Publications by authors named "Liu K"

16,472 Publications

Risk Factors for Mortality After Uncemented Bipolar Hemiarthroplasty for Geriatric Displaced Femoral Neck Fracture.

Orthopedics 2021 Jul-Aug;44(4):e570-e576. Epub 2021 Jul 1.

Uncemented bipolar hemiarthroplasty (UBHA) has been widely used to treat geriatric displaced femoral neck fracture (GDFNF), which results in a high 30-day mortality rate among the elderly. To date, few studies have focused on the risk factors for mortality after UBHA for GDFNF. In this retrospective study, elderly patients (age ≥70 years) who underwent UBHA for GDFNF were studied in order to provide helpful insight into the risk factors for mortality postoperatively. This retrospective study enrolled 835 elderly patients who underwent UBHA for GDFNF from January 2010 to December 2017. The Kaplan-Meier method and Cox regression analysis were used to identify significant risk factors predicting mortality after UBHA for GDFNF. Univariate analysis showed that underweight (body mass index <18.5 kg/m), smoking, alcohol use, hypertension, chronic kidney disease, hypoproteinemia, low activities of daily living (ADL) score (0 to 2), and postoperative delirium were identified as the potential risk factors responsible for mortality after UBHA for GDFNF. Multivariate analysis suggested that underweight, hypoproteinemia, low ADL score, and postoperative delirium were significant risk factors predicting mortality after UBHA for GDFNF. Postoperative delirium was the most robust risk factor for mortality after UBHA for GDFNF. Underweight, hypoproteinemia, and low ADL score were also closely associated with mortality after UBHA for GDFNF. [. 2021;44(4):e570-e576.].
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http://dx.doi.org/10.3928/01477447-20210618-19DOI Listing
July 2021

Solvent-Evaporation Induced and Mechanistic Entropy-Enthalpy-Balance Controlled Polymer Patch Formation on Nanoparticle Surfaces.

J Phys Chem Lett 2021 Jul 22:7100-7105. Epub 2021 Jul 22.

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130021, China.

The formation of polymer-patch nanoparticles (PNPs) involves a condensation process of grafted chains on a nanoparticle (NP) surface, which is conventionally achieved via a fine-tuning of the solvent quality. However, such a critical solvent condition differs dramatically between polymers, and the formation mechanism of different patchy structures remains under debate. In this study, we demonstrate by a combined simulation and experimental study that such a surface-patterning process can be easily achieved via a simple solvent evaporation process, which creates a natural nonsolvent condition and is, in principle, adaptable for all polymers. More importantly, we find that patchy structures are controlled by a delicate balance between enthalpic interaction and the entropy penalty of grafted chains. A small variation of cohesive energy density can lead to a dramatic change in patch structure. This work offers a robust yet easy approach for the fabrication of PNPs and provides new insights into polymer segregation on spherical surfaces.
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http://dx.doi.org/10.1021/acs.jpclett.1c01979DOI Listing
July 2021

Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice.

Neurosci Bull 2021 Jul 22. Epub 2021 Jul 22.

Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing, 400038, China.

Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER; Tau-mGFP), we found that myelinogenesis was highly active in most brain regions, such as the motor cortex and corpus callosum. After exposure to hypoxia (10% oxygen) 12 h per day for 4 weeks, myelinogenesis was largely inhibited in the 4-month old brain and the mice displayed motor coordination deficits revealed by the beam-walking test. To determine the relationship between the inhibited myelination and functional impairment, we induced oligodendroglia-specific deletion of the transcription factor Olig2 by tamoxifen (NG2-CreER; Tau-mGFP; Olig2 fl/fl) in adult mice to mimic the decreased myelinogenesis caused by hypoxia. The deletion of Olig2 inhibited myelinogenesis and consequently impaired motor coordination, suggesting that myelinogenesis is required for motor function in adult mice. To understand whether enhancing myelination could protect brain functions against hypoxia, we treated hypoxic mice with the myelination-enhancing drug-clemastine, which resulted in enhanced myelogenesis and improved motor coordination. Taken together, our data indicate that chronic hypoxia inhibits myelinogenesis and causes functional deficits in the brain and that enhancing myelinogenesis protects brain functions against hypoxia-related deficits.
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http://dx.doi.org/10.1007/s12264-021-00745-1DOI Listing
July 2021

Association Between Kidney Dysfunction Types and Mortality Among Hospitalized Patients with Cirrhosis.

Dig Dis Sci 2021 Jul 22. Epub 2021 Jul 22.

Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA.

