Publications by authors named "Mi Zhou"

538 Publications

Recent advances in the application of water-stable metal-organic frameworks: Adsorption and photocatalytic reduction of heavy metal in water.

Chemosphere 2021 Jul 6;285:131432. Epub 2021 Jul 6.

College of Environmental Science and Engineering, Hunan University and Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha, 410082, PR China.

Heavy metals pollution in water is a global environmental issue, which has threatened the human health and environment. Thus, it is important to remove them under practical water environment. In recent years, metal-organic frameworks (MOFs) with water-stable properties have attracted wide interest with regard to the capture of hazardous heavy metal ions in water. In this review, the synthesis strategy and postsynthesis modification preparation methods are first summarized for water-stable MOFs (WMOFs), and then the recent advances on the adsorption and photocatalytic reduction of heavy metal ions in water by WMOFs are reviewed. In contrast to the conventional adsorption materials, WMOFs not only have excellent adsorption properties, but also lead to photocatalytic reduction of heavy metal ions. WMOFs have coupling and synergistic effects on the adsorption and photocatalysis of heavy metal ions in water, which make it more effective in treating single pollutants or different pollutants. In addition, by introducing appropriate functional groups into MOFs or synthesizing MOF-based composites, the stability and ability to remove heavy metal ions of MOFs can be effectively enhanced. Although WMOFs and WMOF-based composites have made great progress in removing heavy metal ions from water, they still face many problems and challenges, and their application potential needs to be further improved in future research. Finally, this review aims at promoting the development and practical application of heavy metal ions removal in water by WMOFs.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131432DOI Listing
July 2021

Synthesis of a Thermal-Responsive Dual-Modal Supramolecular Probe for Magnetic Resonance Imaging and Fluorescence Imaging.

Macromol Rapid Commun 2021 Jul 17:e2100248. Epub 2021 Jul 17.

College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China.

Dual-modal imaging can integrate the advantages of different imaging technologies, which could improve the accuracy and efficiency of clinical diagnosis. Herein, a novel amphiphilic thermal-responsive copolymer obtained from three types of monomers, N-isopropyl acrylamide, 2-(acetoacetoxy) ethyl methacrylate, and propargyl methacrylate, by RAFT copolymerization, is reported. It can be grafted with β-cyclodextrin and aggregation-induced emission (AIE) luminogens tetraphenylethylene by click chemistry and Biginelli reaction. The multifunctional supramolecular polymer (P4) can be constructed by host-guest inclusion between the copolymer and the Gd-based contrast agent (CA) modified by adamantane [Ad-(DOTA-Gd)]. And it can form vesicles with a bilayer structure in aqueous which will enhance the AIE and magnetic resonance imaging effects. As fluorescent thermometer, P4 can enter HeLa cells for intracellular fluorescence imaging (FI) and is sensitive to temperature with detection limit value of 1.5 °C. As magnetic resonance CA, P4 exhibits higher relaxation compared to Magnevist, which can prolong the circulation time in vivo. In addition, Gd in the polymer can be quickly released from the body by disassembly that reduced the biological toxicity. This work introduces new synthetic ideas for dual-modal probe, which has great potential for clinical diagnostic applications in bioimaging.
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http://dx.doi.org/10.1002/marc.202100248DOI Listing
July 2021

Maternal GALNT2 Variations Affect Blood Pressure, Atherogenic Index, and Fetal Growth, Depending on BMI in Gestational Diabetes Mellitus.

Front Endocrinol (Lausanne) 2021 29;12:690229. Epub 2021 Jun 29.

Laboratory of Genetic Disease and Perinatal Medicine and Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: GALNT2 is a GalNAc transferase that regulates serum lipid fractions, insulin signaling, and lipogenesis. Genetic variants are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of GDM and related traits.

Methods: Two SNPs were genotyped, and clinical and metabolic parameters were determined in 461 GDM patients and 626 control subjects. Genetic associations with related traits were also analyzed.

Results: The genotype distributions of the two SNPs in GDM patients were similar to those in normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables in subjects in a BMI-dependent manner. The rs4846914 and rs2144300 SNPs of GALNT2 were significantly associated with systolic blood pressure and/or diastolic blood pressure levels in nonobese GDM patients and atherogenic index (AI) in overweight/obese GDM patients. The rs4846914 SNP was also associated with fetal growth in overweight/obese GDM patients, and apo A1 and pregnancy weight gain in overweight/obese control women (all P<0.05).

Conclusions: The two polymorphisms in the GALNT2 gene are associated with variations in blood pressure, atherogenic index, and fetal growth in GDM, depending on BMI, but not with GDM. Our findings highlight a link between related phenotypes in GDM mothers and their fetuses and the genetic components.
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http://dx.doi.org/10.3389/fendo.2021.690229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276310PMC
June 2021

Copper-Catalyzed Chloro-Arylsulfonylation of Styrene Derivatives via the Insertion of Sulfur Dioxide.

Org Lett 2021 Jul 14. Epub 2021 Jul 14.

Department of Dermatology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital and West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China.

A copper-catalyzed four-component chloro-arylsulfonylation of styrene derivatives with aryldiazonium tetrafluoroborates, lithium chloride, and generated sulfur dioxide (from SOgen) is presented. This sulfonylation features good functional group compatibility, mild reaction conditions, excellent regioselectivity, and good yields. The robustness and potential of this method have also been successfully demonstrated by a gram-scale reaction. Based on experimental study, a radical-involved mechanism is proposed for the transformation.
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http://dx.doi.org/10.1021/acs.orglett.1c02001DOI Listing
July 2021

Real-World Outcomes of Revascularization Strategies in Patients With Left Ventricular Dysfunction and Three-Vessel Coronary Disease Stratified by Mitral Regurgitation.

