correlation was demonstrated between the claudin-1 expression and CSFV titer. In conclusion, claudin-1 might be a barrier for CSFV infection in PK-15 cells, while CSFV bypasses the barrier through lysosome mediated degradation of claudin-1, which could be repressed by bafilomycin A1. Although the elaborate mechanisms how claudin-1 plays its roles in CSFV infection require further investigations, this study may advance our understanding of the molecular host-pathogen interaction mechanisms underlying CSFV infection and suggests enhancement of porcine claudin-1 as a potential preventive or therapeutic strategy for CSF control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2021.105012DOI Listing
May 2021

Clinical characteristic of prodromal symptoms between bipolar I and II disorder among Chinese patients: a retrospective study.

BMC Psychiatry 2021 May 31;21(1):275. Epub 2021 May 31.

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.

Background: This study aimed to identify the clinical characteristic of prodromal symptoms in Chinese patients with bipolar disorder (BD), prior to the first affective episode. It further aimed to characterize the prodromal traits between bipolar disorder type I (BD-I) and type II (BD-II).

Methods: 120 individuals with BD-I (n = 92) and BD- II (n = 28) were recruited to the study. Semi-structured interviews were then administered to evaluate prodromal symptoms in patients, within 3 years of BD onset, by using the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R).

Results: In the prodromal phase of the first depressive episode, patients with BD-II experienced more prodromal symptoms (p = 0.0028) compared to BD-I. Additionally, more frequent predictors were reported in patients with BD-II than BD-I including educational and occupational dysfunction (p = 0.0023), social isolation (p < 0.001), difficulty making decisions (p = 0.0012), oppositionality (p = 0.012), and suspiciousness/persecutory ideas (p = 0.017). There were also differences in the duration of the precursors. The duration of "weight loss or decrease in appetite" (p = 0.016) lasted longer in patients with BD-I, while "obsessions and compulsions" (p = 0.023) started earlier in patients with BD-II and occurred during the pre-depressive period. The prevalence and duration of each reported prodrome, preceding a first (hypo) manic episode, showed no difference between patients with BD-I and BD-II.

Conclusions: Specific affective, general, or psychotic symptoms occurred prior to both affective episodes. The characteristic of prodromal symptoms were key predictors for later episodes of BD including attenuated mania-like symptoms, subthreshold depressed mood, mood swings/lability, and anxiety. In the pre-depressive state, when compared to BD-II, BD-I presented with more prodromal symptoms in nonspecific dimensions, which indicated the substantial burden of BD-II. In conclusion, this study extends the understanding of the characteristics of prodromes of BD-I and BD-II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12888-021-03295-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168043PMC
May 2021

Investigation of microstructure and dissimilar materials connection patterns of mantis shrimp saddle.

Microsc Res Tech 2021 May 28. Epub 2021 May 28.

The Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, China.

The microstructure and dissimilar materials connection patterns of mantis shrimp saddle were investigated. The outer layer with layered helical structure and inner layer with slablike laminae structure constructed the microstructure characteristics of saddle. The merus and membrane were characterized by layered structure. The lamina of saddle connected the corresponding lamina in merus and membrane, building the continuous and smooth coupling connection patterns. The entitative "hard-hard" and "hard-soft" transitions of dissimilar materials at micro level enhanced the steady transmit of driven force. The saddle exhibited high mechanical strength. With the increase of in-situ tensile displacement, the number of fractured fragments on saddle outer layer surface increased, which subjected to tensile load and defused the damage in the form of mineralized surface fragmentation. In the inner part of saddle, the fracture of mineralized laminae and crack deflection mechanisms bore the tensile load influence. The combination of microstructure with high mechanical strength and continues micro lamina connection endowed the concise dissimilar materials connection and efficient elastic energy storage property of saddle, which can be treated as the bionic models for design and preparation of fiber reinforced resin composite, hyperelastic material and so on.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jemt.23763DOI Listing
May 2021

Author Correction: The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans.

