Publications by authors named "Yi Zheng"

1,618 Publications

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Self-adaptive metasurface platform based on computer vision.

Opt Lett 2021 Aug;46(15):3520-3523

Programmable metasurfaces allow real-time electromagnetic (EM) manipulation in a digital manner, showing great potential to construct advanced multifunctional EM devices. However, the current programmable metasurfaces typically need human participation to achieve various EM functions. In this Letter, we propose, design, and construct a self-adaptive metasurface platform that can achieve beam control automatically based on image recognition. Such a platform is composed of a metasurface with 36×36 active units, a single-board computer, and two independent cameras that can detect the position of the objects. The single-board computer, Raspberry Pi, is used to calculate the information of the objects and generate the coding sequences to control the digital metasurface based on a low complexity binocular localization algorithm. Such a smart metasurface platform can generate different beams according to the location of the receiver and can be used as intelligent antennas in future communications and radars.
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http://dx.doi.org/10.1364/OL.427527DOI Listing
August 2021

Machine learning-assisted imaging analysis of a human epiblast model.

Integr Biol (Camb) 2021 Jul 30. Epub 2021 Jul 30.

Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

The human embryo is a complex structure that emerges and develops as a result of cell-level decisions guided by both intrinsic genetic programs and cell-cell interactions. Given limited accessibility and associated ethical constraints of human embryonic tissue samples, researchers have turned to the use of human stem cells to generate embryo models to study specific embryogenic developmental steps. However, to study complex self-organizing developmental events using embryo models, there is a need for computational and imaging tools for detailed characterization of cell-level dynamics at the single cell level. In this work, we obtained live cell imaging data from a human pluripotent stem cell (hPSC)-based epiblast model that can recapitulate the lumenal epiblast cyst formation soon after implantation of the human blastocyst. By processing imaging data with a Python pipeline that incorporates both cell tracking and event recognition with the use of a CNN-LSTM machine learning model, we obtained detailed temporal information of changes in cell state and neighborhood during the dynamic growth and morphogenesis of lumenal hPSC cysts. The use of this tool combined with reporter lines for cell types of interest will drive future mechanistic studies of hPSC fate specification in embryo models and will advance our understanding of how cell-level decisions lead to global organization and emergent phenomena. Insight, innovation, integration: Human pluripotent stem cells (hPSCs) have been successfully used to model and understand cellular events that take place during human embryogenesis. Understanding how cell-cell and cell-environment interactions guide cell actions within a hPSC-based embryo model is a key step in elucidating the mechanisms driving system-level embryonic patterning and growth. In this work, we present a robust video analysis pipeline that incorporates the use of machine learning methods to fully characterize the process of hPSC self-organization into lumenal cysts to mimic the lumenal epiblast cyst formation soon after implantation of the human blastocyst. This pipeline will be a useful tool for understanding cellular mechanisms underlying key embryogenic events in embryo models.
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http://dx.doi.org/10.1093/intbio/zyab014DOI Listing
July 2021

New media platform's understanding of Chinese social workers' anti-epidemic actions: an analysis of network public opinion based on COVID-19.

Soc Work Public Health 2021 Jul 30:1-16. Epub 2021 Jul 30.

School of Education, Renmin University of China, Beijing, P.R.China.

Research on social public opinion of new media is currently an important interdisciplinary topic in the international academic community. Under the background of COVID-19, the major public health event of in China, this research took social workers as the research object who worked during the period of epidemic prevention and control. It referred to the international research on public opinion and selected 63 related hotly discussed articles and public comments on the WeChat public platform, the new Chinese Internet media. Moreover, the research conducted text mining on related public opinion with the 5 W communication model from public opinion evolution, text content, communication media, audiences, and public opinion influence, and used grounded theory building a development model of the generation of network public opinion. It also put forward the development needs of social work in the aspects of community resilience, social work practice, lack of public health social workers, and big data warning, etc., and pointed out that social work lacks its proper structural status in China's public health system and emergency management system.
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http://dx.doi.org/10.1080/19371918.2021.1954127DOI Listing
July 2021

Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion.

Sci Transl Med 2021 Jul;13(604)

Joint Program in Transfusion Medicine, Department of Pathology, Harvard Medical School; Division of Blood Bank, Department of Laboratory Medicine, Stem Cell Program, Boston Children's Hospital; and Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.

Clinical outcomes from granulocyte transfusion (GTX) are disadvantaged by the short shelf life and compromised function of donor neutrophils. Spontaneous neutrophil death is heterogeneous and mediated by multiple pathways. Leveraging mechanistic knowledge and pharmacological screening, we identified a combined treatment, caspases-lysosomal membrane permeabilization-oxidant-necroptosis inhibition plus granulocyte colony-stimulating factor (CLON-G), which altered neutrophil fate by simultaneously targeting multiple cell death pathways. CLON-G prolonged human and mouse neutrophil half-life in vitro from less than 1 day to greater than 5 days. CLON-G-treated aged neutrophils had equivalent morphology and function to fresh neutrophils, with no impairment to critical effector functions including phagocytosis, bacterial killing, chemotaxis, and reactive oxygen species production. Transfusion with stored CLON-G-treated 3-day-old neutrophils enhanced host defenses, alleviated infection-induced tissue damage, and prolonged survival as effectively as transfusion with fresh neutrophils in a clinically relevant murine GTX model of neutropenia-related bacterial pneumonia and systemic candidiasis. Last, CLON-G treatment prolonged the shelf life and preserved the function of apheresis-collected human GTX products both ex vivo and in vivo in immunodeficient mice. Thus, CLON-G treatment represents an effective and applicable clinical procedure for the storage and application of neutrophils in transfusion medicine, providing a therapeutic strategy for improving GTX efficacy.
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http://dx.doi.org/10.1126/scitranslmed.abb1069DOI Listing
July 2021

Effects of graphite, graphene, and graphene oxide on the anaerobic co-digestion of sewage sludge and food waste: Attention to methane production and the fate of antibiotic resistance genes.