Background And Aims: Kidney dysfunction is associated with increased mortality among patients with cirrhosis. We investigated whether kidney dysfunction types [e.g., acute kidney injury (AKI), chronic kidney disease (CKD), and AKI on CKD] were differentially associated with inpatient mortality.

Methods: We utilized the nationwide inpatient sample, a nationally representative database, from 2007 to 2014. We included all hospitalizations with previously validated codes for cirrhosis or associated decompensated cirrhosis diagnoses. We defined kidney dysfunction types also from previously validated codes, and we grouped hospitalizations into the following diagnoses: normal, AKI, CKD, and AKI on CKD. Our primary outcome was inpatient mortality.

Results: There were 1,293,779 hospitalizations with cirrhosis sampled in this study. Of these hospitalizations, 849,193 (66%) had normal kidney function, 176,418 (14%) had AKI, 157,600 (12%) had CKD, and 110,568 (9%) had AKI on CKD. We found that the proportion of hospitalizations with AKI, CKD, and AKI on CKD increased significantly throughout the study period (p < 0.001, test for trend for all). Kidney dysfunction type was differentially associated with inpatient mortality, even after adjustment: as compared to those with CKD, normal kidney function: OR 0.75 [95 CI 0.73-0.78], AKI: OR 2.40 [95 CI 2.32-2.48], and AKI on CKD: OR 1.66 [95 CI 1.60-1.72].

Discussion: Using a nationally representative cohort of all hospitalizations with cirrhosis, our study highlights that the burden of kidney dysfunction, especially AKI, among hospitalizations with cirrhosis is rising, and the inclusion of kidney dysfunction type may be an opportunity to improve prognostication.
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http://dx.doi.org/10.1007/s10620-021-07159-zDOI Listing
July 2021

Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion.

J Exp Med 2021 Sep 21;218(9). Epub 2021 Jul 21.

Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA.

Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.
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http://dx.doi.org/10.1084/jem.20210324DOI Listing
September 2021

Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke.

Brain Pathol 2021 Jul 19:e13006. Epub 2021 Jul 19.

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

The breakdown of the blood-brain barrier (BBB) is related to the occurrence and deterioration of neurological dysfunction in ischemic stroke, which leads to the extravasation of blood-borne substances, resulting in vasogenic edema and increased mortality. However, a limited understanding of the molecular mechanisms that control the restrictive properties of the BBB hinders the manipulation of the BBB in disease and treatment. Here, we found that the glycocalyx (GCX) is a critical factor in the regulation of brain endothelial barrier integrity. First, endothelial GCX displayed a biphasic change pattern, of which the timescale matched well with the biphasic evolution of BBB permeability to tracers within the first week after t-MCAO. Moreover, GCX destruction with hyaluronidase increased BBB permeability in healthy mice and aggravated BBB leakage in transient middle cerebral artery occlusion (t-MCAO) mice. Surprisingly, ultrastructural observation showed that GCX destruction was accompanied by increased endothelial transcytosis at the ischemic BBB, while the tight junctions remained morphologically and functionally intact. Knockdown of caveolin1 (Cav1) suppressed endothelial transcytosis, leading to reduced BBB permeability, and brain edema. Lastly, a coimmunoprecipitation assay showed that GCX degradation enhanced the interaction between syndecan1 and Src by promoting the binding of phosphorylated syndecan1 to the Src SH2 domain, which led to rapid modulation of cytoskeletal proteins to promote caveolae-mediated endocytosis. Overall, these findings demonstrate that the dynamic degradation and reconstruction of GCX may account for the biphasic changes in BBB permeability in ischemic stroke, and reveal an essential role of GCX in suppressing transcellular transport in brain endothelial cells to maintain BBB integrity. Targeting GCX may provide a novel strategy for managing BBB dysfunction and central nervous system drug delivery.
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http://dx.doi.org/10.1111/bpa.13006DOI Listing
July 2021

An ether-linked halogenated phenazine-quinone prodrug model for antibacterial applications.

Org Biomol Chem 2021 Jul 20. Epub 2021 Jul 20.

Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.

Antibiotic-resistant infections present significant challenges to patients. As a result, there is considerable need for new antibacterial therapies that eradicate pathogenic bacteria through non-conventional mechanisms. Our group has identified a series of halogenated phenazine (HP) agents that induce rapid iron starvation that leads to potent killing of methicillin-resistant Staphylococcus aureus biofilms. Here, we report the design, chemical synthesis and microbiological assessment of a HP-quinone ether prodrug model aimed to (1) eliminate general (off-target) iron chelation, and (2) release an active HP agent through the bioreduction of a quinone trigger. Here, we demonstrate prodrug analogue HP-29-Q to have a stable ether linkage that enables HP release and moderate to good antibacterial activities against lab strains and multi-drug resistant clinical isolates.
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http://dx.doi.org/10.1039/d1ob01107cDOI Listing
July 2021

Crystallization-induced emission enhancement of highly electron-deficient dicyanomethylene-bridged triarylboranes.

