Publications by authors named "Xiaodong Wang"

1,212 Publications

  • Page 1 of 1

Discovery of novel ibrutinib analogues to treat malignant melanoma.

Bioorg Chem 2021 Oct 12;117:105419. Epub 2021 Oct 12.

School of Pharmaceutical Sciences, Nation-Regional Engineering Lab for Synthetic Biology of Medicine, International Cancer Center, Shenzhen University Health Science Center, Shenzhen University, Shenzhen 518060, Guangdong, China. Electronic address:

A series of novel ibrutinib analogues was synthesized, and their proliferation inhibitory activities against various B lymphoma cell lines (DaudiB and Raji) and solid tumor cells (B16, CT26, HepG2 and 4T1) were evaluated. The most potent compound, YL7, exhibited strong antiproliferative activity in all cell lines, and its IC value in B16 cells was almost 9-fold better than that of ibrutinib. Mechanism of action studies showed that YL7 inhibited proliferation and migration and induced G1 cell cycle arrest, apoptosis and autophagy in B16 cells. Further assessment of in vivo antitumor efficacies demonstrated that YL7 significantly inhibited the growth of B16 melanoma. These preliminary studies suggest that it is reasonable to modify the structure of ibrutinib for antimelanoma treatment.
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http://dx.doi.org/10.1016/j.bioorg.2021.105419DOI Listing
October 2021

QTL Mapping and GWAS Reveal the Genetic Mechanism Controlling Soluble Solids Content in Shoots.

Foods 2021 Oct 11;10(10). Epub 2021 Oct 11.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.

Oilseed-vegetable-dual-purpose (OVDP) rapeseed can effectively alleviate the land contradiction between crops and it supplements vegetable supplies in winter or spring. The soluble solids content (SSC) is an important index that is used to evaluate the quality and sugar content of fruits and vegetables. However, the genetic architecture underlying the SSC in shoots is still unclear. Here, quantitative trait loci (QTLs) for the SSC in shoots were investigated by performing linkage mapping using a recombinant inbred line population containing 189 lines. A germplasm set comprising 302 accessions was also used to conduct a genome-wide association study (GWAS). The QTL mapping revealed six QTLs located on chromosomes A01, A04, A08, and A09 in two experiments. Among them, two major QTLs, and , accounted for 12.92% and 10.18% of the phenotypic variance, respectively. In addition, eight single-nucleotide polymorphisms with phenotypic variances between 5.62% and 10.18% were identified by the GWAS method. However, no locus was simultaneously identified by QTL mapping and GWAS. We identified AH174 (7.55 °Brix and 7.9 °Brix), L166 (8.9 °Brix and 8.38 °Brix), and L380 (8.9 °Brix and 7.74 °Brix) accessions can be used as superior parents. These results provide valuable information that increases our understanding of the genetic control of SSC and will facilitate the breeding of high-SSC shoots.
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http://dx.doi.org/10.3390/foods10102400DOI Listing
October 2021

A novel CCDC39 mutation causes multiple morphological abnormalities of the flagella in a primary ciliary dyskinesia patient.

Reprod Biomed Online 2021 Jul 22. Epub 2021 Jul 22.

Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Research Question: Male infertility is a widespread symptom in patients with primary ciliary dyskinesia (PCD). PCD-related male infertility is often caused by asthenozoospermia, with barely normal sperm morphology. Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenozoospermia, characterized by various malformed morphologies of sperm flagella. To date, a limited number of genes have been suggested to be involved in the pathogenesis of both PCD and MMAF. What other genes associated with both PCD and MMAF are waiting to be discovered?

Design: Whole-exome sequencing (WES) was performed to identify the pathogenic mutation associated with MMAF in a PCD patient. Peripheral venous blood and semen samples were collected from the PCD patient. Transmission electron microscopy (TEM), immunofluorescence staining and western blotting were conducted to confirm the pathogenicity of the identified mutation.

Results: A novel homozygous mutation in CCDC39, c.983 T>C (p. Leu328Pro), was identified in two PCD-affected siblings of a consanguineous family showing a typical PCD phenotype, while the proband was infertile, which is associated with characterized MMAF. Furthermore, TEM revealed the abnormal ultrastructure of the patient's sperm flagella. Moreover, immunofluorescence staining revealed that CCDC39 was almost undetectable in the spermatozoa, which was further confirmed by western blotting. The outcome of intracytoplasmic sperm injection (ICSI) in the patient with the CCDC39 mutation was also favourable.

Conclusion: This study demonstrates that a novel loss-of-function mutation of CCDC39 is involved in the pathogenesis of PCD and MMAF and initially reported that ICSI treatment has a good outcome. Therefore, the novel variant of CCDC39 contributes to the genetic diagnosis, counselling and treatment of male infertility in PCD patients with MMAF phenotype.
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http://dx.doi.org/10.1016/j.rbmo.2021.07.005DOI Listing
July 2021

Anti-tumour effect of Odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway.

Basic Clin Pharmacol Toxicol 2021 Oct 11. Epub 2021 Oct 11.

School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.

Oleandrigenin-3-O-β-D-diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia-suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin-3-O-β-D-diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK-8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and western blot. Xenograft model of nude mice was also applied to measure the leukaemia-suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells, and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose-dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time-dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose-dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl-2, the release of cyto c to cytosol and the activation of caspase-3 and -9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS-JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially Acute myeloid leukaemia (AML).
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http://dx.doi.org/10.1111/bcpt.13673DOI Listing
October 2021

Efficacy and safety of mitoxantrone hydrochloride liposome injection in Chinese patients with advanced breast cancer: a randomized, open-label, active-controlled, single-center, phase II clinical trial.

Invest New Drugs 2021 Oct 11. Epub 2021 Oct 11.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: This trial aimed to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection (Lipo-MIT) in advanced breast cancer (ABC).