Bioresour Technol 2021 Jul 17;339:125585. Epub 2021 Jul 17.

State Environmental Protection Key Laboratory of Food Chain Pollution Control, School of Ecology and Environment, Beijing Technology and Business University, Beijing 100048, China. Electronic address:

This study explored and compared the influence of graphite, graphene, and graphene oxide (GO) on the performance of anaerobic co-digestion fed with sewage sludge and food waste, the variations of antibiotic resistance genes (ARGs), and the evolution of microbial community. Graphene exhibited the best performance for improving methane production and organic degradation, which increased by 36.09% and 23.07% compared with control group. The experimental results showed that graphene had the greatest influence on the removal efficiency of blaOXA-1, macrolide resistance genes (ermF and ermB), and some tetracycline resistance genes (tetQ and tetX); however, the removal efficiency of sulfonamide resistance genes (sul1 and sul2), intI1, and some tetracycline resistance genes (tetM, tetO, and tetW) were highest when GO was added. Network analysis indicated that the host cells of mefA, ermB, and tetO were different from other ARG host cells; moreover, graphene controlled the horizontal transfer of ARGs between microbial communities.
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http://dx.doi.org/10.1016/j.biortech.2021.125585DOI Listing
July 2021

Developmental Pharmacogenetics of CYP2D6 in Chinese Children: Loratadine as a Substrate Drug.

Front Pharmacol 2021 6;12:657287. Epub 2021 Jul 6.

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.

The elucidation of CYP2D6 developmental pharmacogenetics in children has improved, however, these findings have been largely limited to studies of Caucasian children. Given the clear differences in CYP2D6 pharmacogenetic profiles in people of different ancestries, there remains an unmet need to better understand the developmental pharmacogenetics in populations of different ancestries. We sought to use loratadine as a substrate drug to evaluate the effects of ontogeny and pharmacogenetics on the developmental pattern of CYP2D6 in Chinese pediatric patients. Chinese children receiving loratadine treatment were enrolled in the present study. The metabolite-to-parent ratio (M/P ratio), defined as the molar ratio of desloratadine to loratadine of trough concentrations samples at steady-state condition, was used as a surrogate of CYP2D6 activity. Loratadine and desloratadine were determined by LC/MS/MS method. Variants of CYP2D6 were genotyped by polymerase chain reaction for CYP2D6 *4, *10, *41 and long polymerase chain reaction for CYP2D6 *5. A total of 40 patients were available for final analysis. The mean age was 4.50 (range 0.50-9.00) years and the mean weight was 19.64 (range 7.00-42.00) kg. The M/P ratio was significantly lower in intermediate metabolizers (IMs) compared to normal metabolizers (NMs) (10.18 ± 7.97 vs. 18.80 ± 15.83, = 0.03). Weight was also found to be significantly associated with M/P ratio ( = 0.03). The developmental pharmacogenetics of CYP2D6 in Chinese children was evaluated using loratadine as a substrate drug. This study emphasizes the importance of evaluating the developmental pharmacogenetics in populations of different ancestries.
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http://dx.doi.org/10.3389/fphar.2021.657287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292113PMC
July 2021

The chromatin remodeler CHD8 governs hematopoietic stem/progenitor survival by regulating ATM-mediated P53 protein stability.

Blood 2021 Jul;138(3):221-233

Division of Experimental Hematology and Cancer Biology, Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.

The Chd8 gene encodes a member of the chromodomain helicase DNA-binding (CHD) family of SNF2H-like adenosine triphosphate (ATP)-dependent chromatin remodeler, the mutations of which define a subtype of autism spectrum disorders. Increasing evidence from recent studies indicates that ATP-dependent chromatin-remodeling genes are involved in the control of crucial gene-expression programs in hematopoietic stem/progenitor cell (HSPC) regulation. In this study, we identified CHD8 as a specific and essential regulator of normal hematopoiesis. Loss of Chd8 leads to severe anemia, pancytopenia, bone marrow failure, and engraftment failure related to a drastic depletion of HSPCs. CHD8 forms a complex with ATM and its deficiency increases chromatin accessibility and drives genomic instability in HSPCs causing an activation of ATM kinase that further stabilizes P53 protein by phosphorylation and leads to increased HSPC apoptosis. Deletion of P53 rescues the apoptotic defects of HSPCs and restores overall hematopoiesis in Chd8-/- mice. Our findings demonstrate that chromatin organization by CHD8 is uniquely necessary for the maintenance of hematopoiesis by integrating the ATM-P53-mediated survival of HSPCs.
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http://dx.doi.org/10.1182/blood.2020009997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310427PMC
July 2021

CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients.

Front Pharmacol 2021 5;12:692922. Epub 2021 Jul 5.

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.