Chem Commun (Camb) 2021 Jul 20. Epub 2021 Jul 20.

Key Laboratory of Cluster Science, Ministry of Education of China, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488, P. R. China.

A highly electron-deficient dicyanomethylene-bridged triarylborane, FMesB-TCN, was reported with a low-lying LUMO and crystallization-induced emission enhancement in its block-shape crystal. DFT calculations revealed lower re-organization energy of the block crystal than that of the weakly emissive acicular crystal. This work explored a novel boron-containing skeleton with interesting optical properties.
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http://dx.doi.org/10.1039/d1cc03311eDOI Listing
July 2021

Time-Resolved Pair-Correlated Imaging of the Photodissociation of Acetaldehyde at 267 nm: Pathway Partitioning.

J Phys Chem A 2021 Jul 21. Epub 2021 Jul 21.

Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan.

Photodissociation of acetaldehyde (CHCHO) by UV excitation involves interwoven multiple reaction pathways, including nonradiative decay, isomerization, transition-state pathway, roaming, and other dissociation mechanisms. Recently, we employed picosecond time-resolved, pair-correlated product imaging in a study of acetaldehyde photodissociation at 267 nm to disentangle those competing mechanisms and to elucidate the possible roaming pathways (Yang, C. H.; 2020, 11, 6423-6430). Here, we complement the pair-correlated product speed distribution of CO( = 0) at the high- side of the CO rotational state distribution in the CO + CH channel and detail the two-dimensional data analysis of the time-resolved images. As a result, extensive comparisons with other studies can be made and the branching fractions of the previously assigned TS(S), non-TS(S), and CI(S/S) pathways for the CO( = 0) + CH molecular channel are evaluated to be 0.74 ± 0.08, 0.15 ± 0.02, and 0.11 ± 0.02, respectively. Together with the macroscopic branching ratio between the molecular (CO + CH) and radical (CH + HCO) channels at 267 nm from the literature, a global view of the microscopic pathways can then be delineated, which provides invaluable insights and should pave the way for further studies of this interesting system.
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http://dx.doi.org/10.1021/acs.jpca.1c04773DOI Listing
July 2021

High Dimensional Functionomic Analysis of Human Hematopoietic Stem and Progenitor Cells at a Single Cell Level.

Bio Protoc 2018 May 20;8(10):e2851. Epub 2018 May 20.

Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.

The ability to conduct investigation of cellular transcription, signaling, and function at the single-cell level has opened opportunities to examine heterogeneous populations at unprecedented resolutions. Although methods have been developed to evaluate high-dimensional transcriptomic and proteomic data (relating to cellular mRNA and protein), there has not been a method to evaluate corresponding high-dimensional functionomic data (relating to cellular functions) from single cells. Here, we present a protocol to quantitatively measure the differentiation potentials of single human hematopoietic stem and progenitor cells, and then cluster the cells according to these measurements. High dimensional functionomic analysis of cell potential allows cell function to be linked to molecular mechanisms within the same progenitor population.
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http://dx.doi.org/10.21769/BioProtoc.2851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275246PMC
May 2018

Preemptive donor-derived anti-CD19 CAR T-cell infusion showed a promising anti-leukemia effect against relapse in MRD-positive B-ALL after allogeneic hematopoietic stem cell transplantation.

Leukemia 2021 Jul 20. Epub 2021 Jul 20.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

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http://dx.doi.org/10.1038/s41375-021-01351-wDOI Listing
July 2021

PLA2G4A promotes right-sided colorectal cancer progression by inducing CD39+γδ Tregs polarization.

JCI Insight 2021 Jul 20. Epub 2021 Jul 20.

Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

γδ T cell is a promising candidate cell in tumor immunotherapy. However, γδ T cells polarized to CD39+γδ Tregs upon colorectal cancer (CRC) induction and the underlying mechanism remains unclear. Here, we discovered that the frequency of CD39+γδ Tregs, which positively correlated with poor prognosis, was significantly higher in right-sided CRC (RSCRC) than in the left-sided CRC (LSCRC). Interestingly, CD39+γδ Tregs from RSCRC showed stronger immunosuppressive phenotype and function than LSCRC. Further, the quantitative mass spectrometry data showed that CD39+γδ Tregs polarization was related to the abnormal activation of the PLA2G4A/AA metabolic pathway in RSCRC. Using an in vitro co-culture system and an orthotopic murine model of CRC, we proved that the overexpression of Pla2g4a in CT26 cells induced CD39+γδ Tregs inhibiting the anti-tumor immune response. Finally, we found that the overall survival of the PLA2G4Ahigh group was significantly shortened compared to PLA2G4Alow RSCRC, while the survival of LSCRC was on the contrary. Collectively, RSCRC with abnormal PLA2G4A expression educates γδ T cells into CD39+γδ Tregs to promote tumor progression and metastasis. Our work highlights the interaction between cancer cells and immune cells by distinguishing the primary tumor site and deepens the understanding of tumor microenvironment and immunosuppression.
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http://dx.doi.org/10.1172/jci.insight.148028DOI Listing
July 2021

Engineering of hybrid anticancer drug-loaded polymeric nanoparticles delivery system for the treatment and care of lung cancer therapy.

Drug Deliv 2021 Dec;28(1):1539-1547

Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, PR China.

Chemotherapy with combination drugs has become one of the most commonly used cancer prevention treatments, with positive clinical results. The goal of this study was to develop compostable polymeric nanomaterials (NMs) for the delivery of puerarin (PRN) and 5-fluorouracil (5FU), as well as to investigate the anticancer activity of the drug delivery system (PRN-5FU NMs) against and lung cancer cells. Since double antitumor drugs PRN and 5FU are insufficiently compressed in polymer-based bio-degradable nanoparticles, encapsulation of PRN and 5FU antitumor drugs were co-encapsulated with polyethylene glycol and polylactidecoglycolide nanoparticles (NMs) is efficient. The arrangement of PRN NMs, 5FU NMs, and PRN-5FU NMs, as well as the nanoparticles shape and scale, were studied using transmission electron microscopy (TEM). 5FU-PRN NMs triggered apoptosis in lung carcinoma cell lines such as HEL-299 and A549 . Acridine orange/ethidium bromide (AO/EB) and nuclear damaging staining techniques were used to observe morphologies and cell death. The mechanistic analysis of apoptosis was also confirmed by flow cytometry analysis using dual staining. When compared to free anticancer products, the hemolysis analysis findings of the 5FU-PRN NMs showed excellent biocompatibility. Taken together the advantages, this combination drug conveyance strategy exposed that 5FU-PRN NMs could have a significant promising to improve the effectiveness of lung cancer cells.
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http://dx.doi.org/10.1080/10717544.2021.1934187DOI Listing
December 2021

Granulocyte-macrophage colony-stimulating factor: an immunotarget for sepsis and COVID-19.

Cell Mol Immunol 2021 Jul 19. Epub 2021 Jul 19.

Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

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http://dx.doi.org/10.1038/s41423-021-00719-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287545PMC
July 2021

Multiple Warthin Tumors With Epithelial-Myoepithelial Carcinoma of the Ipsilateral Parotid Gland: A Case Report.

Ear Nose Throat J 2021 Jul 19:1455613211028086. Epub 2021 Jul 19.

School and Hospital of Stomatology, 159344Jilin University, Changchun, China.

Multiple primary tumors of the parotid gland refer to the occurrence of 2 or more primary tumors in the ipsilateral or bilateral parotid gland metachronously or synchronously, which do not originate from postoperative recurrence or metastasis. Multiple primary tumors of the parotid gland, especially synchronous benign and malignant tumors, are extremely uncommon. A rare case of multiple Warthin tumors with epithelial-myoepithelial carcinoma of the ipsilateral parotid gland is reported as follows.
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http://dx.doi.org/10.1177/01455613211028086DOI Listing
July 2021

A multi-proxy record of hurricanes, tsunami, and post-disturbance ecosystem changes from coastal southern Baja California.

Sci Total Environ 2021 Jul 14;796:149011. Epub 2021 Jul 14.

Indiana Geological and Water Survey, Indiana University, 420 N Walnut St., Bloomington, IN 47404, USA.

