Publications by authors named "Shuxin Zhang"

57 Publications

Elevated GIGYF2 expression suppresses tumor migration and enhances sensitivity to temozolomide in malignant glioma.

Cancer Gene Ther 2021 May 31. Epub 2021 May 31.

Department of Neurosurgery, West China Hospital, Sichuan University, 610041, Chengdu, People's Republic of China.

Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.
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http://dx.doi.org/10.1038/s41417-021-00353-1DOI Listing
May 2021

Data-driven estimation of COVID-19 community prevalence through wastewater-based epidemiology.

Sci Total Environ 2021 May 23;789:147947. Epub 2021 May 23.

School of Civil, Mining and Environmental Engineering, University of Wollongong, Australia; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, Australia. Electronic address:

Wastewater-based epidemiology (WBE) has been regarded as a potential tool for the prevalence estimation of coronavirus disease 2019 (COVID-19) in the community. However, the application of the conventional back-estimation approach is currently limited due to the methodological challenges and various uncertainties. This study systematically performed meta-analysis for WBE datasets and investigated the use of data-driven models for the COVID-19 community prevalence in lieu of the conventional WBE back-estimation approach. Three different data-driven models, i.e. multiple linear regression (MLR), artificial neural network (ANN), and adaptive neuro fuzzy inference system (ANFIS) were applied to the multi-national WBE dataset. To evaluate the robustness of these models, predictions for sixteen scenarios with partial inputs were compared against the actual prevalence reports from clinical testing. The performance of models was further validated using unseen data (data sets not included for establishing the model) from different stages of the COVID-19 outbreak. Generally, ANN and ANFIS models showed better accuracy and robustness over MLR models. Air and wastewater temperature played a critical role in the prevalence estimation by data-driven models, especially MLR models. With unseen datasets, ANN model reasonably estimated the prevalence of COVID-19 (cumulative cases) at the initial phase and forecasted the upcoming new cases in 2-4 days at the post-peak phase of the COVID-19 outbreak. This study provided essential information about the feasibility and accuracy of data-driven estimation of COVID-19 prevalence through the WBE approach.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141262PMC
May 2021

Effect of Root Canal Therapy on the Success Rate of Teeth with Complete Roots in Autogenous Tooth Transplantation.

Scanning 2021 14;2021:6675604. Epub 2021 Apr 14.

Department of Oral and Maxillofacial Surgery, Graduate School of Clinical Dentistry, Korea University, Seoul 02841, Republic of Korea.

Background: Autogenous tooth transplantation is a reliable method for repairing missing teeth. Although it recently became a recognized and feasible treatment method in dentistry, the long-term efficacy of root canal therapy (RCT) has not been well confirmed. This study is aimed at determining whether RCT has a good effect on the success rate of teeth with complete roots in autogenous tooth transplantation.

Materials And Methods: Data were collected from the Korea University Guro Hospital. Data of patients who underwent autogenous tooth transplantation within 9 years were collected. We selected 29 teeth with complete roots as the research subjects in our study. None of the patients had any systemic diseases. All cases in this study were obtained with patient permission.

Results: According to the tooth vitality test, the autogenous teeth tested negative in dental pulp test and function. Nine of the 29 teeth with autogenous tooth transplantation were treated with RCT and survived throughout the observation period. However, 20 autogenous teeth were not treated with RCT, and eight of them did not survive. All statistical analyses were performed using IBM SPSS 20.0. The null hypothesis was rejected ( < 0.05).

Conclusion: For complete root teeth, the success rate after autogenous tooth transplantation after RCT is higher than that of teeth not treated with RCT.
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http://dx.doi.org/10.1155/2021/6675604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062180PMC
April 2021

Comparison of Autogenous Tooth Materials and Other Bone Grafts.

Tissue Eng Regen Med 2021 Jun 30;18(3):327-341. Epub 2021 Apr 30.

Department of Oral and Maxillofacial Surgery, Graduate School of Clinical Dentistry, Korea University, Seoul, 02841, Republic of Korea.

Autogenous odontogenic materials are a new, highly biocompatible option for jaw restoration. The inorganic component of autogenous teeth acts as a scaffold to maintain the volume and enable donor cell attachment and proliferation; the organic component contains various growth factors that promote bone reconstruction and repair. The composition of dentin is similar to that of bone, which can be a rationale for promoting bone reconstruction. Recent advances have been made in the field of autogenous odontogenic materials, and studies have confirmed their safety and feasibility after successful clinical application. Autogenous odontogenic materials have unique characteristics compared with other bone-repair materials, such as the conventional autogenous, allogeneic, xenogeneic, and alloplastic bone substitutes. To encourage further research into odontogenic bone grafts, we compared the composition, osteogenesis, and development of autogenous odontogenic materials with those of other bone grafts. In conclusion, odontogenic bone grafts should be classified as a novel bone substitute.
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http://dx.doi.org/10.1007/s13770-021-00333-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169722PMC
June 2021

Effects of Physical Stimulation in the Field of Oral Health.

Scanning 2021 7;2021:5517567. Epub 2021 Apr 7.

Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, Shandong 271016, China.

Physical stimulation has been widely used in clinical medicine and healthcare due to its noninvasiveness. The main applications of physical stimulation in the oral cavity include laser, ultrasound, magnetic field, and vibration, which have photothermal, cavitation, magnetocaloric, and mechanical effects, respectively. In addition, the above four stimulations with their unique biological effects, which can play a role at the gene, protein, and cell levels, can provide new methods for the treatment and prevention of common oral diseases. These four physical stimulations have been used as important auxiliary treatment methods in the field of orthodontics, implants, periodontal, dental pulp, maxillofacial surgery, and oral mucosa. This paper systematically describes the application of physical stimulation as a therapeutic method in the field of stomatology to provide guidance for clinicians. In addition, some applications of physical stimulation in specific directions are still at the research stage, and the specific mechanism has not been fully elucidated. To encourage further research on the oral applications of physical stimulation, we elaborate the research results and development history of various physical stimuli in the field of oral health.
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http://dx.doi.org/10.1155/2021/5517567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049832PMC
April 2021

Clinical Significance of Preoperative Fibrinogen to Albumin Ratio in Patients with Glioblastoma: A Singe Center Experience.