Methods: In this randomized, open-label, active-controlled, single-center, phase II clinical trial, eligible patients were randomized in a ratio of 1:1 to receive Lipo-MIT or mitoxantrone hydrochloride injection (MIT) intravenously. The primary endpoint was objective response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), and safety outcomes.

Results: Sixty patients were randomized to receive Lipo-MIT or MIT. The ORR was 13.3% (95% confidence interval (CI): 3.8-30.7%) for Lipo-MIT and 6.7% (95% CI: 0.8-22.1%) for MIT. The DCR was 50% (95% CI: 31.3-68.7%) with Lipo-MIT vs. 30% (95% CI: 14.7-49.4%) with MIT. The median PFS was 1.92 months (95% CI: 1.75-3.61) for Lipo-MIT and 1.85 months (95% CI: 1.75-2.02) for MIT. The most common toxicity was myelosuppression. Lipo-MIT resulted in an incidence of 86.7% of leukopenia and 80.0% of neutropenia, which was marginally superior to MIT (96.7% and 96.7%, respectively). Lipo-MIT showed a lower incidence of cardiovascular events (13.3% vs. 20.0%) and increased cardiac troponin T (3.3% vs. 36.7%); but higher incidence of anemia (76.7% vs. 46.7%), skin hyperpigmentation (66.7% vs. 3.3%), and fever (23.3% vs. 10.0%) than MIT. Conclusions The clinical benefit parameters of Lipo-MIT and MIT were comparable. Lipo-MIT provided a different toxicity profile, which might be associated with the altered distribution of the drug. Additional study is needed to elucidate the potential benefit of Lipo-MIT in ABC.

Clinical Trial Registration: This study is registered with ClinicalTrials.gov (No. NCT02596373) on Nov 4, 2015.
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http://dx.doi.org/10.1007/s10637-021-01182-7DOI Listing
October 2021

Description and Analysis of a Novel Subtype of the Anti-Synthetase Syndrome Characterized by Frequent Attacks of Fever and Systemic Inflammation in a Single-Center Cohort Study.

Front Immunol 2021 23;12:729602. Epub 2021 Sep 23.

Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objectives: The aim of this study was to investigate anti-synthetase syndrome (ASyS) patients who presented with recurrent episodes of fever and systemic inflammation.

Methods: A retrospective cohort of Chinese ASyS patients (n=126) in our center (between January 2013 and January 2020) was included. Patients presenting with concomitant autoimmune rheumatic diseases or malignancies were subsequently excluded. The number of non-infectious fever attacks and attack frequency were recorded and calculated. Patients with two or more attacks and within the upper three quartiles of attack frequency were defined as high-inflammation group. Univariate and multivariate analyses were carried out to characterize the high-inflammation subtype.

Results: Out of 113 eligible patients with an average of 5 years follow up, 25 patients were defined as the high-inflammation group (16 for anti-Jo1, 9 for anti-PL7), with an average of 1.12 attack/patient-year. Compared to low-inflammation group (0-1 attack only and a frequency lower than 0.5 attack/patient-year), the high-inflammation group had higher occurrence of fever and rapid progressive interstitial lung disease (RPILD) as the first presentation (84% 21% and 40% 9%, respectively, both p<0.01). Anti-PL-7 was related to the more inflammatory phenotype (p=0.014). Cumulative disease-modifying agent exposures (>=3) were much higher in the high-inflammation group (60% 26%), while biological agents, i.e., rituximab and tocilizumab, showed better "drug survival" for Jo-1+ and PL-7+ ASyS patients with high inflammation, respectively, in our cohort.

Conclusions: ASyS with recurrent systemic inflammatory episodes reflects a subtype of more aggressive and refractory disease in the spectrum of ASyS. Increased awareness of this subtype might lead to more appropriate management.
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http://dx.doi.org/10.3389/fimmu.2021.729602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495196PMC
September 2021

Machine learning methods to predict the cultivation age of Panacis Quinquefolii Radix.

Chin Med 2021 Oct 9;16(1):100. Epub 2021 Oct 9.

National Institutes for Food and Drug Control, Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, Beijing, 100050, China.

Background: American ginseng (AG) is a valuable medicine widely consumed as a herbal remedy throughout the world. Huge price difference among AG with different growth years leads to intentional adulteration for higher profits. Thus, developing reliable approaches to authenticate the cultivation ages of AG products is of great use in preventing age falsification.

Methods: A total of 106 batches of AG samples along with their 9 physicochemical features were collected and measured from experiments, which was then split into a training set and two test sets (test set 1 and 2) according to the cultivation regions. Principle component analysis (PCA) was carried out to examine the distribution of the three data sets. Four machine learning (ML) algorithms, namely elastic net, k-nearest neighbors, support vector machine and multi-layer perception (MLP) were employed to construct predictive models using the features as inputs and their growth years as outputs. In addition, a similarity-based applicability domain (AD) was defined for these models to ensure the reliability of the predictive results for AG samples produced in different regions.

Results: A positive correlation was observed between the several features and the growth years. PCA revealed diverse distributions among different cultivation regions. The most accurate model derived from MLP shows good prediction power for the fivefold cross validation and the test set 1 with mean square error (MSE) of 0.017 and 0.016 respectively, but a higher MSE value of 1.260 for the test set 2. After applying the AD, all models showed much lower prediction errors for the test samples within AD (IDs) than those outside the AD (ODs). MLP remains the best predictive model with an MSE value of 0.030 for the IDs.

Conclusion: Cultivation years have a close relationship with bioactive components of AG. The constructed models and AD are also able to predict the cultivation years and discriminate samples that have inaccurate prediction results. The AD-equipped models used in this study provide useful tools for determining the age of AG in the market and are freely available at https://github.com/dreadlesss/Panax_age_predictor .
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http://dx.doi.org/10.1186/s13020-021-00511-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501543PMC
October 2021

Embedding constructed refractive index graded antireflective coating with high abrasion resistance and environmental stability for polycarbonate glass.

J Colloid Interface Sci 2021 Sep 27;608(Pt 1):13-21. Epub 2021 Sep 27.

Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092, PR China. Electronic address:

Polycarbonate (PC) is a durable and transparent optical plastic material commonly used as shatter-resistant alternative to traditional optical glass. Broadband antireflective (AR) coatings with excellent mechanical strength and environmental stability are essential for PC to achieve high light transmission and visual quality. In this work, chloroform vapor treatment was employed to partially embed the silica coating into the PC substrate for adhesion enhancement, which also divided the silica coating layer into bottom and middle layers with different refractive indices. The contact between the silica nanoparticles and the substrate was transformed from "point-contact" to "area-contact", which enhanced the adhesion between coating and PC substrate. After the deposition of a top layer coating consisted of silica nanoparticles with smaller diameter, a triple-layer refractive index graded AR structure was constructed. Hexamethyldisilazane vapor surface modification was performed to decrease the surface free energy of top coating layer. The triple-layer coating coated PC exhibits superior antireflection property with an average reflectance of only 0.43% over a wide wavelength range of 400-1000 nm. After 100 times of friction or 5 months of exposure to a contaminated environment, the reflectance of coated PC shows barely noticeable difference, indicating its excellent mechanical strength and environmental stability.
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http://dx.doi.org/10.1016/j.jcis.2021.09.152DOI Listing
September 2021

[Clinical and genetic analysis of a child with transcobalamin II deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Oct;38(10):993-996

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong 518000, China.

Objective: To investigate the genetic etiology, clinical diagnosis and treatment of a child with pancytopenia, failure to thrive and pulmonary infection.

Methods: Peripheral blood samples of the child and her parents were collected. Genomic DNA was extracted. Genetic variants associated with hematological diseases were detected by high-throughput sequencing.

Results: Three variants of TCN2 gene were found, one of which located in exon 5 upstream(c.581-8A>T), the parents has carried this variant; one in exon 6 (c.924_927del), the variant was originated from the mother; one in exon 7 (c.973C>T), the variant has ocurred de novo. The variants pathogenic analysis combined with clinical manifestation, pancytopenia, the increase in methylmalonic acid level and increased homocysteine, the child was diagnosed with transcobalaminIIdeficiency. The patient presented with respiratory infection, which was confirmed to be pneumocystosis by lung radioscopy and pathogenic high-throughput sequencing of broncho-alveolar lavage fluid. The patient presented with acute respiratory distress syndrome during the treatment with intramuscular injection of vitamin B, and improved after anti-infection with compound sulfamethoxazole and symptomatic support treatment.

Conclusion: We reported a case of Chinese child with TCNII deficiency due to novel gene variant, and analyzed the pathogenicity of the three variants. The treatment of TCNII deficiency with cobalamin should be individualized.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200408-00247DOI Listing
October 2021

Conjoined twins in dichorionic diamniotic triplet pregnancy: a report of three cases and literature review.

BMC Pregnancy Childbirth 2021 Oct 8;21(1):687. Epub 2021 Oct 8.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: Conjoined twins are a rare and serious complication of monochorionic twins. The total incidence is 1.5 per 100,000 births, and about 50% are liveborn. Prenatal screening and diagnosis of conjoined twins is usually performed by ultrasonography. Magnetic resonance imaging can be used to assist in the diagnosis if necessary. Conjoined twins in dichorionic diamniotic triplet pregnancy are extremely rare.

Case Presentation: We reported three cases of dichorionic diamniotic triplet pregnancy with conjoined twins. Due to the poor prognosis of conjoined twins evaluated by multidisciplinary teams, selective termination of conjoined twins was performed in three cases. In case 1, selective reduction of the conjoined twins was performed at 16 gestational weeks, and a healthy female baby weighing 3270 g was delivered at 37 weeks. In case 2, the conjoined twins were selectively terminated at 17 weeks of gestation, and a healthy female baby weighing 2760 g was delivered at 37 weeks and 4 days. In case 3, the conjoined twins were selectively terminated at 15 weeks and 2 days, and a healthy female baby weighing 2450 g was delivered at 33 weeks and 6 days. The babies of all three cases were followed up and are in good health.

Conclusion(s): Surgical separation is the only treatment for conjoined twins after birth. Early determination of chorionicity and antenatal diagnosis of conjoined twins in triplet gestations are critical for individualized management options and the prognosis of normal triplets. Expecting parents should be extensively counseled by multidisciplinary teams. If there are limitations in successful separation after birth, early selective termination of the conjoined twins by intrathoracic injection of potassium chloride may be a procedure in dichorionic diamniotic triplet pregnancy to improve perinatal outcomes of the normal triplet.
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http://dx.doi.org/10.1186/s12884-021-04165-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501706PMC
October 2021

Clinical Study of Cranioplasty Combined With Ipsilateral Ventriculoperitoneal Shunt in the Treatment of Skull Defects With Hydrocephalus.

J Craniofac Surg 2021 Sep 29. Epub 2021 Sep 29.

The Second Affiliated Hospital of Soochow University, Suzhou Clinical Medical College of Yangzhou University, Yangzhou The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China.

Objective: To explore the clinical effect and safety of cranioplasty combined with ipsilateral ventriculoperitoneal shunts in the treatment of skull defects with hydrocephalus.

Methods: The clinical data of 78 patients with skull defects with hydrocephalus were analyzed retrospectively. All patients were treated with cranioplasty and ventriculoperitoneal shunts in 1 stage, including 35 cases of cranioplasty combined with ipsilateral ventriculoperitoneal shunts (ipsilateral operation group) and 43 cases of contralateral operations (contralateral operation group).