Tsunamis and hurricanes are two earth surface processes that can dramatically impact coastal landforms and ecosystems. This study uses a combination of palynological, grain-size, X-ray fluorescence, and loss-on-ignition analyses, short-lived isotopic and radiocarbon dating, and statistical analysis to differentiate the tsunami and hurricane deposits, establish a Late-Holocene record of extreme events, and document the landscape and vegetation transformation in response to disturbance events and environmental changes from a small coastal lagoon in Baja California, Mexico. Prior to ~530 cal yr BP, Playa Los Cocos was occupied by a short-hydroperiod tidal marsh bounded by desert vegetation on the surrounding hillslopes. At ~530 cal yr BP, a tsunami created a backbarrier lagoon and introduced mangrove propagules from other coastal localities, and the lagoonal environment and substrates also provided suitable habitats for red mangroves to proliferate. Once established, red mangrove populations rapidly expanded until ~180 cal yr BP, when modern human activities diminished the mangrove forest in our study area. Overall, the multi-proxy dataset revealed four hurricane events at ~770, ~600, ~280, and ~0 cal yr BP, and one tsunami event at ~530 cal yr BP. The hurricane deposits were preserved in the form of fluvial and slope-wash deposits characterized by low organic and water contents, low concentration of marine elements, and high concentration of terrestrial elements. The tsunami run-up deposits are characterized by abundant broken and intact sea shells, high content of carbonate and marine elements, low concentration of terrestrial elements, and sharp basal contact with the underlying sediments. The tsunami backwash deposits are characterized by a mixed physical and chemical signature resembling both marine and terrestrial sediments. Results also suggest that both hurricanes and tsunamis can help propagule dispersal and create suitable coastal habitats favorable for the spread and proliferation of mangroves in a desert coastal environment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149011DOI Listing
July 2021

Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up.

J Control Release 2021 Jul 16;337:144-154. Epub 2021 Jul 16.

Boston University, Department of Biomedical Engineering, Boston, MA, United States of America; Ionic Pharmaceuticals, LLC, Brookline, MA, United States of America; Boston University, Department of Chemistry, Boston, MA, United States of America.

One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate level of production, i.e., "pilot-scale" production, can be achieved. Pilot-scale production at the one-liter scale serves as a proof-of-concept that large-scale production will be possible. Here, we describe the pilot-scale production of the expansile nanoparticle (eNP) technology including verification of activity and efficacy following scaleup. We describe the challenges of sonication-based emulsification procedures and how these were overcome by use of a Microfluidizer technology. We also describe the problem-solving process that led to pre-polymerization of the nanoparticle polymer-a fundamental change from the lab-scale and previously published methods. Furthermore, we demonstrate good control over particle diameter, polydispersity and drug loading and the ability to sterilize the particles via filtration using this method. To facilitate long-term storage of these larger quantities of particles, we investigated six lyoprotectants and determined that sucrose is the most compatible with the current system. Lastly, we demonstrate that these changes to the manufacturing method do not adversely affect the swelling functionality of the particles, their highly specific localization to tumors, their non-toxicity in vivo or their efficacy in treating established intraperitoneal mesothelioma xenografts.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.012DOI Listing
July 2021

Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed acute leukemia post-chemotherapy plus modified donor lymphocyte infusion.

Front Med 2021 Jul 19. Epub 2021 Jul 19.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing, 100044, China.

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo + m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo + m-DLI in our center. With a median follow-up of 918 (457-1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1% ± 4.9% and 25.0% ± 8.4%. The cumulative incidences of relapse were 50.0% ± 9.8% and 53.5% ± 9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo + m-DLI.
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http://dx.doi.org/10.1007/s11684-021-0833-xDOI Listing
July 2021

Response characteristics and optimization of electroporation: simulation based on finite element method.

Electromagn Biol Med 2021 Jul 18:1-17. Epub 2021 Jul 18.

Department of Light Sources & Illuminating Engineering, Fudan University, Shanghai China.

Electroporation has been widely used in biology, medicine, and the food industry as a means to transport various molecules through the cell membrane. The phenomenon of electroporation is the result of cell membrane damage caused by the application of an electric field. In order to understand more precisely how cells function, we established a dielectric model of a spherical cell and analyzed its characteristics by the finite element method. The effects of altering different electrical parameters were determined. The results showed that the electric field strength was positively related to the transmembrane voltage (TMV) and pore density. There was a minimum electric field strength necessary to induce a critical TMV for the formation of pores. Pulse width also had to be long enough to charge the cell membrane, compared with the normal membrane charging time constant of about 1 μs. When the pulse width was shorter than the charging time constant, it was necessary to increase pulse frequency to create a high enough TMV. The rise-time of the electric pulse also affected electroporation: a fast rise-time pulse not only allowed penetration of the plasma membrane but also the organelle membrane. With slow rise-time pulse, the organelle was shielded from electroporation. This study defines the response characteristics of electrical parameters on the electric load cell and establishes the specificity of parameters for different purposes.
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http://dx.doi.org/10.1080/15368378.2021.1951484DOI Listing
July 2021

The regulatory effect of acetylation of HMGN2 and H3K27 on pyocyanin-induced autophagy in macrophages by affecting Ulk1 transcription.