Front Cardiovasc Med 2021 24;8:675722. Epub 2021 Jun 24.

Department of Vascular and Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Limited information exists regarding optimal revascularization options for patients with triple-vessel coronary artery disease (TVD), heart failure (HF), and different degrees of mitral regurgitation (MR). Thus, we aimed to compare the effect of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery in the indicated patients. In the real-world prospective study, 1190 patients with multi-vessel disease and decreased left ventricular systolic function but without severe MR, who underwent PCI or CABG, were enrolled and followed-up for 4.7 ± 1.8 years. The primary endpoint was a composite of cardiovascular death and HF hospitalization. Secondary endpoints were the individual components of the primary outcome. Risk of the primary endpoint was higher in the PCI than in the CABG group (HR = 1.38, 95%CI: 1.14-1.67, and < 0.01), particularly in patients with moderate MR (HR = 1.85, 95%CI: 1.35-2.55, and < 0.01). In patients with no-mild MR, the risk of the primary endpoint did not differ significantly between PCI and CABG ( = 0.09). Treatment with PCI was associated with an increased risk for cardiovascular death and HF hospitalization in the moderate MR cohort, while PCI was comparable to CABG in the no-mild MR cohort. In this real-world study, for patients with HF and TVD, CABG was related to lower adverse outcome rates compared to PCI. Assessment of MR can aid in selecting optimal revascularization therapies and in risk stratification.
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http://dx.doi.org/10.3389/fcvm.2021.675722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265779PMC
June 2021

Production of bioactive recombinant human fibroblast growth factor 12 using a new transient expression vector in E. coli and its neuroprotective effects.

Appl Microbiol Biotechnol 2021 Jul 10;105(13):5419-5431. Epub 2021 Jul 10.

School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

In recent years, an increasing number of studies have shown that fibroblast growth factor 12 (FGF12) plays important roles in regulating neural development and function. Importantly, changes of FGF12 expression are thought to be related to the pathophysiology of many neurological diseases. However, little research has been performed to explore the protective effect of FGF12 on nerve damage. This study aims to explore its neuroprotective effects using our recombinant humanized FGF12 (rhFGF12). The hFGF12 gene was cloned and ligated into an expression vector to construct a recombinant plasmid pET-3a-hFGF12. Single colonies were screened to obtain high expression engineering strains, and fermentation and purification protocols for rhFGF12 were designed and optimized. The biological activities and related mechanisms of rhFGF12 were investigated by MTT assay using NIH3T3 and PC12 cell lines. The in vitro neurotoxicity model of HO-induced oxidative injury in PC12 cells was established to explore the protective effects of rhFGF12. The results indicate that the beneficial effects of rhFGF12 were most likely achieved by promoting cell proliferation and reducing apoptosis. Moreover, a transgenic zebrafish (islet) with strong GFP fluorescence in the motor neurons of the hindbrain was used to establish a central injury model caused by mycophenolate mofetil (MMF). The results suggested that rhFGF12 could ameliorate central injury induced by MMF in zebrafish. In conclusion, we have established an efficient method to express and purify active rhFGF12 using an Escherichia coli expression system. Besides, rhFGF12 plays a protective effect of on nerve damage, and it provides a promising therapeutic approach for nerve injury. KEY POINTS: • Effective expression and purification of bioactive rhFGF12 protein in E. coli. • ERK/MAPK pathway is involved in rhFGF12-stimulated proliferation on PC12 cells. • The rhFGF12 has the neuroprotective effects by inhibiting apoptosis.
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http://dx.doi.org/10.1007/s00253-021-11430-8DOI Listing
July 2021

Homology and Immune Checkpoint Dual-Targeted Sonocatalytic Nanoagents for Enhancing Sonodynamic Tumor Therapy.

ACS Appl Mater Interfaces 2021 Jul 7;13(28):32810-32822. Epub 2021 Jul 7.

Department of Ultrasound, National Clinical Research Center for Geriatrics, West China Hospital, College of Polymer Science and Engineering, Sichuan University, Chengdu 610041, China.

Sonocatalytic nanoagents (SCNs), a kind of sonosensitizers, could catalyze oxygen to generate abundant reactive oxygen species (ROS) under stimulations of noninvasive and deep-penetrating ultrasound (US), which is commonly used for sonodynamic therapy (SDT) of tumors such as malignant melanoma. However, poor bioavailability of most SCNs and fast quenching of extracellular-generating ROS from SDT limit further applications of SCNs in the SDT of tumors. Herein, we synthesized a new kind of TiO-based SCN functionalized with the malignant melanoma cell membrane (B16F10M) and programmed cell death-ligand 1 antibody (aPD-L1) for homology and immune checkpoint dual-targeted and enhanced sonodynamic tumor therapy. Under US irradiation, the synthesized SCN can catalytically generate a large amount of O. In vitro experiments validate that functionalized SCNs exhibit precise targeting effects, high tumor cell uptake, and intracellular sonocatalytic killing of the B16F10 cells by a large amount of localized ROS. Utilizing the melanoma animal model, the functionalized SCN displays visible long-term retention in the tumor area, which assists the homology and immune checkpoint synergistically dual-targeted and enhanced in vivo SDT of the tumor. We suggest that this highly bioavailable and dual-functionalized SCN may provide a promising strategy and nanoplatform for enhancing sonodynamic tumor therapies.
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http://dx.doi.org/10.1021/acsami.1c08105DOI Listing
July 2021

Structure-Based Optimization of 3-Phenyl--(2-(3-phenylureido)ethyl)thiophene-2-sulfonamide Derivatives as Selective Mcl-1 Inhibitors.