Nat Commun 2021 May 28;12(1):3315. Epub 2021 May 28.

Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-University Freiburg, Freiburg, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23820-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163770PMC
May 2021

An In Situ Generated Prussian Blue Nanoparticle-Mediated Multimode Nanozyme-Linked Immunosorbent Assay for the Detection of Aflatoxin B1.

ACS Appl Mater Interfaces 2021 Jun 27;13(22):25738-25747. Epub 2021 May 27.

Laboratory of Micro & Nano Biosensing Technology in Food Safety, Hunan Provincial Key Laboratory of Food Science and Biotechnology, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China.

This work aims to develop a novel multimode (photothermal/colorimetric/fluorescent) nanozyme-linked immunosorbent assay (NLISA) based on the in situ generation of Prussian blue nanoparticles (PBNPs) on the surface of magnetic nanoparticles (MNPs). Being considered the most toxic among the mycotoxins, aflatoxin B1 (AFB1) was chosen as the proof-of-concept target. In this strategy, MNPs, on which an AFB1 aptamer was previously assembled via streptavidin-biotin linkage, are anchored to 96-well plates by AFB1 and antibody. In the presence of HCl and KFe(CN), PBNPs formed in situ on the MNP surface, thereby achieving photothermal and colorimetric signal readout due to their photothermal effect and intrinsic peroxidase-like activity. Based on fluorescence quenching by MNPs, Cy5 fluorescence was recovered by the in situ generation of PBNPs to facilitate ultrasensitive fluorescence detection. Photothermal and colorimetric signals allow portable/visual point-of-care testing, and fluorescent signals enable accurate determination with a detection limit of 0.54 fg/mL, which is 6333 and 28 times lower than those of photothermal and colorimetric analyses, respectively. We expect that this proposed multimode NLISA can not only reduce the false-positive/negative rates through the multisignal crossdetection in AFB1 monitoring but also provide a universal way of sophisticated instrumentation-free, easy-to-use, cost-effective, and highly sensitive detection of other food hazards.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c04751DOI Listing
June 2021

Correlation between neonatal hyperbilirubinemia and vitamin D levels: A meta-analysis.

PLoS One 2021 27;16(5):e0251584. Epub 2021 May 27.

The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Objective: Hyperbilirubinemia is a common disease in the neonatal period, and hyperbilirubinemia may cause brain damage. Therefore, prevention and diagnosis and management of hyperbilirubinemia is very important, and vitamin D may affect bilirubin levels. To evaluate the relationship between neonatal hyperbilirubinemia and vitamin D levels.

Method: The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and Embase databases as well as clinical trial registries in China and the United States were searched for relevant studies from inception to September 2020 without restrictions on language, population, or year. The studies was screened by two reviewers independently, the data were extracted, and the risk of bias of the included studies was evaluated using the NOS. A meta-analysis was conducted on the included studies using Stata11 software.

Results: Six case-control studies were included, and the methodological quality of the studies was high (grade A). The studies included 690 newborns; more than 409 were diagnosed with hyperbilirubinemia. The means and standard deviations were calculated. Meta-analysis results showed that neonatal vitamin D levels were 7.1 ng/ml lower among infants with hyperbilirubinemia than among healthy newborn levels (z = 6.95, 95% CI 9.10 ~ 5.09, P < 0.05). Subgroup analysis was conducted based on whether the bilirubin levels were concentrated in the 15 to 20 mg/dl range. Vitamin D level of infants with hyperbilirubinemia (the bilirubin levels were concentrated in the 15 to 20 mg/dl range) was 9.52 ng/ml (Z = 15.55, 95% CI-10.72~-8.32, P<0.05) lower than that of healthy infants. The bilirubin levels in four cases were not concentrated in the 15-20 mg/dl range. The results showed that the vitamin D level of hyperbilirubinemia (The bilirubin levels were not concentrated in the 15-20 mg/dl range) neonates were 5.35 ng/ml lower than that of healthy neonates (Z = 6.43, 95% CI-6.98~-3.72, P<0.05).

