Publications by authors named "Jia Hao"

272 Publications

A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers.

Micromachines (Basel) 2021 Oct 16;12(10). Epub 2021 Oct 16.

Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA.

Chemotactic cell migration plays a crucial role in physiological and pathophysiological processes. In tissues, cells can migrate not only through extracellular matrix (ECM), but also along stromal cell surfaces via membrane-bound receptor-ligand interactions to fulfill critical functions. However, there remains a lack of models recapitulating chemotactic migration mediated through membrane-bound interactions. Here, using micro-milling, we engineered a multichannel diffusion device that incorporates a chemoattractant gradient and a supported lipid bilayer (SLB) tethered with membrane-bound factors that mimics stromal cell membranes. The chemoattractant channels are separated by hydrogel barriers from SLB in the cell loading channel, which enable precise control of timing and profile of the chemokine gradients applied on cells interacting with SLB. The hydrogel barriers are formed in pillar-free channels through a liquid pinning process, which eliminates complex cleanroom-based fabrications and distortion of chemoattractant gradient by pillars in typical microfluidic hydrogel barrier designs. As a proof-of-concept, we formed an SLB tethered with ICAM-1, and demonstrated its lateral mobility and different migratory behavior of Jurkat T cells on it from those on immobilized ICAM-1, under a gradient of chemokine CXCL12. Our platform can thus be widely used to investigate membrane-bound chemotaxis such as in cancer, immune, and stem cells.
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http://dx.doi.org/10.3390/mi12101254DOI Listing
October 2021

Impact of microplastics on bioaccumulation of heavy metals in rape (Brassica napus L.).

Chemosphere 2021 Oct 14:132576. Epub 2021 Oct 14.

College of Forestry, Northeast Forestry University, Harbin, 150040, China. Electronic address:

Microplastics have become a global environmental problem due to the ubiquitous existence. The impacts of microplastics on heavy metals behaviors in aquatic environment are widely investigated, however, the impacts of microplastics on bioaccumulation of heavy metals in vegetables in terrestrial environment are seldom investigated. Herein, batch experiments were carried out, the microplastics (0.001%, 0.01%, 0.1%) and heavy metal (50, 100 mg/kg Cu or 25, 50 mg/kg Pb) were single or combined spiked into soil to cultivate rapes (Brassica napus L.) in greenhouse. Copper and lead contents of rapes in MP0.1+Cu100 and MP0.1+Pb50 treatments reached 38.9 mg/kg and 9.4 mg/kg, which were significantly (p < 0.05) higher than those of Cu100 (35.3 mg/kg) and Pb50 (8.7 mg/kg) treatments, respectively. Results showed that microplastics in soil would facilitate heavy metals entering rape plants. In addition, contents of total chlorophyll, soluble sugar, vitamin C, malondialdehyde contents, activities of superoxide dismutase and guaiacol peroxidase, as well as related gene expression were analyzed to investigate the toxic effects of these pollutants (microplastics, Cu, and Pb) to rape plants. Malondialdehyde contents of rapes in MP0.1+Cu50, MP0.1+Cu100, MP0.1+Pb25, and MP0.1+Pb50 treatments reached 0.102 mmol/mg Protein, 0.123 mmol/mg Protein, 0.101 mmol/mg Protein, and 0.119 mmol/mg Protein, which were 1.42, 1.37, 1.46, and 1.45 times of those in Cu50, Cu100, Pb25, and Pb50 treatments, respectively. The changes of malondialdehyde content, activities of superoxide dismutase and guaiacol peroxidase, as well as contents of sugar and vitamin C indicated that microplastics in soil would bring severer damage and deteriorate quality of rape plants. The data in this study indicated that microplastics would increase the bioaccumulation of heavy metals in vegetables and damage to vegetables.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132576DOI Listing
October 2021

Circulating soluble receptor of advanced glycation end product is associated with bicuspid aortic aneurysm progression via NF-κB pathway.

Interact Cardiovasc Thorac Surg 2021 Oct 14. Epub 2021 Oct 14.

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Objectives: Patients with bicuspid aortic valve (BAV) have a high risk of aortic dilation and adverse vascular events. Previous studies had reported soluble receptor for advanced glycation end products (sRAGE) to compete with receptor of advanced glycation end products (RAGE) for ligand binding and inhibit the activation of nuclear-factor kappa-B (NF-κB) pathway and matrix metalloproteinases (MMP) transcription. Thus, sRAGE serum levels may contribute to the clinical diagnosis and monitoring of ascending aorta aneurysm in patients with BAV.

Methods: To eliminate the confounding factors, 44 patients with BAV were divided into 3 subgroups according to the diameter of ascending aorta, and 20 patients with tricuspid aortic valve and normal-sized ascending aorta were selected as a control group. Protein levels and gene transcription of several variates were evaluated in the tissue and serum samples from these patients. Human aortic smooth muscle cells were treated with AGE-BSA in gradient concentrations, and changes in phenotype and protein and mRNA levels were detected.

Results: Serum levels of sRAGE in the 3 BAV groups were obviously higher than those in the tricuspid aortic valve group, although there was negative correlation between the serum sRAGE levels and ascending aortic diameters among patients with BAV. Transcript expression levels of RAGE and NF-κBp65 mRNA were increased in the 3 BAV groups and RAGE/NF-κB pathway was activated with the progression of ascending aortic aneurysm. Abnormal activation of RAGE/NF-κB pathway was observed in AGE-BSA-treated human aortic smooth muscle cells.

