Publications by authors named "Yun Liu"

1,985 Publications

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The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis.

Oncogene 2021 Jul 22. Epub 2021 Jul 22.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

K-RAS mutation and molecular alterations of its surrogates function essentially in lung tumorigenesis and malignant progression. However, it remains elusive how tumor-promoting and deleterious events downstream of K-RAS signaling are coordinated in lung tumorigenesis. Here, we show that USP16, a deubiquitinase involved in various biological processes, functions as a promoter for the development of K-RAS-driven lung tumor. Usp16 deletion significantly attenuates K-ras-mutation-induced lung tumorigenesis in mice. USP16 upregulation upon RAS activation averts reactive oxygen species (ROS)-induced p38 activation that would otherwise detrimentally influence the survival and proliferation of tumor cells. In addition, USP16 interacts with and deubiquitinates JAK1, and thereby promoting lung tumor growth by augmenting JAK1 signaling. Therefore, our results reveal that USP16 functions critically in the K-RAS-driven lung tumorigenesis through modulating the strength of p38 and JAK1 signaling.
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http://dx.doi.org/10.1038/s41388-021-01964-6DOI Listing
July 2021

Self-Healing Solid Polymer Electrolyte with High Ion Conductivity and Super Stretchability for All-Solid Zinc-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jul 26. Epub 2021 Jul 26.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

The zinc-ion battery (ZIB) is a novel energy storage device, an attractive alternative to the lithium-ion battery. The frequently used aqueous electrolyte suffers from many problems such as zinc dendrites and leakage, which prompts hydrogel electrolytes and solid electrolytes as good replacements. However, hydrogel electrolytes are usually unstable, owing to water volatilization. Herein, a novel solid polymer electrolyte (SPE) utilizing coordination of zinc ions is designed and then introduced into an all-solid ZIB. Benefiting from the unique coordination structure between the polymer and zinc ions, the SPE shows outstanding flexibility, high ion conductivity, and self-healing properties. In addition, the imine bonds in the polymer allow the electrolyte to degrade in acid environments, endowing its recyclability. More importantly, solid-state ZIBs based on the polymer electrolytes exhibit an impressive cycling stability (125% capacity retention after 300 cycles) and a high coulombic efficiency (94% after 300 cycles). The results demonstrate the promising potentials of the developed SPEs that can be used in all-solid ZIBs.
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http://dx.doi.org/10.1021/acsami.1c09200DOI Listing
July 2021

Current research progress in targeted anti-angiogenesis therapy for osteosarcoma.

Cell Prolif 2021 Jul 26:e13102. Epub 2021 Jul 26.

Division of Regenerative Biology, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.

Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%-70% 5-year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre-clinical and developmental research of targeted anti-angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti-angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti-angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti-angiogenesis therapy in OS.
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http://dx.doi.org/10.1111/cpr.13102DOI Listing
July 2021

Identifying Lung Cancer Patients Suitable for Segmentectomy: A Brief Review.

Front Surg 2021 8;8:637441. Epub 2021 Jul 8.

Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.

In 1995, a clinical randomized controlled study (RCT) conducted by the Lung Cancer Study Group (LCSG) pointed out that the lobectomy was the gold standard for treating early lung cancer. However, with the development of technology, the results of several retrospective studies have shown that the efficacy of pulmonary segmentectomy is equivalent to that of lobectomy. Currently, it is still controversial whether segmental resection or lobectomy should be performed for early lung cancer. Thus, we aim to summarize the indications of segmentectomy. To conduct the review, previous researches involving indications of segmentectomy were collected from the literature using Pubmed. These articles were published and accepted in English in the medical literature from 2013 to 2020. We have focused on segmentectomy and its indications. A total of 176 articles were retrieved from the Pubmed database, of which 31 articles included indications for segmentectomy. We summarized the relevant content, and the potential and prospect of segmentectomy for the treatment of lung cancer were emphasized. These findings have a number of important implications for future practice. Pulmonary segmentectomy is a very vital surgical procedure for select patients with lung cancer, which provides a novel approach for the treatment of lung cancer and the survival of lung cancer patients.
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http://dx.doi.org/10.3389/fsurg.2021.637441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295684PMC
July 2021

Understanding the enhancement effect of boron doping on the electrochemical performance of single-crystalline Ni-rich cathode materials.

J Colloid Interface Sci 2021 Jul 9;604:776-784. Epub 2021 Jul 9.

Engineering Research Center of the Ministry of Education for Advanced Battery Materials, School of Metallurgy and Environment, Central South University, Changsha 410083, China. Electronic address:

Ni-rich layered oxides are considered as promising cathode materials for Li-ion batteries (LIBs) due to their satisfying theoretical specific capacity and reasonable cost. However, poor cycling stability caused by structural collapse and interfacial instability of the Ni-rich cathode material limits the further applications of commercialization. Herein, a series of B-doped single-crystal LiNiCoMnO (NCM) are designed and fabricated, aiming to improve the structural stability and enlarge the Li-ions diffusion paths simultaneously. It reveals that B-doping at TM layers will facilitate the formation of stronger B-O covalent bonds and expand the layered distance, significantly enhancing the thermodynamics and kinetic of NCM electrode. With the synergistic effect of single-crystalline architecture and appropriate B-doping, it can effectively alleviate the occurrence of internal strain with structural degradation and boost the intrinsic rate capability synchronously. As anticipated, the 0.6 mol % B-doped NCM electrode exhibits enhanced rate property and superior cycle stability, even at the harsh condition of high-temperature and elevated cut-off voltage. Remarkably, when tested in pouch-type full-cell, it maintains high reversible capacity with superior capacity retention of 91.35% over 500 cycles with only 0.0173% decay per cycle. This research illustrates the feasibility of B-doping and single-crystalline architecture to improve the electrochemical performance, which is beneficial to understand the enhancement effect and provides the design strategy for the commercialization progress of Ni-rich cathode materials.
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http://dx.doi.org/10.1016/j.jcis.2021.07.027DOI Listing
July 2021

Impact of Orientational Glass Formation and Local Strain on Photo-Induced Halide Segregation in Hybrid Metal-Halide Perovskites.