Results: The incision length (28.97 ± 4.55 cm), operation time (139.00 ± 42.27 minutes), and intraoperative hemorrhage (174.57 ± 79.35 mL) in the ipsilateral operation group were significantly better than those in the contralateral operation group (respectively they were 37.15 ± 5.83 cm, 214.07 ± 34.35 minutes, and 257.21 ± 72.02 mL), and the difference was statistically significant (t = 6.786, 8.656, and 4.815, all P < 0.05). The degree of postoperative hydrocephalus was significantly improved in both groups, but there was no statistically significant difference in the degree of hydrocephalus between the 2 groups (P > 0.05). Among the postoperative complications, there was no statistically significant difference in infection, epilepsy, subdural effusion, titanium plate effusion, or excessive cerebrospinal fluid drainage between the 2 groups (P > 0.05), but the incidence of intracranial hemorrhage in the ipsilateral operation group (2.86%) was significantly lower than that in the contralateral operation group (20.93%, χ2 = 4.138, P = 0.042). The postoperative Glasgow Coma Scale scores of the 2 groups were improved compared with those before the operation (P < 0.05), and there was no statistically significant difference in the postoperative Glasgow Coma Scale scores (P > 0.05). At 6 months after surgery, there was no statistically significant difference in Glasgow Outcome Scale effectiveness between the 2 groups (χ2 = 0.005, P = 0.944).

Conclusions: Cranioplasty combined with ipsilateral ventriculoperitoneal shunt has the same therapeutic effect as a contralateral operation, but it has the advantage of a short operation time, less intraoperative trauma, less bleeding, and less risk of intracranial hemorrhage, which is suitable for clinical applications.
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http://dx.doi.org/10.1097/SCS.0000000000008227DOI Listing
September 2021

Incidence, trends and risk factors for obstetric massive blood transfusion in China from 2012 to 2019: an observational study.

BMJ Open 2021 09 28;11(9):e047983. Epub 2021 Sep 28.

Department of Obstetrics, Sichuan University West China Second University Hospital, Chengdu, Sichuan, China

Objectives: This study aims to use the high-quality national monitoring data from the China's National Maternal Near Miss Surveillance System (NMNMSS) to ascertain the incidence, trends and risk factors of obstetric massive blood transfusion (MBT) from 2012 to 2019 in China and determine its clinical outcomes.

Settings: Observational study of hospitalised pregnancies who had given birth or ended their pregnancy among member hospitals of NMNMSS.

Participants: 11 667 406 women were included in this study.

Primary And Secondary Outcome Measures: We screened for the incidence, trends, risk factors and main reasons for obstetric MBT, and the outcomes after obstetric MBT. MBT was defined as the transfusion of ≥5 units of red blood cells or ≥1000 mL of whole blood. The incidence of MBT was defined as the MBT cases per 10 000 pregnancies.

Results: Obstetric MBT occurred in 27 626 cases, corresponding to an incidence of 23.68 per 10 000 maternities, which exhibited an increasing trend in China during 2012-2019 (14.03-29.59 per 10 000 maternities, p for trend <0.001). Obstetric MBT was mainly associated with amniotic fluid embolism, uterine atony, abnormal placenta, severe anaemia, ectopic pregnancy, abortion, caesarean section, advanced maternal age and multiparous from biological effect. While from sociological effects, uterine atony, severe anaemia and placenta previa are the top three complications which more likely to undergo obstetric MBT in the Chinese population. Overall, the secular trends of hysterectomy incidence (25.07%-9.92%) and MMR during hospitalisation (21.41‰-7.48‰) among women who underwent MBT showed decreasing trends (p for trend <0.001).

Conclusion: To minimise the incidence of obstetric MBT, more attention should be paid to education on the importance of the antenatal visit, evidence-based transfusion practice and females who are multiparous and have an advanced age, amniotic fluid embolism, uterine atony, severe anaemia and placenta previa.
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http://dx.doi.org/10.1136/bmjopen-2020-047983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479942PMC
September 2021

Modified ticagrelor loading doses according to the vasodilator-stimulated phosphoprotein phosphorylation index improve the clinical outcome in ST-elevation myocardial infarction patients with high on-treatment platelet reactivity.

Cardiol J 2021 Oct 8. Epub 2021 Oct 8.

Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Background: Current guidelines recommend a standard ticagrelor loading dose (LD) in ST-segment elevation myocardial infarction (STEMI) patients. However, antiplatelet therapy in STEMI patients at high risk of thrombotic events is suboptimal. The study was conducted to validate whether vasodilator-stimulated phosphoprotein (VASP)-guided ticagrelor dosing individual therapy may result in more effective platelet inhibition and better clinical outcomes.

Methods: This trial included 374 STEMI patients with a low platelet response after ticagrelor LD. The patients were randomized into a control group and a VASP-guided group, where the ticagrelor pretreatment was individually adjusted before and after percutaneous coronary intervention (PCI) to obtain a VASP index < 50%. Up to 2 additional boluses of ticagrelor (every additional dosing was 90 mg) were prescribed after the first LD, and the VASP index was assessed 2 hours after each administration until a VASP index < 50% was obtained or up to 3 dosages (360 mg). The primary endpoint was major adverse cardiovascular events (MACEs) at 30 days. The secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding.

Results: The characteristics were similar in the 2 groups. After the ticagrelor doses increased, the platelet reactivity index (PRI) decreased, and 98.4% of patients reached PRI < 50% in the VASP-guided group. The adenosine concentration increased, and the rate of MACE was significantly lower in the VASP-guided group (10 [5.3%] vs. 20 [10.8%], hazard ratio 2.38, 95% confidence interval 1.21-3.28, p = 0.007). There were no major hemorrhagic complications (0 vs. 0, p = 1.0). The rate of minor bleeding in the VASP-guided group was higher than that in the control group, but the difference was not significant (24 [12.8%] vs. 16 [8.6%], p = 0.068).

Conclusions: The incremental ticagrelor dosing strategy decreases the rate of MACE after PCI without increasing major and minor bleeding.
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http://dx.doi.org/10.5603/CJ.a2021.0105DOI Listing
October 2021

Development of [F]MIPS15692, a radiotracer with in vitro proof-of-concept for the imaging of MER tyrosine kinase (MERTK) in neuroinflammatory disease.