J Cell Mol Med 2021 Jul 18. Epub 2021 Jul 18.

Department of Pathophysiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.

Pyocyanin (PYO) is a major virulence factor secreted by Pseudomonas aeruginosa, and autophagy is a crucial homeostatic mechanism for the interaction between the pathogens and the host. It remains unknown whether PYO leads to autophagy in macrophages by regulating histone acetylation. The high mobility group nucleosomal binding domain 2 (HMGN2) has been reported to regulate the PYO-induced autophagy and oxidative stress in the epithelial cells; however, the underlying molecular mechanism has not been fully elucidated. In this study, PYO was found to induce autophagy in macrophages, and the mechanism might be correlated with the up-regulation of HMGN2 acetylation (HMGN2ac) and the down-regulation of H3K27 acetylation (H3K27ac) by modulation of the activities of acetyltransferases and deacetylases. Moreover, we further demonstrated that the up-regulated HMGN2ac enhances its recruitment to the Ulk1 promoter, while the down-regulation of H3K27ac reduces its recruitment to the Ulk1 promoter, thereby promoting or inhibiting the transcription of Ulk1. In conclusion, HMGN2ac and H3K27ac play regulatory roles in the PYO-induced autophagy in macrophages.
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http://dx.doi.org/10.1111/jcmm.16788DOI Listing
July 2021

Profiles of NK cell subsets are associated with successful tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia and changes following interferon treatment.

Ann Hematol 2021 Jul 19. Epub 2021 Jul 19.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.

Recent studies have shown that approximately 50% of patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy with a sustained deep molecular response (DMR) (BCR-ABL1 ≤ 0.01%) can achieve treatment-free remission (TFR, stopping TKI without relapse) and that prior interferon (IFN)-α therapy and higher NK cell counts at and after TKI discontinuation are associated with TFR. We recently reported that post-TKI discontinuation of IFN-α therapy could prevent molecular relapse (MR, BCR-ABL1 > 0.1%). Here, we evaluated whether NK cells are associated with MR and investigated the effects of post-TKI discontinuation IFN-α therapy on lymphocyte subsets. A total of 34 patients measuring blood lymphocyte subclasses were included. In the 22 patients who did not receive IFN-α therapy, at 1 month after TKI discontinuation, the nonrelapsed patients showed a significantly higher proportion and count of NK cells than the relapsed patients. In particular, the proportion and count of CD56dim NK cells were significantly higher in the nonrelapsed patients than in the relapsed patients. In the 12 patients who received IFN-α therapy, the level of CD56bright NK cells increased significantly after 3 and 6 months of IFN-α therapy. In summary, NK cells, in particular CD56dim NK cells, were associated with MR after TKI discontinuation in patients with CML. Additionally, IFN-α therapy gradually increased the level of CD56bright NK cells in patients with CML.
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http://dx.doi.org/10.1007/s00277-021-04606-9DOI Listing
July 2021

Corrigendum to: Computational design of ultrashort peptide inhibitors of the receptor-binding domain of the SARS-CoV-2 S protein.

Brief Bioinform 2021 Jul 17. Epub 2021 Jul 17.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

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http://dx.doi.org/10.1093/bib/bbab298DOI Listing
July 2021

Multifunctional Lignin-Based Composite Materials for Emerging Applications.

Front Bioeng Biotechnol 2021 2;9:708976. Epub 2021 Jul 2.

Tianjin Key Laboratory of Pulp and Paper, Tianjin University of Science and Technology, Tianjin, China.

Lignin exhibited numerous advantages such as plentiful functional groups, good biocompatibility, low toxicity, and high carbon content, which can be transformed into composites and carbon materials. Lignin-based materials are usually environmentally friendly and low cost, and are widely used in energy storage, environment, electronic devices, and other fields. In this review article, the pretreatment separation methods like hydrothermal process are illustrated briefly, and the properties and categories of technical lignin are introduced. Then, the latest progress of lignin-based composites and lignin-derived carbon materials is summarized. Finally, the current challenges and future developments were suggested based on our knowledge. It is expected that this review paper favored the applications of composites and lignin-derived carbon materials in the future.
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http://dx.doi.org/10.3389/fbioe.2021.708976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284057PMC
July 2021

Fungal Community Composition and Diversity Vary With Soil Horizons in a Subtropical Forest.

Front Microbiol 2021 1;12:650440. Epub 2021 Jul 1.

CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.