Conclusions: Our study has shown a trend in serum levels of sRAGE among patients with BAV, and that the cellular and extracellular pathological processes are quite serious even in the normal-sized or slightly dilated aorta. Together, the findings indicated that sRAGE may be used as a biomarker to predict aneurysm expansion rates and the risk of adverse vascular events.
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http://dx.doi.org/10.1093/icvts/ivab242DOI Listing
October 2021

Integrating Highly Porous and Flexible Au Hydrogels with Soft-MEMS Technologies for High-Performance Wearable Biosensing.

Anal Chem 2021 Oct 12. Epub 2021 Oct 12.

State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University and Shaanxi Joint Laboratory of Graphene (NPU), Xi'an 710072, P. R. China.

Wearable biosensors for real-time and non-invasive detection of biomarkers are of importance in early diagnosis and treatment of diseases. Herein, a high-performance wearable biosensing platform was proposed by combining a three-dimensional hierarchical porous Au hydrogel-enzyme electrode with high biocompatibility, activity, and flexibility and soft-MEMS technologies with high precision and capability of mass production. Using glucose oxidase as the model enzyme, the glucose sensor exhibits a sensitivity of 10.51 μA mM cm, a long durability over 15 days, and a good selectivity. Under the mechanical deformation (0 to 90°), it is able to maintain an almost constant performance with a low deviation of <1.84%. With the assistance of a wireless or a Bluetooth module, this wearable sensing platform achieves real-time and non-invasive glucose monitoring on human skins. Similarly, continuous lactic acid monitoring was also realized with lactate oxidase immobilized on the same sensing platform, further verifying the universality of this sensing platform. Therefore, our work holds promise to provide a universal, high-performance wearable biosensing platform for various biomarkers in sweat and reliable diagnostic information for health management.
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http://dx.doi.org/10.1021/acs.analchem.1c01581DOI Listing
October 2021

Ajuba functions as a co-activator of C/EBPβ to induce expression of PPARγ and C/EBPα during adipogenesis.

Mol Cell Endocrinol 2021 Oct 5;539:111485. Epub 2021 Oct 5.

Hongqiao International Institute of Medicine, Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry & Molecular Cellular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. Electronic address:

Adipogenesis is regulated by a complicated network of transcription factors among which PPARγ and C/EBP family members are the major regulators. During adipogenesis, C/EBPβ is induced early and then transactivates PPARγ and C/EBPα, which cooperatively induce genes whose expressions give rise to the mature adipocyte phenotype. Identifying the factors that influence the expression and activity of C/EBPβ should provide additional insight into the mechanisms regulating adipogenesis. Here, we demonstrate that depletion of Ajuba in 3T3-L1 cells significantly decreases mRNA and protein levels of PPARγ and C/EBPα and impairs adipocyte differentiation, while overexpression increases expression of these genes and promotes adipocyte differentiation. Moreover, restoration of C/EBPα or PPARγ expression in Ajuba-deficient 3T3-L1 cells improves the impaired lipid accumulation. Mechanistically, Ajuba interacts with C/EBPβ and recruits CBP to facilitate the binding of C/EBPβ to the promoter of PPARγ and C/EBPα, resulting in increased H3 histone acetylation and target gene expression. Collectively, these data indicate that Ajuba functions as a co-activator of C/EBPβ, and may be an important therapeutic target for combating obesity-related diseases.
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http://dx.doi.org/10.1016/j.mce.2021.111485DOI Listing
October 2021

Gradient-probability-driven discrete search algorithm for on-chip photonics inverse design.

Opt Express 2021 Aug;29(18):28751-28766

The inverse-designed photonic device, with the characteristics of high performance and ultra-high compactness, is suitable for on-chip photonics applications. The gradient-based algorithms have high convergence efficiency. However, they depend on the continuous independent variable, so they cannot be directly applied to the pixel-based discrete search methods. In this paper, we propose a gradient-probability-driven discrete search (GPDS) algorithm for photonics inverse design. The algorithm establishes a connection between the gradient and the discrete value set by introducing the method of probability sampling. As an intrinsic discrete search algorithm in which the values of pixels are selected from a finite number of the discrete set, no additional discretization process is needed. Compared with the traditional brute-force search (BFS) method and traditional gradient method, the probability sampling process of our proposed GPDS algorithm can improve device performance efficiently and provide better stability to the initial states. We illustrate several component designs which are commonly used in the silicon photonics platform, and the results show that the algorithm can achieve high-performance structures within fewer iterations and has the ability of multi-objective optimization. With good flexibility and manufacturing-friendly geometry control, the algorithms are potential to be a powerful tool in solving multi-objective problems.
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http://dx.doi.org/10.1364/OE.432313DOI Listing
August 2021

Vascular damage mechanism and parameter optimization under alexandrite laser irradiation: a theoretical study.

Lasers Med Sci 2021 Sep 25. Epub 2021 Sep 25.

National and Local Joint Engineering Laboratory of Fluid Transmission System Technology, Zhejiang University of Science and Technology, Zhejiang, 310018, China.

The 755-nm Alexandrite Laser has a good clinical effect in treating resistant port wine stain, without causing thermal damage of normal tissue and side effects such as purpura. However, little is known about the mechanism of vascular damage induced by 755-nm laser irradiation, which restricts the optimization of laser parameters. In this work, the thermal damage model and the pressure damage model were used to study the damage mechanism of 755-nm laser irradiation on vessels, and the incident energy density and pulse width required for vascular damage were determined according to the damage mode. Under the irradiation of 755-nm laser, the vascular injury pattern was the co-occurrence of vessel rupture and vessel constriction, and the energy density required for the treatment of vessels with a diameter of 200 μm to reach the damage threshold was the lowest.
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http://dx.doi.org/10.1007/s10103-021-03375-1DOI Listing
September 2021

Impact of Hyperinsulinemia on Long-Term Clinical Outcomes of Percutaneous Coronary Intervention in Patients without Diabetes Who Have Acute Myocardial Syndrome.