Eur J Med Chem 2021 Sep 4;226:113822. Epub 2021 Sep 4.

School of Pharmaceutical Sciences, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, People's Republic of China; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia. Electronic address:

MER tyrosine kinase (MERTK) upregulation is associated with M2 polarization of microglia, which plays a vital role in neuroregeneration following damage induced by neuroinflammatory diseases such as multiple sclerosis (MS). Therefore, a radiotracer specific for MERTK could be of great utility in the clinical management of MS, for the detection and differentiation of neuroregenerative and neurodegenerative processes. This study aimed to develop an [F] ligand with high affinity and selectivity for MERTK as a potential positron emission tomography (PET) radiotracer. MIPS15691 and MIPS15692 were synthesized and kinase assays were utilized to determine potency and selectivity for MERTK. Both compounds were shown to be potent against MERTK, with respective IC values of 4.6 nM and 4.0 nM, and were also MERTK-selective. Plasma and brain pharmacokinetics were measured in mice and led to selection of MIPS15692 over MIPS15691. X-ray crystallography was used to visualize how MIPS15692 is recognized by the enzyme. [F]MIPS15692 was synthesized using an automated iPHASE FlexLab module, with a molar activity (A) of 49 ± 26 GBq/μmol. The radiochemical purity of [F]MIPS15692 was >99% and the decay-corrected radiochemical yields (RCYs) were determined as 2.45 ± 0.85%. Brain MERTK protein density was measured by a saturation binding assay in the brain slices of a cuprizone mouse model of MS. High levels of specific binding of [F]MIPS15692 to MERTK were found, especially in the corpus callosum/hippocampus (CC/HC). The in vivo PET imaging study of [F]MIPS15692 suggested that its neuroPK is sub-optimal for clinical use. Current efforts are underway to optimize the neuroPK of our next generation PET radiotracers for maximal in vivo utility.
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http://dx.doi.org/10.1016/j.ejmech.2021.113822DOI Listing
September 2021

Classifiers for Predicting Coronary Artery Disease Based on Gene Expression Profiles in Peripheral Blood Mononuclear Cells.

Int J Gen Med 2021 15;14:5651-5663. Epub 2021 Sep 15.

Department of Cardiology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People's Republic of China.

Objective: Coronary artery disease (CAD) is a serious global health concern. Current diagnostic methods for CAD involve risk to the patient and are costly, so better diagnostic tools are needed. We defined four classifiers based on gene expression profiles in peripheral blood mononuclear cells and determined their potential for CAD detection.

Methods: We downloaded a CAD-related data set (GSE113079) from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells between CAD samples and healthy controls. DEGs were analyzed for functional enrichment. To create a robust CAD classifier, DEGs were identified by feature selection using the principal component analysis. Then, least absolute shrinkage and selection operator (LASSO) logistic regression, random forest, and support vector machine (SVM) models were created. Gene set variation analysis (GSVA) score and gene set enrichment analysis (GSEA) were also conducted. The performance of the models was evaluated in terms of the area under receiver operating characteristic curves (AUC).

Results: In the training set, we found 135 up-regulated genes and 104 down-regulated genes in CAD patients compared with controls. The DEGs were involved in some pathways associated with CAD, such as pathways involving calcium and interleukin-17 signaling. Twenty genes were identified as optimal features and used to generate the logistic classifier based on LASSO. The AUC for the classifier was 1.00 in the training set and 0.997 in the test set. Using the 20 DEGs, SVM and random forest classifiers were also generated and showed high diagnostic efficacy, with respective AUCs of 0.997 and 1.00 against the training set. A GSVA score was also established using the top 20 significant DEGs, which showed an AUC of 0.971 in the training set and 0.989 in the test set. Furthermore, GSEA showed autophagy and the proteasome to be major pathways involving the DEGs.

Conclusion: We identified a set of genes specific for CAD whose expression can be measured non-invasively. Using these genes, we defined four diagnostic classifiers using multiple methods.
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http://dx.doi.org/10.2147/IJGM.S329005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450378PMC
September 2021

Effect of prophylactic balloon occlusion of internal iliac artery in pregnancies complicated by placenta previa and accreta.

BMC Pregnancy Childbirth 2021 Sep 21;21(1):640. Epub 2021 Sep 21.

Department of Obstetrics and Gynecology, Ministry of Education, West China Second University Hospital of Sichuan University/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), No. 20, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China.

Background: Placenta previa and accreta are serious obstetric conditions that are associated with a high risk of intraoperative massive hemorrhage, the prophylactic intravascular balloon occlusion technique is increasingly used in managing uncontrolled hemorrhage in cesarean section (CS). We aim to examine the clinical effectiveness of prophylactic balloon occlusion of the internal iliac artery (PBOIIA) during CS in improving maternal outcomes for patients with placenta previa and accreta.

Methods: A total of 420 women with placenta previa and accreta who underwent CS from January 2014 to December 2018 were included retrospectively. Patients were divided into balloon group in which patients had PBOIIA (n = 248) and the control group in which patients did not have PBOIIA (n = 172). Meanwhile, we performed a subgroup analysis in whether taking parallel transverse uterine incision (PTUI) surgery. Information on conditions of patients and newborns, perioperative blood indicators, surgical outcomes were collected.

Results: Median estimated blood loss (mEBL) was 2200 mL in the balloon group and 2150 mL in the control group respectively, there was no significant difference between two-groups comparison (P > 0.05), and the rate of patients with hysterectomy was also has no difference between the two groups (36.3% verus 35.5%, P > 0.05), while there is a significant difference between two groups in the amount of PRBCs transfused [3 (0-31.5) verus 3 (0-39), P <0.05], moreover, the proportion of PRBCS> 8 units in the balloon group is significantly lower than that in control group (11.29% verus 23.26%, P <0.05).. However, the total hospitalization costs (45,624.4 ± 11,061.9 verus 37,523.1 ± 14,662.2, CYN) and surgery costs (19,910.6 ± 2622.6 verus 11,850.5 ± 3146.1, CYN) in balloon group were significantly higher than those in control group (P < 0.05). Subgroup analysis showed PTUI surgery had no significant differences in EBL (P >0.05), but it could significantly decrease hysterectomy rates (P <0.05).