J Phys Chem C Nanomater Interfaces 2021 Jul 30;125(27):15025-15034. Epub 2021 Jun 30.

Cavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, U.K.

Band gap tuning of hybrid metal-halide perovskites by halide substitution holds promise for tailored light absorption in tandem solar cells and emission in light-emitting diodes. However, the impact of halide substitution on the crystal structure and the fundamental mechanism of photo-induced halide segregation remain open questions. Here, using a combination of temperature-dependent X-ray diffraction and calorimetry measurements, we report the emergence of a disorder- and frustration-driven orientational glass for a wide range of compositions in CHNHPb(Cl Br ). Using temperature-dependent photoluminescence measurements, we find a correlation between halide segregation under illumination and local strains from the orientational glass. We observe no glassy behavior in CsPb(Cl Br ), highlighting the importance of the A-site cation for the structure and optoelectronic properties. Using first-principles calculations, we identify the local preferential alignment of the organic cations as the glass formation mechanism. Our findings rationalize the superior photostability of mixed-cation metal-halide perovskites and provide guidelines for further stabilization strategies.
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http://dx.doi.org/10.1021/acs.jpcc.1c03169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287560PMC
July 2021

Efficient RNA virus targeting via CRISPR-CasRx in fish.

J Virol 2021 Jul 21:JVI0046121. Epub 2021 Jul 21.

Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.

The emergence of the CRISPR-Cas system as a technology has transformed our ability to modify nucleic acids, and the CRISPR-Cas13 system has been used to target RNA. CasRx is a small sized type VI-D effector (Cas13d) with RNA knockdown efficiency that may have an interference effect on RNA viruses. However, the RNA virus-targeting activity of CasRx still needs to be verified in vertebrates. In this study, we successfully engineered a highly effective CasRx system for fish virus interference. We designed synthetic mRNA coding for CasRx and used CRISPR RNAs to guide it to target the grouper nervous necrosis virus (RGNNV). This technique resulted in significant interference with virus infections both and . These results indicate that CRISPR/CasRx can be used to engineer interference against RNA viruses in fish, which provides a potential novel mechanism for RNA-guided immunity against other RNA viruses in vertebrates. RNA viruses are most important viral pathogens infecting vertebrates and mammals. RNA virus populations are highly dynamic due to short generation times, large population sizes, and high mutation frequencies. Therefore, it is difficult to find a widely effective ways to inhibit RNA viruses. Therefore, we urgently need to develop effective antiviral methods. CasRx is a small sized type VI-D effector (Cas13d) with RNA knockdown efficiency that can have an interference effect on RNA viruses. Nervous necrosis virus (NNV), a non-enveloped positive-strand RNA virus, is one of the most serious viral pathogens infecting more than 40 cultured fish species resulting in huge economic losses worldwide. Here, we establish a novel efective CasRx system for RNA virus interference using NNV and grouper (Epinephelus coioices) as model. Our data show that CasRx have the most robust for RNA virus interference applications in fish and demonstrate its suitability for studying key questions relating to virus biology.
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http://dx.doi.org/10.1128/JVI.00461-21DOI Listing
July 2021

[Retracted] MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression.

Int J Mol Med 2021 Sep 19;48(3). Epub 2021 Jul 19.

Department of Neurosurgery, Baotou Eighth Hospital, Baotou, Inner Mongolia 014040, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration data shown in Figs. 2D and 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 38: 1587‑1595, 2016; DOI: 10.3892/ijmm.2016.2754].
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http://dx.doi.org/10.3892/ijmm.2021.5003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285045PMC
September 2021

Molecular dynamics investigation of the stopping power of warm dense hydrogen for electrons.

Phys Rev E 2021 Jun;103(6-1):063215

Department of Physics, National University of Defense Technology, Changsha 410073, China.

A variety of theoretical models have been proposed to calculate the stopping power of charged particles in matter, which is a fundamental issue in many fields. However, the approximation adopted in these theories will be challenged under warm dense matter conditions. Molecular dynamics (MD) simulation is a good way to validate the effectiveness of these models. We investigate the stopping power of warm dense hydrogen for electrons with projectile energies ranging from 400-10000 eV by means of an electron force field (eFF) method, which can effectively avoid the Coulomb catastrophe in conventional MD calculations. It is found that the stopping power of warm dense hydrogen decreases with increasing temperature of the sample at those high projectile velocities. This phenomenon could be explained by the effect of electronic structure dominated by bound electrons, which is further explicated by a modified random phase approximation (RPA) model based on local density approximation proper to inhomogeneous media. Most of the models extensively accepted by the plasma community, e.g., Landau-Spitzer model, Brown-Preston-Singleton model and RPA model, cannot well address the effect caused by bound electrons so that their predictions of stopping power contradict our result. Therefore, the eFF simulations of this paper reveals the important role played by the bound electrons on stopping power in warm dense plasmas.
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http://dx.doi.org/10.1103/PhysRevE.103.063215DOI Listing
June 2021

Tuning Hybrid exciton-Photon Fano Resonances in Two-Dimensional Organic-Inorganic Perovskite Thin Films.

Nano Lett 2021 07 16;21(14):6124-6131. Epub 2021 Jul 16.

Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.