Diabetes Metab Syndr Obes 2021 7;14:3949-3957. Epub 2021 Sep 7.

Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People's Republic of China.

Background And Objectives: Hyperinsulinemia plays a key role in the development of cardiovascular impairment in patients with metabolic syndrome. The aim of this study was to evaluate the influence of hyperinsulinemia on long-term clinical outcomes of percutaneous coronary intervention (PCI) in patients without diabetes mellitus who have acute myocardial syndrome (ACS).

Methods: Between March 2016 and January 2019, we enrolled 468 patients with ACS and without diabetes mellitus who received primary PCI. Patients were divided into a low-insulin group (n = 157), medium-insulin group (n = 154), and high-insulin group (n = 157) according to tertiles of fasting insulin level. The primary endpoint was major adverse cardiac events (MACE; all-cause death, non-fatal myocardial infarction, target vessel revascularization [TVR]) at 24 months. The secondary endpoint was angina hospitalization.

Results: Patients in the high-insulin group had an unfavorable prognosis, with a higher rate of MACE (34.39%) than the low-insulin group (22.29%) and medium-insulin group (23.37%) at 24 months (P < 0.05). This difference was mainly driven by the increase in TVR. The high-insulin group also had a higher rate of angina hospitalization than the low-insulin group. Cox proportional hazards regression showed that high-insulin level (hazard ratio [HR] 1.870, 95% confidence interval [CI] 1.202-2.909), small-vessel lesion (HR 1.713, 95% CI 1.111-2.642), bifurcation lesion (HR 3.394, 95% CI 2.033-5.067), SYNTAX score (HR 1.084, 95% CI 1.039-1.130), and stent length (HR 1.017, 95% CI 1.002-1.032) increased the incidence of MACE in patients with ACS and without diabetes who underwent PCI.

Conclusion: Hyperinsulinemia might be a valid predictor of clinical outcomes in patients with ACS undergoing PCI.
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http://dx.doi.org/10.2147/DMSO.S318852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434865PMC
September 2021

Toward the Practical Use of Cobalt-Free Lithium-Ion Batteries by an Advanced Ether-Based Electrolyte.

ACS Appl Mater Interfaces 2021 Sep 8;13(37):44339-44347. Epub 2021 Sep 8.

Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, Washington 99354, United States.

The criticality of cobalt (Co) has been motivating the quest for Co-free positive electrode materials for building lithium (Li)-ion batteries (LIBs). However, the LIBs based on Co-free positive electrode materials usually suffer from relatively fast capacity decay when coupled with conventional LiPF-organocarbonate electrolytes. To address this issue, a 1,2-dimethoxyethane-based localized high-concentration electrolyte (LHCE) was developed and evaluated in a Co-free Li-ion cell chemistry (graphite||LiNiMgTiO). Extraordinary capacity retentions were achieved with the LHCE in coin cells (95.3%), single-layer pouch cells (79.4%), and high-capacity loading double-layer pouch cells (70.9%) after being operated within the voltage range of 2.5-4.4 V for 500 charge/discharge cycles. The capacity retentions of counterpart cells using the LiPF-based conventional electrolyte only reached 61.1, 57.2, and 59.8%, respectively. Mechanistic studies reveal that the superior electrode/electrolyte interphases formed by the LHCE and the intrinsic chemical stability of the LHCE account for the excellent electrochemical performance in the Co-free Li-ion cells.
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http://dx.doi.org/10.1021/acsami.1c12072DOI Listing
September 2021

The emerging role of transcription factor FOXP3 in thyroid cancer.

Rev Endocr Metab Disord 2021 Aug 31. Epub 2021 Aug 31.

Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Transcription factor FOXP3 is a crucial regulator in the development and function of regulatory T cells (Treg) that are essential for immunological tolerance and homeostasis. Numerous studies have indicated the correlation of tumor infiltrating FOXP3+ Treg upregulation with poor prognostic parameters in thyroid cancer, including lymph node metastases, extrathyroidal extension, and multifocality. Most immune-checkpoint molecules are expressed in Treg. The blockage of such signals with checkpoint inhibitors has been approved for several solid tumors, but not yet for thyroid cancer. Thyroid abnormalities may be induced by checkpoint inhibitors. For example, hypothyroidism, thyrotoxicosis, painless thyroiditis, or even thyroid storm are more frequently associated with anti-PD-1 antibodies (pembrolizumab and nivolumab). Therefore, Targeting FOXP3+ Treg may have impacts on checkpoint molecules and the growth of thyroid cancer. Several factors may impact the role and stability of FOXP3, such as alternative RNA splicing, mutations, and post-translational modification. In addition, the role of FOXP3+ Treg in the tumor microenvironment is also affected by the complex regulatory network formed by FOXP3 and its transcriptional partners. Here we discussed how the expression and function of FOXP3 were regulated and how FOXP3 interacted with its targets in Treg, aiming to help the development of FOXP3 as a potential therapeutic target for thyroid cancer.
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http://dx.doi.org/10.1007/s11154-021-09684-8DOI Listing
August 2021

Membrane-bound SCF and VCAM-1 synergistically regulate the morphology of hematopoietic stem cells.

J Cell Biol 2021 Oct 17;220(10). Epub 2021 Aug 17.

Department of Biomedical Engineering, University of Southern California, Los Angeles, CA.

