Publications by authors named "Hao Sun"

1,048 Publications

  • Page 1 of 1

Effects of unilateral and bilateral pedicle screw fixation on symptoms and quality of life of patients with lumbar degenerative diseases.

Am J Transl Res 2021 15;13(5):5216-5223. Epub 2021 May 15.

Department of Orthopedics, Clinical Medical College Yangzhou University, Subei People's Hospital Yangzhou 225000, Jiangsu Province, China.

Objective: This research was designed to probe into the effects of unilateral and bilateral pedicle screw fixation on the VAS scores of low back pain, leg pain, ODI indexes and JOA scores in patients with lumbar degenerative diseases.

Methods: Totally 113 patients with lumbar degenerative diseases admitted in our hospital from February 2016 to December 2018 were collected as the research objects. Among them, 52 received bilateral pedicle screw fixation (BPSF) and 61 were treated by unilateral pedicle screw fixation (UPSF). The intraoperative blood loss, time of operation and hospitalization, and incidence of perioperative complications of the two groups were compared. The VAS scores, ODI indexes and JOA scores were assessed before operation and 6 and 12 months after treatment. The intervertebral fusion rates were compared, and the quality of life was evaluated by SF-36.

Results: The intraoperative blood loss in the observation group (OG) was higher than that in the control group (CG) (P<0.05), while the time of operation and hospital stay were obviously shorter (P<0.05). There was no marked difference in the incidence of perioperative complications (P>0.05). Before treatment, there was no remarkable difference in the VAS scores of low back pain, leg pain, ODI indexes and JOA scores (P>0.05). At 6 and 12 months after treatment, the first two parameters were remarkably lower than those before treatment, but the rest of the parameters were dramatically higher (P<0.05). The VAS scores and ODI indexes of the OG were markedly lower than those of the CG, while the JOA scores, fusion rates and quality of life were obviously higher (P<0.05).

Conclusion: Bilateral pedicle screw fixation is valid and safe on lumbar degenerative diseases, which can improve patients' quality of life.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205759PMC
May 2021

Novel Graphene Biosensor Based on the Functionalization of Multifunctional Nano-bovine Serum Albumin for the Highly Sensitive Detection of Cancer Biomarkers.

Nanomicro Lett 2019 Mar 9;11(1):20. Epub 2019 Mar 9.

State Key Laboratory of Transducer Technology; Key Laboratory of Terahertz Solid-State Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China.

A simple, convenient, and highly sensitive bio-interface for graphene field-effect transistors (GFETs) based on multifunctional nano-denatured bovine serum albumin (nano-dBSA) functionalization was developed to target cancer biomarkers. The novel graphene-protein bioelectronic interface was constructed by heating to denature native BSA on the graphene substrate surface. The formed nano-dBSA film served as the cross-linker to immobilize monoclonal antibody against carcinoembryonic antigen (anti-CEA mAb) on the graphene channel activated by EDC and Sulfo-NHS. The nano-dBSA film worked as a self-protecting layer of graphene to prevent surface contamination by lithographic processing. The improved GFET biosensor exhibited good specificity and high sensitivity toward the target at an ultralow concentration of 337.58 fg mL. The electrical detection of the binding of CEA followed the Hill model for ligand-receptor interaction, indicating the negative binding cooperativity between CEA and anti-CEA mAb with a dissociation constant of 6.82 × 10 M. The multifunctional nano-dBSA functionalization can confer a new function to graphene-like 2D nanomaterials and provide a promising bio-functionalization method for clinical application in biosensing, nanomedicine, and drug delivery.
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http://dx.doi.org/10.1007/s40820-019-0250-8DOI Listing
March 2019

Acid-Induced Self-Catalyzing Platform Based on Dextran-Coated Copper Peroxide Nanoaggregates for Biofilm Treatment.

ACS Appl Mater Interfaces 2021 Jun 18. Epub 2021 Jun 18.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China.