As easy-to-grow quantum wells with narrow excitonic features at room temperature, two-dimensional (2D) Ruddleson-Popper perovskites are promising for realizing novel nanophotonic devices based on exciton-photon interactions. Here, we demonstrate a distinct hybrid exciton-photon Fano resonance in (CHNH)PbI thin films prepared via spin coating. Using a classical coupled-oscillator model and finite-difference time-domain simulations, we link the Fano interference to the coupling of the exciton with the Rayleigh-like scattering of the film microstructure. Combining colloidal plasmonic cavities with the 2D perovskite films, we demonstrate tuning of the Fano resonance. In combination with silver nanoparticles, the exciton-photon Fano interference couples to the in-plane plasmonic modes with indications of Rabi splitting. By creating a nanoparticle on mirror geometry, we address the out-of-plane excitonic component, reaching an intermediate coupling regime. These structures suggest possible photonic targets for biomolecular self-assembly applications.
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http://dx.doi.org/10.1021/acs.nanolett.1c01504DOI Listing
July 2021

Effects of sodium humate and glutamine combined supplementation on growth performance, diarrhea incidence, blood parameters, and intestinal microflora of weaned calves.

Anim Sci J 2021 Dec;92(1):e13584

Heilongjiang Key Laboratory of Experimental Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

This experiment was conducted to investigate the effects of sodium humate (HNa) and glutamine (Gln) alone or combined supplementation on growth performance, diarrhea incidence, blood parameters, and intestinal microflora of weaned Holstein calves. In a 14-day experiment, 40 calves at 51 ± 3 days of age were randomly allocated to four treatment groups: (1) NC (basal diet), (2) NC + 5% HNa, (3) NC + 1% Gln, and (4) NC + 5% HNa + 1% Gln. Calves combined supplementation with HNa and Gln had a higher (P < .05) ADG, serum concentration of glucose (GLU), IgA, and IgG but lower fecal scores, diarrhea incidence, serum concentration of TNF-α, and IL-10 compared with NC group (P < .05). Compared with NC group, HNa + Gln group showed higher (P < .05) serum GSH and T-AOC activities but lower (P < .05) concentration of MDA and D-lac. Furthermore, the abundances of Prevotella ruminicola, Bifidobacterium, and Lactobacillus in rectal digesta were increased (P < .05), but the Escherichia coli was significantly decreased. In conclusion, combined supplementation with HNa and Gln can effectively improve the immune status, antioxidant capacity, and intestinal microflora of the weaned calves while reducing diarrhea incidence.
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http://dx.doi.org/10.1111/asj.13584DOI Listing
December 2021

Pancreatoduodenectomy within 2 weeks after endoscopic retrograde cholangio-pancreatography increases the risk of organ/space surgical site infections: a 5-year retrospective cohort study in a high-volume centre.

Gland Surg 2021 Jun;10(6):1852-1864

Department of Geriatrics Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Organ/space surgical site infections (OSSI) after pancreaticoduodenectomy (PD) are not rare events. The role of diagnosis and treatment for pancreatic and biliary diseases with an endoscopic retrograde cholangio-pancreatography (ERCP) procedure is currently controversial. However, the ERCP procedure might play a role in surgical outcomes after PD.

Methods: We conducted a retrospective cohort study for patients who underwent PD in the First Affiliated Hospital with the Nanjing Medical University from 1st September 2012 to 31st January 2018. The relationship between ERCP exposure and OSSI after PD was analyzed by univariate and forward stepwise multivariate logistic regression model.

Results: Of the 1,365 patients who underwent PD, 136 developed OSSI (10.0%). We found that ERCP exposure before PD (EEBPD) was significantly associated with an increased incidence rate of post-operative pancreas fistula (POPF) [24.2% (23/95) 14.9% (189/1,270), risk ratio (RR) =1.63, 95% confidence interval (CI), 1.11-2.38, P=0.015]. Hypertension, a higher level of preoperative low-density lipoprotein (LDL) and creatinine (Cr) were associated with elevated risks of post-operative OSSI [adjusted odds ratio (Adj-OR) (95% CI) were 1.59 (1.09-2.32), 1.70 (1.16-2.51), 1.99 (1.36-2.92)], whereas a preoperatively higher level of aspartate aminotransferase (AST) would decrease the risk [Adj-OR (95% CI), 0.62 (0.42-0.91)]. Remarkably, EEBPD would significantly increase and more than double the OSSI risk [Adj-OR (95% CI), 2.56 (1.46-4.47)] especially if it was within 14 days before surgery (Spearman =-0.698, P<0.001).

Conclusions: ERCP, as an independent risk factor, significantly increased the risk of post-operative OSSI after PD if it is performed within 14 days prior to surgery. Our findings would assist clinical decision-making, and improve OSSI control and prevention.
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http://dx.doi.org/10.21037/gs-20-826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258873PMC
June 2021

Improved clinical outcomes of tocilizumab cyclophosphamide for IgG4-related disease: insights from a prospective IgG4-related disease registry.

Ther Adv Chronic Dis 2021 30;12:20406223211028776. Epub 2021 Jun 30.

Department of Rheumatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China Center of Clinical Epidemiology and Evidence-Based Medicine, Fudan University, Shanghai, China.

Objective: To compare the clinical outcomes of patients with active immunoglobulin G (IgG) 4 related disease (IgG4-RD) receiving tocilizumab those receiving cyclophosphamide (CYC).

Methods: This IgG4-RD registry study was a prospective cohort study conducted among patients with active IgG4-RD hospitalized at Zhongshan Hospital, Fudan University. Patients who were treated with tocilizumab or CYC along with glucocorticoids (GCs) were enrolled. All participants were followed up at the hospital clinic at 3 and 6 months after discharge. Primary clinical outcomes were measured the IgG4-RD responder index (RI), complete response (CR), and partial response (PR), as well as side effects.