Conclusion: Vitamin D levels were observed to be lower in neonates with hyperbilirubinemia as compared to term neonates without hyperbilirubinemia in this study. This can possibly suggest that neonates with lower vitamin D levels are at higher risk for developing hyperbilirubinemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251584PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158937PMC
May 2021

Personalised Variable vs Fixed Dose Systemic Corticosteroid Therapy in Hospitalized Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Prospective, Multicentered, Randomised, Open-Label Clinical Trial.

Chest 2021 May 20. Epub 2021 May 20.

Department of Respiratory Medicine, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address:

Background: Systemic corticosteroids for treatment of chronic obstructive pulmonary disease (COPD) exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear.

Research Question: Is personalized-dose corticosteroid by a dosing scale more effective than fixed-dose in hospitalized COPD patients with exacerbations?

Study Design And Methods: This was a prospective, randomised, open-labeled trial. In-hospital COPD patients with exacerbations were randomly assigned in a 1:1 ratio to either fixed-dose group (40mg prednisolone equivalent) or personalised-dose group for 5 days. The primary endpoint was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (post-discharge) failure. Secondary endpoints were length of stay and cost.

Results: A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalised-dose group (n = 124). One patient in each group was not included in the intention-to-treat (ITT) population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalised-dose group, compared to 48.8% in the fixed-dose group (RR 0.40, 95% CI 0.24-0.68, p = 0.001). The in-hospital failure of therapy was significantly lower in the personalised-dose group (10.6% vs 24.4%, p = 0.005), whilst the medium-term failure rate, adverse event rate, hospital length of stay and costs were similar between two groups. Following treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment was needed in the personalised-dose group to achieve control of the exacerbation. In the personalized cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared to 22.9% in those receiving higher than 40mg (p=0.027).

Interpretation: Personalised dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially >60mg, while 40mg or less was too low in either group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.05.024DOI Listing
May 2021

Free Carriers versus Self-Trapped Excitons at Different Facets of Ruddlesden-Popper Two-Dimensional Lead Halide Perovskite Single Crystals.

J Phys Chem Lett 2021 May 20;12(20):4965-4971. Epub 2021 May 20.

Department of Chemistry, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.

The physical origin of sub-band gap photoluminescence in Ruddlesden-Poppers two-dimensional (2D) lead halide perovskites (LHPs) is still under debate. In this paper, we studied the photoluminescence features from two different facets of 2D LHP single crystals: the in-plane facet (IF) containing the 2D inorganic layers and the facet perpendicular to the 2D layers (PF). At the IF, the free carriers (FCs) dominate due to the weak electron-phonon coupling in a symmetric lattice. At the PF, the strain accumulation along the 2D layers enhances the electron-phonon coupling and facilitates self-trapped exciton (STE) formation. The time-resolved PL studies indicate that free carriers (FCs) at the IF can move freely and display the trapping by the intrinsic defects. The STEs at the PF are not likely trapped by the defects due to the reduced mobility. However, with increasing STE density, the STE transport is promoted, enabling the trapping of STE by the intrinsic defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.1c01148DOI Listing
May 2021

Optimization of sunflower head pectin extraction by ammonium oxalate and the effect of drying conditions on properties.

Sci Rep 2021 May 19;11(1):10616. Epub 2021 May 19.

School of Chemical Engineering and Technology, North University of China, Taiyuan, 030051, China.