The drug-drug interactions (DDIs) of tacrolimus greatly contributed to pharmacokinetic variability. Nifedipine, frequently prescribed for hypertension, is a competitive CYP3A5 inhibitor which can inhibit tacrolimus metabolism. The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-nifedipine DDI in Chinese renal transplant patients. All renal transplant patients were divided into homozygotes (group I) and allele carriers ( + ) (group II). Each group was subdivided into patients taking tacrolimus co-administered with nifedipine (CONF) and that administrated with tacrolimus alone (Controls). Tacrolimus trough concentrations (C) were measured using high performance liquid chromatography. A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C) (C/D) between CONF and Controls in group I and II, respectively. At the same time, a multivariate line regression analysis was made to evaluate the effect of variates on C/D. In this study, a significant DDI between tacrolimus and nifedipine with respect to the polymorphism was confirmed. In group I ( = 43), the C/D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/ml/(mg/kg); = 0.002]. However, this difference was not detected in group II ( = 27) ( = 0.216). The co-administrated nifedipine and homozygotes significantly increased tacrolimus concentrations in multivariate line regression analysis. A CYP3A5 genotype-dependent DDI was found between tacrolimus and nifedipine. Therefore, personalized therapy accounting for CYP3A5 genotype detection as well as therapeutic drug monitoring are necessary for renal transplant patients when treating with tacrolimus and nifedipine.
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http://dx.doi.org/10.3389/fphar.2021.692922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287726PMC
July 2021

A New Measure of Students' Perceived Conflict between Evolution and Religion (PCoRE) Is a Stronger Predictor of Evolution Acceptance than Understanding or Religiosity.

CBE Life Sci Educ 2021 Sep;20(3):ar42

Biology Education Research Lab, Research for Inclusive STEM Education Center, School of Life Sciences, Arizona State University, Tempe, AZ 85282.

Evolution is controversial among students and religiosity, religious affiliation, understanding of evolution, and demographics are predictors of evolution acceptance. However, quantitative research has not explored the unique impact of student perceived conflict between their religion and evolution as a major factor influencing evolution acceptance. We developed an instrument with validity evidence called "Perceived Conflict between Evolution and Religion" (PCoRE). Using this measure, we find that, among students in 26 biology courses in 11 states, adding student perceived conflict between their religion and evolution to linear mixed models more than doubled the capacity of the models to predict evolution acceptance compared with models that only included religiosity, religious affiliation, understanding of evolution, and demographics. Student perceived conflict between evolution and their religion was the strongest predictor of evolution acceptance among all variables and mediated the impact of religiosity on evolution acceptance. These results build upon prior literature that suggests that reducing perceived conflict between students' religious beliefs and evolution can help raise evolution acceptance levels. Further, these results indicate that including measures of perceived conflict between religion and evolution in evolution acceptance studies in the future is important.
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http://dx.doi.org/10.1187/cbe.21-02-0024DOI Listing
September 2021

Global, Regional, and National Burden of Diabetes-Related Chronic Kidney Disease From 1990 to 2019.

Front Endocrinol (Lausanne) 2021 1;12:672350. Epub 2021 Jul 1.

Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Chronic kidney disease (CKD) is a public health problem largely caused by diabetes. The epidemiology of diabetes mellitus-related CKD (CKD-DM) could provide specific support to lessen global, regional, and national CKD burden.

Methods: Data were derived from the GBD 2019 study, including four measures and age-standardized rates (ASRs). Estimated annual percentage changes and 95% CIs were calculated to evaluate the variation trend of ASRs.

Results: Diabetes caused the majority of new cases and patients with CKD in all regions. All ASRs for type 2 diabetes-related CKD increased over 30 years. Asia and Middle socio-demographic index (SDI) quintile always carried the heaviest burden of CKD-DM. Diabetes type 2 became the second leading cause of CKD and CKD-related death and the third leading cause of CKD-related DALYs in 2019. Type 2 diabetes-related CKD accounted for most of the CKD-DM disease burden. There were 2.62 million incident cases, 134.58 million patients, 405.99 thousand deaths, and 13.09 million disability-adjusted life-years (DALYs) of CKD-DM worldwide in 2019. Age-standardized incidence (ASIR) and prevalence rate (ASPR) of type 1 diabetes-related CKD increased, whereas age-standardized death rate (ASDR) and DALY rate decreased for females and increased for males. In high SDI quintile, ASIR and ASPR of type 1 diabetes-related CKD remained the highest, with the slowest increase, whereas the ASDR and age-standardized DALY rate remained the lowest there. In high SDI quintile, ASIR of type 2 diabetes-related CKD was the highest, with the lowest increasing rate. In addition, type 2 diabetes-related CKD occurred most in people aged 80-plus years worldwide. The main age of type 2 diabetes-related CKD patients was 55-64 years in Asia and Africa. The prevalence, mortality, and DALY rate of type 2 diabetes-related CKD increased with age. As for incidence, there was a peak at 80 years, and after age of 80, the incidence declined. CKD-DM-related anemia was mainly in mild to moderate grade.

Conclusions: Increasing burden of CKD-DM varied among regions and countries. Prevention and treatment measures should be strengthened according to CKD-DM epidemiology, especially in middle SDI quintile and Asia.
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http://dx.doi.org/10.3389/fendo.2021.672350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281340PMC
July 2021

Continuous optical zoom microscopy imaging system based on liquid lenses.

Opt Express 2021 Jun;29(13):20322-20335

In this paper, a continuous optical zoom microscopy imaging system based on liquid lenses is proposed. Compared with traditional microscopes, which have discrete magnification, requiring manual conversion of the objective lens to change the magnification, the proposed microscope can continuously change the magnification of the targets in real-time. An adaptive zoom microscope, a liquid lens driving board, a microscope bracket, an adjustable three-dimensional stage and a light source are stacked to form the main framework of the continuous optical zoom microscopy imaging system. The adaptive zoom microscope which is composed of four electrowetting liquid lenses and six glass lenses form the main imaging element of the microscope. By changing the driving voltage which is applied to the four liquid lenses, the focal length of the liquid lenses can be modulated to achieve continuous zooming. By contrast, in traditional microscopes, the zooming process can only be achieved by rotating the eyepieces at different magnifications. At a fixed working distance, the magnification of the proposed microscope can change continuously from ∼9.6× to ∼22.2× with a response time of ∼50ms. Moreover, an axial depth scanning of ∼1000µm can be achieved without any mechanical movement. Our experiments proved that the microscope has stable performance and high consistency during zooming. Therefore, the proposed microscope has obvious advantages over the traditional microscopes in observing dynamic samples with different magnifications and can be commercialized for further expanding the applications in biochemical and pathological analysis.
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http://dx.doi.org/10.1364/OE.432290DOI Listing
June 2021

Topology identification of fractional-order complex dynamical networks based on auxiliary-system approach.