Cancer Manag Res 2021 14;13:3259-3269. Epub 2021 Apr 14.

Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People's Republic of China.

Objective: To explore the prognostic value of preoperative fibrinogen to albumin ratio (FAR) in patients with glioblastoma (GBM) and its association with clinical characteristics.

Patients And Methods: A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2015 to June 31st 2018. Receiver operating characteristic (ROC) curves were performed to determine the optimal cut-off values for fibrinogen, albumin, neutrophil to lymphocyte ratio (NLR), and FAR by calculating the maximum Youden index. Kaplan-Meier curves and Cox regression analyses were applied to evaluate the prognostic value of FAR in GBM. Harrell concordance index (C-index) and Akaike information criterion (AIC) were calculated to compare different prognostic models.

Results: A total of 206 GBM patients were included in this research. The optimal cut-off value for fibrinogen, albumin, NLR, and FAR were 2.57, 42.4, 2.28, and 0.068 respectively. High FAR was significantly related to older age, KPS≤80, IDH-1 wildtype, presence of preoperative seizures, higher NLR, and tumor location. In Cox regression analyses, high FAR was significantly associated with poor prognosis. Prognostic models including FAR had the largest C-index and lowest AIC.

Conclusion: FAR was determined to be an independent risk factor of prognosis in patients with newly-diagnosed GBM. And the prognostic predictive ability of FAR is stronger than fibrinogen and albumin.
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http://dx.doi.org/10.2147/CMAR.S305025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053713PMC
April 2021

Portable smartphone device-based multi-signal sensing system for on-site and visual determination of alkaline phosphatase in human serum.

Mikrochim Acta 2021 Apr 6;188(5):157. Epub 2021 Apr 6.

College of Information Engineering, Sichuan Agricultural University, Xinkang Road, Yucheng District, Ya'an, 625014, People's Republic of China.

To provide the basis for clinical diagnosis in an emergency case, a portable smartphone device-based multi-signal sensing system for on-site determination of alkaline phosphatase (ALP) is introduced. In this system, cobalt hydroxide (CoOOH) nanoflakes can oxidize O-phenylenediamine (OPD) to produce 2,3-diaminophenazine (OxOPD), resulting in a strong fluorescence at 565 nm and an absorbance at 420 nm, respectively. The ascorbic acid 2-phosphate (AAP) can be hydrolyzed by alkaline phosphatase (ALP) to yield ascorbic acid (AA). Then, AA reduces the CoOOH nanoflakes to produce Co, and AA is oxidized to form dehydroascorbic acid (DHAA), thereby inhibiting the formation of OxOPD. The reaction product DHAA further combines with OPD to yield 3-(1,2-dihydroxyethyl)furo[3,4-b]quinoxalin-1(3H)-one (DFQ) accompanied by a strong fluorescence at 430 nm. Based on this, the fluorometric assay for ALP has a wide linear range from 0.8 to 190 U/L with a low detection limit of 0.16 U/L, and the colorimetric assay from 3 to 130 U/L with a detection limit of 1.94 U/L. Moreover, a portable smartphone sensing platform integrated with fluorescent and colorimetric signals was established for rapid determination of ALP without spectrometers. Recoveries of 97-104% for spiked samples and relative standard deviations (RSD) of less than 2% (n = 3) confirmed the feasibility of the developed platform in complicated samples, opening up new horizons for on-site evaluation in the biomedical field.
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http://dx.doi.org/10.1007/s00604-021-04803-3DOI Listing
April 2021

Molecular cytogenetic characterization and fusarium head blight resistance of five wheat-Thinopyrum intermedium partial amphiploids.

Mol Cytogenet 2021 Mar 6;14(1):15. Epub 2021 Mar 6.

Key Laboratory of Molecular Cytogenetics and Genetic Breeding of Heilongjiang Province, College of Life Science and Technology, Harbin Normal University, Harbin, 150025, China.

Background: Partial amphiploids created by crossing octoploid tritelytrigia(2n = 8× = 56, AABBDDEE) and Thinopyrum intermedium (2n = 6× = 42, StStJJJJ) are important intermediates in wheat breeding because of their resistance to major wheat diseases. We examined the chromosome compositions of five wheat-Th. intermedium partial amphiploids using GISH and multicolor-FISH.

Results: The result revealed that five lines had 10-14 J-genome chromosomes from Th. intermedium and 42 common wheat chromosomes, using the J-genomic DNA from Th. bessarabicum as GISH probe and the oligo probes pAs1-1, pAs1-3, AFA-4, (GAA) 10, and pSc119.2-1 as FISH probe. Five lines resembled their parent octoploid tritelytrigia (2n = 8× = 56, AABBDDEE) but had higher protein contents. Protein contents of two lines HS2-2 and HS2-5 were up to more than 20%. Evaluation of Fusarium head blight (FHB) resistance revealed that the percent of symptomatic spikelets (PSS) of these lines were below 30%. Lines HS2-2, HS2-4, HS2-5, and HS2-16 were less than 20% of PPS. Line HS2-5 with 14 J-genome chromosomes from Th. intermedium showed the best disease resistance, with PSS values of 10.8% and 16.6% in 2016 and 2017, respectively.

Conclusions: New wheat-Th. intermedium amphiploids with the J-genome chromosomes were identified and can be considered as a valuable source of FHB resistance in wheat breeding.
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http://dx.doi.org/10.1186/s13039-021-00536-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937273PMC
March 2021

Uncertainties in estimating SARS-CoV-2 prevalence by wastewater-based epidemiology.