Membrane-bound factors expressed by niche stromal cells constitute a unique class of localized cues and regulate the long-term functions of adult stem cells, yet little is known about the underlying mechanisms. Here, we used a supported lipid bilayer (SLB) to recapitulate the membrane-bound interactions between hematopoietic stem cells (HSCs) and niche stromal cells. HSCs cluster membrane-bound stem cell factor (mSCF) at the HSC-SLB interface. They further form a polarized morphology with aggregated mSCF under a large protrusion through a synergy with VCAM-1 on the bilayer, which drastically enhances HSC adhesion. These features are unique to mSCF and HSCs among the factors and hematopoietic populations we examined. The mSCF-VCAM-1 synergy and the polarized HSC morphology require PI3K signaling and cytoskeletal reorganization. The synergy also enhances nuclear retention of FOXO3a, a crucial factor for HSC maintenance, and minimizes its loss induced by soluble SCF. Our work thus reveals a unique role and signaling mechanism of membrane-bound factors in regulating stem cell morphology and function.
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http://dx.doi.org/10.1083/jcb.202010118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374872PMC
October 2021

MicroRNAs involve in bicuspid aortic aneurysm: pathogenesis and biomarkers.

J Cardiothorac Surg 2021 Aug 12;16(1):230. Epub 2021 Aug 12.

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, 1069 Xietu Road, 200032, Shanghai, People's Republic of China.

The incidence of bicuspid aortic valves (BAV) is high in the whole population, BAV-related thoracic aortic aneurysm (TAA) is accompanied by many adverse vascular events. So far, there are two key points in dealing with BAV-related TAA. First is fully understanding on its pathogenesis. Second is optimizing surgical intervention time. This review aims to illustrate the potential role of miRNAs in both aspects, that is, how miRNAs are involved in the occurrence and progression of BAV-related TAA, and the feasibilities of miRNAs as biomarkers.
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http://dx.doi.org/10.1186/s13019-021-01613-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359579PMC
August 2021

[Changes of FLI-1 protein expression in mice with pulmonary endothelial barrier dysfunction following acute lung injury induced by lipopolysaccharide].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 Jul;37(4):393-396

Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325035, China.

To observe changes of Friend leukemia virus integration 1 (FLI-1) protein expression of pulmonary tissue in mice with pulmonary endothelial barrier dysfunction following acute lung injury (ALI) induced by lipopolysaccharide (LPS). The mouse model of ALI was established by injection of LPS (7.5 mg/kg, i.p. ). At 0 h, 12 h, 24 h and 48 h after LPS injection, pulmonary microvascular endothelial permeability and lung wet/dry weight ratio (W/D) were assessed. The contents of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were detected by ELISA method. The protein levels of FLI-1 and Src protein tyrosine kinase (SRC) were analyzed by Western blotting. ①Pulmonary microvascular endothelial permeability at 12 h and 24 h were significantly higher than those of 0 h by 74.3% and 162.4%, respectively, while that of 48 h was lower than that of 24 h by 27.0% (<0.05). The W/D at 12 h and 24 h were significantly higher than those of 0 h by 50.1% and 122.9%, respectively, while that of 48 h was lower than that of 24 h by 10.7% (<0.05). ②The contents of IL-6 and TNF-α in BALF at 12 h and 24 h were significantly higher than those of 0 h, while those of 48 h were significantly lower than those of 24 h by 28.3% and 21.6% (<0.05), respectively. ③The protein level of FLI-1 in lung at 12 h and 24 h were down-regulated than those of 0 h by 20.4% and 56.9%, respectively, while that of 48 h was up-regulated than that of 24 h by 18.2% (<0.05). The protein level of SRC in lung at 12 h and 24 h were up-regulated than those of 0 h by 76.8% and 176.7%, respectively, while that of 48 h was down-regulated than that of 24 h by 33.4% (<0.05).④Same as the protein level of FLI-1 with the protein level of SRC in lung, pulmonary microvascular endothelial permeability was significantly negative correlated with the protein level of FLI-1 in lung, while it was significantly positive correlated with the protein level of SRC (<0.01). FLI-1 participates in the pathological proceeding of pulmonary endothelial barrier dysfunction following ALI induced by LPS.
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http://dx.doi.org/10.12047/j.cjap.6080.2021.040DOI Listing
July 2021

Ultrathin MXene/Polymer Coatings with an Alternating Structure on Fabrics for Enhanced Electromagnetic Interference Shielding and Fire-Resistant Protective Performances.

ACS Appl Mater Interfaces 2021 Aug 9;13(32):38761-38772. Epub 2021 Aug 9.

National Manufacturing Innovation Centre of Advanced Dyeing and Finishing Technology, Key Laboratory of Eco-Textiles, Ministry of Education, Jiangnan University, Wuxi, Jiangsu 214122, China.

Wearable electromagnetic interference (EMI) shielding fabrics are highly desirable with the rapid development of electronic devices and wireless communications where electromagnetic pollution is a great concern for human health and the reliability of precision equipment. The balance between EMI shielding efficiency (SE) and the flexibility of fabric is still challenging because of the generally opposite requirements for coating thickness. In this work, MXene/insulative polymer coating with an alternating structure is fabricated a stepwise assembly technique to judiciously combine excellent shielding elements, a reasonable structure, and high nanofiller content together in the coating. Owing to this novel strategy, the coating with nanoscale thickness (∼500 nm) has realized the commercial requirement for EMI SE and well retained the flexibility and air permeability of the fabric. Compared with the corresponding pure MXene coating, such multilayered coating demonstrates 138.95% enhancement of EMI SE due to the improved dielectrical properties and intensive multiple reflections of electromagnetic waves. Additionally, this hybrid coating also acts as an excellent fire-resistant barrier for the inner flammable fabric to protect human beings and electronic devices in case of accidental fire. This work provides new insights into the rational design of shields with nanometer thickness to realize high EMI shielding performance and good fire resistance for new-generation portable and wearable EMI shielding products.
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http://dx.doi.org/10.1021/acsami.1c11638DOI Listing
August 2021

Associations of plasma uromodulin and genetic variants with blood pressure responses to dietary salt interventions.