Soil fungal communities, which drive many ecosystem processes, vary across soil horizons. However, how fungal communities are influenced by soil horizon layers remains largely unstudied. In this study, soil samples were collected from the organic horizon (O horizon) and mineral matter horizon (M horizon) in two sites of Dabie Mountain, China, and the effects of the two horizons on the soil fungal community composition were assessed based on Illumina MiSeq sequencing. Our results showed that soil fungal community composition varied with soil horizons, and soil fungal species richness and diversity in the O horizon were significantly higher than that in the M horizon. Total organic carbon (TOC), total organic nitrogen (TON), alkali-hydrolyzable nitrogen (AHN), available potassium (AK), and available phosphorus (AP) significantly influenced fungal community composition, abundance, and diversity across the two horizons ( < 0.05). Furthermore, precipitation was found to have a significant effect on fungal community composition. Our results demonstrate changes in fungal communities across soil horizons and highlight the importance of soil organic matter on fungal communities and diversity.
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http://dx.doi.org/10.3389/fmicb.2021.650440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281208PMC
July 2021

An observation approach in evaluation of ozone production to precursor changes during the COVID-19 lockdown.

Atmos Environ (1994) 2021 Oct 14;262:118618. Epub 2021 Jul 14.

Institute for Environmental and Climate Research, Jinan University, Guangzhou, 511443, China.

The increase of surface ozone during the Corona Virus Disease 2019 (COVID-19) lockdown in China has aroused great concern. In this study, we combine 1.5 years of measurements for ozone, volatile organic compounds (VOCs), and nitrogen oxide (NO) at four sites to investigate the effect of COVID-19 lockdown on surface ozone in Dongguan, an industrial city in southern China. We show that the average concentrations of NO and VOCs decreased by 70%-77% and 54%-68% during the lockdown compared to pre-lockdown, respectively. Based on the source apportionment of VOCs, the contribution of industrial solvent use reduced significantly (86%-94%) during the lockdown, and climbed back slowly along with the re-opening of the industry after lockdown. A slight increase in mean ozone concentration (3%-14%) was observed during the lockdown. The rise of ozone was the combined effect of substantial increase at night (58%-91%) and small reduction in the daytime (1%-17%). These conflicting observations in ozone response between day and night to emission change call for a more detailed approach to diagnostic ozone production response with precursor changes, rather than directly comparing absolute concentrations. We propose that the ratio of daily Ox (i.e. ozone + NO) enhancement to solar radiation can provide a diagnostic parameter for ozone production response during the lockdown period. Smaller ratio of daily O (ozone + NO) enhancement to solar radiation during the lockdown were observed from the long-term measurements in Dongguan, suggesting significantly weakened photochemistry during the lockdown successfully reduces local ozone production. Our proposed approach can provide an evaluation of ozone production response to precursor changes from restrictions of social activities during COVID-19 epidemic and also other regional air quality abatement measures (e.g. public mega-events) around the globe.
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http://dx.doi.org/10.1016/j.atmosenv.2021.118618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277545PMC
October 2021

Arsenite and monomethylarsonous acid disrupt erythropoiesis through combined effects on differentiation and survival pathways in early erythroid progenitors.

Toxicol Lett 2021 Jul 15;350:111-120. Epub 2021 Jul 15.

The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM, 87131, USA. Electronic address:

Strong epidemiological evidence demonstrates an association between chronic arsenic exposure and anemia. We recently found that As impairs erythropoiesis by disrupting the function of GATA-1; however the downstream pathways impacted by the loss of GATA-1 function have not been evaluated. Additionally, our previous findings indicate that the predominant arsenical in the bone marrow of mice exposed to As in their drinking water for 30 days was MMA, but the impacts of this arsenical on erythorpoisis also remain largely unknown. The goal of this study was to address these critical knowledge gaps by evaluating the comparative effects of arsenite (As) and the As metabolite, monomethyarsonous acid (MMA) on two critical regulatory pathways that control the differentiation and survival of early erythroid progenitor cells. We found that 500 nM As and 100 and 500 nM MMA suppress erythropoiesis by impairing the differentiation of early stage erythroid progenitors. The suppression of early erythroid progenitor cell development was attributed to combined effects on differentiation and survival pathways mediated by disruption of GATA-1 and STAT5. Our results show that As primarily disrupted GATA-1 function; whereas, MMA suppressed both GATA-1 and STAT5 activity. Collectively, these findings provide novel mechanistic insights into arsenic-induced dyserythropoiesis and suggest that MMA may be more toxic than As to early developing erythroid cells.
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http://dx.doi.org/10.1016/j.toxlet.2021.07.008DOI Listing
July 2021

Associations of plasma metal concentrations with incident dyslipidemia: Prospective findings from the Dongfeng-Tongji cohort.