J Med Chem 2021 Jul 6;64(14):10260-10285. Epub 2021 Jul 6.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, People's Republic of China.

Selective Mcl-1 inhibitors may overcome the drug resistance caused by current anti-apoptotic Bcl-2 protein inhibitors in tumors with Mcl-1 overexpression. Based on previously discovered compounds with a 3-phenylthiophene-2-sulfonamide core moiety, in this work, we have obtained new compounds with improved binding affinity and/or selectivity under the guidance of structure-based design. The most potent compounds achieved sub-micromolar binding affinities to Mcl-1 ( ∼ 0.4 μM) and good cytotoxicity (IC < 10 μM) on several tumor cells. N-heteronuclear single-quantum coherence NMR spectra suggested that these compounds bound to the BH3-binding groove on Mcl-1. Several cellular assays revealed that as well as its precursor effectively induced caspase-dependent apoptosis, and their target engagement at Mcl-1 was confirmed by co-immunoprecipitation experiments. Treatment with at 50 mg/kg every 2 days on an RS4;11 xenograft mouse model for 22 days led to 75% reduction in tumor volume without body weight loss.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00690DOI Listing
July 2021

Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms.

Front Immunol 2021 11;12:670398. Epub 2021 Jun 11.

Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Anti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed.

Objectives: The aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents.

Methods: The Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events.

Results: Forty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events.

Conclusions: The application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles.
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http://dx.doi.org/10.3389/fimmu.2021.670398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226270PMC
June 2021

Incremental Values of T1 Mapping in the Prediction of Sudden Cardiac Death Risk in Hypertrophic Cardiomyopathy: A Comparison With Two Guidelines.

Front Cardiovasc Med 2021 8;8:661673. Epub 2021 Jun 8.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

MRI native T1 mapping and extracellular volume fraction (ECV) are quantitative values that could reflect various myocardial tissue characterization. The role of these parameters in predicting the risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is still poorly understood. This study aims to investigate the ability of native T1 mapping and ECV values to predict major adverse cardiovascular events (MACE) in HCM, and its incremental values over the 2014 European Society of Cardiology (ESC) and enhanced American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Between July 2016 and October 2020, HCM patients and healthy individuals with sex and age matched who underwent cardiac MRI were prospectively enrolled. The native T1 and ECV parameters were measured. The SCD risk was evaluated by the 2014 ESC guidelines and enhanced ACC/AHA guidelines. MACE included cardiac death, transplantation, heart failure admission, and implantable cardioverter-defibrillator implantation. A total of 203 HCM patients (54.2 ± 14.9 years) and 101 healthy individuals (53.2 ± 14.7 years) were evaluated. During a median follow-up of 15 months, 25 patients (12.3%) had MACE. In multivariate Cox regression analysis, global native T1 mapping (hazard ratio (HR): 1.446; 95% confidence interval (CI): 1.195-1.749; < 0.001) and non-sustained ventricular tachycardia (NSVT) (HR: 4.949; 95% CI, 2.033-12.047; < 0.001) were independently associated with MACE. Ten of 86 patients (11.6%) with low SCD risk assessed by the two guidelines had MACE. In this subgroup of patients, multivariate Cox regression analysis showed that global native T1 mapping was independently associated with MACE (HR: 1.532; 95% CI: 1.221-1.922; < 0.001). In 85 patients with conflicting results assessed by the two guidelines, end-stage systolic dysfunction was independently associated with MACE (HR: 7.942, 95% CI: 1.322-47.707, = 0.023). In 32 patients with high SCD risk assessed by the two guidelines, NSVT was independently associated with MACE (HR: 9.779, 95% CI: 1.953-48.964, = 0.006). The global native T1 mapping could provide incremental values and serve as potential supplements to the current guidelines in the prediction of MACE.
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http://dx.doi.org/10.3389/fcvm.2021.661673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217449PMC
June 2021

Pressure-induced structural transitions between successional superconducting phases in GeTe.

J Phys Condens Matter 2021 Jul 6;33(35). Epub 2021 Jul 6.

International Center of Computational Method & Software, College of Physics, Jilin University, Changchun 130012, People's Republic of China.

Being a best-known prototype of phase-change materials, GeTe was reported to possess many high-pressure phases, whose structural evolution and superconductivity remain under debate for decades. Herein, we systematically investigated the pressure dependence of electrical transport and the structural evolution of the GeTe viaangle-dispersive synchrotron x-ray diffraction and resistance measurements up to 55 GPa. At room temperature, the structural phase transitions from the initial rhombohedral phase to theFm3̄mphase, and then to an orthorhombicphase, were observed at pressures of about 4 and 13.4 GPa, respectively. Furthermore, the metallization occurred at around 11 GPa, where the superconductivity could also be observed. With increasing pressure, the superconducting transition temperature increases monotonically from 5.7 to 6.4 K and then is independent of pressure above 23 GPa in the purephase. These results provide insights into the pressure-dependent evolution of the structure and superconductivity in GeTe and have implications for the understanding of other IV-VI semiconductors at high pressure.
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http://dx.doi.org/10.1088/1361-648X/ac0c3aDOI Listing
July 2021

Impact of Shock-Induced Cavitation Bubble Collapse on the Damage of Cell Membranes with Different Lipid Peroxidation Levels.

J Phys Chem B 2021 Jun 16. Epub 2021 Jun 16.