Results: From January 2015 to June 2020, 29 patients enrolled. Fourteen and 15 patients were treated with tocilizumab and CYC, respectively. At the 6-month follow-up, disease activity parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgG4, and IgG4-RD RI, decreased significantly in both groups. At 6 months, tocilizumab demonstrated its superiority, with 50% of patients achieving CR in the Tocilizumab group 20% in the CYC group. However, no statistical significance was identified ( = 0.128). The GC dosage at 6 months was significantly lower in the tocilizumab group than in the CYC group [10 (9.4-15) mg/d 15 (15-15) mg/d,  = 0.025]. In the CYC group, two patients experienced lumbar vertebral compression fractures related to GCs. Other patients in both groups showed mild adverse effects.

Conclusions: Tocilizumab could be a better steroid-sparing agent, with a comparable curative effect and tolerance, than CYC, in the treatment of IgG4-RD.
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http://dx.doi.org/10.1177/20406223211028776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252355PMC
June 2021

Small-Angle Neutron Scattering Characterization of SrCl-ENG Composites for Thermochemical Heat Storage.

ACS Appl Mater Interfaces 2021 Jul 14;13(29):34213-34226. Epub 2021 Jul 14.

Department of Energy Conversion and Storage, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.

This work presents an in situ nanoscale structural characterization of a SrCl-expanded natural graphite (ENG) composite during ammonia absorption and desorption using small-angle neutron scattering (SANS) together with X-ray powder diffraction and sorption measurements. For the processing of the composite material SANS patterns, we developed and implemented two methods, which showed comparable results. The study allowed following the evolution of the SrCl particles and the nanopores inside the particles during five sorption cycles. The structural changes were compared to the absorption and desorption kinetic measurements, allowing us to make qualitative analysis of the impact of the structural changes on the material properties, such as thermal conductivity and permeability. It was shown that the structural evolution of the composite material did not affect the desorption rate but significantly influenced the absorption rate after the first cycle. We also observed a significant improvement of the absorption kinetics due to the formation of nanopores in the fully deammoniated sample. In addition, the ENG matrix was shown to hinder the agglomeration of the SrCl particles during sorption processes, which is in contrast to literature findings reported for a nonsupported metal halide. The findings presented in this study can be of great interest in the research areas where SrCl-ENG composites are widely studied, i.e., heat storage, heat pumps/refrigerators, deNO removal, and solid-state ammonia storage.
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http://dx.doi.org/10.1021/acsami.1c07449DOI Listing
July 2021

Extracellular Vesicles Carry lncRNA SNHG16 to Promote Metastasis of Breast Cancer Cells the miR-892b/PPAPDC1A Axis.

Front Cell Dev Biol 2021 25;9:628573. Epub 2021 Jun 25.

Department of Breast and Thyroid Surgery, Division of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Breast cancer (BC) represents the most commonly diagnosed malignancy among women. Long non-coding RNAs (lncRNAs) can be transferred by extracellular vesicles (EVs) to participate in BC progression. This study demonstrated that SNHG16 expression was significantly increased in BC tissues and cells. Overexpression of SNHG16 promoted the migration, invasion, and epithelial-mesenchymal transition (EMT) of BC cells. SNHG16 was carried by EVs. Bioinformatics analysis predicted that SNHG16 regulated PPAPDC1A expression by sponging miR-892b, which was confirmed by RNA-fluorescence hybridization (FISH), RT-qPCR, dual-luciferase gene reporter assay, and RNA immunoprecipitation (RIP). MDA-MB-157 and HS578T cells were transfected with pcDNA3.1-SNHG16, miR-892b-mimic, or si-PPAPDC1A for functional rescue experiments , and the cells were treated with MDA-MB-231 cell-derived EVs. The results confirmed that enhanced miR-892b expression partially eliminated the increase of migration, invasion, and EMT of BC cells mediated by SNHG16 or EVs. The lung metastasis model in nude mice was established by injecting HS578T cells tail vein. The results showed that si-SNHG16 reduced the metastatic nodules and decreased the vimentin expression. In conclusion, EVs derived from BC cells transferred SNHG16 the miR-892b/PPAPDC1A axis, thus promoting EMT, migration, and invasion of BC.
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http://dx.doi.org/10.3389/fcell.2021.628573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267525PMC
June 2021

Flyby reaction trajectories: Chemical dynamics under extrinsic force.

Science 2021 07;373(6551):208-212

Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Dynamic effects are an important determinant of chemical reactivity and selectivity, but the deliberate manipulation of atomic motions during a chemical transformation is not straightforward. Here, we demonstrate that extrinsic force exerted upon cyclobutanes by stretching pendant polymer chains influences product selectivity through force-imparted nonstatistical dynamic effects on the stepwise ring-opening reaction. The high product stereoselectivity is quantified by carbon-13 labeling and shown to depend on external force, reactant stereochemistry, and intermediate stability. Computational modeling and simulations show that, besides altering energy barriers, the mechanical force activates reactive intramolecular motions nonstatistically, setting up "flyby trajectories" that advance directly to product without isomerization excursions. A mechanistic model incorporating nonstatistical dynamic effects accounts for isomer-dependent mechanochemical stereoselectivity.
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http://dx.doi.org/10.1126/science.abi7609DOI Listing
July 2021

Validation and Clinical Applicability of Whole-Volume Automated Segmentation of Optical Coherence Tomography in Retinal Disease Using Deep Learning.

JAMA Ophthalmol 2021 Jul 8. Epub 2021 Jul 8.

Google Health, London, United Kingdom.

Importance: Quantitative volumetric measures of retinal disease in optical coherence tomography (OCT) scans are infeasible to perform owing to the time required for manual grading. Expert-level deep learning systems for automatic OCT segmentation have recently been developed. However, the potential clinical applicability of these systems is largely unknown.