Chem Eng J 2021 Jul 20;415:129039. Epub 2021 Feb 20.

School of Civil, Mining and Environmental Engineering, University of Wollongong, Australia.

Wastewater-based epidemiology (WBE) is a promising approach for estimating population-wide COVID-19 prevalence through detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater. However, various methodological challenges associated with WBE would affect the accuracy of prevalence estimation. To date, the overall uncertainty of WBE and the impact of each step on the prevalence estimation are largely unknown. This study divided the WBE approach into five steps (i.e., virus shedding; in-sewer transportation; sampling and storage; analysis of SARS-CoV-2 RNA concentration in wastewater; back-estimation) and further summarized and quantified the uncertainties associated with each step through a systematic review. Although the shedding of SARS-CoV-2 RNA varied greatly between COVID-19 positive patients, with more than 10 infected persons in the catchment area, the uncertainty caused by the excretion rate became limited for the prevalence estimation. Using a high-frequency flow-proportional sampling and estimating the prevalence through actual water usage data significantly reduced the overall uncertainties to around 20-40% (relative standard deviation, RSD). And under such a scenario, the analytical uncertainty of SARS-CoV-2 RNA in wastewater was the dominant factor. This highlights the importance of using surrogate viruses as internal or external standards during the wastewater analysis, and the need for further improvement on analytical approaches to minimize the analytical uncertainty. This study supports the application of WBE as a complementary surveillance strategy for monitoring COVID-19 prevalence and provides methodological improvements and suggestions to enhance the reliability for future studies.
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http://dx.doi.org/10.1016/j.cej.2021.129039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896122PMC
July 2021

Inhibition of mitochondrial carrier homolog 2 (MTCH2) suppresses tumor invasion and enhances sensitivity to temozolomide in malignant glioma.

Mol Med 2021 01 28;27(1). Epub 2021 Jan 28.

Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma.

Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy.

Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling.

Conclusion: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.
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http://dx.doi.org/10.1186/s10020-020-00261-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842075PMC
January 2021

Surface Characterization and Corrosion Resistance of Biomedical AZ31 Mg Alloy Treated by Microarc Fluorination.

Scanning 2020 27;2020:5936789. Epub 2020 Oct 27.

Department of Oral and Maxillofacial Surgery, Graduate School of Clinical Dentistry, Korea University, Seoul 08308, Republic of Korea.

The application prospect of biodegradable materials is being studied extensively. However, the high corrosion rate and its alloys in body fluids have been major limitations of the application of pure Mg (magnesium). To improve corrosion resistance of biodegradable AZ31 Mg alloy, we adopted microarc fluorination within a voltage range of 100-300 V in 46% hydrofluoric acid. To obtain morphologies, chemical compositions, and structural characteristics, field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) were performed, respectively. Results showed that the coating was mainly composed of MgF. Electrochemical corrosion and immersion tests proved that the corrosion resistance of MAF-treated AZ31 Mg alloy was significantly improved compared with untreated AZ31 Mg alloy in HBSS (Hank's Balanced Salt Solution). Current densities of AZ31, MAF100, MAF150, MAF200, MAF250, and MAF300 were 342.4, 0.295, 0.228, 0.177, 0.199, and 0.212 A/cm, respectively. The roughness test indicated that samples under MAF treatment of 200 V, 250 V, and 300 V had large surface roughness. Meanwhile, the contact angle measurement and surface free energy test suggested that those samples had smaller contact angle and higher SFE than Ti. Thus, MAF-treated AZ31 Mg alloy might have promising application in various fields.
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http://dx.doi.org/10.1155/2020/5936789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641723PMC
October 2020

A biomimetic soft robotic pinna for emulating dynamic reception behavior of horseshoe bats.

Bioinspir Biomim 2020 Sep 29. Epub 2020 Sep 29.

Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, 1075 Life Science Cir, Blacksburg, Virginia, VA 24061-0238, USA, Blacksburg, Virginia, 24061, UNITED STATES.

Encoding of sensory information is fundamental to closing the performance gapbetween man-made and biological sensing. It has been hypothesized that the coupling of sensingand actuation, a phenomenon observed in bats among other species, is critical to accomplishingthis. Using horseshoe bats as a model, we have developed a biomimetic pinna model with asoft actuation system along with a prototype strain sensor for enabling motor feedback. Theactuation system used three individually controlled pneumatic actuators per pinna which actuateddifferent portions of the baffle. This prototype produced eight different possible motions thatwere shown to have significant effects on incoming sound and could hence function as a substratefor adaptive sensing. The range of possible motions could be expanded by adjusting the fill andrelease parameters of the actuation system. Additionally, the strain sensor was able to representthe deformation of the pinna as measurements from this sensor were highly correlated withdeformation estimates based on stereo vision. However, the relationship between displacementsof points on the pinna and the sensor output was nonlinear. The improvements embodied inthe system discussed here could lead to enhancements in the ability of autonomous systems toencode relevant information about the real world.
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http://dx.doi.org/10.1088/1748-3190/abbc73DOI Listing
September 2020

Bioresorbable magnesium-reinforced PLA membrane for guided bone/tissue regeneration.

J Mech Behav Biomed Mater 2020 12 26;112:104061. Epub 2020 Aug 26.