Institute of Chemical Materials, China Academy of Engineering and Physics, Mianyang 621900, China.

Although the interaction mechanism between shock waves and cells is critical for advancing the medical applications of shock waves, we still have little understanding about it. This work aims to study the response of diseased cells subjected to lipid peroxidation to the nanojet from shock wave-induced bubble collapse by using the coarse-grained molecular dynamics simulation. Factors considered in the simulations include the shock velocity (), movement time of piston (τ), bubble size (), and peroxidation level of membranes. Here, we mainly focus on the role of peroxidation levels, that is, the degree (%) and the distribution of oxidized lipids in membranes. The results indicate that the shock damage threshold ( at which the pore in membranes is formed) of peroxidation membranes is less than that of normal membranes and decreases with the peroxidation degree. Importantly, the distribution of oxidized lipids has more effect on the damage threshold than the peroxidation degree. The threshold of membrane with 33% localized oxidized lipids is lower than that of membrane with 50% average oxidized lipids. The results can be explained by the stretching modulus (κ) and bending modulus (κ) of cell membranes. For example, the κ value (4.3 × 10 J) of 100% peroxidation membrane is about half of that (8.4 × 10 J) of a membrane without peroxidation. A lower modulus means high deformation under the same impact. Further analysis shows that peroxidation introduces a polar hydrophobic group to the tail of phospholipids that increases the hydrophilicity of tails and warps the tail of phospholipids toward the membrane-water interface, resulting in looser accumulation. This can be confirmed by the increased average phospholipid area with peroxidation levels. Indeed, most of the pores formed during the shock can heal. However, the permeation of water molecules across the healing membrane still increased. All these membrane-level information obtained from this study will be useful for improving the biomedical applications of shock waves.
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http://dx.doi.org/10.1021/acs.jpcb.1c02483DOI Listing
June 2021

Metal- and Base-Free C(sp)-H Arylsulfonylation of Enamides for Synthesis of ()-β-Amidovinyl Sulfones via the Insertion of Sulfur Dioxide.

Org Lett 2021 Jul 11;23(13):4991-4996. Epub 2021 Jun 11.

Department of Dermatology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, P.R. China.

A metal- and base-free C(sp)-H direct arylsulfonylation of secondary and tertiary enamides with aryldiazonium salts and ex situ generated SO (from SOgen) is presented. This method runs smoothly to produce β-amidovinyl sulfones with excellent stereoselectivities in moderate to excellent yields. Moreover, this strategy features good functional group tolerance and environmentally benign reaction conditions. Mechanistic experiments indicate that this sulfonylation may proceed in a radical pathway.
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http://dx.doi.org/10.1021/acs.orglett.1c01419DOI Listing
July 2021

Genome editor-directed in vivo library diversification.

Cell Chem Biol 2021 May 26. Epub 2021 May 26.

Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA. Electronic address:

The generation of a library of variant genes is a prerequisite of directed evolution, a powerful tool for biomolecular engineering. As the number of all possible sequences often far exceeds the diversity of a practical library, methods that allow efficient library diversification in living cells are essential for in vivo directed evolution technologies to effectively sample the sequence space and allow hits to emerge. While traditional whole-genome mutagenesis often results in toxicity and the emergence of "cheater" mutations, recent developments that exploit the targeting and editing abilities of genome editors to facilitate in vivo library diversification have allowed for precise mutagenesis focused on specific genes of interest, higher mutational density, and reduced the occurrence of cheater mutations. This minireview summarizes recent advances in genome editor-directed in vivo library diversification and provides an outlook on their future applications in chemical biology.
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http://dx.doi.org/10.1016/j.chembiol.2021.05.008DOI Listing
May 2021

Cytokine Levels at Birth in Children Who Developed Acute Lymphoblastic Leukemia.

Cancer Epidemiol Biomarkers Prev 2021 Jun 2. Epub 2021 Jun 2.

School of Public Health, University of California, Berkeley, Berkeley, California.

Background: Prenatal immune development may play an important role in the etiology of childhood acute lymphoblastic leukemia (ALL).

Methods: Seven cytokines, IL1β, IL4, IL6, IL8, GM-CSF, TNFα, and VEGF, were analyzed in blood spots collected at birth from 1,020 ALL cases and 1,003 controls participating in the California Childhood Leukemia Study. ORs and 95% confidence intervals (95% CI) associated with an interquartile range increment in cytokine levels were calculated using logistic regression, adjusting for sociodemographic and birth characteristics.

Results: We found that patients with ALL were born with higher levels of a group of correlated cytokines than controls [IL1β: OR of 1.18 (95% confidence interval [CI], 1.03-1.35); IL8: 1.19 (1.03-1.38); TNFα: 1.15 (1.01-1.30); VEGF: 1.16 (1.01-1.33)], especially among children of Latina mothers (ORs from 1.31 to 1.40) and for ALL with high hyperdiploidy (ORs as high as 1.27). We found that neonatal cytokine levels were correlated with neonatal levels of endogenous metabolites which had been previously associated with ALL risk; however, there was no evidence that the cytokines were mediating the relationship between these metabolites and ALL risk.

Conclusions: We posit that children born with altered cytokine levels are set on a trajectory towards an increased risk for subsequent aberrant immune reactions that can initiate ALL.

Impact: This is the first study to evaluate the interplay between levels of immunomodulatory cytokines at birth, prenatal exposures, and the risk of childhood ALL.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1704DOI Listing
June 2021

Heterogeneous postassembly modification of zirconium metal-organic cages in supramolecular frameworks.

Chem Commun (Camb) 2021 Jun;57(51):6276-6279

Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.