J Clin Hypertens (Greenwich) 2021 Aug 7. Epub 2021 Aug 7.

Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.
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http://dx.doi.org/10.1111/jch.14347DOI Listing
August 2021

Long noncoding RNA MALAT1 sponging miR-26a-5p to modulate Smad1 contributes to colorectal cancer progression by regulating autophagy.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.

Accumulating evidences have suggested that bone morphogenetic protein (BMP) -Smad have a functional role in regulating autophagy in the development of human colorectal cancer (CRC). However, the regulatory mechanisms controlling this process remain unclear. Here, we showed that Smad1, the key effector of BMP2-Smad signaling, induces autophagy by upregulating autophagy-related gene 5 (ATG5) expression, and Smad1 binds to the proximal promoter to induce its expression. Moreover, BMP2 induces autophagy in CRC. Overexpression of Smad1 promotes tumorigenesis and migration of CRC cells, and knockdown of ATG5 is able to rescue the Smad1-induced promotion of CRC proliferation and migration partially. Mechanistically, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) may act as a competing endogenous RNA by binding with miR-26a-5p competitively and thus modulating the de-repression of downstream target Smad1. Furthermore, clinical analysis results show that Smad1 is positively correlated with MALAT1 and negatively correlated with miR-26a-5p in CRC samples. In conclusion, our results demonstrated that Smad1 may serve as an oncogene in CRC through autophagy.
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http://dx.doi.org/10.1093/carcin/bgab069DOI Listing
July 2021

Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice.

BMC Complement Med Ther 2021 Jul 20;21(1):202. Epub 2021 Jul 20.

Department of Pharmacology, School of Basic and Life Science, Hainan Medical University, Haikou, 571199, China.

Background: Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model.

Methods: After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 μl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed.

Results: SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1β and TNF-α. In addition, NLRP3, Caspase-1 and IL-1β, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle.

Conclusions: These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.
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http://dx.doi.org/10.1186/s12906-021-03364-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293507PMC
July 2021

Reconfigurable Spin-Wave Interferometer at the Nanoscale.

Nano Lett 2021 Jul 16;21(14):6237-6244. Epub 2021 Jul 16.

Fert Beijing Institute, MIIT Key Laboratory of Spintronics, School of Integrated Circuit Science and Engineering, Beihang University, Beijing 100191, China.

Spin waves can transfer information free of electron transport and are promising for wave-based computing technologies with low-power consumption as a solution to severe energy losses in modern electronics. Logic circuits based on the spin-wave interference have been proposed for more than a decade, while it has yet been realized at the nanoscale. Here, we demonstrate the interference of spin waves with wavelengths down to 50 nm in a low-damping magnetic insulator. The constructive and destructive interference of spin waves is detected in the frequency domain using propagating spin-wave spectroscopy, which is further confirmed by the Brillouin light scattering. The interference pattern is found to be highly sensitive to the distance between two magnetic nanowires acting as spin-wave emitters. By controlling the magnetic configurations, one can switch the spin-wave interferometer on and off. Our demonstrations are thus key to the realization of spin-wave computing system based on nonvolatile nanomagnets.
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http://dx.doi.org/10.1021/acs.nanolett.1c02010DOI Listing
July 2021

Responses of the macrobenthic community to the Dalian Bay oil spill based on co-occurrence patterns and interaction networks.

Mar Pollut Bull 2021 Oct 6;171:112662. Epub 2021 Jul 6.

National Marine Environmental Monitoring Center, Dalian 116023, China. Electronic address:

On July 16, 2010, a pipeline explosion spilled 1500 tons of crude oil into the Port of Dalian, China. To identify taxa responses to the spill, we exploited seven years of monitoring data to examine the co-occurrence of taxon pairs and the variation of the macrobenthic community. Non-parametric correlation analysis was used to construct interaction networks of relationships between oil spill contaminants and macrobenthic taxa. We observed that the impacted macrobenthic community not restored before 2016. The tolerance/sensitivity of taxa was inconsistent with the studies of oil impacts in other locations. We suggest revision of the ecological group classification of Sabellidae, Lumbrineridae, Terebellidae, Sternaspidae, and Spionidae. The variation in the frequency of coexistence indicates the potential impact of oil spill pollution on resource occupation. The interaction network involving macrobenthic families and stressors associated with the oil spill highlights how different macrobenthic families respond to different combinations of stressors.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112662DOI Listing
October 2021

Snail enhances arginine synthesis by inhibiting ubiquitination-mediated degradation of ASS1.

EMBO Rep 2021 08 29;22(8):e51780. Epub 2021 Jun 29.

Tongren Hospital/Faculty of Basic Medicine, Hongqiao International Institute of Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Snail is a dedicated transcriptional repressor and acts as a master inducer of EMT and metastasis, yet the underlying signaling cascades triggered by Snail still remain elusive. Here, we report that Snail promotes colorectal cancer (CRC) migration by preventing non-coding RNA LOC113230-mediated degradation of argininosuccinate synthase 1 (ASS1). LOC113230 is a novel Snail target gene, and Snail binds to the functional E-boxes within its proximal promoter to repress its expression in response to TGF-β induction. Ectopic expression of LOC113230 potently suppresses CRC cell growth, migration, and lung metastasis in xenograft experiments. Mechanistically, LOC113230 acts as a scaffold to facilitate recruiting LRPPRC and the TRAF2 E3 ubiquitin ligase to ASS1, resulting in enhanced ubiquitination and degradation of ASS1 and decreased arginine synthesis. Moreover, elevated ASS1 expression is essential for CRC growth and migration. Collectively, these findings suggest that TGF-β and Snail promote arginine synthesis via inhibiting LOC113230-mediated LRPPRC/TRAF2/ASS1 complex assembly and this complex can serve as potential target for the development of new therapeutic approaches to treat CRC.
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http://dx.doi.org/10.15252/embr.202051780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339691PMC
August 2021

Distinct BTK inhibitors differentially induce apoptosis but similarly suppress chemotaxis and lipid accumulation in mantle cell lymphoma.