Department and Research Institute of Dental Biomaterials and Bioengineering, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea; BK21 PLUS Project, Yonsei University College of Dentistry, Seou, 03722, Republic of Korea. Electronic address:

Considering the inferior mechanical properties of the current bioresorbable polymers, a novel bioresorbable magnesium-reinforced polylactide (PLA) membrane was designed for the application in critical defect sites in guided bone/tissue regeneration. The PLA-FAZ91 membrane was fabricated by combining two PLA membranes with a fluoride-coated AZ91 (9 wt% Al, 1 wt% Zn) (FAZ91) magnesium alloy core by hot pressing. A combined double-layered PLA membrane was used as the control group. A three-point bending test was performed to compare their maximum load and stiffness. Samples were immersed in the HBSS for 20 weeks, and their weight loss percentages were recorded, and a three-point bending test was performed after immersion. An ion release test was performed by immersing samples in the HBSS for 4 weeks and determining the pH and ion concentrations of the HBSS. Cell viability was tested by culturing pre-osteoblast cells with sample extracts in the culture medium obtained from degraded samples. As a result, PLA-FAZ91 showed a significantly higher maximum load and stiffness than those of the non-reinforced PLA membrane. The weight loss of PLA-FAZ91 was much faster, as FAZ91 showed major degradation and was completely degraded after 16-20 weeks of immersion. The degradation of the PLA wrap was accelerated by FAZ91. The mechanical superiority of PLA-FAZ91 over PLA endured for at least 3 weeks during immersion. The pH, magnesium- and fluoride-ion concentration in the PLA-FAZ91 group increased at an appropriate rate. The cell viability was not adversely affected by the addition of FAZ91 to PLA. Therefore, the bioresorbable magnesium-reinforced PLA membrane has the potential to be used as a good alternative to pure PLA membrane in guided bone/tissue regeneration.
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http://dx.doi.org/10.1016/j.jmbbm.2020.104061DOI Listing
December 2020

GhWRKY21 regulates ABA-mediated drought tolerance by fine-tuning the expression of GhHAB in cotton.

Plant Cell Rep 2020 Sep 5. Epub 2020 Sep 5.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, 271018, Shandong, People's Republic of China.

Key Message: We report that GhWRKY21, a WRKY transcription factor, plays essential roles in regulating the intensity of the drought-induced ABA signalling pathway by facilitating the expression of GhHAB in cotton (Gossypium hirsutum). Abscisic acid (ABA) is one of the most important plant hormones in response to abiotic stress. However, activation of the ABA signalling pathway often leads to growth inhibition. The mechanisms that regulate the intensity of ABA signals are poorly understood. Here, we isolated and analysed the cotton group IId WRKY transcription factor (TF) gene GhWRKY21. Functional analysis indicated that GhWRKY21 plays a negative role in the drought response of cotton. Silencing of GhWRKY21 in cotton dramatically increased drought tolerance, whereas ectopic GhWRKY21 overexpression in Nicotiana benthamiana decreased drought tolerance. Furthermore, the GhWRKY21-mediated drought tolerance was ABA dependent. To clarify the mechanism underlying the GhWRKY21-mediated regulation of drought tolerance, 17 clade-A-type type 2C protein phosphatase (PP2C) genes, which are negative regulators of ABA signalling, were identified in cotton. Notably, GhWRKY21 interacted specifically with the W-box element within the promoter of GhHAB and regulated its expression. Silencing of GhHAB in cotton yielded a phenotype similar to that of GhWRKY21-silenced cotton. These results suggest that GhWRKY21 regulates the intensity of ABA signals by facilitating the expression of GhHAB. In summary, these findings dramatically improve our understanding of the function of WRKY TFs and provide insights into the mechanism of ABA-mediated drought tolerance.
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http://dx.doi.org/10.1007/s00299-020-02590-4DOI Listing
September 2020

MAC5, an RNA-binding protein, protects pri-miRNAs from SERRATE-dependent exoribonuclease activities.

Proc Natl Acad Sci U S A 2020 09 4;117(38):23982-23990. Epub 2020 Sep 4.

School of Biological Sciences and Center for Plant Science Innovation, University of Nebraska-Lincoln, Lincoln, NE 68588-0666;

MAC5 is a component of the conserved MOS4-associated complex. It plays critical roles in development and immunity. Here we report that MAC5 is required for microRNA (miRNA) biogenesis. MAC5 interacts with Serrate (SE), which is a core component of the microprocessor that processes primary miRNA transcripts (pri-miRNAs) into miRNAs and binds the stem-loop region of pri-miRNAs. MAC5 is essential for both the efficient processing and the stability of pri-miRNAs. Interestingly, the reduction of pri-miRNA levels in is partially caused by XRN2/XRN3, the nuclear-localized 5'-to-3' exoribonucleases, and depends on SE. These results reveal that MAC5 plays a dual role in promoting pri-miRNA processing and stability through its interaction with SE and/or pri-miRNAs. This study also uncovers that pri-miRNAs need to be protected from nuclear RNA decay machinery, which is connected to the microprocessor.
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http://dx.doi.org/10.1073/pnas.2008283117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519324PMC
September 2020

Validity of Wrist-Worn photoplethysmography devices to measure heart rate: A systematic review and meta-analysis.

J Sports Sci 2020 Sep 19;38(17):2021-2034. Epub 2020 Jun 19.

Department of Exercise Science, Arnold School of Public Health, University of South Carolina , Columbia, SC, USA.

Heart rate (HR), when combined with accelerometry, can dramatically improve estimates of energy expenditure and sleep. Advancements in technology, via the development and introduction of small, low-cost photoplethysmography devices embedded within wrist-worn consumer wearables, have made the collection of heart rate (HR) under free-living conditions more feasible. This systematic review and meta-analysis compared the validity of wrist-worn HR estimates to a criterion measure of HR (electrocardiography ECG or chest strap). Searches of PubMed/Medline, Web of Science, EBSCOhost, PsycINFO, and EMBASE resulted in a total of 44 articles representing 738 effect sizes across 15 different brands. Multi-level random effects meta-analyses resulted in a small mean difference (beats per min, bpm) of -0.40 bpm (95 confidence interval (CI) -1.64 to 0.83) during sleep, -0.01 bpm (-0.02 to 0.00) during rest, -0.51 bpm (-1.60 to 0.58) during treadmill activities (walking to running), while the mean difference was larger during resistance training (-7.26 bpm, -10.46 to -4.07) and cycling (-4.55 bpm, -7.24 to -1.87). Mean difference increased by 3 bpm (2.5 to 3.5) per 10 bpm increase of HR for resistance training. Wrist-worn devices that measure HR demonstrate acceptable validity compared to a criterion measure of HR for most common activities.
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http://dx.doi.org/10.1080/02640414.2020.1767348DOI Listing
September 2020

Short-Term Effect of Different Taping Methods on Local Skin Temperature in Healthy Adults.