Chaos 2021 Apr;31(4):043125

School of Automation Science and Electrical Engineering, Beihang University, Beijing 100191, China.

Many practical systems can be well described by various fractional-order equations. This paper focuses on identifying the topology of the response layer of a drive-response fractional-order complex dynamical network using the auxiliary-system approach. Specifically, the response layer and the auxiliary layer receive the same input signals from the drive layer. By a designed adaptive control law, the unknown topology of the response layer is successfully identified. Moreover, the proposed method is effective even if the drive layer is made up of isolated nodes. The correctness of the theoretical results is demonstrated by numerical simulations.
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http://dx.doi.org/10.1063/5.0032932DOI Listing
April 2021

Rethinking Autonomous Surgery: Focusing on Enhancement over Autonomy.

Eur Urol Focus 2021 Jul 7. Epub 2021 Jul 7.

Department of Mechanical Engineering, University of Texas at Austin, Austin, TX, USA. Electronic address:

Context: As robot-assisted surgery is increasingly used in surgical care, the engineering research effort towards surgical automation has also increased significantly. Automation promises to enhance surgical outcomes, offload mundane or repetitive tasks, and improve workflow. However, we must ask an important question: should autonomous surgery be our long-term goal?

Objective: To provide an overview of the engineering requirements for automating control systems, summarize technical challenges in automated robotic surgery, and review sensing and modeling techniques to capture real-time human behaviors for integration into the robotic control loop for enhanced shared or collaborative control.

Evidence Acquisition: We performed a nonsystematic search of the English language literature up to March 25, 2021. We included original studies related to automation in robot-assisted laparoscopic surgery and human-centered sensing and modeling.

Evidence Synthesis: We identified four comprehensive review papers that present techniques for automating portions of surgical tasks. Sixteen studies relate to human-centered sensing technologies and 23 to computer vision and/or advanced artificial intelligence or machine learning methods for skill assessment. Twenty-two studies evaluate or review the role of haptic or adaptive guidance during some learning task, with only a few applied to robotic surgery. Finally, only three studies discuss the role of some form of training in patient outcomes and none evaluated the effects of full or semi-autonomy on patient outcomes.

Conclusions: Rather than focusing on autonomy, which eliminates the surgeon from the loop, research centered on more fully understanding the surgeon's behaviors, goals, and limitations could facilitate a superior class of collaborative surgical robots that could be more effective and intelligent than automation alone.

Patient Summary: We reviewed the literature for studies on automation in surgical robotics and on modeling of human behavior in human-machine interaction. The main application is to enhance the ability of surgical robotic systems to collaborate more effectively and intelligently with human surgeon operators.
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http://dx.doi.org/10.1016/j.euf.2021.06.009DOI Listing
July 2021

The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR.

Redox Biol 2021 09 29;45:102058. Epub 2021 Jun 29.

Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, PR China. Electronic address:

Tripartite motif (TRIM) 31 has been implicated in diverse biological and pathological conditions. However, whether TRIM31 plays a role in ischemic stroke progression is not clarified. Here we demonstrated that TRIM31 was significantly downregulated in the ischemic brain and the deficiency of TRIM31 alleviated brain injury induced by middle cerebral artery occlusion by reducing reactive oxygen species production and maintaining mitochondrial homeostasis. Mechanistically, we found that TRIM31 is an E3 ubiquitin ligase for TP53-induced glycolysis and apoptosis regulator (TIGAR), which confers protection against brain ischemia by increasing the pentose phosphate pathway flux and preserving mitochondria function. TRIM31 interacted with TIGAR and promoted the polyubiquitination of TIGAR, consequently facilitated its degradation in a proteasome-dependent pathway. Furthermore, TIGAR knockdown effectively abolished the protective effect of TRIM31 deficiency after cerebral ischemia. In conclusion, we identified that TRIM31 was a novel E3 ubiquitin ligase for TIGAR, played a critical role in regulating its protein level, and subsequently involved in the ischemic brain injury, suggesting TRIM31 as a potential therapeutic target for ischemic stroke.
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http://dx.doi.org/10.1016/j.redox.2021.102058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260875PMC
September 2021

Incremental prognostic value of biventricular longitudinal strain and high-sensitivity troponin I in COVID-19 patients.

Echocardiography 2021 Jun 29. Epub 2021 Jun 29.

Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Whether the combination of ventricular strain with high-sensitivity troponin I (hs-TNI) has an incremental prognostic value in coronavirus disease 2019 (COVID-19) patients has not been evaluated. The study aimed to evaluate the prognostic value of biventricular longitudinal strain and its combination with hs-TNI in COVID-19 patients.

Methods: A total of 160 COVID-19 patients who underwent both echocardiography and hs-TNI testing were enrolled in our study. COVID-19 patients were divided into two groups (critical and non-critical) according to severity-of-illness. The clinical characteristics, cardiac structure and function were compared between the two groups. The prognostic value of biventricular longitudinal strain and its combination with hs-TNI were evaluated by logistic regression analyses and receiver operating characteristic curves. Left ventricular longitudinal strain (LV LS) and right ventricular free wall longitudinal strain (RVFWLS) were determined by 2D speckle-tracking echocardiography.