Objective: To evaluate a deep learning model for whole-volume segmentation of 4 clinically important pathological features and assess clinical applicability.

Design, Setting, Participants: This diagnostic study used OCT data from 173 patients with a total of 15 558 B-scans, treated at Moorfields Eye Hospital. The data set included 2 common OCT devices and 2 macular conditions: wet age-related macular degeneration (107 scans) and diabetic macular edema (66 scans), covering the full range of severity, and from 3 points during treatment. Two expert graders performed pixel-level segmentations of intraretinal fluid, subretinal fluid, subretinal hyperreflective material, and pigment epithelial detachment, including all B-scans in each OCT volume, taking as long as 50 hours per scan. Quantitative evaluation of whole-volume model segmentations was performed. Qualitative evaluation of clinical applicability by 3 retinal experts was also conducted. Data were collected from June 1, 2012, to January 31, 2017, for set 1 and from January 1 to December 31, 2017, for set 2; graded between November 2018 and January 2020; and analyzed from February 2020 to November 2020.

Main Outcomes And Measures: Rating and stack ranking for clinical applicability by retinal specialists, model-grader agreement for voxelwise segmentations, and total volume evaluated using Dice similarity coefficients, Bland-Altman plots, and intraclass correlation coefficients.

Results: Among the 173 patients included in the analysis (92 [53%] women), qualitative assessment found that automated whole-volume segmentation ranked better than or comparable to at least 1 expert grader in 127 scans (73%; 95% CI, 66%-79%). A neutral or positive rating was given to 135 model segmentations (78%; 95% CI, 71%-84%) and 309 expert gradings (2 per scan) (89%; 95% CI, 86%-92%). The model was rated neutrally or positively in 86% to 92% of diabetic macular edema scans and 53% to 87% of age-related macular degeneration scans. Intraclass correlations ranged from 0.33 (95% CI, 0.08-0.96) to 0.96 (95% CI, 0.90-0.99). Dice similarity coefficients ranged from 0.43 (95% CI, 0.29-0.66) to 0.78 (95% CI, 0.57-0.85).

Conclusions And Relevance: This deep learning-based segmentation tool provided clinically useful measures of retinal disease that would otherwise be infeasible to obtain. Qualitative evaluation was additionally important to reveal clinical applicability for both care management and research.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.2273DOI Listing
July 2021

Association between continuous renal replacement therapy and 28-day mortality of critically ill patients with COVID-19 receiving mechanical ventilation.

Clin Nephrol 2021 Jul 8. Epub 2021 Jul 8.

Background: Continuous renal replacement therapy (CRRT) has become an important multiple organ support therapy and it is widely used in the intensive care unit (ICU). The aim of this study was to clarify the association between CRRT and 28-day mortality in critically ill coronavirus disease 2019 (-COVID-19) patients receiving mechanical ventilation.

Materials And Methods: 112 respiratory decompensated critically ill adult patients with COVID-19 admitted to a COVID-19-designated ICU were included in this retrospective cohort study. Data on demographic information, comorbidities, laboratory findings upon ICU admission, and clinical outcomes were collected. The Kaplan-Meier method and Cox proportional hazard model were applied to determine the potential risk factors associated with 28-day mortality.

Results: The median age was 65.7 years, 67.8% were males, and 58.9% patients had at least one comorbidity. The median scores of the Charlson Comorbidity Index and Sequential Organ Failure Assessment (SOFA) were 3 and 7, respectively. Acute kidney injury (AKI) occurred in 57 critically ill patients upon ICU admission; 43 patients were classified as stage 2 - 3 AKI, and 36 patients were treated with CRRT. Age > 65 years, high SOFA score, damaged cardiac function, poor nutrition, and severe infection were significantly associated with increased 28-day mortality. AKI patients receiving CRRT had lower 28-day mortality compared with those not receiving CRRT (HR = 0.35, 95% CI: 0.21 - 0.58, p < 0.001). Initiating CRRT within 72 hours after mechanical ventilation did not improve survival after CRRT initiation.

Conclusion: AKI prevalence and 28-day mortality are high in critically ill patients with COVID-19 receiving mechanical ventilation. CRRT plays a part in decreasing the mortality of critically ill COVID-19 patients with AKI receiving mechanical ventilation.
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http://dx.doi.org/10.5414/CN110474DOI Listing
July 2021

LncRNA-42060 Regulates Tamoxifen Sensitivity and Tumor Development via Regulating the miR-204-5p/SOX4 Axis in Canine Mammary Gland Tumor Cells.

Front Vet Sci 2021 21;8:654694. Epub 2021 Jun 21.

Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Key Laboratory of Comparative Medicine, Harbin, China.

Tamoxifen is the drug of choice for endocrine therapy of breast cancer. Its clinical use is limited by the development of drug resistance. There is increasing evidence that long non-coding RNAs (lncRNAs) are associated with tumor drug resistance. Therefore, we established two TAM-resistant cell lines, CHMp and CHMm. The different expression levels of lncRNA and miRNA in CHMm and CHMm were screened by RNA sequencing, and the lncRNA-miRNA interactions were analyzed. LncRNA ENSCAFG42060 (lnc-42060) was found to be significantly upregulated in drug-resistant cells and tumor tissues. Further functional validation revealed that the knockdown of lnc-42060 inhibited proliferation, migration, clone formation, restoration of TAM sensitivity, and reduction of stem cell formation in drug-resistant cells, whereas overexpression of lnc-4206 showed opposite results. Bioinformatics and dual-luciferase reporter gene assays confirmed that lnc-42060 could act as a sponge for miR-204-5p, further regulating SOX4 expression activity and thus influencing tumor cell progression. In conclusion, we screened lncRNAs and miRNAs associated with TAM resistance in canine mammary gland tumor cells for the first time. lnc-42060 served as a novel marker that may be used as an important biomarker for future diagnosis and treatment.
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http://dx.doi.org/10.3389/fvets.2021.654694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255626PMC
June 2021

Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4.