Nanoantibacterial agents based on catalytic activity were limited due to the low levels of endogenous HO in the microenvironment of bacterial biofilms. However, the additional HO will trigger more side effects to healthy surroundings, which is still a great challenge. Herein, we report an acid-induced self-catalyzing platform based on dextran-coated copper peroxide nanoaggregates (DCPNAs) for antibiofilm and local infection therapy applications. The dextran-functionalized DCPNAs were mediated and conveniently purified via a dextran and ethanol precipitation method, which can also cluster nanodots into nanoaggregates and show good penetrability as well as biocompatibility. Bacterial biofilms were inhibited and destroyed by the reactive oxygen species generated from the Fenton reaction between the Cu and HO released from DCPNAs in an acidic environment, which did not require additional HO. As expected, the DCPNAs exhibit low cytotoxicity and excellent acid-induced antibacterial and antibiofilm ability. Moreover, the DCPNAs realized great therapeutic outcomes in the application for in vivo wound healing. The overall excellent properties associated with the DCPNAs highlight that they could be considered as a kind of ideal antimicrobial agents for microbial biofilm infection treatment.
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http://dx.doi.org/10.1021/acsami.1c03409DOI Listing
June 2021

Homologous Strategy to Construct High-Performance Coupling Electrodes for Advanced Potassium-Ion Hybrid Capacitors.

Nanomicro Lett 2020 Oct 30;13(1):14. Epub 2020 Oct 30.

School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People's Republic of China.

Potassium-ion hybrid capacitors (PIHCs) have been considered as promising potentials in mid- to large-scale storage system applications owing to their high energy and power density. However, the process involving the intercalation of K into the carbonaceous anode is a sluggish reaction, while the adsorption of anions onto the cathode surface is relatively faster, resulting in an inability to exploit the advantage of high energy. To achieve a high-performance PIHC, it is critical to promote the K insertion/desertion in anodic materials and design suitable cathodic materials matching the anodes. In this study, we propose a facile "homologous strategy" to construct suitable anode and cathode for high-performance PIHCs, that is, unique multichannel carbon fiber (MCCF)-based anode and cathode materials are firstly prepared by electrospinning, and then followed by sulfur doping and KOH activation treatment, respectively. Owing to a multichannel structure with a large interlayer spacing for introducing S in the sulfur-doped multichannel carbon fiber (S-MCCF) composite, it presents high capacity, super rate capability, and long cycle stability as an anode in potassium-ion cells. The cathode composite of activated multichannel carbon fiber (aMCCF) has a considerably high specific surface area of 1445 m g and exhibits outstanding capacitive performance. In particular, benefiting from advantages of the fabricated S-MCCF anode and aMCCF cathode by homologous strategy, PIHCs assembled with the unique MCCF-based anode and cathode show outstanding electrochemical performance, which can deliver high energy and power densities (100 Wh kg at 200 W kg, and 58.3 Wh kg at 10,000 W kg) and simultaneously exhibit superior cycling stability (90% capacity retention over 7000 cycles at 1.0 A g). The excellent electrochemical performance of the MCCF-based composites for PIHC electrodes combined with their simple construction renders such materials attractive for further in-depth investigations of alkali-ion battery and capacitor applications.
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http://dx.doi.org/10.1007/s40820-020-00524-zDOI Listing
October 2020

β2 integrin activation and signaling transduction in leukocyte recruitment.

Am J Physiol Cell Physiol 2021 06 16. Epub 2021 Jun 16.

Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT, United States.

Leukocyte recruitment is a critical step in the pathogenesis of inflammatory and immunological responses. Cell adhesion molecules (CAMs) are involved in controlling cell movements and the recruitment process, and the integrin family of CAMs plays a key role. During cell movement, integrin function is dynamically and precisely regulated. However, this balance might be broken under pathological conditions. Thus, the functional regulation and molecular mechanisms of integrins related to diseases are often a focus of research. Integrin β2 is one of the most commonly expressed integrins in leukocytes that mediates leukocyte adhesion and migration, and it plays an important role in immune responses and inflammation. In this review, we focus on specific functions of integrin β2 in leukocyte recruitment, the conformational changes and signal transduction of integrin β2 activation, and how new insights into these processes can inform future therapies for inflammation and immune diseases.
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http://dx.doi.org/10.1152/ajpcell.00560.2020DOI Listing
June 2021

FeO nanorods/CuO nanoparticles p-n heterojunction photoanode: Effective charge separation and enhanced photoelectrochemical properties.