We report a heterogeneous postassembly modification (PAM) to synthesize a zirconium metal-organic cage decorated with acrylate functional groups, ZrT-1-AA, which cannot be synthesized by direct coordination-driven self-assembly owing to the reactivity and instability of the ligand. The PAM process is carried out in a single-crystal-to-single-crystal transformation under mild reaction conditions with high efficiency, which is confirmed by ESI-TOF-MS and 1H NMR. In addition, ZrT-1-AA is crosslinked into shaped materials to demonstrate its potential applications. The proposed PAM strategy sheds light on the development of Zr-MOCs decorated with reactive functional groups, whose introduction is challenging or impossible via direct self-assembly.
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http://dx.doi.org/10.1039/d1cc01606gDOI Listing
June 2021

A radiomic approach to predict myocardial fibrosis on coronary CT angiography in hypertrophic cardiomyopathy.

Int J Cardiol 2021 08 5;337:113-118. Epub 2021 May 5.

Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No. 197 Ruijin 2nd Rd, Shanghai 200025, China. Electronic address:

Background: Late gadolinium enhancement (LGE) derived from cardiac magnetic resonance (CMR) represents myocardial fibrosis (MF) and is associated with prognosis in hypertrophic cardiomyopathy (HCM). However, it cannot be evaluated when CMR is unavailable. Hence, we aimed to investigate the ability of radiomic features derived from coronary computed tomography angiography (CCTA) to detect the presence and extent of MF in HCM, with LGE as references.

Methods: 161 patients with HCM who underwent CCTA and CMR were retrospectively enrolled and randomly divided into training (107 patients, 1712 segments) and testing cohorts (54 patients, 864 segments). Segments were obtained according to AHA 17-segment method. Radiomic features were extracted from per-segment and entire myocardium regions, and multiple machine-learning algorithms were used for radiomic signatures (Rad-sig) generation and model building. Four models were established by multivariable logistic regression using Rad-sig (R-model), clinical characteristic (C-model), echocardiography parameters (E-model), and all features integrated (Integ-model) to identify LGE/left ventricular mass ≥ 15%.

Results: The model achieved good diagnostic accuracy in both training (area under the curve [AUC]:0.81, 95% confidence interval [CI]: 0.78-0.83) and testing cohort (AUC: 0.78, 95%CI: 0.75-0.81) on a per-segment basis for the presence of MF. The Integ-model owned the highest discriminative ability for patients with LGE/left ventricular mass ≥ 15% in both training and testing cohorts with AUC of 0.94 (95%CI: 0.89-0.98) and 0.92 (95%CI: 0.85-0.99), respectively.

Conclusions: Our radiomic models were considered as useful and complementary biomarkers for the evaluation of the presence and extent of MF on CCTA, facilitating clinical decision-making and risk stratification in HCM patients.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.060DOI Listing
August 2021

Tetrahedral Framework Nucleic Acids Induce Immune Tolerance and Prevent the Onset of Type 1 Diabetes.

Nano Lett 2021 05 6;21(10):4437-4446. Epub 2021 May 6.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

A failure in immune tolerance leads to autoimmune destruction of insulin-producing β-cells, leading to type 1 diabetes (T1D). Inhibiting autoreactive T cells and inducing regulatory T cells (Tregs) to re-establish immune tolerance are promising approaches to prevent the onset of T1D. Here, we investigated the ability of tetrahedral framework nucleic acids (tFNAs) to induce immune tolerance and prevent T1D in nonobese diabetic (NOD) mice. In prediabetic NOD mice, tFNAs treatment led to maintenance of normoglycemia and reduced incidence of diabetes. Moreover, the tFNAs (250 nM) treatment preserved the mass and function of β-cells, increased the frequency of Tregs, and suppressed autoreactive T cells, leading to immune tolerance. Collectively, our results demonstrate that tFNAs treatment aids glycemic control, provides β-cell protection, and prevents the onset of T1D in NOD mice by immunomodulation. These results highlight the potential of tFNAs for the prevention of autoimmune T1D.
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http://dx.doi.org/10.1021/acs.nanolett.1c01131DOI Listing
May 2021

Targeting of the COX-2/PGE2 axis enhances the antitumor activity of T7 peptide and .

Drug Deliv 2021 Dec;28(1):844-855

Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3β1 not αvβ3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide and .
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http://dx.doi.org/10.1080/10717544.2021.1914776DOI Listing
December 2021

Author Correction: Robust MFC anti-windup scheme for LTI systems with norm-bounded uncertainty.

Sci Rep 2021 Apr 29;11(1):9603. Epub 2021 Apr 29.

Haikou Power Supply Bureau, Hainan Power Grid Company, Haikou City, 570100, Hainan Province, China.

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http://dx.doi.org/10.1038/s41598-021-89265-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085206PMC
April 2021

How do soil microbes exert impact on soil respiration and its temperature sensitivity?

Environ Microbiol 2021 Jun 4;23(6):3048-3058. Epub 2021 May 4.

College of Resources and Environmental Sciences, Hunan Normal University, Changsha, Hunan, 410081, China.