Stem Cell Res Ther 2021 07 7;12(1):387. Epub 2021 Jul 7.

Department of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.

Aims: Neointimal hyperplasia remains a major obstacle in vascular regeneration. Sca-1-positive progenitor cells residing within the vascular adventitia play a crucial role in the assemblage of vascular smooth muscle cell (VSMC) and the formation of the intimal lesion. However, the underlying mechanisms during vascular injury are still unknown.

Methods And Results: Aneointimal formation rat model was prepared by carotid artery injury using 2F-Forgaty. After vascular injury, Meox1 expressions time-dependently increased during the neointima formation, with its levels concurrently increasing in the adventitia, media, and neointima. Meox1 was highly expressed in the adventitia on the first day after vascular injury compared to the expression levels in the media. Conversely, by the 14th day post-injury, Meox1 was extensively expressed more in the media and neointima than the adventitia. Analogous to the change of Meox1 in injured artery, Sca-1+ progenitor cells increased in the adventitia wall in a time-dependent manner and reached peak levels on the 7th day after injury. More importantly, this effect was abolished by Meox1 knockdown with shRNA. The enhanced expression of SDF-1α after vascular injury was associated with the markedly enhanced expression levels of Sca1+ progenitor cell, and these levels were relatively synchronously increased within neointima by the 7th day after vascular injury. These special effects were abolished by the knockdown of Meox1 with shRNA and inhibition of CXCR4 by its inhibitor, AMD3100. Finally, Meox1 concurrently regulated SDF-1α expressions in VSMC via activating CDC42, and CDC42 inhibition abolished these effects by its inhibitor, ZCL278. Also, Meox1 was involved in activation of the CXCR4 expression of Sca-1+ progenitor cells by CDC42.

Conclusions: Spatio-temporal model of Meox1 expression regulates theSca-1+progenitor cell migration during the formation of the neointima through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4.
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http://dx.doi.org/10.1186/s13287-021-02466-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262022PMC
July 2021

Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging.

Bioengineered 2021 Dec;12(1):3485-3502

Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Age-related skeletal muscle deterioration (sarcopenia) has a significant effect on the elderly's health and quality of life, but the molecular and gene regulatory mechanisms remain largely unknown. It is necessary to identify the candidate genes related to skeletal muscle aging and prospective therapeutic targets for effective treatments. The age-line-related genes (ALRGs) and age-line-related transcripts (ALRTs) were investigated using the gene expression profiles of GSE47881 and GSE118825 from the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) networks were performed to identify the key molecules with Cytoscape, and Gene Set Enrichment Analysis (GSEA) was used to clarify the potential molecular functions. Two hub molecules were finally obtained and verified with quantitative real-time PCR (qRT-PCR). The results showed that the expression of mitochondria genes involved in mitochondrial electron transport, complex assembly of the respiratory chain, tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis were down-regulated in skeletal muscle with aging. We further identified a primary hub gene of CYCS (Cytochrome C) and a key transcription factor of ESRRA (Estrogen-related Receptor Alpha) to be associated closely with skeletal muscle aging. PCR analysis confirmed the expressions of CYCS and ESRRA in gastrocnemius muscles of mice of different ages were significantly different, and decreased gradually with age. In conclusion, the main cause of skeletal muscle aging may be the systematically reduced expression of mitochondrial functional genes. The CYCS and ESRRA may play significant roles in the progression of skeletal muscle aging and serve as potential biomarkers for future diagnosis and treatment.
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http://dx.doi.org/10.1080/21655979.2021.1948951DOI Listing
December 2021

Noble-Metal-Free Multicomponent Nanointegration for Sustainable Energy Conversion.

Chem Rev 2021 Jul 6. Epub 2021 Jul 6.

Research School of Chemistry, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.

Global energy and environmental crises are among the most pressing challenges facing humankind. To overcome these challenges, recent years have seen an upsurge of interest in the development and production of renewable chemical fuels as alternatives to the nonrenewable and high-polluting fossil fuels. Photocatalysis, photoelectrocatalysis, and electrocatalysis provide promising avenues for sustainable energy conversion. Single- and dual-component catalytic systems based on nanomaterials have been intensively studied for decades, but their intrinsic weaknesses hamper their practical applications. Multicomponent nanomaterial-based systems, consisting of three or more components with at least one component in the nanoscale, have recently emerged. The multiple components are integrated together to create synergistic effects and hence overcome the limitation for outperformance. Such higher-efficiency systems based on nanomaterials will potentially bring an additional benefit in balance-of-system costs if they exclude the use of noble metals, considering the expense and sustainability. It is therefore timely to review the research in this field, providing guidance in the development of noble-metal-free multicomponent nanointegration for sustainable energy conversion. In this work, we first recall the fundamentals of catalysis by nanomaterials, multicomponent nanointegration, and reactor configuration for water splitting, CO reduction, and N reduction. We then systematically review and discuss recent advances in multicomponent-based photocatalytic, photoelectrochemical, and electrochemical systems based on nanomaterials. On the basis of these systems, we further laterally evaluate different multicomponent integration strategies and highlight their impacts on catalytic activity, performance stability, and product selectivity. Finally, we provide conclusions and future prospects for multicomponent nanointegration. This work offers comprehensive insights into the development of cost-competitive multicomponent nanomaterial-based systems for sustainable energy-conversion technologies and assists researchers working toward addressing the global challenges in energy and the environment.
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http://dx.doi.org/10.1021/acs.chemrev.0c01328DOI Listing
July 2021

Abnormal Coagulation Function of Patients With COVID-19 Is Significantly Related to Hypocalcemia and Severe Inflammation.