Chemosphere 2021 Jul 9;285:131497. Epub 2021 Jul 9.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Metal exposures are ubiquitous around the world, while it is lack of prospective studies to evaluate the associations of exposure to multiple metal/metalloids with incident dyslipidemia. A total of 2947 participants without dyslipidemia at baseline were included in the analyses. We utilized inductively coupled plasma mass spectrometry to measure the baseline plasma metal concentrations. Unconditional logistic regression models were applied to estimate the relations between plasma metals and risk of incident dyslipidemia, and principal component analysis was performed to extract principal components of metals. During 5.01 ± 0.31 years of follow-up, 521 subjects were diagnosed with incident dyslipidemia. After multivariable adjustment, the odds ratios (ORs) of dyslipidemia comparing the highest quartiles to the lowest were 1.58 (95% CI: 1.20, 2.08; P = 0.001) for aluminum, 1.34 (95% CI: 1.03, 1.75; P = 0.03) for arsenic, 1.44 (1.09, 1.91; P = 0.03) for strontium, and 1.47 (95% CI: 1.09, 2.00; P = 0.005) for vanadium. The four metals also showed significant associations with the subtypes of dyslipidemia, including low HDL-C and high LDL-C. The first principal component, which mainly represented aluminum, arsenic, barium, lead, vanadium, and zinc, was associated with increased risk of incident dyslipidemia, and the adjusted OR was 1.40 (95% CI: 1.07, 1.84; P = 0.02) comparing extreme quartiles. The study indicated that elevated plasma aluminum, arsenic, strontium, and vanadium concentrations were associated with a higher incidence of dyslipidemia. These findings highlight the importance of controlling metal exposures for dyslipidemia prevention.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131497DOI Listing
July 2021

Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements.

Med J Aust 2021 Jul 17. Epub 2021 Jul 17.

AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW.

Objective: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements.

Design: Retrospective electronic medical record data analysis.

Setting, Participants: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020.

Main Outcome Measures: 90-day transplant-free survival; drugs implicated as causal agents in DILI.

Results: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 11 (15%) during 2009-11 to 10 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36).

Conclusion: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.
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http://dx.doi.org/10.5694/mja2.51173DOI Listing
July 2021

A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion.

Nat Commun 2021 07 16;12(1):4358. Epub 2021 Jul 16.

Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.

Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores protein function by selectively suppressing translation termination at PTCs. Poor efficacy of current readthrough agents prompted us to search for better compounds. An NMD-sensitive NanoLuc readthrough reporter was used to screen 771,345 compounds. Among the 180 compounds identified with readthrough activity, SRI-37240 and its more potent derivative SRI-41315, induce a prolonged pause at stop codons and suppress PTCs associated with cystic fibrosis in immortalized and primary human bronchial epithelial cells, restoring CFTR expression and function. SRI-41315 suppresses PTCs by reducing the abundance of the termination factor eRF1. SRI-41315 also potentiates aminoglycoside-mediated readthrough, leading to synergistic increases in CFTR activity. Combining readthrough agents that target distinct components of the translation machinery is a promising treatment strategy for diseases caused by PTCs.
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http://dx.doi.org/10.1038/s41467-021-24575-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285393PMC
July 2021

Expression mode and prognostic value of FXYD family members in colon cancer.

Aging (Albany NY) 2021 Jul 15;13(undefined). Epub 2021 Jul 15.

Department of Radiation Oncology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.

The FXYD gene family comprises seven members that encode a class of small-membrane proteins characterized by an FXYD motif and interact with Na/K-ATPase. Until now, the expression patterns and prognostic roles of the FXYD family in colon cancer (CC) have not been systematically reported. Gene expression, methylation, clinicopathological features and the prognoses of CC patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression feature and prognostic values of FXYD members were identified. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism underlying the function of the FXYD family in CC. Tumor Immune Estimation Resource (TIMER) and CIBERSORT analysis were used to assess the correlations between FXYD family members and tumor immune infiltrating cells (TIICs). FXYD family members were differentially expressed in CC except for FXYD2. FXYD2, FXYD3 and FXYD4 were revealed as independent prognostic factors for recurrence, while FXYD3 and FXYD7 were identified as prognostic factors for survival according to univariate and multivariate analyses with Cox regression. GSEA revealed that FXYD family members were involved in complicated biological functions underlying cancer progression. TIMER and CIBERSORT analyses showed significant associations between FXYD family genes and TIICs. The present study comprehensively revealed the expression mode and prognostic value of FXYD members in CC, providing insights for further study of the FXYD family as potential clinical biomarkers in CC.
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http://dx.doi.org/10.18632/aging.203290DOI Listing
July 2021
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