Understanding how soil microorganisms influence the direction and magnitude of soil carbon feedback to global warming is vital to predict future climate change. Although microbial activities are major contributors to soil respiration (R ) and its temperature sensitivity (Q ), the mechanisms underpinning microbial influence on R and Q remain unclear. Coupling variation partitioning analysis (VPA), correlation analysis and multiple stepwise linear regression analysis, we illustrate that bacteria mainly affect R and its temperature sensitivity (Q ) by shifting bacterial community composition (denoted by principal coordinates analysis). We also found that soil water content (SWC) and available nutrient (AN) were the factor key to changing bacterial community composition (P < 0.05). Co-occurrence network demonstrated that Mod 0 ecological cluster composed of copiotrophic taxa groups was significantly associated with R and Q (P < 0.01, R > 0.5), including Proteobacteria, Actinobacteria, and Bacteroidetes. Illuminating the mechanisms underpinning the influence of soil microbes on R and Q values is fundamental to understanding mechanistic soil-climate carbon cycles.
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http://dx.doi.org/10.1111/1462-2920.15520DOI Listing
June 2021

Plasma Metabolic Profiling in Patients with Silicosis and Asbestosis.

J Occup Environ Med 2021 Apr 20. Epub 2021 Apr 20.

Department of Occupational Medicine and Toxicology, Clinical Center for Interstitial Lung Diseases, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Workers' Stadium South Road, Chao-Yang District, Beijing 100020, China (Zhou, Xue, Fan, Wu, Ma, Ye), Department of Occupational Diseases and Chemical Poisoning, the Fifth People's Hospital of Suzhou, the Affiliated Infectious Hospital of Soochow University, 10 Guangqian Road, Xiang-cheng District, Suzhou 215131, Jiangsu Province, China (Zhou).

Objectives: To explore the circulating metabolites and related pathways in silicosis and asbestosis exposure to different mineral dusts.

Methods: Plasma of 30 silicosis, 30 asbestosis, and 20 healthy controls was analyzed using liquid chromatography-mass spectrometry. Metabolic networks and the relevance of the identified metabolic derangements were explored.

Results: Compared with healthy controls, 37 and 39 dysregulated plasma metabolites were found in silicosis and asbestosis respectively, of which the levels of 22 metabolites differed. Three major pathways were identified, among which arginine and proline metabolism was identified as the most closely related metabolic pathway.

Conclusions: The types and quantities of up-regulated metabolites including lipids, amino acids, and carnitines were differed between silicosis and asbestosis. Pathways inducing lung fibrosis were common to mineral dusts exposure, while pathways related to oxidative stress and tumorigenesis differed between silicosis and asbestosis.
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http://dx.doi.org/10.1097/JOM.0000000000002232DOI Listing
April 2021

A mixed-methods study of American Millennials' views about celebrity endorsement of foods and beverages.

Health Promot Int 2021 Apr 21. Epub 2021 Apr 21.

Department of Human Nutrition, Foods, and Exercise, Virginia Tech, 257 Wallace Hall, 295 West Campus Drive, Blacksburg, VA 24061, USA.

More than one-third of American Millennial adults have obesity, and a significant amount of their household budget is spent on purchasing energy-dense and nutrient-poor food and beverage products. Consumers' brand awareness and purchasing behaviors are influenced by celebrity credibility measured by trustworthiness, expertise and attractiveness; and celebrity 'fit' between products, brands and consumer' self-image. This empirical mixed-methods study combined Q methodology with questionnaires to explore the shared and distinct viewpoints of demographically diverse Millennial adults about celebrity endorsement of food and beverage products or marketing campaigns in the United States (USA). Millennials (n = 40; aged 26-39 years) sorted photo images (n = 48) of US celebrities associated with branded food and beverage product endorsements on a 9-point normal distribution scale from 'most trusted' (+4) to 'most distrusted' (-4). Participants also completed a 4-item post Q-sort questionnaire to interpret their thoughts during the card sorting process, and a 3-item questionnaire to examine their views about celebrity credibility, 'fit' and multiple brand and product endorsements. Three distinct viewpoints were identified that included: (i) healthy lifestyle champions who trusted celebrities associated with healthy products or campaigns; (ii) female role-model admirers who trusted female celebrities associated with positive social impacts and (ii) African-American celebrity fans who trusted African-American celebrities who endorsed any brand or products. Qualitative analysis of the questionnaire identified the potential negative influence of celebrity endorsement for unhealthy products on Millennials' dietary behaviors. Businesses and organizations should carefully select credible celebrities trusted by Millennials to encourage food and beverage products associated with a healthy diet.
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http://dx.doi.org/10.1093/heapro/daab048DOI Listing
April 2021

AIF3 splicing switch triggers neurodegeneration.

Mol Neurodegener 2021 04 14;16(1):25. Epub 2021 Apr 14.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Background: Apoptosis-inducing factor (AIF), as a mitochondrial flavoprotein, plays a fundamental role in mitochondrial bioenergetics that is critical for cell survival and also mediates caspase-independent cell death once it is released from mitochondria and translocated to the nucleus under ischemic stroke or neurodegenerative diseases. Although alternative splicing regulation of AIF has been implicated, it remains unknown which AIF splicing isoform will be induced under pathological conditions and how it impacts mitochondrial functions and neurodegeneration in adult brain.

Methods: AIF splicing induction in brain was determined by multiple approaches including 5' RACE, Sanger sequencing, splicing-specific PCR assay and bottom-up proteomic analysis. The role of AIF splicing in mitochondria and neurodegeneration was determined by its biochemical properties, cell death analysis, morphological and functional alterations and animal behavior. Three animal models, including loss-of-function harlequin model, gain-of-function AIF3 knockin model and conditional inducible AIF splicing model established using either Cre-loxp recombination or CRISPR/Cas9 techniques, were applied to explore underlying mechanisms of AIF splicing-induced neurodegeneration.