Pectin is a kind of natural and complex carbohydrates which is extensively used in food, chemical, cosmetic, and pharmaceutical industries. Fresh sunflower (Helianthus annuus L.) heads were utilized as a novel source of pectin extracted by ammonium oxalate. The conditions of the extraction process were optimized implementing the response surface methodology. Under optimal extraction parameters (extraction time 1.34 h, liquid-solid ratio 15:1 mL/g, ammonium oxalate concentration 0.76% (w/v)), the maximum experimental yield was 7.36%. The effect of spray-drying and freeze-drying on the physiochemical properties, structural characteristics, and antioxidant activities was investigated by FT-IR spectroscopy, high performance size exclusion chromatography, and X-ray diffraction. The results showed freeze-drying lead to decrease in galacturonic acid (GalA) content (76.2%), molecular weight (M 316 kDa), and crystallinity. The antioxidant activities of pectin were investigated utilizing the in-vitro DPPH and ABTS radical-scavenging systems. This study provided a novel and efficient extraction method of sunflower pectin, and confirmed that different drying processes had an effect on the structure and properties of pectin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-89886-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134464PMC
May 2021

Down-regulated FST expression is involved in the poor prognosis of triple-negative breast cancer.

Cancer Cell Int 2021 May 17;21(1):267. Epub 2021 May 17.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, China.

Background: Triple-negative breast cancer (TNBC) is more commonly associated with young patients, featuring high histological grade, visceral metastasis, and distant recurrence. Follistatin (FST) is a secreted extracellular regulatory protein that antagonizes TGF-β superfamily such as activin and TGF-β related superfamily such as bone morphogenetic protein (BMP). The implication of FST in the proliferation, angiogenesis, and metastasis of solid tumors documents good or poor outcome of patients with BC. However, the role of FST in TNBC remains unclear.

Methods: Data of 935 patients with breast cancer (BC) were extracted from TCGA. Case-control study, Kaplan-Meier, uni-multivariate COX, and ROC curve were utilized to investigate the relationship between FST expression and the clinical characteristics and prognosis of BC. Functional studies were used to analyze the effect of FST expression on proliferation, apoptosis, migration, and invasion of TNBC cell lines. Bioinformatic methods such as volcanoplot, GO annd KEGG enrichment, and protein-protein interactions (PPI) analyses were conducted to further confirm the different roles of FST in the apoptotic pathways among mesenchymal and mesenchymal stem-like cells of TNBC.

Results: Data from TCGA showed that low FST expression correlated with poor prognosis (for univariate analysis, HR = 0.47, 95% CI: 0.27-0.82, p = 0.008; for multivariate analysis, HR = 0.40, 95% CI: 0.21-0.75, p = 0.004). Low FST expression provided high predicted value of poor prognosis in TNBC amongst BCs. FST knockdown promoted the proliferation, migration and invasion of BT549 and HS578T cell lines. FST inhibited the apoptosis of mesenchymal cells by targeting BMP7.

Conclusions: Low FST expression is associated with poor prognosis of patients with TNBC. FST expressions exhibit the anisotropic roles of apoptosis between mesenchymal and mesenchymal stem-like cells but promote the proliferation, migration, invasion in both of two subtypes of TNBC in vitro. FST may be a subtype-heterogeneous biomarker for monitoring the progress of TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-01977-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130405PMC
May 2021

The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China.

J Ovarian Res 2021 May 17;14(1):68. Epub 2021 May 17.

Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42# Baiziting street, Nanjing, Jiangsu, 210009, People's Republic of China.

Background: Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China.

Methods: Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity.

Results: Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060-0.759) and disease control rate (DCR) of 50% (95%CI = 0.140-0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event.

Conclusion: It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-021-00803-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127179PMC
May 2021

OLFML2A is necessary for anti-triple negative breast cancer effect of selective activator protein-1 inhibitor T-5224.

Transl Oncol 2021 May 13;14(8):101100. Epub 2021 May 13.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China. Electronic address:

Previous studies have shown that expression of activator protein-1 (AP-1) family is significantly elevated in triple-negative breast cancer (TNBC), compared with that in other breast cancer subtypes. Here we investigated the anti-tumor effect and mechanism of T-5224, an inhibitor of c-Fos/AP-1, on TNBC. We identified that T-5224 inhibited the proliferation, migration, and invasion of TNBC cells and resulted in an increase in apoptosis. Furthermore, we found that OLFML2A is a key regulatory protein acting downstream of AP-1 and is involved in T-5224-targeted AP-1 action. Multiple clinical databases online have identified that high OLFML2A level is associated with poor prognosis in TNBC patients. In summary, our experimental and bioinformatic studies indicated that OLFML2A is necessary for AP-1-overexpressing TNBC. These findings demonstrate that AP-1-overexpressing TNBC dependent on OLFML2A, and targeting both AP-1 and OLFML2A through T-5224 may be a synergistic therapeutic strategy for this clinically challenging subset of breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2021.101100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138778PMC
May 2021

SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline.