Front Med (Lausanne) 2021 16;8:638194. Epub 2021 Jun 16.

Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

This study aimed to detect, analyze, and correlate the clinical characteristics, blood coagulation functions, blood calcium levels, and inflammatory factors in patients with mild and severe COVID-19 infections. The enrolled COVID-19 infected patients were from Wuhan Jin Yin-tan Hospital (17 cases, Wuhan, China), Suzhou Infectious Disease Hospital (87 cases, Suzhou, China), and Xuzhou Infectious Disease Hospital (14 cases, Xuzhou, China). After admission, basic information was collected; X-ray and chest CT images were obtained; and data from routine blood tests, liver and kidney function, myocardial enzymes, electrolytes, blood coagulation function, (erythrocyte sedimentation rate) ESR, C-reactive protein (CRP), IL-6, procalcitonin (PCT), calcitonin, and other laboratory tests were obtained. The patients were grouped according to the clinical classification method based on the pneumonia diagnosis and treatment plan for new coronavirus infection (trial version 7) in China. The measurements from mild (56 cases) and severe cases (51 cases) were compared and analyzed. Most COVID-19 patients presented with fever. Chest X-ray and CT images showed multiple patchy and ground glass opacities in the lungs of COVID 19 infected patients, especially in patients with severe cases. Compared with patients with mild infection, patients with severe infection were older ( = 0.023) and had a significant increase in AST and BUN. The levels of CK, LDH, CK-MB, proBNP, and Myo in patients with severe COVID-19 infection were also increased significantly compared to those in patients with mild cases. Patients with severe COVID-19 infections presented coagulation dysfunction and increased D-dimer and fibrin degradation product (FDP) levels. Severe COVID-19 patients had low serum calcium ion (Ca) concentrations and high calcitonin and PCT levels and exhibited serious systemic inflammation. Ca in COVID-19 patients was significantly negatively correlated with PCT, calcitonin, D-dimer, PFDP, ESR, CRP and IL-6. D-dimer in COVID-19 patients was a significantly positively correlated with CRP and IL-6. In conclusion, patients with severe COVID-19 infection presented significant metabolic dysfunction and abnormal blood coagulation, a sharp increase in inflammatory factors and calcitonin and procalcitonin levels, and a significant decrease in Ca. Decreased Ca and coagulation dysfunction in COVID-19 patients were significantly correlated with each other and with inflammatory factors.
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http://dx.doi.org/10.3389/fmed.2021.638194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242574PMC
June 2021

Detection of elusive polyps via a large-scale artificial intelligence system (with videos).

Gastrointest Endosc 2021 Jun 30. Epub 2021 Jun 30.

Google Research, Israel.

Background And Aims: Colorectal cancer is a leading cause of death. Colonoscopy is the criterion standard for detection and removal of precancerous lesions and has been shown to reduce mortality. The polyp miss rate during colonoscopies is 22% to 28%. DEEP DEtection of Elusive Polyps (DEEP) is a new polyp detection system based on deep learning, which alerts the operator in real-time to the presence and location of polyps. The primary outcome was the performance of DEEP on the detection of elusive polyps.

Methods: The DEEP system was trained on 3,611 hours of colonoscopy videos derived from 2 sources, and was validated on a set comprising 1,393 hours, from a third unrelated source. The ground truth labeling was provided by offline gastroenterologist annotators, who were able to watch the video in slow-motion and pause/rewind as required. To assess the applicability, stability, user experience and in order to obtain some preliminary data on performance in a real-life scenario, a preliminary prospective clinical validation study was performed, comprising 100 procedures (clinicaltrial.gov ID: NCT04693078).

Results: DEEP achieved a sensitivity of 97.1% at 4.6 false alarms per video for all polyps, 88.5% and 84.9% for polyps that are in the field of view for less than 5 and 2 seconds, respectively. DEEP was able to detect polyps, not seen by live real-time endoscopists or offline annotators in an average of 0.22 polyps per sequence. In the clinical validation study the system detected an average of 0.89 additional polyps per procedure. No adverse events occurred.

Conclusions: DEEP has a high sensitivity for polyp detection and was effective in increasing the detection of polyps both in colonoscopy videos and in real procedures with a low number of false alarms.
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http://dx.doi.org/10.1016/j.gie.2021.06.021DOI Listing
June 2021

Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice.

Molecules 2021 Jun 3;26(11). Epub 2021 Jun 3.

Guangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

Total body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow recovery of recipients after BMT. In the early weeks following transplantation, recipients are at high risk of severe infection due to weakened hematopoiesis. Thus, it is imperative to improve engraftment capacity and accelerate bone marrow recovery in BMT recipients. In this study, we constructed recombinant copper/zinc superoxide dismutase 1 (SOD1) fused with the cell-penetrating peptide (CPP), the trans-activator of transcription (Tat), and showed that this fusion protein has penetrating ability and antioxidant activity in both RAW264.7 cells and bone marrow cells in vitro. Furthermore, irradiated mice transplanted with SOD1-Tat-treated total bone marrow donor cells showed an increase in total bone marrow engraftment capacity two weeks after transplantation. This study explored an innovative method for enhancing engraftment efficiency and highlights the potential of CPP-SOD1 in ROS manipulation during BMT.
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http://dx.doi.org/10.3390/molecules26113395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200013PMC
June 2021

17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats.

Int J Mol Sci 2021 Jun 28;22(13). Epub 2021 Jun 28.

Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17β-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.
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http://dx.doi.org/10.3390/ijms22136945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269106PMC
June 2021

2021 Frank Stinchfield Award: A novel cemented hip hemiarthroplasty infection model with real-time in vivo imaging in rats : an animal study.