Results: We identified a nature splicing AIF isoform lacking exons 2 and 3 named as AIF3. AIF3 was undetectable under physiological conditions but its expression was increased in mouse and human postmortem brain after stroke. AIF3 splicing in mouse brain caused enlarged ventricles and severe neurodegeneration in the forebrain regions. These AIF3 splicing mice died 2-4 months after birth. AIF3 splicing-triggered neurodegeneration involves both mitochondrial dysfunction and AIF3 nuclear translocation. We showed that AIF3 inhibited NADH oxidase activity, ATP production, oxygen consumption, and mitochondrial biogenesis. In addition, expression of AIF3 significantly increased chromatin condensation and nuclear shrinkage leading to neuronal cell death. However, loss-of-AIF alone in harlequin or gain-of-AIF3 alone in AIF3 knockin mice did not cause robust neurodegeneration as that observed in AIF3 splicing mice.

Conclusions: We identified AIF3 as a disease-inducible isoform and established AIF3 splicing mouse model. The molecular mechanism underlying AIF3 splicing-induced neurodegeneration involves mitochondrial dysfunction and AIF3 nuclear translocation resulting from the synergistic effect of loss-of-AIF and gain-of-AIF3. Our study provides a valuable tool to understand the role of AIF3 splicing in brain and a potential therapeutic target to prevent/delay the progress of neurodegenerative diseases.
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http://dx.doi.org/10.1186/s13024-021-00442-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048367PMC
April 2021

In utero and early-life exposure to thirdhand smoke causes profound changes to the immune system.

Clin Sci (Lond) 2021 Apr;135(8):1053-1063

Department of Laboratory Medicine, University of California, San Francisco, CA, U.S.A.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Thirdhand smoke (THS) is the residual tobacco contamination that remains after the smoke clears. We investigated the effects of THS exposure in utero and during early life in a transgenic Cdkn2a knockout mouse model that is vulnerable to the development of leukemia/lymphoma. Female mice, and their offspring, were exposed from the first day of pregnancy to weaning. Plasma cytokines, body weight and hematologic parameters were measured in the offspring. To investigate THS exposure effects on the development of leukemia/lymphoma, bone marrow (BM) was collected from control and THS-exposed mice and transplanted into BM-ablated recipient mice, which were followed for tumor development for 1 year. We found that in utero and early-life THS exposure caused significant changes in plasma cytokine concentrations and in immune cell populations; changes appeared more pronounced in male mice. Spleen (SP) and BM B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia/lymphoma-free survival in BM transplantation recipient mice, potentially caused by THS-induced B-cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS-exposed BM stimulates the hypothesis that the immunosuppressive effects of in utero and early-life THS exposure might contribute to carcinogenesis by lowering the host defense to other toxic exposures. Our study adds to expanding evidence that THS exposure alters the immune system and that in utero and early-life developmental periods represent vulnerable windows of susceptibility for these effects.
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http://dx.doi.org/10.1042/CS20201498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086195PMC
April 2021

An Explainable Artificial Intelligence Framework for the Deterioration Risk Prediction of Hepatitis Patients.

J Med Syst 2021 Apr 13;45(5):61. Epub 2021 Apr 13.

Department of Computer Science, Guangdong University of Education, Guangzhou, 510303, China.

In recent years, artificial intelligence-based computer aided diagnosis (CAD) system for the hepatitis has made great progress. Especially, the complex models such as deep learning achieve better performance than the simple ones due to the nonlinear hypotheses of the real world clinical data. However,complex model as a black box, which ignores why it make a certain decision, causes the model distrust from clinicians. To solve these issues, an explainable artificial intelligence (XAI) framework is proposed in this paper to give the global and local interpretation of auxiliary diagnosis of hepatitis while retaining the good prediction performance. First, a public hepatitis classification benchmark from UCI is used to test the feasibility of the framework. Then, the transparent and black-box machine learning models are both employed to forecast the hepatitis deterioration. The transparent models such as logistic regression (LR), decision tree (DT)and k-nearest neighbor (KNN) are picked. While the black-box model such as the eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), random forests (RF) are selected. Finally, the SHapley Additive exPlanations (SHAP), Local Interpretable Model-agnostic Explanations (LIME) and Partial Dependence Plots (PDP) are utilized to improve the model interpretation of liver disease. The experimental results show that the complex models outperform the simple ones. The developed RF achieves the highest accuracy (91.9%) among all the models. The proposed framework combining the global and local interpretable methods improves the transparency of complex models, and gets insight into the judgments from the complex models, thereby guiding the treatment strategy and improving the prognosis of hepatitis patients. In addition, the proposed framework could also assist the clinical data scientists to design a more appropriate structure of CAD.
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http://dx.doi.org/10.1007/s10916-021-01736-5DOI Listing
April 2021

Laboratory and simulation study on the Cd(Ⅱ) adsorption by lake sediment: Mechanism and influencing factors.

Environ Res 2021 06 13;197:111138. Epub 2021 Apr 13.

College of Environmental Science and Engineering, Hunan University, Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha, 410082, PR China. Electronic address:

Sediments are the major sinks for Cd(Ⅱ) in the aquatic environment. Here, the detailed binding mechanisms and effects of environmental factors on Cd(Ⅱ) adsorption onto lake sediment were tested by a batch of adsorption and characteristic experiments. Sediment samples and sediment-Cd complexes were characterized using Scanning electron microscopy, Energy dispersive spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction spectral analyses. The interactive and main effect of parameters such as pH, flow velocity, Cd(II) concentration, sediment particle size, humic acid, fulvic acid and adsorption time involved in the adsorption process were determined using two models based on response surface methodology (RSM) and a back-propagation neural network with genetic algorithm (GABP). Results showed that Cd(II) adsorption onto sediment was mainly achieved through surface complexation with O-containing groups and precipitation with carbonate and sulfide. RSM was favorable for modeling Cd(II) adsorption in lake systems because it intuitively reflected the influence of the factors and had a good fitting precision (R = 0.8838, RSME = 2.5496) close to that of the GABP model (R = 0.8959, RSME = 2.5410). pH, sediment particle size, and humic acid exerted strong influences on Cd(II) immobilized by the sediment. Overall, our findings facilitate a better understanding of Cd(II) mobility in lakes and provide a reference for controlling heavy metals derived from both aqueous and sediment sources.
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http://dx.doi.org/10.1016/j.envres.2021.111138DOI Listing
June 2021

Treatment challenges in patients with early acute massive pulmonary thrombosis embolism (PTE) after lung cancer surgery: A case report.