BMJ 2021 05 11;373:n1091. Epub 2021 May 11.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada

Clinical Question: What are the benefits and harms of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists when added to usual care (lifestyle interventions and/or other diabetes drugs) in adults with type 2 diabetes at different risk for cardiovascular and kidney outcomes?

Current Practice: Clinical decisions about treatment of type 2 diabetes have been led by glycaemic control for decades. SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. This has changed through trials demonstrating atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) benefits independent of medications' glucose-lowering potential.

Recommendations: The guideline panel issued risk-stratified recommendations concerning the use of SGLT-2 inhibitors or GLP-1 receptor agonists in adults with type 2 diabetes• Three or fewer cardiovascular risk factors without established CVD or CKD: Weak recommendation against starting SGLT-2 inhibitors or GLP-1 receptor agonists.• More than three cardiovascular risk factors without established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and weak against starting GLP-1 receptor agonists.• Established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and GLP-1 receptor agonists.• Established CVD and CKD: Strong recommendation for starting SGLT-2 inhibitors and weak recommendation for starting GLP-1 receptor agonists.• For those committed to further reducing their risk for CVD and CKD outcomes: Weak recommendation for starting SGLT-2 inhibitors rather than GLP-1 receptor agonists.

How This Guideline Was Created: An international panel including patients, clinicians, and methodologists created these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel applied an individual patient perspective.

The Evidence: A linked systematic review and network meta-analysis (764 randomised trials included 421 346 participants) of benefits and harms found that SGLT-2 inhibitors and GLP-1 receptor agonists generally reduce overall death, and incidence of myocardial infarctions, and end-stage kidney disease or kidney failure (moderate to high certainty evidence). These medications exert different effects on stroke, hospitalisations for heart failure, and key adverse events in different subgroups. Absolute effects of benefit varied widely based on patients' individual risk (for example, from five fewer deaths in the lowest risk to 48 fewer deaths in the highest risk, for 1000 patients treated over five years). A prognosis review identified 14 eligible risk prediction models, one of which (RECODe) informed most baseline risk estimates in evidence summaries to underpin the risk-stratified recommendations. Concerning patients' values and preferences, the recommendations were supported by evidence from a systematic review of published literature, a patient focus group study, a practical issues summary, and a guideline panel survey.

Understanding The Recommendation: We stratified the recommendations by the levels of risk for CVD and CKD and systematically considered the balance of benefits, harms, other considerations, and practical issues for each risk group. The strong recommendation for SGLT-2 inhibitors in patients with CVD and CKD reflects what the panel considered to be a clear benefit. For all other adults with type 2 diabetes, the weak recommendations reflect what the panel considered to be a finer balance between benefits, harms, and burdens of treatment options. Clinicians using the guideline can identify their patient's individual risk for cardiovascular and kidney outcomes using credible risk calculators such as RECODe. Interactive evidence summaries and decision aids may support well informed treatment choices, including shared decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.n1091DOI Listing
May 2021

gene rs600231 polymorphism positively associated with acute coronary syndrome in Chinese population: a case-control study.

Cardiovasc Diagn Ther 2021 Apr;11(2):435-446

Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Background: Metastasis-associated lung adenocarcinoma transcript 1 () has been recognized as a major player in the pathogenesis of coronary artery disease (CAD). The aim of the study was to determine the association between polymorphisms of the gene and acute coronary syndrome (ACS) in a Chinese population in Xinjiang.