Conclusions: PBOIIA has no significant effect on reducing intraoperative EBL and hysterectomy rate in patients with placenta previa and accreta. and although it could reduce the intraoperative PRBCs in patients with massive hemorrhage, it significantly increases the financial cost for patients. Therefore, PBOIIA should not be routinely recommended to patients with placenta previa and accreta.
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http://dx.doi.org/10.1186/s12884-021-04103-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456564PMC
September 2021

Quantitative analysis of exposure and surgical maneuverability of three purely endoscopic keyhole approaches to the floor of the third ventricle.

J Neurosurg Sci 2021 Sep 21. Epub 2021 Sep 21.

Department of Neurosurgery, College of the first clinical medicine, Dalian Medical University, Dalian, China -

Background: The quantitative anatomic analysis of comprehensively endoscopic approaches to the third ventricle is scarce at present. The objective of the study is to quantitatively assess and compare the exposure and microsurgical maneuverability of three absolutely endoscopic keyhole approaches, including interhemispheric transcallosal transchoroidal (TCTC), frontal transforminal transchoroidal (TFTC) and supraorbital subfrontal translamina terminalis (SFTL) approaches.

Methods: Anatomical dissections and exposure of the important structures of the third ventricle were performed using six formalin-fixed cadaveric human heads (twelve sides) under endoscope. Tubular retractor system was used in the TFTC approach. Quantitative anatomical relationship between the important landmarks were obtained. Moreover, the exposure and surgical operability of three approaches were evaluated through applying the rating scale and accomplishing the quantitative anatomic analysis, area of surgical freedom and angle of attack.

Results: The mediolateral, anteroposterior (AM: between aqueduct and mammillary body; IM: between infundibular recess and mammillary body) and superoinferior distance of TCTC, TFTC and SFTL approaches were 4.0±1.0, 4.2±0.4, 4.1±1.1mm; 17.3±1.4, 17.6±0.5, 12.8±3.3mm (AM); 7.7±0.3, 7.8±0.5 mm, not measured (IM); and 5.6±0.3, 7.8±0.8, 7.8±1.5mm, respectively. Similar to TFTC, the exposed landmarks of TCTC were almost scored a "4" by three neurosurgeons except the infundibular recess scored a "3" according to the rating scale. During the SFTL approach, apart from the roof, the majority of the landmarks were scored a "4" except for the infundibular recess, which was scored a "3". The mean area of surgical freedom of TCTC (0° endoscope: 220±47; 30°: 247±56mm2) was not significantly different from that of TFTC approach (0° endoscope: 216±49; 30°: 245±53mm2) under same endoscope, P>0.05. Mean angle of attack of TCTC (0° endoscope: 21±4°; 30°: 26±4°) was significantly larger than that of TFTC approach (0° endoscope: 16±3°; 30°: 19±3°), P<0.05.

Conclusions: Purely endoscopic TCTC and TFTC approaches offer brilliant exposure of the anterior, middle and posterior third ventricle. TCTC approach may have better surgical maneuverability than TFTC approach. Despite the long working distance, the whole third ventricle are exposed well except for the roof in the SFTL approach, and surgical manipulation can be accomplished smoothly.
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http://dx.doi.org/10.23736/S0390-5616.21.05455-2DOI Listing
September 2021

Copper adhesive tape attached to the reverse side of a non-conductive glass slide to achieve protein MALDI-imaging in FFPE-tissue sections.

Chem Commun (Camb) 2021 Oct 14;57(82):10707-10710. Epub 2021 Oct 14.

Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), State Ethnic Affairs Commission, Beijing 100081, China.

Herein, copper adhesive tape attached to the reverse side of a glass slide was developed as a new method to achieve protein detection and imaging in a formalin fixed paraffin-embedded (FFPE) tissue section on a non-conductive glass slide by MALDI-MSI. The use of this new method led to 223 protein ions being imaged from a rat brain FFPE-tissue section on a non-conductive glass slide by MALDI-MS, compared to only 145 and 163 protein ions detected on an ITO glass slide and an AnchorChip target plate, respectively. This new method has great potential to become standard practice for protein MALDI-imaging in FFPE-tissue sections on non-conductive glass slides.
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http://dx.doi.org/10.1039/d1cc03629gDOI Listing
October 2021

Near 100% ethene selectivity achieved by tailoring dual active sites to isolate dehydrogenation and oxidation.

Nat Commun 2021 Sep 14;12(1):5447. Epub 2021 Sep 14.

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.

Prohibiting deep oxidation remains a challenging task in oxidative dehydrogenation of light alkane since the targeted alkene is more reactive than parent substrate. Here we tailor dual active sites to isolate dehydrogenation and oxidation instead of homogeneously active sites responsible for these two steps leading to consecutive oxidation of alkene. The introduction of HY zeolite with acid sites, three-dimensional pore structure and supercages gives rise to Ni Lewis acid sites (LAS) and NiO nanoclusters confined in framework wherein catalytic dehydrogenation of ethane occurs on Ni LAS resulting in the formation of ethene and hydrogen while NiO nanoclusters with decreased oxygen reactivity are responsible for selective oxidation of hydrogen rather than over-oxidizing ethene. Such tailored strategy achieves near 100% ethene selectivity and constitutes a promising basis for highly selective oxidation catalysis beyond oxidative dehydrogenation of light alkane.
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http://dx.doi.org/10.1038/s41467-021-25782-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440631PMC
September 2021

Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients.

Front Mol Biosci 2020 24;7:595395. Epub 2021 Aug 24.

Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu, China.