Front Physiol 2020 20;11:488. Epub 2020 May 20.

Department of Rehabilitation, School of International Medical Technology, Shanghai Sanda University, Shanghai, China.

Background: There were limited studies on the effect of skin temperature and local blood flow using kinesio tape (KT) adhered to the skin in different taping methods. This study aimed to determine the short-term effect of KT and athletic tape (AT) on skin temperature in the lower back and explore the possible effect of different taping methods (Y-strip and fan-strip taping) on local microcirculation.

Materials And Methods: Twenty-six healthy participants completed the test-retest reliability measurement of the infrared thermography (IRT), intraclass correlation coefficient (ICC), and standard error of measurement (SEM) were calculated to evaluate the reliability. Then, 21 healthy participants received different taping condition randomly for 5 times, including Y-strip of kinesio taping (KY), fan-strip of kinesio taping (Kfan), Y-strip of athletic taping (AY), fan-strip of athletic taping (Afan), and no taping (NT). Above taping methods were applied to the participants' erector spinae muscles on the same side. Skin temperature of range of interest (ROI) was measured in the taping area through IRT at pre taping and 10 min after taping. Additionally, participants completed self-perceived temperature evaluation for different taping methods through visual analog scaling. One-way repeated-measured analysis of variance was used to compare the temperature difference among different taping methods. Bonferroni test was used for post hoc analysis.

Results: There was a good test-retest reliability (ICC = 0.82, 95% CI = 0.60-0.92; SEM = 0.33; and MD = 0.91) of the IRT. Significant differences were observed in the short-term effect on skin temperature among all different taping methods ( = 0.012, = 3.435, and η = 0.147), test showed a higher significantly skin temperature difference in Kfan taping compared to no taping ( = 0.026, 95% CI = 0.051-1.206); However, no significant differences were observed among self-perceived temperature ( = 0.055, = 2.428, and η = 0.108).

Conclusion: This study showed that the fan-strip of KT increased significantly the skin temperature of the waist after taping for 10 min. The application of KT may modify the skin temperature of the human body and promote local microcirculation, although it remained unclear for the real application.
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http://dx.doi.org/10.3389/fphys.2020.00488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251151PMC
May 2020

Ribbon of DNA Lattice on Gold Nanoparticles for Selective Drug Delivery to Cancer Cells.

Angew Chem Int Ed Engl 2020 08 9;59(34):14584-14592. Epub 2020 Jul 9.

Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis, Chemoprevention and Chemotherapy, National & Local Joint Biomedical Engineering Research Center on, Photodynamic Technologies, Pharmaceutical Photocatalysis of State Key Laboratory of, Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350002, China.

Herein, we report on the design of a programmable DNA ribbon using long-chain DNA molecules with a user-defined repetitive padlock sequence. The DNA ribbon can be further combined with gold nanoparticles (AuNPs) to create a composite nanomaterial that contains an AuNP core and a high-density DNA crown carrying a cancer-cell-targeting DNA aptamer, a fluorescent tag for location tracking, and a cell-killing drug. This composite material can be efficiently internalized by cancer cells and its cellular location can be tracked by fluorescence imaging. The system offers several attractive characteristics, including simple design, tunable DNA crown, high drug-loading capacity, selective cell targeting, and pH-sensitive drug release. These features make such a material a promising therapeutic agent.
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http://dx.doi.org/10.1002/anie.202005624DOI Listing
August 2020

Risk Factors for Early Mortality in Patients with Primary Central Nervous System Lymphoma: A Large-Cohort Retrospective Study.

World Neurosurg 2020 06 3;138:e905-e912. Epub 2020 Apr 3.

Department of Neurosurgery, West China Hospital, Chengdu, People's Republic of China. Electronic address:

Objective: The present study assessed early mortality (within 1 and 3 months) in patients with primary central nervous system lymphoma (PCNSL) and identified the risk factors associated with early mortality.

Methods: We extracted the data for patients with PCNSL from the Surveillance, Epidemiology, and End Results dataset using the SEER∗Stat, version 8.3.5, software.

Results: A total of 8091 patients with PCNSL were enrolled in the present study. Of the 8091 patients, 57.94% were men and 42.06% were women. The mean age was 59.50 ± 16.11 years. The rate of death within 1 and 3 months was 10.67% and 29.16%, respectively. During the past 20 years, early mortality declined significantly. The common causes of early death were non-Hodgkin lymphoma and other infectious and parasitic diseases, including human immunodeficiency virus. Our results showed that gender, age at diagnosis, ethnicity, histological subtype, marital status, tumor location, surgery, radiotherapy, and chemotherapy were associated with early mortality within 1 or 3 months.

Conclusion: The rate of early mortality has declined significantly during the past 20 years. The risk factors for early mortality within 1 or 3 months after a PCNSL diagnosis included advanced age, male gender, black race, frontal lobe location, unmarried, diffuse large B-cell lymphoma, no surgery, no chemotherapy, and no radiotherapy.
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http://dx.doi.org/10.1016/j.wneu.2020.03.150DOI Listing
June 2020

Engrailed 2 (EN2) acts as a glioma suppressor by inhibiting tumor proliferation/invasion and enhancing sensitivity to temozolomide.

Cancer Cell Int 2020 2;20:65. Epub 2020 Mar 2.

1Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041 Sichuan People's Republic of China.

Background: Glioma is one of the most malignant brain tumors and accounts for the majority of brain cancer related death. Despite progress on mechanistic studies, current understandings of the initiation and progression of glioma are still incomplete. Previous studies demonstrate that - (EN2), a homeobox-containing transcription factor, is associated with tumorigenesis in a range of cancers heterogeneously, however, the profiles of EN2 expression and its potential functions in gliomas remain unclear.

Methods: Real-time PCR was used to identify the expression of EN2 in glioma tissues. To study the biological function of EN2 in glioma, we compared the cell viability and proliferation profiles between EN2 overexpressed and control cells using cell counting kit-8 (CCK8) assay, EdU incorporation assay and colony formation assay. Flow cytometry and Hoechst staining assays were performed to investigate the role of EN2 on glioma cell death. Finally, wound healing and transwell assays were carried out to investigate the role of EN2 on glioma cell invasion.

Results: We identified that EN2 was downregulated in human gliomas compared with paired adjacent normal tissues and negatively associated with glioma malignancy. Elevated EN2 expression inhibits cell proliferation, enhances glioma sensitivity to temozolomide and inhibits migration/invasion of glioma cells.

Conclusions: Our data identify a novel function of EN2 in glioma suppression and provide potential therapeutic targets for glioma therapy.
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http://dx.doi.org/10.1186/s12935-020-1145-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053055PMC
March 2020

Risk Factors for Early Mortality Among Patients with Glioma: A Population-Based Study.

World Neurosurg 2020 Apr 16;136:e496-e503. Epub 2020 Jan 16.

Department of Neurosurgery, West China Hospital, Chengdu, People's Republic of China. Electronic address:

Objective: The present study evaluated the early death and factors associated with early mortality in patients with glioma.

Methods: The data used for analysis in the present study was extracted from the Surveillance, Epidemiology, and End Results data set.

Results: A total of 58,700 patients with glioma were enrolled in the present study. The proportion of patient death within 1 month and 3 months after the diagnosis was 9.24% and 19.15% for all patients, respectively. The factors significantly associated with death within 1 month after tumor resection on multivariate analysis included age at diagnosis, year of diagnosis, tumor location, histological features, tumor size, and the absence of gross total resection, radiotherapy, and chemotherapy. We also observed similar findings in the evaluation of the factors associated with 3-month mortality.

Conclusion: The early deaths rates, including 1 and 3 months after tumor resection in patients with glioma, have decreased slightly during the previous 40 years. The risk factors for early mortality included advanced age, male sex, tumor located in the lateral ventricle, cerebellum, or brainstem, receipt of biopsy only, no chemotherapy or radiotherapy, and specific histopathological types.
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http://dx.doi.org/10.1016/j.wneu.2020.01.041DOI Listing
April 2020

miR-143 inhibits migration and invasion through regulating LASP1 in human esophageal cancer.

Int J Clin Exp Pathol 2019 1;12(2):466-476. Epub 2019 Feb 1.

Department of Thoracic Surgery, PLA 309 Hospital Haidian, Beijing 100091, China.

Background: Esophageal cancer (EC) is one of the common cancers in China with high incidence and poor prognosis. Increasing evidence has emphasized the important roles of differentially expressed miRNAs in esophageal squamous cell carcinoma (ESCC) progression. Previous studies indicated that miR-143-3p and LASP1 influence cell growth in ESCC and other cancer types. However, the function and molecular mechanism of action of miR-143 and LASP1 in ESCC have not been fully explored.

Methods: miR-143 and LASP1 expression were detected by quantitative real-time PCR. The protein level of LASP1 was measured by western blot. Cell proliferation was evaluated by MTT assay. Cell migration and invasion capacity was measured by transwell assay. Targeting of LASP1 mRNA by miR-143 was verified by luciferase reporter assay. Overall survival of ESCC patients with different miR-143 expression level was evaluated by Kaplan-Meier survival analysis.

Results: miR-143 expression was down-regulated, while LASP1 expression was up-regulated in ESCC tissues and cells compared to non-malignant counterparts. LASP1 mRNA was identified as a target of miR-143. Low miR-143 expression or high LASP1 expression significantly associated with ESCC patients' decreased survival. miR-143 mimic transfection inhibited ESCC cell proliferation, migration and invasion in vitro, which was impaired by LASP1 overexpression.

Conclusion: miR-143 suppressed cell proliferation, migration, and invasion by down-regulating LASP1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945078PMC
February 2019

Scaffold protein GhMORG1 enhances the resistance of cotton to Fusarium oxysporum by facilitating the MKK6-MPK4 cascade.

Plant Biotechnol J 2020 06 20;18(6):1421-1433. Epub 2019 Dec 20.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, China.

In eukaryotes, MAPK scaffold proteins are crucial for regulating the function of MAPK cascades. However, only a few MAPK scaffold proteins have been reported in plants, and the molecular mechanism through which scaffold proteins regulate the function of the MAPK cascade remains poorly understood. Here, we identified GhMORG1, a GhMKK6-GhMPK4 cascade scaffold protein that positively regulates the resistance of cotton to Fusarium oxysporum. GhMORG1 interacted with GhMKK6 and GhMPK4, and the overexpression of GhMORG1 in cotton protoplasts dramatically increased the activity of the GhMKK6-GhMPK4 cascade. Quantitative phosphoproteomics was used to clarify the mechanism of GhMORG1 in regulating disease resistance, and thirty-two proteins were considered as the putative substrates of the GhMORG1-dependent GhMKK6-GhMPK4 cascade. These putative substrates were involved in multiple disease resistance processes, such as cellular amino acid metabolic processes, calcium ion binding and RNA binding. The kinase assays verified that most of the putative substrates were phosphorylated by the GhMKK6-GhMPK4 cascade. For functional analysis, nine putative substrates were silenced in cotton, respectively. The resistance of cotton to F. oxysporum was decreased in the substrate-silenced cottons. These results suggest that GhMORG1 regulates several different disease resistance processes by facilitating the phosphorylation of GhMKK6-GhMPK4 cascade substrates. Taken together, these findings reveal a new plant MAPK scaffold protein and provide insights into the mechanism of plant resistance to pathogens.
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http://dx.doi.org/10.1111/pbi.13307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206998PMC
June 2020

Hepatopulmonary Syndrome Mimics Pulmonary Embolism on Pulmonary Ventilation/Perfusion SPECT/CT Study.