Methods: In the case-control study, we genotyped three nucleotide polymorphisms (rs3200401, rs4102217, rs600231) of the gene using SNPscan typing assays (1,053 controls and 929 ACS patients). Furthermore, we explored a predictive model using rs600231 and clinical variables to predict the risk of ACS. Finally, the relative expression of long noncoding RNA (lncRNA) was also measured in 92 ACS patients and 92 controls using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: The prevalence of the GG genotype of rs600231 in ACS group was higher than that in control group (15.7% . 14.7%, P=0.048). The dominant model differed (AG + GG . AA) and the G allele of rs600231 in ACS group was higher than that in control group (for dominant model: 66.2% . 60.9%, P=0.014; for allele: 41.0% . 37.8%, P=0.042). Multivariate logistic regression analysis and the predictive nomogram model showed that the dominant model of rs600231 remained an independent risk factor for ACS [odds ratio (OR) =1.32, 95% confidence interval (CI): 1.07-1.63, P=0.009]. The area under the receiver operating characteristic (ROC) curve (AUC) for the nomogram model for the prediction of ACS was 0.738 (95% CI: 0.716-0.761). In addition, in the AG and GG phenotypes, the relative expression of lncRNA was significantly higher in ACS patients than in controls with the same phenotypes (P<0.05). Among ACS group, compared to other genotype carriers, the relative expression level of in GG genotype carriers was higher (P<0.05).

Conclusions: The present study suggested that the AG and GG genotype of rs600231 in gene was independently associated with ACS, and could be a risk genetic marker of ACS in a Chinese population in Xinjiang.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/cdt-20-906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102249PMC
April 2021

External application of N alleviates toxicity of Cd on poplars via starch and sucrose metabolism.

Tree Physiol 2021 May 7. Epub 2021 May 7.

College of Landscape Architecture, Sichuan Agricultural University, Chengdu 611130, China.

Phytoremediation technology can help achieve moderate cost and considerable effect, with respect to the remediation of heavy metal pollution in soil and water. Many previous studies have suggested the role of N in the alleviation of effects of heavy metal on plants. Herein, we sought to determine the molecular mechanisms by which additional N supplementation mitigates Cd toxicity in poplars using a combination of physiological, transcriptomic, and phosphoproteomic analyses. The application of N can alleviate the toxicity of Cd to Populus by reducing chlorophyll degradation, maintaining the stability of ions inside and outside the cell membrane, and increasing the soluble sugar content. Plant samples from the control (CK), Cd stress, and Cd_N treatments were used for an integrated analysis of the transcriptome, as well as for phosphoproteomics analysis. Moreover, 1,314 differentially expressed genes (DEGs) and 119 differentially expressed kinase genes were discovered. Application of additional N under Cd stress promoted the phosphorylation process. Furthermore, 51 significantly enriched phosphorylated protein sites and 23 differentially expressed kinases were identified using phosphoproteomic and proteomic analyses. Importantly, transcriptomic and phosphoproteomic analyses jointly determined that the application of N could activate corresponding gene expression [UDP-glucose-dehydrogenase (UGD), GAUT, PME, pectin lyase, UDP-glucose-pyrophosphorylase 2 (UGP2), sucrose phosphate synthase (SPS), SUS, and SPP2] and protein phosphorylation (UGP2 and SPS) in the sugar and starch synthesis pathways, which promoted the synthesis of sucrose and soluble sugar and subsequently alleviated the damage caused by Cd.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/treephys/tpab065DOI Listing
May 2021

Bioinspired Dual-Mode Temporal Communication via Digitally Programmable Phase-Change Materials.

Adv Mater 2021 May 7:e2008119. Epub 2021 May 7.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.