To reverse the early-stage relapse post-hematopoietic stem cell transplantation, we investigated the safety and efficacy of a new epigenetic regimen (chidamide and decitabine plus thymalfasin simultaneously) on acute myeloid leukemia patients (excluding acute promyelocytic leukemia). Twenty-four patients were enrolled in this observational study during April 2015 to May 2018. The most common adverse event was reversible CTCAE grade 2 thrombocytopenia (20/24). Strikingly, all 24 patients had response to this epigenetic regimen accompanied with decreased measurable residual disease. The overall survival rate is 79.2% (19/24), with a relapse-free survival rate of 79.2% (19/24). During this regimen treatment, Th1 cells and CD3+CD4-CD8+T cells increased, and Th17 cells decreased gradually. The status of high Th1 and low Th17 cells was still observed on the 3rd month after discontinuation of this regimen. Interestingly, the significantly elevated ratio of Th1/Th17 seemed to reflect the treatment-related immune effect, which may be a valuable marker to be monitored in the early-relapse stage for evaluating the efficacy and prognosis.
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http://dx.doi.org/10.3389/fmolb.2020.595395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421566PMC
August 2021

MicroRNA-296 Targets Specificity Protein 1 to Suppress Cell Proliferation and Invasion in Cervical Cancer [ 26(5) (2018) 775783].

Oncol Res 2021 Sep;28(7):835

Department of Digestive Endoscopy, The Second Hospital of Jilin UniversityChangchun, JilinP.R. China.

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http://dx.doi.org/10.3727/096504021X16261699250204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420896PMC
September 2021

Characteristics of size-segregated aerosols emitted from an aerobic moving bed biofilm reactor at a full-scale wastewater treatment plant.

J Hazard Mater 2021 08 20;416:125833. Epub 2021 Apr 20.

School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266033, PR China. Electronic address:

Aerosol emissions from wastewater treatment plants (WWTPs) have been associated with health reverberation but studies about characteristics of size-segregated aerosol particulate matter (PM) are scarce. In this study, the measurement of particulate number size distribution in the range of < 10 µm, and the collection of PM, PM and PM, were conducted from an aerobic moving bed biofilm reactor (MBBR) at a full-scale WWTP. MBBR aerosols showed a unimodal number size distribution, with the majority of particles (>94%) in the ultrafine size range (<100 nm). For toxic metal(loid)s or potential pathogens, significant differences were found within MBBR aerosols (PM, PM, and PM), and also between MBBR aerosols and wastewater. Both wastewater and ambient air had important source contributions for MBBR aerosols. The compositions of toxic metal(loid)s in PM, and the populations of potential bacterial or fungal pathogens in PM and PM, were dominated by that from wastewater. Compared to PM and PM, PM had the highest aerosolization potential for the toxic metal(loid)s of As, Cd, Co, Cr, Li, Mn, Ni, U, and Zn, and the genera of Acinetobacter, Pseudomonas and Fusarium. Due to the size-segregated specialty, targeted measures should be employed to reduce the health risks. CAPSULE: The compositions of toxic metal(loid)s in PM, and the populations of potential pathogens in PM and PM, were dominated by that from wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125833DOI Listing
August 2021

Effect of Gambogic Acid on miR-199a-3p Expression and Cell Biological Behavior in Colorectal Cancer Cells.

J Oncol 2021 26;2021:5140621. Epub 2021 Aug 26.

Department of Anus & Intestine Surgery, Taizhou People's Hospital, Taizhou Clinical Medical College of Nanjing Medical University, Taizhou 225300, Jiangsu, China.

Colorectal cancer (CC), as a malignancy threatening life and health, has a rising incidence in recent years. It has been reported that gambogic acid (GA) has antitumor activity in various tumors, but its effect on CC remains to be elucidated. In this investigation, the influence of GA nanoparticles on microRNA-199a-3p (miR-199a-3p) in CC was analyzed to provide a reliable reference for future clinical practice. Through PCR detection, we first determined that miR-199a-3p presented low expression in CC and had a significant effect in predicting the onset and prognosis of CC. Through in vitro experiments, the enhanced CC cell viability after inhibition was determined; however, decreased cell viability and increased miR-199a-3p level were also observed after GA nanoparticles addition. Hence, GA nanoparticles may influence CC cell biological behaviors by modulating miR-199a-3p, providing a novel treatment scheme for CC in the future.
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http://dx.doi.org/10.1155/2021/5140621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416366PMC
August 2021

Innovative Integration of Phase-Change Microcapsules with Metal-Organic Frameworks into an Intelligent Biosensing System for Enhancing Dopamine Detection.

ACS Appl Mater Interfaces 2021 Sep 29;13(35):41753-41772. Epub 2021 Aug 29.

State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

This work focuses on an interdisciplinary issue in energy management and biosensing techniques. Aiming at enhancing the biosensing detection of dopamine at high ambient temperatures, we developed an innovative integration of phase-change microcapsules with a metal-organic framework (MOF) based on zeolitic imidazolate framework-8 to develop an intelligent electrochemical biosensing system with a thermal self-regulation function. We first fabricated a type of electroactive microcapsules containing a MOF-anchored polypyrrole/SiO double-layered shell and a phase-change material (PCM) core. The resultant microcapsules not only exhibit a regular spherical morphology with a layer-by-layer core-shell microstructure but also display an effective temperature-regulation capability to enhance enzymatic bioactivity under phase-change enthalpies of around 124.0 J·g along with good thermal impact resistance and excellent thermal cycling stability for long-term use in thermal energy management. These electroactive microcapsules were then used to modify a working electrode together with laccase as a biocatalyst to construct a thermal self-regulatory biosensor. With a high sensitivity of 3.541 μA·L·μmol·cm and a low detection limit of 0.0069 μmol·L at 50 °C, this biosensor exhibits much better determination effectiveness toward dopamine at higher temperatures than conventional biosensors thanks to thermal management derived from its PCM core in the electroactive microcapsules. This study offers a promising approach for development of intelligent thermal self-regulatory biosensors with an enhanced detection capability to identify various chemicals accurately in a wide range of applicable temperatures.
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http://dx.doi.org/10.1021/acsami.1c13446DOI Listing
September 2021

Research on the biology and ecology of the harmful algal bloom species Phaeocystis globosa in China: Progresses in the last 20 years.