Clin Nucl Med 2020 Jan;45(1):90-91

From the Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, China.

A 64-year-old woman with a history of cirrhosis and progressive difficulty breathing underwent pulmonary ventilation/perfusion SPECT to evaluate possible pulmonary embolism. The images demonstrated multiple mismatched ventilation/perfusion defects in both lungs, suggesting pulmonary embolism. However, there was also Tc-MAA radioactivity in the brain and bilateral kidney, with a right-to-left shunting rate of 8.8%. In addition, CT pulmonary angiography did not demonstrate embolus. The findings indicated that perfusion defects were caused by hepatopulmonary syndrome.
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http://dx.doi.org/10.1097/RLU.0000000000002847DOI Listing
January 2020

Dynamic relationship between noseleaf and pinnae in echolocating hipposiderid bats.

J Exp Biol 2019 09 26;222(Pt 18). Epub 2019 Sep 26.

Shandong University-Virginia Tech International Laboratory, School of Physics, Shandong University, Jinan 250100, China

Old World leaf-nosed bats (family Hipposideridae) can deform the shapes of their 'noseleaves' (i.e. ultrasonic emission baffles) and outer ears during echolocation behaviors. Prior work has shown that deformations on the emission as well as on the reception side can have an impact on the properties of the emitted/received sonar signals. The occurrence of the deformations on the emission and reception sides raises the question of whether the bats coordinate these two dynamic biosonar features to achieve synergistic effects. To address this question, simultaneous three-dimensional reconstructions of the trajectories of landmarks on the dynamic noseleaf and pinna geometries have been obtained in great roundleaf bats (). These joint kinematics data on the noseleaf and pinnae have shown both qualitative and quantitative relationships between the noseleaf and pinna motions: large noseleaf deformations (opening or closing) tended to be associated with non-rigid pinna motions. Furthermore, closing deformations of the noseleaves tended to co-occur with closing motions of the pinna. Finally, a canonical correlation analysis of the motion trajectories has revealed a tight correlation between the motions of the landmarks on the noseleaf and both pinnae. These results demonstrate that the biosonar system of hipposiderid bats includes coordinated emission and reception dynamics.
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http://dx.doi.org/10.1242/jeb.210252DOI Listing
September 2019

Total Syntheses of Resin Glycosides Murucoidins IV and V.

Org Lett 2019 08 24;21(16):6213-6216. Epub 2019 Jun 24.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy , Huazhong University of Science and Technology , 13 Hangkong Road , Wuhan , Hubei 430030 , P.R. China.

Murucoidins IV and V, two bioactive resin glycosides with complex yet similar structures isolated from the morning glory family, were synthesized in a convergent manner. All of the glycosylations in these syntheses including the key [3 + 2] coupling were achieved by our recently developed interrupted Pummerer reaction mediated (IPRm) glycosylations. The broad functional group compatibility of IPRm glycosylation allowed us to employ a latent-active concept and a single-pot transient protection-glycosylation-deprotection strategy which significantly improved the global synthetic efficiency.
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http://dx.doi.org/10.1021/acs.orglett.9b02004DOI Listing
August 2019

Hydrogen-Bonding-Assisted Exogenous Nucleophilic Reagent Effect for β-Selective Glycosylation of Rare 3-Amino Sugars.

J Am Chem Soc 2019 05 15;141(21):8509-8515. Epub 2019 May 15.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy , Huazhong University of Science and Technology , 13 Hangkong Road , Wuhan , Hubei 430030 , China.

Challenges for stereoselective glycosylation of deoxy sugars are notorious in carbohydrate chemistry. We herein report a novel strategy for the construction of the less investigated β-glycosidic bonds of 3,5- trans-3-amino-2,3,6-trideoxy sugars (3,5- trans-3-ADSs), which constitute the core structure of several biologically important antibiotics. Current protocol leverages a C-3 axial sulfonamide group in 3,5- trans-3-ADSs as a hydrogen-bond (H-bond) donor and repurposes substoichiometric phosphine oxide as an exogenous nucleophilic reagent (exNu) to establish an intramolecular H-bond between the former and the derived α-oxyphosphonium ion. This pivotal interaction stabilizes the α-face-covered intermediate to inhibit the formation of the more reactive β-intermediate, thereby yielding reversed β-selectivity, which is unconventional for an exNu-mediated glycosylation system. A wide range of substrates was accommodated, and good to excellent β-selectivities were ensured by this H-bonding-assisted exNu effect. The robustness of the current strategy was further attested by the architectural modification of natural products and drugs containing 3,5- trans-3-ADSs, as well as the synthesis of a trisaccharide unit in avidinorubicin.
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http://dx.doi.org/10.1021/jacs.9b01862DOI Listing
May 2019

The first steps in the evaluation of a "black-box" decision support tool: a protocol and feasibility study for the evaluation of Watson for Oncology.

J Clin Transl Res 2018 Dec 27;3(Suppl 3):411-423. Epub 2018 Jul 27.

Department of medical oncology, Cancer Center Amsterdam, Academic Medical Center, University of Amsterdam, the Netherlands.