Switchable optical properties are essential for numerous technologies including communication, anticounterfeiting, camouflage, and imaging/sensing. Typically, the switching is enabled by applying external stimulation such as UV light for fluorescence detection. In contrast, ground squirrels utilize spontaneous live infrared emission for fencing off predators as a unique way of communication. Inspired by this, live evolution of both optical and thermal images for temporal communication in which time is the encoded information is demonstrated. This system is based on a digitally light-cured polymeric phase-change material for which the crystallization kinetics can be controlled in a pixelated manner. Consequently, live evolution in optical transparency during the crystallization process enables temporal optical communication. Additionally, by harnessing the dynamic evolution of the thermal enthalpy, multiple sets of time-specific information can be reversibly retrieved as self-evolving infrared thermal images. The versatility of this dual-mode temporal system expands the scope for secured communication, with potential implications for various other areas including optics, thermal regulation, and 3D/4D printing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202008119DOI Listing
May 2021

Reck-Notch1 Signaling Mediates miR-221/222 Regulation of Lung Cancer Stem Cells in NSCLC.

Front Cell Dev Biol 2021 20;9:663279. Epub 2021 Apr 20.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Cancer stem cells (CSCs) contribute to the cancer initiation, metastasis and drug resistance in non-small cell lung cancer (NSCLC). Herein, we identified a miR-221/222 cluster as a novel regulator of CSCs in NSCLC. Targeted overexpression or knockdown of miR-221/222 in NSCLC cells revealed the essential roles of miR-221/222 in regulation of lung cancer cell proliferation, mammosphere formation, subpopulation of CD133 CSCs and the expression of stemness genes including OCT4, NANOG and h-TERT. The animal study showed that overexpression of miR-221/222 significantly enhanced the capacity of lung cancer cells to develop tumor and grow faster, indicating the importance of miR-221/222 in tumorigenesis and tumor growth. Mechanistically, Reck was found to be a key direct target gene of miR-221/222 in NSCLC. Overexpression of miR-221/222 significantly suppressed Reck expression, activated Notch1 signaling and increased the level of NICD. As an activated form of Notch1, NICD leads to enhanced stemness in NSCLC cells. In addition, knockdown of Reck by siRNA not only mimicked miR-221/222 effects, but also demonstrated involvement of Reck in the miR-221/222-induced activation of Notch1 signaling, verifying the essential roles of the miR-221/222-Reck-Notch1 axis in regulating stemness of NSCLC cells. These findings uncover a novel mechanism by which lung CSCs are significantly manipulated by miR-221/222, and provide a potential therapeutic target for the treatment of NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.663279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093830PMC
April 2021

Exposure-Response Modeling to Support Dosing Selection for Phase IIb Development of Kukoamine B in Sepsis Patients.

Front Pharmacol 2021 19;12:645130. Epub 2021 Apr 19.

Clinical Pharmacology Research Center and State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Kukoamine B, a small molecule compound, is being developed for the treatment of sepsis in a Phase II clinical trial. The objective of this study was to optimize dosing selection for a Phase IIb clinical trial using an exposure-response model. Data of 34 sepsis patients from a Phase IIa clinical trial were used in the model: 10 sepsis patients from the placebo group and a total of 24 sepsis patients from the 0.06 mg/kg, 0.12 mg/kg, and 0.24 mg/kg drug groups. Exposure-response relationship was constructed to model the impact of the standard care therapy and area under curve (AUC) of kukoamine B to the disease biomarker (SOFA score). The model was evaluated by goodness of fit and visual predictive check. The simulation was performed 1,000 times based on the built model. The data of the placebo and the drug groups were pooled and modeled by a nonlinear mixed-effect modeling approach in sepsis. A latent-variable approach in conjunction with an inhibitory indirect response model was used to link the standard care therapy effect and drug exposure to SOFA score. The maximum fraction of the standard care therapy was estimated to 0.792. The eliminate rate constant of the SOFA score was 0.263/day for the standard care therapy. The production rate of SOFA score (K) was estimated at 0.0569/day and the AUC at half the maximal drug effect (EAUC) was estimated at 1,320 h*ng/mL. Model evaluation showed that the built model could well describe the observed SOFA score. Model-based simulations showed that the SOFA score on day 7 decreased to a plateau when AUC increased to 1,500 h*ng/mL. We built an exposure-response model characterizing the pharmacological effect of kukoamine B from the standard care therapy in sepsis patients. A dose regimen of 0.24 mg/kg was finally recommended for the Phase IIb clinical trial of kukoamine B based on modeling and simulation results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.645130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091127PMC
April 2021

-Toluenesulfonic acid functionalized imidazole ionic liquids encapsulated into bismuth SBA-16 as high-efficiency catalysts for Friedel-Crafts acylation reaction.