Results: The LV LS and RVFWLS both were significantly lower in critical patients than non-critical patients (LV LS: -16.6±2.4 vs -17.9±3.0, P = .003; RVFWLS :-18.8±3.6 vs -23.9±4.4, P<.001). During a median follow-up of 60 days, 23 (14.4%) patients died. The multivariant analysis revealed that LV LS and RVFWLS [Odd ratio (95% confidence interval): 1.533 (1.131-2.079), P = .006; 1.267 (1.036-1.551), P = .021, respectively] were the independent predictors of higher mortality. Further, receiver-operating characteristic analysis revealed that the accuracy for predicting death was greater for the combination of hs-TNI levels with LV LS than separate LV LS (AUC: .91 vs .77, P = .001), and the combination of hs-TNI levels with RVFWLS than RVFWLS alone (AUC: .89 vs .83, P = .041).

Conclusions: Our study highlights that the combination of ventricular longitudinal strain with hs-TNI can provide higher accuracy for predicting mortality in COVID-19 patients, which may enhance risk stratification in COVID-19 patients.
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http://dx.doi.org/10.1111/echo.15133DOI Listing
June 2021

The Correlation Between SPP1 and Immune Escape of EGFR Mutant Lung Adenocarcinoma Was Explored by Bioinformatics Analysis.

Front Oncol 2021 10;11:592854. Epub 2021 Jun 10.

Department of Oncology, Shijiazhuang People's Hospital, Shijiazhuang, China.

Background: Immune checkpoint inhibitors have achieved breakthrough efficacy in treating lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR), leading to the revision of the treatment guidelines. However, most patients with EGFR mutation are resistant to immunotherapy. It is particularly important to study the differences in tumor microenvironment (TME) between patients with and without EGFR mutation. However, relevant research has not been reported. Our previous study showed that secreted phosphoprotein 1 (SPP1) promotes macrophage M2 polarization and PD-L1 expression in LUAD, which may influence response to immunotherapy. Here, we assessed the role of SPP1 in different populations and its effects on the TME.

Methods: We compared the expression of SPP1 in LUAD tumor and normal tissues, and in samples with wild-type and mutant EGFR. We also evaluated the influence of SPP1 on survival. The LUAD data sets were downloaded from TCGA and CPTAC databases. Clinicopathologic characteristics associated with overall survival in TCGA were assessed using Cox regression analysis. GSEA revealed that several fundamental signaling pathways were enriched in the high SPP1 expression group. We applied CIBERSORT and xCell to calculate the proportion and abundance of tumor-infiltrating immune cells (TICs) in LUAD, and compared the differences in patients with high or low SPP1 expression and wild-type or mutant EGFR. In addition, we explored the correlation between SPP1 and CD276 for different groups.

Results: SPP1 expression was higher in LUAD tumor tissues and in people with EGFR mutation. High SPP1 expression was associated with poor prognosis. Univariate and multivariate cox analysis revealed that up-regulated SPP1 expression was independent indicator of poor prognosis. GSEA showed that the SPP1 high expression group was mainly enriched in immunosuppressed pathways. In the SPP1 high expression group, the infiltration of CD8+ T cells was lower and M2-type macrophages was higher. These results were also observed in patients with EGFR mutation. Furthermore, we found that the SPP1 expression was positively correlated with CD276, especially in patients with EGFR mutation.

Conclusion: SPP1 levels might be a useful marker of immunosuppression in patients with EGFR mutation, and could offer insight for therapeutics.
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http://dx.doi.org/10.3389/fonc.2021.592854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222997PMC
June 2021

The Role of B and T Lymphocyte Attenuator in Respiratory System Diseases.

Front Immunol 2021 7;12:635623. Epub 2021 Jun 7.

General Department, Hunan Institute for Tuberculosis Control, Changsha, China.

B and T lymphocyte attenuator (BTLA), an immunomodulatory molecule widely expressed on the surface of immune cells, can influence various signaling pathways and negatively regulate the activation and proliferation of immune cells by binding to its ligand herpes virus entry mediator (HVEM). BTLA plays an important role in immunoregulation and is involved in the pathogenesis of various respiratory diseases, including airway inflammation, asthma, infection, pneumonia, acute respiratory distress syndrome and lung cancer. In recent years, some studies have found that BTLA also has played a positive regulatory effect on immunity system in the occurrence and development of respiratory diseases. Since severe pulmonary infection is a risk factor for sepsis, this review also summarized the new findings on the role of BTLA in sepsis.
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http://dx.doi.org/10.3389/fimmu.2021.635623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215117PMC
June 2021

Pharmacologic targeting of Cdc42 GTPase by a small molecule Cdc42 activity-specific inhibitor prevents platelet activation and thrombosis.

Sci Rep 2021 Jun 23;11(1):13170. Epub 2021 Jun 23.

Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA.