BMC Cancer 2021 Jun 26;21(1):732. Epub 2021 Jun 26.

Interdisciplinary Institute of Cancer Diagnosis and Treatment, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beihang University, Beijing, 100083, China.

Background: The more selective second-generation BTK inhibitors (BTKi) Acalabrutinib and Zanubrutinib and the first-generation BTKi Ibrutinib are highlighted by their clinical effectiveness in mantle cell lymphoma (MCL), however, similarities and differences of their biological and molecular effects on anti-survival of MCL cells induced by these BTKi with distinct binding selectivity against BTK remain largely unknown.

Methods: AlamarBlue assays were performed to define cytotoxicity of BTKi against MCL cells, Jeko-1 and Mino. Cleaved PARP and caspase-3 levels were examined by immunoblot analysis to study BTKi-induced apoptotic effects. Biological effects of BTKi on MCL-cell chemotaxis and lipid droplet (LD) accumulation were examined in Jeko-1, Mino and primary MCL cells via Transwell and Stimulated Raman scattering imaging analysis respectively. Enzyme-linked immunoassays were used to determine CCL3 and CCL4 levels in MCL-cell culture supernatants. RNA-seq analyses identified BTKi targets which were validated by quantitative RT-PCR (qRT-PCR) and immunoblot analysis.

Results: Acalabrutinib and Zanubrutinib induced moderate apoptosis in Ibrutinib high-sensitive JeKo-1 cells and Ibrutinib low-sensitive Mino cells, which was accompanied by cleaved PARP and caspase-3. Such effects might be caused by the stronger ability of Ibrutinib to upregulate the expression of pro-apoptotic genes, such as HRK, GADD45A, and ATM, in JeKo-1 cells than in Mino cells, and the expression of such apoptotic genes was slightly changed by Acalabrutinib and Zanubrutinib in both JeKo-1 and Mino cells. Further, Acalabrutinib, Zanubrutinib and Ibrutinib reduced MCL-cell chemotaxis with similar efficiency, due to their similar abilities to downmodulate chemokines, such as CCL3 and CCL4. Also, these three BTKi similarly suppressed MCL-cell LD accumulation via downregulating lipogenic factors, DGAT2, SCD, ENPP2 and ACACA without significant differences.

Conclusion: BTKi demonstrated differential capacities to induce MCL-cell apoptosis due to their distinct capabilities to regulate the expression of apoptosis-related genes, and similar biological and molecular inhibitory effects on MCL-cell chemotaxis and LD accumulation.
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http://dx.doi.org/10.1186/s12885-021-08475-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235860PMC
June 2021

A Polymer-in-Salt Electrolyte with Enhanced Oxidative Stability for Lithium Metal Polymer Batteries.

ACS Appl Mater Interfaces 2021 Jul 25;13(27):31583-31593. Epub 2021 Jun 25.

Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, Washington 99354, United States.

The lithium (Li) metal polymer battery (LMPB) is a promising candidate for solid-state batteries with high safety. However, high voltage stability of such a battery has been hindered by the use of polyethylene oxide (PEO), which oxidizes at a potential lower than 4 V versus Li. Herein, we adopt the polymer-in-salt electrolyte (PISE) strategy to circumvent the disadvantage of the PEO-lithium bis(fluorosulfonyl)imide (LiFSI) system with EO/Li ≤ 8 through a dry ball-milling process to avoid the contamination of the residual solvent. The obtained solid-state PISEs exhibit distinctly different morphologies and coordination structures which lead to significant improvement in oxidative stability. P(EO)LiFSI has a low melting temperature, a high ionic conductivity at 60 °C, and an oxidative stability of ∼4.5 V versus Li/Li. With an effective interphase rich in inorganic species and a good stability of the hybrid polymer electrolyte toward Li metal, the LMPB constructed with Li||LiNiCoMnO can retain 74.4% of capacity after 186 cycles at 60 °C under the cutoff charge voltage of 4.3 V. The findings offer a promising pathway toward high-voltage stable polymer electrolytes for high-energy-density and safe LMPBs.
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http://dx.doi.org/10.1021/acsami.1c04637DOI Listing
July 2021

TRPV2-spike protein interaction mediates the entry of SARS-CoV-2 into macrophages in febrile conditions.

Theranostics 2021 25;11(15):7379-7390. Epub 2021 May 25.