Bone Joint J 2021 Jul;103-B(7 Supple B):9-16

The Ottawa Hospital Division of Orthopaedic Surgery, Ottawa, Canada.

Aims: The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time.

Methods: Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces.

Results: All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head.

Conclusion: This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article:  2021;103-B(7 Supple B):9-16.
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http://dx.doi.org/10.1302/0301-620X.103B7.BJJ-2020-2435.R1DOI Listing
July 2021

HIV infection and risk of COVID-19 mortality: A meta-analysis.

Medicine (Baltimore) 2021 Jul;100(26):e26573

Department of Imaging, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.

Background: This meta-analysis aimed to estimate the association of human immunodeficiency virus (HIV) infection and risk of coronavirus disease 2019 (COVID-19) mortality.

Methods: We systematically retrieved articles published on HIV infection and risk of COVID-19 mortality through PubMed, EMBase, China National Knowledge Infrastructure, WanFang, and Chongqing VIP databases using a predefined search strategy from December 1, 2019 to January 31, 2021. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Cochran Q test and I2 statistics were quantified to measure heterogeneity. Odds ratio (OR) and 95% confidence intervals (CI) were computed and displayed in the form of forest plots. Subgroup analysis was performed to explore the source of heterogeneity. Funnel plot, Begg test, and Egger test were used to assess potential publication bias. Stata software version 11.0 was used to analyze all the statistical data.

Results: We included 10 studies with 18,122,370 COVID-19 patients, of whom 41,113 were with HIV infection and 18,081,257 were without HIV infection. The pooled overall results suggested that people living with HIV infection had a higher risk of mortality from COVID-19 than those without HIV infection (OR = 1.252, 95% CI 1.027-1.524). Subgroup analysis showed that people living with HIV infection had a higher risk of COVID-19 mortality than those without HIV infection in the United States (OR = 1.520, 95% CI 1.252-1.845) and in South Africa (OR = 1.122, 95% CI 1.032-1.220); however, no significant association was found in the United Kingdom (OR = 0.878, 95% CI 0.657-1.174).

Conclusion: Patients with HIV infection should be the emphasis population to prevent the risk of mortality during the clinical treatment of COVID-19 patients.
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http://dx.doi.org/10.1097/MD.0000000000026573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257842PMC
July 2021

Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip method.

Nanomedicine (Lond) 2021 Jul 29;16(17):1487-1504. Epub 2021 Jun 29.

School of Radiation Medicine & Protection, State Key Laboratory of Radiation Medicine & Protection, School for Radiological & Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, PR China.

To explore the hepatotoxicity of copper sulfide nanoparticles (CuSNPs) toward hepatocyte spheroids. Other than the traditional agarose method to generate hepatocyte spheroids, we developed a multi-concave agarose chip (MCAC) method to investigate changes in hepatocyte viability, morphology, mitochondrial membrane potential, reactive oxygen species and hepatobiliary transporter by CuSNPs. The MCAC method allowed a large number of spheroids to be obtained per sample. CuSNPs showed hepatotoxicity through a decrease in spheroid viability, albumin/urea production and glycogen deposition. CuSNPs also introduced hepatocyte spheroid injury through alteration of mitochondrial membrane potential and reactive oxygen species, that could be reversed by N-acetyl-l-cysteine. CuSNPs significantly decreased the activity of BSEP transporter by downregulating its mRNA and protein levels. Activity of the MRP2 transporter remained unchanged. We observed the hepatotoxicity of CuSNPs with associated mechanisms in an advanced 3D culture system.
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http://dx.doi.org/10.2217/nnm-2021-0011DOI Listing
July 2021

Repeated use of SSRIs potentially associated with an increase on serum CK and CK-MB in patients with major depressive disorder: a retrospective study.

Sci Rep 2021 Jun 28;11(1):13365. Epub 2021 Jun 28.

Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), No. 36, Mingxin Road, Liwan District, Guangzhou, 510370, Guangdong, China.

There is a large amount of evidence that selective serotonin reuptake inhibitors (SSRIs) are related to cardiovascular toxicity, which has aroused concern regarding their safety. However, few studies have evaluated the effects of SSRIs on cardiac injury biomarkers, such as creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether SSRIs elevated CK and CK-MB levels of prior medicated depressive patients (PMDP) compared to first-episode drug-naïve depressive patients (FDDPs). We performed an observational and retrospective study involving 128 patients with major depressive disorder. Patients who had never used any type of antidepressant were designated FDDP; patients who had used only one type of SSRI but were not treated after a recent relapse were designated PMDP. Serum CK and CK-MB levels were measured before and after using SSRIs for a period of time. The duration of current treatment in the FDDP and PMDP groups was 16.200 ± 16.726 weeks and 15.618 ± 16.902 weeks, respectively. After SSRI treatment, levels of serum CK in the PMDP group were significantly higher than in the FDDP group. Univariate ANCOVA results revealed that PMDP was 22.313 times more likely to elevate CK (OR 22.313, 95% CI 9.605-35.022) and 2.615 times more likely to elevate CK-MB (OR 2.615, 95% CI 1.287-3.943) than FDDP. Multivariate ANCOVA revealed an interaction between the group and sex of CK and CK-MB. Further pairwise analysis of the interaction results showed that in female patients, the mean difference (MD) of CK and CK-MB in PMDP was significantly greater than that in FDDP (MD = 33.410, P = 0.000, 95% CI 15.935-50.886; MD = 4.613, P = 0.000, 95% CI 2.846-6.381). Our findings suggest that patients, especially females, who had previously used SSRI antidepressants were more likely to have elevated CK and CK-MB, indicators of myocardial muscle injury. Use of SSRIs should not be assumed to be completely safe and without any cardiovascular risks.
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http://dx.doi.org/10.1038/s41598-021-92807-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239012PMC
June 2021
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