Gene targeting of Cdc42 GTPase has been shown to inhibit platelet activation. In this study, we investigated a hypothesis that inhibition of Cdc42 activity by CASIN, a small molecule Cdc42 Activity-Specific INhibitor, may down regulate platelet activation and thrombus formation. We investigated the effects of CASIN on platelet activation in vitro and thrombosis in vivo. In human platelets, CASIN, but not its inactive analog Pirl7, blocked collagen induced activation of Cdc42 and inhibited phosphorylation of its downstream effector, PAK1/2. Moreover, addition of CASIN to washed human platelets inhibited platelet spreading on immobilized fibrinogen. Treatment of human platelets with CASIN inhibited collagen or thrombin induced: (a) ATP secretion and platelet aggregation; and (b) phosphorylation of Akt, ERK and p38-MAPK. Pre-incubation of platelets with Pirl7, an inactive analog of CASIN, failed to inhibit collagen induced aggregation. Washing of human platelets after incubation with CASIN eliminated its inhibitory effect on collagen induced aggregation. Intraperitoneal administration of CASIN to wild type mice inhibited ex vivo aggregation induced by collagen but did not affect the murine tail bleeding times. CASIN administration, prior to laser-induced injury in murine cremaster muscle arterioles, resulted in formation of smaller and unstable thrombi compared to control mice without CASIN treatment. These data suggest that pharmacologic targeting of Cdc42 by specific and reversible inhibitors may lead to the discovery of novel antithrombotic agents.
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http://dx.doi.org/10.1038/s41598-021-92654-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222210PMC
June 2021

Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens.

Eur J Clin Pharmacol 2021 Jun 23. Epub 2021 Jun 23.

EA7323, Evaluation des Thérapeutiques et Pharmacologie Périnatale et Pédiatrique, Université de Paris, 89 rue d'Assas, 75014, Paris, France.

Purpose: This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme.

Methods: Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC/MIC ratio ≥ 125.

Results: A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance.

Conclusion: The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.
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http://dx.doi.org/10.1007/s00228-021-03174-1DOI Listing
June 2021

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N-Methyladenosine Modification.

Front Cell Dev Biol 2021 4;9:684398. Epub 2021 Jun 4.

Key Laboratory for Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.

Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, and any damage to SSCs may result in spermatogenic disorder and male infertility. Chromium (Cr) (VI) is a proven toxin, mutagen, and carcinogen, perpetually detrimental to environmental organisms due to its intricate and enduring detoxification process . Despite this, the deleterious effects of Cr (VI) on SSCs and the underlying mechanisms remain poorly understood. In this study, we identified that Cr (VI) impaired male reproductive system in mouse testes and induced mitochondrial dynamic imbalance and mitophagy in SSCs/progenitors. Cr (VI) also downregulated the RNA N-methyladenosine (mA) modification levels in mitochondrial dynamic balance and mitophagy genes in SSCs/progenitors. Inspiringly, the toxic effects of Cr (VI) could be relieved by melatonin pretreatment. Melatonin alleviated Cr (VI)-induced damage to male reproductive system and autophagy in mouse testes. Melatonin also attenuated Cr (VI)-induced cell viability loss and reactive oxygen species (ROS) generation, as well as mitochondrial dynamic disorders and mitophagy in SSCs/progenitors. The protective roles of melatonin against Cr (VI)-induced mitophagy were exerted by restoration of METTL3-mediated RNA mA modification and activation of mitochondrial fusion proteins MFN2 and OPA1, as well as inhibition of the mitophagy BNIP3/NIX receptor pathway. Thus, our study provides novel insights into the molecular mechanisms for RNA mA modification underlying the gene regulatory network responsible for mitochondrial dynamic balance, and also lays new experimental groundwork for treatment of Cr (VI)-induced damage to male fertility.
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http://dx.doi.org/10.3389/fcell.2021.684398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212693PMC
June 2021

Natural Genetic Diversity in Tomato Flavor Genes.

Front Plant Sci 2021 4;12:642828. Epub 2021 Jun 4.

Center for Applied Genetic Technologies, University of Georgia, Athens, GA, United States.

Fruit flavor is defined as the perception of the food by the olfactory and gustatory systems, and is one of the main determinants of fruit quality. Tomato flavor is largely determined by the balance of sugars, acids and volatile compounds. Several genes controlling the levels of these metabolites in tomato fruit have been cloned, including , , , , and . The aim of this study was to identify any association of these genes with trait variation and to describe the genetic diversity at these loci in the red-fruited tomato clade comprised of the wild ancestor , the semi-domesticated species and early domesticated . High genetic diversity was observed at these five loci, including novel haplotypes that could be incorporated into breeding programs to improve fruit quality of modern tomatoes. Using newly available high-quality genome assemblies, we assayed each gene for potential functional causative polymorphisms and resolved a duplication at the locus found in several wild and semi-domesticated accessions which caused lower accumulation of lipid derived volatiles. In addition, we explored gene expression of the five genes in nine phylogenetically diverse tomato accessions. In general, the expression patterns of these genes increased during fruit ripening but diverged between accessions without clear relationship between expression and metabolite levels.
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http://dx.doi.org/10.3389/fpls.2021.642828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212054PMC
June 2021

Imidazolidinyl urea activates mast cells via MRGPRX2 to induce non-histaminergic allergy.

Toxicol Res (Camb) 2021 May 29;10(3):467-475. Epub 2021 Apr 29.

Department of Pharmaceutical analysis, School of Pharmacy, Xi'an Jiaotong University, 76, Yanta west road, Xi'an, China.

Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and Kit/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation . Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators . WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.
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http://dx.doi.org/10.1093/toxres/tfab035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201555PMC
May 2021

Clinical characteristics of interstitial lung diseases positive to different anti-synthetase antibodies.

Medicine (Baltimore) 2021 May;100(19):e25816

Department of Rheumatology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China.