Key Laboratory of the Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Yinchuan 750021, China.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel strain of highly contagious coronaviruses that infects humans. Prolonged fever, particularly that above 39.5 °C, is associated with SARS-CoV-2 infection. However, little is known about the pathological effects of fever caused by SARS-CoV-2. Primary bovine alveolar macrophages (PBAMs), RAW264.7 mouse macrophages, and THP-1 human cells were transfected with plasmids carrying the genes encoding the SARS-CoV-2 spike (S) protein or receptor-binding domain (RBD). Proteins in the macrophages interacting with S-RBD at 39.5 °C or 37 °C were identified by immunoprecipitation-mass spectrometry. Glutathione -transferase pulldown, surface plasmon resonance, and immunofluorescence were performed to evaluate the transient receptor potential vanilloid 2 (TRPV2) interaction with SARS-CoV-2-S-RBD at 39.5 °C. Using an RNA sequencing-based approach, cytokine gene expression induced by SARS-CoV-2 S transfection at 39.5 °C and 37.5 °C in primary alveolar macrophages was measured. Fluo-4 staining and enzyme-linked immunosorbent assays were used to assess the regulatory function of TRPV2 in intracellular Ca and cytokines under SARS-CoV-2-S-RBD at 39.5 °C. Additionally, cytokine release was examined after TRPV2 knockdown with shRNA oligonucleotides or inhibition using the SKF-96365 antagonist. We identified an interaction between the primary alveolar macrophage receptor TRPV2 and S-RBD under febrile conditions. Febrile temperature promotes Ca influx through SARS-CoV-2 infection in PBAMs, further activates the NF-κB p65 signaling pathway, and enhances the secretion of cytokines. Furthermore, knockdown or antagonist (with SKF-96365) of TRPV2 significantly decreased the release of cytokines that drive the inflammatory response. Collectively, our findings identified TRPV2 as a receptor of SARS-CoV-2 in conditions of febrile temperature, providing insight into critical interactions of SARS-CoV-2 with macrophages, as well as a useful resource and potential drug target for coronavirus disease 2019.
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http://dx.doi.org/10.7150/thno.58781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210595PMC
June 2021

Simultaneously Regulating Uniform Zn Flux and Electron Conduction by MOF/rGO Interlayers for High-Performance Zn Anodes.

Nanomicro Lett 2021 Feb 15;13(1):73. Epub 2021 Feb 15.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen, 518055, People's Republic of China.

Owing to the merits of low cost, high safety and environmental benignity, rechargeable aqueous Zn-based batteries (ZBs) have gained tremendous attention in recent years. Nevertheless, the poor reversibility of Zn anodes that originates from dendrite growth, surface passivation and corrosion, severely hinders the further development of ZBs. To tackle these issues, here we report a Janus separator based on a Zn-ion conductive metal-organic framework (MOF) and reduced graphene oxide (rGO), which is able to regulate uniform Zn flux and electron conduction simultaneously during battery operation. Facilitated by the MOF/rGO bifunctional interlayers, the Zn anodes demonstrate stable plating/stripping behavior (over 500 h at 1 mA cm), high Coulombic efficiency (99.2% at 2 mA cm after 100 cycles) and reduced redox barrier. Moreover, it is also found that the Zn corrosion can be effectively retarded through diminishing the potential discrepancy on Zn surface. Such a separator engineering also saliently promotes the overall performance of Zn|MnO full cells, which deliver nearly 100% capacity retention after 2000 cycles at 4 A g and high power density over 10 kW kg. This work provides a feasible route to the high-performance Zn anodes for ZBs.
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http://dx.doi.org/10.1007/s40820-021-00594-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187534PMC
February 2021

A semi-supervised deep learning approach for predicting the functional effects of genomic non-coding variations.

BMC Bioinformatics 2021 Jun 2;22(Suppl 6):128. Epub 2021 Jun 2.

Department of Computer Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Background: Understanding the functional effects of non-coding variants is important as they are often associated with gene-expression alteration and disease development. Over the past few years, many computational tools have been developed to predict their functional impact. However, the intrinsic difficulty in dealing with the scarcity of data leads to the necessity to further improve the algorithms. In this work, we propose a novel method, employing a semi-supervised deep-learning model with pseudo labels, which takes advantage of learning from both experimentally annotated and unannotated data.

Results: We prepared known functional non-coding variants with histone marks, DNA accessibility, and sequence context in GM12878, HepG2, and K562 cell lines. Applying our method to the dataset demonstrated its outstanding performance, compared with that of existing tools. Our results also indicated that the semi-supervised model with pseudo labels achieves higher predictive performance than the supervised model without pseudo labels. Interestingly, a model trained with the data in a certain cell line is unlikely to succeed in other cell lines, which implies the cell-type-specific nature of the non-coding variants. Remarkably, we found that DNA accessibility significantly contributes to the functional consequence of variants, which suggests the importance of open chromatin conformation prior to establishing the interaction of non-coding variants with gene regulation.

Conclusions: The semi-supervised deep learning model coupled with pseudo labeling has advantages in studying with limited datasets, which is not unusual in biology. Our study provides an effective approach in finding non-coding mutations potentially associated with various biological phenomena, including human diseases.
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http://dx.doi.org/10.1186/s12859-021-03999-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171027PMC
June 2021

Integrated Resonant Micro/Nano Gravimetric Sensors for Bio/Chemical Detection in Air and Liquid.

Micromachines (Basel) 2021 May 31;12(6). Epub 2021 May 31.

State Key Lab of Transducer Technology, Shanghai Institute of Microsystem & Information Technology, Chinese Academy of Sciences, 865 Changning Road, Shanghai 200050, China.

Resonant micro/nanoelectromechanical systems (MEMS/NEMS) with on-chip integrated excitation and readout components, exhibit exquisite gravimetric sensitivities which have greatly advanced the bio/chemical sensor technologies in the past two decades. This paper reviews the development of integrated MEMS/NEMS resonators for bio/chemical sensing applications mainly in air and liquid. Different vibrational modes (bending, torsional, in-plane, and extensional modes) have been exploited to enhance the quality () factors and mass sensing performance in viscous media. Such resonant mass sensors have shown great potential in detecting many kinds of trace analytes in gas and liquid phases, such as chemical vapors, volatile organic compounds, pollutant gases, bacteria, biomarkers, and DNA. The integrated MEMS/NEMS mass sensors will continuously push the detection limit of trace bio/chemical molecules and bring a better understanding of gas/nanomaterial interaction and molecular binding mechanisms.
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http://dx.doi.org/10.3390/mi12060645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227694PMC
May 2021

Study on Fabrication and Properties of Graphite/Al Composites by Hot Isostatic Pressing-Rolling Process.