Medicine (Baltimore) 2021 Apr;100(14):e25371

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Introduction: Early acute massive pulmonary thrombosis embolism (PTE) after lung cancer surgery is one of the most fatal surgical complications. It is often accompanied by shock and hypotension, with high mortality rate. Due to surgical wounds, patients with early acute massive PTE after lung cancer surgery have a high risk of thrombolytic bleeding, which renders treatment more challenging and there is currently no standard protocol on how to safely and effectively treat these patients in the clinic.

Patient Concerns: A 66-year-old woman after video-assisted thoracoscopic surgery for lung cancer, experienced sudden severe dyspnea, shock and hypotension with high D-Dimer, changed electrocardiogram (ECG), right ventricular dilatation, severe tricuspid regurgitation, and raised pulmonary arterial pressure on ultrasonic cardiogram (UCG), thromboses found on Ultrasonography of lower extremity vein.

Diagnosis: Because of her clinical manifestations and results of bedside auxiliary examinations, the patient was finally diagnosed with acute high-risk PTE after lung cancer surgery.

Interventions: 1.5 hours after onset of symptoms, thrombolysis using a continuous micropump infusion of 20,000 units/kg urokinase into the peripheral vein for 2 hours was initiated for this patient.

Outcomes: The patient died of massive hemorrhage after thrombolysis.

Lessons: Treatment for patients with early acute PTE after lung cancer surgery is challenging due to a high risk of thrombolytic bleeding at the surgical site. Real-time monitoring of vital signs during thrombolysis and catheter-directed thrombolysis are recommended for these patients, in order to use the minimum drug dosage for quick curative effects and a low risk of bleeding.
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http://dx.doi.org/10.1097/MD.0000000000025371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036128PMC
April 2021

Designing MOF Nanoarchitectures for Electrochemical Water Splitting.

Adv Mater 2021 Apr 22;33(17):e2006042. Epub 2021 Mar 22.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.

Electrochemical water splitting has attracted significant attention as a key pathway for the development of renewable energy systems. Fabricating efficient electrocatalysts for these processes is intensely desired to reduce their overpotentials and facilitate practical applications. Recently, metal-organic framework (MOF) nanoarchitectures featuring ultrahigh surface areas, tunable nanostructures, and excellent porosities have emerged as promising materials for the development of highly active catalysts for electrochemical water splitting. Herein, the most pivotal advances in recent research on engineering MOF nanoarchitectures for efficient electrochemical water splitting are presented. First, the design of catalytic centers for MOF-based/derived electrocatalysts is summarized and compared from the aspects of chemical composition optimization and structural functionalization at the atomic and molecular levels. Subsequently, the fast-growing breakthroughs in catalytic activities, identification of highly active sites, and fundamental mechanisms are thoroughly discussed. Finally, a comprehensive commentary on the current primary challenges and future perspectives in water splitting and its commercialization for hydrogen production is provided. Hereby, new insights into the synthetic principles and electrocatalysis for designing MOF nanoarchitectures for the practical utilization of water splitting are offered, thus further promoting their future prosperity for a wide range of applications.
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http://dx.doi.org/10.1002/adma.202006042DOI Listing
April 2021

MicroRNAomes of Cattle Intestinal Tissues Revealed Possible miRNA Regulated Mechanisms Involved in O157 Fecal Shedding.

Front Cell Infect Microbiol 2021 24;11:634505. Epub 2021 Feb 24.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.

Cattle have been suggested as the primary reservoirs of O157 mainly as a result of colonization of the recto-anal junction (RAJ) and subsequent shedding into the environment. Although a recent study reported different gene expression at RAJ between super-shedders (SS) and non-shedders (NS), the regulatory mechanisms of altered gene expression is unknown. This study aimed to investigate whether bovine non-coding RNAs play a role in regulating the differentially expressed (DE) genes between SS and NS, thus further influencing O157 shedding behavior in the animals through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 (duodenum) to 413 ± 49 (descending colon). Comparison between SS and NS revealed the number of differentially expressed (DE) miRNAs ranged from one (in descending colon) to eight (in distal jejunum), and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (eight and seven, respectively). The miRNAs, bta-miR-378b, bta-miR-2284j, and bta-miR-2284d were down-regulated in both distal jejunum and rectum of SS (logfold-change: -2.7 to -3.8), bta-miR-2887 was down-regulated in the rectum of SS (logfold-change: -3.2), and bta-miR-211 and bta-miR-29d-3p were up-regulated in the rectum of SS (logfold-change: 4.5 and 2.2). Functional analysis of these miRNAs indicated their potential regulatory role in host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that altered expression of miRNA in the gut of SS may lead to differential regulation of immune functions involved in O157 super-shedding in cattle.
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http://dx.doi.org/10.3389/fcimb.2021.634505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959717PMC
July 2021
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