Abstract: To analyze the clinical, serological, and imaging characteristics of patients with interstitial lung diseases (ILD) positive to different anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies.The clinical data, serological indexes, pulmonary high-resolution computed tomography (HRCT) imaging features and pulmonary functions, and bronchoalveolar lavage fluid of 84 ILD patients with anti-ARS antibody positive in Beijing Chao-yang Hospital, Capital Medical University were reviewed.(1) Anti-ARS antibodies included anti-Jo-1 (42.86%), anti-PL-7 (26.19%), anti-PL-12 (10.71%), anti-EJ (14.29%), and anti-OJ (5.95%). (2) Nonspecific interstitial pneumonia was the main type of patients with ILD positive to antibodies of anti-Jo-1, anti-PL-7, and anti-EJ, organizing pneumonia was the main type of patients with ILD positive to anti-PL-12 antibody and usual interstitial pneumonia was the main type of patients with ILD positive to anti-OJ antibody. (3) Only 14.29% of the patients had typical "triad syndrome" (interstitial pneumonia, myositis, and non-erosive arthritis). Myositis mainly occurred in patients with ILD positive to antibodies of anti-PL-7, anti-Jo-1, and anti-EJ. The incidence of arthritis in ILD patients with anti-Jo-1 was higher than that in ILD patients with anti-PL-12 and anti-EJ (P < .05). The incidence of mechanic's hand in ILD patients with anti-Jo-1 was higher than that in ILD patients with anti-PL-12 (P < .05).ILD positive to anti-Jo-1 antibody is associated with multiple organ involvement, mainly manifested as myositis, mechanic's hand, and arthritis. As other clinical manifestations of some ILD patients are relatively hidden, ILD patients should pay attention to the screening of the anti-ARS antibodies and guard against anti-synthetase syndrome.
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http://dx.doi.org/10.1097/MD.0000000000025816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133147PMC
May 2021

Ubiquitin-related molecular classification and risk stratification of hepatocellular carcinoma.

Mol Ther Oncolytics 2021 Jun 17;21:207-219. Epub 2021 Apr 17.

Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

The roles of ubiquitin-related genes in hepatocellular carcinoma (HCC) have not been thoroughly investigated. This study aimed to systematically examine ubiquitin-related genes and identify subtypes and stratify prognosis of HCC by using ubiquitin-related signatures. Survival, biological processes, tumor microenvironment (TME), and genomic alterations of the HCC subtypes were investigated. Patients with HCC were classified into two subtypes (clusters 1 and 2) with distinct survival outcomes, pathways, and genomic alterations. Cluster 2 had better prognosis than did cluster 1. Hepatitis B, hepatitis C, Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, and natural killer cell-mediated cytotoxicity were enriched in cluster 1. Moreover, cluster 2 had a higher immune score and immune cell infiltrations, whereas cluster 1 had a lower immune score and immune infiltrations. Additionally, mutations, amplifications, and deletions among the phosphatidylinositol 3-kinase (PI3K)-AKT, p53, and receptor tyrosine kinase (RTK)-RAS pathways more frequently occurred in cluster 1, while those among the Hippo, MYC, and Notch signaling pathways were found in cluster 2. Finally, a prognostic signature, consisting of eight ubiquitin-related genes, was established and validated. In brief, our study established a new classification and developed a prognostic signature for HCC.
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http://dx.doi.org/10.1016/j.omto.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138213PMC
June 2021

Evaluation of multi-component interventions for prevention of nosocomial pneumonia in older adults: a randomized, controlled trial.

Eur Geriatr Med 2021 Jun 3. Epub 2021 Jun 3.

Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore, Singapore.

Aims: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards.

Methods: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year.

Results: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001).

Conclusions: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections.

Clinical Trial Registration: ClinicalTrial.gov, NCT04347395.
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http://dx.doi.org/10.1007/s41999-021-00506-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173511PMC
June 2021

Downregulation of Renal MRPs Transporters in Acute Lymphoblastic Leukemia Mediated by the IL-6/STAT3/PXR Signaling Pathway.

J Inflamm Res 2021 25;14:2239-2252. Epub 2021 May 25.

Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

Purpose: Considering prior investigations on reductions of renal multidrug resistance-associated protein (MRP) 2 and 4 transporters in mice with acute lymphoblastic leukemia (ALL), we sought to characterize the underlying mechanisms responsible for IL-6/STAT3/PXR-mediated changes in the expression of MRP2 and MRP4 in ALL.

Subjects And Methods: ALL xenograft models were established and intravenously injected with methotrexate (MTX) of MRPs substrate in NOD/SCID mice. Protein expression of MRPs and associated mechanisms were detected by Western blotting and immunocytochemistry. Plasma concentrations of MTX were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Results: Plasma IL-6 levels in patients with newly diagnosed ALL were increased compared to children with pneumonia. Similarly, plasma IL-6 levels in ALL, ALL-tocilizumab (TCZ, an IL-6 receptor inhibitor) and ALL-S3I-201 (a selective inhibitor of STAT3) mice were increased compared to the control group. The MRP2, MRP4, and PXR expression in HK-2 cells treated with IL-6 were decreased, whereas the p-STAT3 expression was significantly increased compared to the control group results. These results are consistent with clearance of MRPs-mediated MTX in the ALL group. These effects were attenuated by blocking IL-6/STAT3/PXR signaling pathway.

Conclusion: Inflammation-mediated changes in pharmacokinetics are thought to be executed through pathways IL-6-activated pathways, which can facilitate a better understanding of the potential for the use of IL-6 to predict the severity of adverse outcomes and the major implications on potential ALL treatments.
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http://dx.doi.org/10.2147/JIR.S310687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164703PMC
May 2021

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis.

Front Pharmacol 2021 13;12:609901. Epub 2021 May 13.

Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

The prevalence rate of hypertension and breast cancer increases with advancing age. Renin-angiotensin system inhibitors (RASIs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics are widely used to treat patients with hypertension. Although, the association between the use of antihypertensive medication and breast cancer has been highly debated, recent evidence supporting this association remains controversial. To evaluate the association between the use of antihypertensive medication and the risk of breast cancer and its prognosis. This study was conducted using data from the PubMed, Embase, and Cochrane Library databases retrieved for the period from January 2000 to April 2021. Articles and their references were checked and summary effects were calculated using random- and fixed-effects models. Heterogeneity test and sensitivity analysis were also performed. This meta-analysis included 57 articles, which were all related to breast cancer risk or prognosis. Assessment of breast cancer risk using the pooled data showed that the use of BBs or CCBs or diuretics was associated with increased cancer risk [BB: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.09-1.32; CCBs: RR = 1.06, 95% CI 1.03-1.08; diuretics: RR = 1.06, 95% CI 1.01-1.11]. Long-term use of diuretic increased the risk of breast cancer (RR = 1.10, 95% CI 1.01-1.20), whereas long-term RASIs treatment reduced the risk (RR = 0.78, 95% CI 0.68-0.91). In addition, we found that diuretic users may be related to elevated breast cancer-specific mortality [hazard ratio (HR) = 1.18, 95% CI 1.04-1.33], whereas using other antihypertensive medications was not associated with this prognosis in patients with breast cancer. Using CCBs, BBs, and diuretics increased the risk of breast cancer. In addition, diuretics may elevate the risk of breast cancer-specific mortality. The long-term use of RASIs was associated with a significantly lower breast cancer risk, compared with non-users. Thus, this analysis provides evidence to support the benefits of the routine use of RASIs in patients with hypertension, which has important public health implications.
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http://dx.doi.org/10.3389/fphar.2021.609901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155668PMC
May 2021

Factors associated with alveolar bone depth mesial to the mandibular third molars after orthodontic protraction.

Am J Orthod Dentofacial Orthop 2021 May 26. Epub 2021 May 26.

Department of Orthodontics, Stomatology Hospital, Guangxi Medical University, Nanning, Guangxi, China. Electronic address:

Introduction: The objective of this research was to study the factors associated with the alveolar bone depth mesial to the mandibular third molars (M8) after the mandibular second (M7) and third molars were protracted into the space of the mandibular first molars (M6), which were newly extracted for orthodontic treatment or extracted more than 1 year before treatment.

Methods: This retrospective study included 57 adult patients (mean age 23.40 ± 4.40 years) in whom M6 were newly extracted for orthodontic treatment or extracted more than 1 year before treatment. The alveolar bone depth mesial to M8 was measured on posttreatment panoramic radiographs. The vertical, horizontal, and angular changes of M8 were measured on both pre- and posttreatment panoramic radiographs. Linear correlation and regression analyses were conducted to explore the factors associated with the alveolar bone depth mesial to M8.

Results: The alveolar bone conditions of M6 (R= -0.391, P <0.001) and the vertical movement directions of M8 (R= -0.433, P <0.001) were significant factors associated with the alveolar bone depth mesial to M8 after orthodontic protraction.

Conclusions: Without considering the pretreatment periodontal status of M8, patients with M6 extracted exceeding 1 year before treatment and with M8 extruded after orthodontic protraction may exhibit deeper alveolar bone depth mesial to M8.
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http://dx.doi.org/10.1016/j.ajodo.2020.08.018DOI Listing
May 2021

PSA controls hepatic lipid metabolism by regulating the NRF2 signaling pathway.

J Mol Cell Biol 2021 May 28. Epub 2021 May 28.

Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, The Second Affiliated Hospital of Army Medical University, Chongqing, China.

The activity of proteinase is reported to correlate with the development and progression of nonalcoholic fatty liver disease (NAFLD). Puromycin-sensitive aminopeptidase (PSA/NPEPPS) is an integral nontransmembrane enzyme that functions to catalyze the cleavage of amino acids near the N-terminus of polypeptides. A previous study suggested that this enzyme acts as a regulator of neuropeptide activity; however, the metabolic function of this enzyme in the liver has not been explored. Here, we identified the novel role of PSA in hepatic lipid metabolism. Specifically, PSA expression was lower in fatty livers from NAFLD patients and mice (HFD, ob/ob, and db/db). PSA knockdown in cultured hepatocytes exacerbated diet-induced triglyceride accumulation through enhanced lipogenesis and attenuated fatty acid β-oxidation. Moreover, PSA mediated activation of the master regulator of antioxidant response, nuclear factor erythroid 2-related factor 2 (NRF2), by stabilizing NRF2 protein expression, which further induced downstream antioxidant enzymes to protect the liver from oxidative stress and lipid overload. Accordingly, liver-specific PSA overexpression attenuated hepatic lipid accumulation and steatosis in ob/ob mice. Furthermore, in human liver tissue samples, decreased PSA expression correlated with the progression of NAFLD. Overall, our findings suggest that PSA is a pivotal regulator of hepatic lipid metabolism and its antioxidant function occurs by suppressing NRF2 ubiquitination. Moreover, PSA may be a potential biomarker and therapeutic target for treating NAFLD.
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http://dx.doi.org/10.1093/jmcb/mjab033DOI Listing
May 2021

Methyltransferase-Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N -methyladenosine Modification.

Adv Sci (Weinh) 2021 May 27:e2100606. Epub 2021 May 27.

Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong, 250012, P. R. China.

Mitochondrial antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for antiviral immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well-defined. Here, it is reported that the MAVS mRNA undergoes N -methyladenosine (m A) modification through methyltransferase-like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon-β production in response to RNA viruses. Compared to wild-type mice, heterozygotes Mettl14 mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post-transcriptionally through m A modification.
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http://dx.doi.org/10.1002/advs.202100606DOI Listing
May 2021
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