Materials (Basel) 2021 May 12;14(10). Epub 2021 May 12.

GRINM Metal Composites Technology Co. Ltd., Beijing 101407, China.

Graphite/Al composites have attracted much attrition due to their excellent thermal properties. However, the improvement of thermal conductivity (TC) is limited by the difficulty in controlling the orientation of graphite and the poor wettability between graphite and aluminum. In this study, a novel process for fabricating the Graphite/Al composites is proposed, which involves fabricating graphite film and aluminum foil into laminate material. Then, taking a rolling method, the fractured and well oriented graphite film can help the composite achieve high TC while maintaining a certain strength. The result reveals that both single and total reduction have a significant influence on the diameter and orientation of the graphite, and by adjusting the process parameters, composites with high TC can be acquired at a relatively low reinforcement volume. This near-net-forming process can directly meet the thickness requirements for electronic packaging and avoids the exposure of graphite to the surface during secondary processing, which is promising to promote the application for high TC Graphite/Al composites in thermal management.
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http://dx.doi.org/10.3390/ma14102522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152070PMC
May 2021

Application of a PBPK model to elucidate the changes of systemic and liver exposures for rosuvastatin, carotegrast, and bromfenac followed by OATP inhibition in monkeys.

Clin Transl Sci 2021 Sep 31;14(5):1924-1934. Epub 2021 May 31.

Drug Metabolism, Gilead Sciences Inc., Foster City, CA, USA.

The impact of organic anion-transporting polypeptide (OATP) inhibition on systemic and liver exposures of three OATP substrates was investigated in cynomolgus monkeys. A monkey physiologically-based pharmacokinetic (PBPK) model was constructed to describe the exposure changes followed by OATP functional attenuation. Rosuvastatin, bromfenac, and carotegrast were administered as a single intravenous cassette dose (0.5 mg/kg each) in monkeys with and without predosing with rifampin (RIF; 20 mg/kg) orally. The plasma exposure of rosuvastatin, bromfenac, carotegrast, and OATP biomarkers, coproporphyrin I (CP-I) and CP-III were increased 2.3, 2.1, 9.1, 5.4, and 8.8-fold, respectively, when compared to the vehicle group. The liver to plasma ratios of rosuvastatin and bromfenac were reduced but the liver concentration of the drugs remained unchanged by RIF treatment. The liver concentrations of carotegrast, CP-I, and CP-III were unchanged at 1 h but increased at 6 h in the RIF-treated group. The passive permeability, active uptake, and biliary excretion were characterized in suspended and sandwich-cultured monkey hepatocytes and then incorporated into the monkey PBPK model. As demonstrated by the PBPK model, the plasma exposure is increased through OATP inhibition while liver exposure is maintained by passive permeability driven from an elevated plasma level. Liver exposure is sensitive to the changes of metabolism and biliary clearances. The model further suggested the involvement of additional mechanisms for hepatic uptakes of rosuvastatin and bromfenac, and of the inhibition of biliary excretion for carotegrast, CP-I, and CP-III by RIF. Collectively, impaired OATP function would not reduce the liver exposure of its substrates in monkeys.
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http://dx.doi.org/10.1111/cts.13047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504809PMC
September 2021

Optimization of Magnesium-Doped Lithium Metal Anode for High Performance Lithium Metal Batteries through Modeling and Experiment.

Angew Chem Int Ed Engl 2021 Jul 21;60(30):16506-16513. Epub 2021 Jun 21.

Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.

Lithium (Li)-magnesium (Mg) alloy with limited Mg amount, which can also be called Mg-doped Li (Li-Mg), has been considered as a potential alternative anode for high energy density rechargeable Li metal batteries. However, the optimum doping-content of Mg in Li-Mg anode and the mechanism of the improved performance are not well understood. Herein, density functional theory (DFT) calculations are used to investigate the effect of Mg amount in Li-Mg anode. The Li-Mg with about 5 wt. % Mg (abbreviated as Li-Mg5) has the lowest absorption energy of Li, thus all the surface area can be "controlled" by Mg atoms, leading to the smooth and continuous deposition of Li on the surface around the Mg center. A localized high concentration electrolyte enables Li-Mg5 to exhibit the best cycling stability in Li metal batteries with high-loading cathode and lean electrolyte under 4.4 V high-voltage, which is approaching the demand of practical application. This electrolyte also helps generate an inorganic-rich solid electrolyte interphase, which leads to smooth, compact and less corrosion layer on the Li-Mg5 surface. Both theoretical simulations and experimental results prove that Li-Mg5 has optimum Mg content and gives best battery cycling performance.
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http://dx.doi.org/10.1002/anie.202103344DOI Listing
July 2021

Trifluoromethyl Thianthrenium Triflate: A Readily Available Trifluoromethylating Reagent with Formal CF, CF, and CF Reactivity.

J Am Chem Soc 2021 May 14;143(20):7623-7628. Epub 2021 May 14.

Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.

Here we report the synthesis and application of trifluoromethyl thianthrenium triflate (TT-CFOTf) as a novel trifluoromethylating reagent, which is conveniently accessible in a single step from thianthrene and triflic anhydride. We demonstrate the use of TT-CFOTf in electrophilic, radical, and nucleophilic trifluoromethylation reactions.
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http://dx.doi.org/10.1021/jacs.1c02606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297735PMC
May 2021
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