Dalton Trans 2021 May;50(17):5871-5882

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, P. R. China.

Bismuth SBA-16 catalyst was synthesized by the hydrothermal method. Four kinds of p-toluenesulfonic acid functionalized imidazole ionic liquids were prepared by a two-step method and their molecular structures were characterized by 1H NMR and MS. The post-synthesis impregnation method was used to functionalize the Bi(10)-SBA-16 silicon mesoporous material with the ionic liquids and the obtained materials were characterized by FT-IR, XRD, BET, XPS, and TG. The results show that the volume and pore size of SBA-16 were changed by loading Bi and ionic liquids, while the three-dimensional cubic pore structure of SBA-16 was not destroyed. The composite catalyst was evaluated in Friedel-Crafts acylation of anisole with acetic anhydride. The effects of reaction temperature and the ratio of anisole and acylating agent on the acylation of anisole were investigated by experimental design. The results showed that [email protected](10)-SBA-16 was used as the catalyst, the conversion of anisole was 85.41% and the yield of aromatic ketone was 69.19% under the conditions of a reaction temperature of 100 °C, a catalyst dosage of 0.5 g, a time period of 4 h and a molar ratio of 1 : 1.5. After 5 recycling runs, the reduction in the overall ratio of reactant conversion and product yield did not exceed 7.5%, indicating that [email protected](10)-SBA-16 has good stability and reusability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1dt00355kDOI Listing
May 2021

Pattern of Recurrence in 428 Patients With Thoracic Esophageal Squamous Cell Carcinoma After Radical Surgery and Its Implication in Postoperative Radiotherapeutic Clinical Target Volume.

Front Oncol 2021 15;11:652365. Epub 2021 Apr 15.

Department VI of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Purpose: This study aimed to analyze the recurrence patterns of thoracic esophageal squamous cell carcinoma (ESCC) after radical surgery, and to understand its implication in the clinical target volume (CTV) design of postoperative radiotherapy (PORT) in patients with ESCC.

Methods And Materials: A total of 428 recurrent ESCC patients after radical surgery between 2014 and 2018 were included in this study. Recurrence patterns, especially anastomotic and regional lymph node recurrence (LNR), were analyzed. A T-shaped CTV were proposed for PORT and were evaluated whether it could cover most of regional LNR.

Results: These patients all experienced anastomotic and/or regional LNR. Among the 428 patients, 27 cases (6.3%) had anastomotic recurrence only, and184 cases (43.0%) had LNR only. Those sites with an LNR rate higher than 15% in upper thoracic ESCC were as follows: No.101, No.104R, No.104L, No.106recR, No.106recL, No.106pre, No.106tb, No.107, and No. 109. Those with middle thoracic ESCC were as follows: No.104R, No.104L, 106recR, No.106recL, No.106pre, No.106tb, and No.107. Lastly, individuals with lower thoracic ESCC were as follows: No.104L, 106recR, No.106recL, No. 106pre, No. 106tb, No.107, and abdominal No. 3. The proportion of LNR not included in the proposed T-shaped CTV was 12.5% (1/8), 4.7% (6/128), and 10.4% (5/48) in the upper, middle, and lower thoracic segments, respectively.

Conclusions: LNR was the most common type of local-regional recurrence in patients after radical surgery. Supraclavicular, superior and middle mediastinal lymph nodes had the highest recurrence rate, the rate of LNR which was outside T-shaped PORT CTV we proposed was less than 15%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.652365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083983PMC
April 2021