Harmful Algae 2021 07 16;107:102057. Epub 2021 Jun 16.

CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory of Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China; Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby V5A 1S6, British Columbia, Canada. Electronic address:

Chinese researchers have made substantial progresses in research on the harmful algal bloom (HAB) species Phaeocystis globosa since the first P. globosa bloom outbreak in the Chinese coastal waters in 1997. However, as many results, especially the earlier ones, were published in non-English literature, much of the research on P. globosa biology, ecology, and biogeochemistry made by Chinese researchers have been unknown to colleagues from other countries. We review current knowledge on taxonomy, morphology, genetics, physiology, survival strategies and mitigation of P. globosa gained by Chinese researchers from the past two decades. P. globosa is the only Phaeocystis species that causes blooms in the Chinese waters, although other Phaeocystis species including P. jahnii and P. cordata have been detected in Chinese coastal regions. P. globosa has a complex life history with at least two morphotypes including a haploid flagellate and a diploid colonial cell. Colonial P. globosa blooms typically occur in winter after a diatom bloom in coastal waters of the South China Sea. P. globosa in Chinese coastal waters usually has extremely large colonial sizes, up to 3 cm in diameter, an order of magnitude greater than that observed in European coastal waters. The development of giant colonies is associated with enhanced sinking rate, limited nutrient diffusion, as well as decreased stability of colonies. The Chinese P. globosa strains also showed strong genetic diversity and physiological plasticity, being able to grow and develop into colonies at higher temperature and irradiance relative to that in European waters. High genetic diversity of P. globosa was revealed by developing high-resolution and high-specificity molecular markers including Phaeocystis globosa chloroplast 1 (pgcp1). Due to the severe impact of P. globosa on ecology and economy, much effort has been made to mitigate P. globosa blooms including the application of modified clays. Overall, P. globosa in the Chinese waters demonstrate unique genetic, phenotypical and physiological features that differ from P. globosa in other ocean regions. Further studies are needed to explore how environmental factors trigger the occurrence of P. globosa blooms and ascertain the impact of P. globosa blooms on the environment.
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http://dx.doi.org/10.1016/j.hal.2021.102057DOI Listing
July 2021

Thermal self-regulatory intelligent biosensor based on carbon-nanotubes-decorated phase-change microcapsules for enhancement of glucose detection.

Biosens Bioelectron 2021 Aug 24;195:113586. Epub 2021 Aug 24.

State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, 100029, China. Electronic address:

Enzyme-based biosensors are sensitive to temperature due to their strong temperature dependency of catalytic activity. Aiming at enhancing biosensing detection for glucose assay over a wide range of applicable temperatures, we designed a thermal self-regulatory intelligent biosensor through an innovative integration of phase change material (PCM) and bioelectrocatalytic substances. An electroactive phase-change microcapsule system was firstly fabricated by microencapsulating n-docosane as a PCM core in the SiO shell, followed by depositing polydopamine along with carbon nanotubes as an electroactive layer on the surface of SiO shell. The resultant microcapsules showed a regularly spherical morphology and well-defined core-shell microstructure. They also exhibited a satisfactory latent heat capacity of around 137 J/g for implementing temperature regulation with a good working stability. An electrochemical biosensing system was constructed with the resultant electroactive microcapsules together with glucose oxidase as a redox enzyme, achieving a thermal self-regulation capability to enhance the biosensing detection of glucose under in-situ thermal management at higher temperatures. With a high sensitivity of 5.95 μA⋅mM⋅cm and a lower detection limit of 13.11 μM at 60 °C, the intelligent biosensor developed by this study demonstrated a superior determination capability and better detection performance toward glucose than conventional biosensors in a high temperature region thanks to effective regulation of microenvironment temperature in the electrode system. This study provides a promising strategy for the development of thermal self-regulatory smart biosensors with an enhanced identification ability to detect various chemical substances over a wide range of applicable temperatures.
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http://dx.doi.org/10.1016/j.bios.2021.113586DOI Listing
August 2021

HepaticIschemia/Reperfusion Injuryinvolves functional tryptase/PAR-2 signaling in liver sinusoidal endothelial cell population.

Int Immunopharmacol 2021 Aug 25;100:108052. Epub 2021 Aug 25.

Geriatric Cancer Center, Huadong Hospital, Fudan University, West 221 Yan-an Road, Shanghai 200040, China. Electronic address:

Mast cells (MCs) are tissue-resident effector cells that could be the earliest responder to release a unique, stimulus-specific set of mediators in hepatic ischemia-reperfusion (IR) injury However, how MCs function in the hepatic IR has remained a formidable challenge due to the substantial redundancy and functional diverse of these mediators. Tryptase is the main protease for degranulation of MCs and its receptor-protease-activated receptor 2 (PAR-2) is widely expressed in endothelial cells. It is unclear whether and how tryptase/PAR-2 axis participates in hepatic IR. We employed an experimental warm 70% liver IR model in mice and found that tryptase was accumulated in the circulation during hepatic IR and positively correlated with liver injury. Tryptase inhibition by protamine can significantly down-regulate the expression of adhesion molecules and reduce neutrophil infiltration within the liver. The level of inflammatory factors and chemokines were also consistent with the pathological change of the liver. In addition, the treatment with exogeneous tryptase in MC-deficient mice can induce the damage observed in wild type mice in the context of liver IR. In vitro, neutrophil infiltration and inflammatory factor secretion were regulated by Tryptase/PAR-2, involving the adhesion molecule expression to regulate neutrophil adhesion dependent on NF-κB pathway. Conclusion: tryptase/PAR-2 participates in liver injury through the activation of LSECs in the early phase of liver IR.
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http://dx.doi.org/10.1016/j.intimp.2021.108052DOI Listing
August 2021
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