Background And Aim: Medical specialists aim to provide evidence-based care based on the most recent scientific insights, but with the ongoing expansion of medical literature it seems unfeasible to remain updated. "Black-box" decision support tools such as Watson for Oncology (Watson) are gaining attention as they offer a promising opportunity to conquer this challenging issue, but it is not known if the advice given is congruent with guidelines or clinically valid in other settings. We present a protocol for the content evaluation of black-box decision support tools and a feasibility study to test the content and usability of Watson using this protocol.

Methods: The protocol consists of developing synthetic patient cases based on Dutch guidelines and expert opinion, entering the synthetic cases into Watson and Oncoguide, noting the response of each system and evaluating the result using a cross-tabulation scoring system resulting in a score range of -12 to +12. Treatment options that were not recommended according to the Dutch guideline were labeled with a "red flag" if Watson recommended it, and an "orange flag" if Watson suggested it for consideration. To test the feasibility of applying the protocol, we developed synthetic patient cases for the adjuvant treatment of stage I to stage III colon cancer based on relevant patient, clinical and tumor characteristics and followed our protocol. Additionally, for the feasibility study we also compared the recommendations from the NCCN guideline with Watson's advice, and evaluated usability by a cognitive walkthrough method.

Results: In total, we developed 190 synthetic patient cases (stage I: n=8; stage II: n=110; and stage III: n=72). Overall concordance scores per case for Watson versus Oncoguide ranged from a minimum score of -4 (n=6) to a maximum score of+12 (n=17) and from -4 (n=9) to +12 (n=24) for Watson versus the NCCN guidelines). In total, 69 cases (36%) were labeled with red flags, 96 cases (51%) with orange flags and 25 cases (13%) without flags. For the comparison of Watson with the NCCN guidelines, no red or orange flags were identified.

Conclusions: We developed a research protocol for the evaluation of a black-box decision support tool, which proved useful and usable in testing the content and usability of Watson. Overall concordance scores ranged considerably between synthetic cases for both comparisons between Watson versus Oncoguide and Watson versus NCCN. Non-concordance is partially attributable to guideline differences between the United States and The Netherlands. This implies that further adjustments and localization are required before implementation of Watson outside the United States.

Relevance For Patients: This study describes the first steps of content evaluation of a decision support tool before implementation in daily oncological patient care. The ultimate goal of the incorporation of decision support tools in daily practice is to improve personalized medicine and quality of care.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412599PMC
December 2018

Recyclable polyvinyl alcohol sponge containing flower-like layered double hydroxide microspheres for efficient removal of As(V) anions and anionic dyes from water.

J Hazard Mater 2019 04 24;367:286-292. Epub 2018 Dec 24.

School of Chemistry and Material Science, Shandong Agricultural University, Taian, 271018, Shandong, PR China. Electronic address:

Layered double hydroxides (LDHs) are very promising adsorbents for the removal of anionic pollutants from water. However, the low adsorption efficiency and recycling difficulty of conventional LDH powders are obstacles to practical applications. Herein, a novel Zn/Fe-LDH composite sponge was successfully fabricated using a simple in-situ hydrothermal method. Characterization studies revealed that the composite sponge contained flower-like Zn/Fe LDH microspheres uniformly dispersed throughout a poly vinyl alcohol (PVA) sponge matrix. The specific surface area of the Zn/Fe-LDH composite sponge was 42.5 m g, approximately 5 times higher than the pristine PVA sponge (8.9 m g). Adsorption experiments revealed that Zn/Fe-LDH composite sponge exhibited a much higher adsorption ability for As(V) anions and methyl orange (MO) compared with a Zn/Fe-LDH powder or the pristine PVA sponge. The maximum adsorption capacity for As(V) was found to be 85.7 mg g. Furthermore, the Zn/Fe-LDH composite sponge showed high thermal stability, good mechanical stability and easy recoverability, thereby allowing reuse. Results guide the development of improved, low cost water treatment materials.
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http://dx.doi.org/10.1016/j.jhazmat.2018.12.092DOI Listing
April 2019

Ultrasensitive assay based on a combined cascade amplification by nicking-mediated rolling circle amplification and symmetric strand-displacement amplification.

Anal Chim Acta 2019 Jan 19;1047:172-178. Epub 2018 Oct 19.

Cancer Metastasis Alert and Prevention Center, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, 350116, China. Electronic address:

MicroRNAs (miRNAs) play an important role in the regulation of various biological processes and have been used as potential biomarkers for biomedical research and clinical diagnosis. Here, nicking-mediated rolling circle amplification (N-RCA)/symmetric isothermal circular strand-displacement amplification (S-SDA)-integrated combined cascade amplification (rs-CCA) was proposed for let-7a miRNA detection. Via introducing a palindromic fragment-integrated recognition sites for nicking endonuclease Nt.AlWI into the padlock probe, the hybridization of target miRNA can induce N-RCA and continuously generate the nicked fragments (NFs). Because the released NFs each have a palindromic sequence and daughter nicking site at the 3' end, they hybridize with each other, followed by alternately extension by polymerase and nicking by endonuclease. This leads to S-SDA effect, and the released single-stranded products in turn hybridize with NFs, accomplishing the rs-CCA process. When the Sybr Green I dyes intercalate into double-stranded DNA products, the amplified fluorescence signal is achieved. Thus, the target miRNA can be detected down to 5 pM. Importantly, the rs-CCA system is capable of distinguishing the single base difference between target miRNAs, indicating the high sequence specificity. Moreover, its potential application in disease diagnosis was demonstrated via detecting target miRNA in complex biological matrix and analyzing the total RNAs extracted from HeLa cells. As a proof-of-concept building, the impressive rs-CCA scheme is expected to provide a valuable insight into constructing powerful signal amplification strategies via sophisticated combination of biotechnologies available for nucleic acid manipulation and significantly benefit biomedical research and disease diagnostics.
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http://dx.doi.org/10.1016/j.aca.2018.10.004DOI Listing
January 2019