J Colloid Interface Sci 2021 May 26;602:32-42. Epub 2021 May 26.

School of Physics, Liaoning University, Shenyang 110036, PR China; Liaoning Key Laboratory of Semiconductor Light Emitting and Photocatalytic Materials, Liaoning University, Shenyang 110036, PR China. Electronic address:

FeO/CuO p-n heterojunction photoelectrode films were fabricated by growing CuO nanoparticles on FeO nanorods via an impregnation method. The content of CuO in FeO/CuO films was changed to study the role of CuO on the p-n heterojunction. The obtained FeO/CuO photoelectrodes exhibited high intensity of visible-light absorption and excellence photoelectrochemical (PEC) performance. The incident photocurrent efficiency (IPCE) of FeO/CuO photoanode reached 11.4% under 365 nm light irradiation, which is 2.6 times higher than that of bare FeO photoanode. In a PEC water splitting reaction, the H and O production rates for FeO/CuO-3 were 0.294 and 0.130 µmol/min. The enhanced PEC performance was mainly contributed by the enhanced charge separation and the synergism achieved in FeO/CuO p-n heterojunctions. This work could provide a new route to construct efficient FeO-based composite photoelectrodes for the PEC.
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http://dx.doi.org/10.1016/j.jcis.2021.05.140DOI Listing
May 2021

A novel 1,8-naphthalimide-based Cu ion fluorescent probe and its bioimaging application.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jun 1;261:120037. Epub 2021 Jun 1.

School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou 221116, People's Republic of China. Electronic address:

A new 1,8-naphthalimide-based Schiff base compound, named as (Z)-2-butyl-6-(((2-hydroxyphenyl)imino)methyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (BHBD), has been simply synthesized with high yields. BHBD can be employed as a "turn-on" fluorescent probe for Cu ion with high sensitivity, high selectivity and relatively low detection limit (0.48 × 10 M). The fluorescence emission of BHBD is very weak in HO/THF (v/v: 7/3) mixture, which is significantly enhanced after addition of Cu ion. The proposed mechanism is verified by H NMR, Job's plot and TOF-MS experiments. Anti-interference experiment, cytotoxicity assay and pH influence results indicated that BHBD meets the requirements of bioimaging. Therefore, BHBD has been successfully applied in detecting Cu ion in HeLa cells.
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http://dx.doi.org/10.1016/j.saa.2021.120037DOI Listing
June 2021

Removing Adversarial Noise via Low-rank Completion of High-sensitivity Points.

IEEE Trans Image Process 2021 Jun 10;PP. Epub 2021 Jun 10.

Deep neural networks are fragile under adversarial attacks. In this work, we propose to develop a new defense method based on image restoration to remove adversarial attack noise. Using the gradient information back-propagated over the network to the input image, we identify high-sensitivity keypoints which have significant contributions to the image classification performance. We then partition the image pixels into the two groups: high-sensitivity and low-sensitivity points. For low-sensitivity pixels, we use a total variation (TV) norm-based image smoothing method to remove adversarial attack noise. For those high-sensitivity keypoints, we develop a structure-preserving low-rank image completion method. Based on matrix analysis and optimization, we derive an iterative solution for this optimization problem. Our extensive experimental results on the CIFAR-10, SVHN, and Tiny-ImageNet datasets have demonstrated that our method significantly outperforms other defense methods which are based on image de-noising or restoration, especially under powerful adversarial attacks.
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http://dx.doi.org/10.1109/TIP.2021.3086596DOI Listing
June 2021

Hypoxia-inducible exosomes facilitate liver-tropic pre-metastatic niche in colorectal cancer.

Hepatology 2021 Jun 10. Epub 2021 Jun 10.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.

Background & Aims: Liver metastasis is a frequent occurrences in patients with colorectal cancer (CRC), 15%-25% of CRC patients have liver metastases at the time of initial diagnosis (1). Specifically, some regional-stage patients with mild symptoms (stage Ⅰ or II) will also advance to liver metastases rapidly, even CRC lesion in situ is resected in time. Nevertheless, the precise mechanism of liver metastasis is still unclear.

Approach & Results: Fresh tumor tissues from CRC patients, adjacent noncancerous tissues (ANT) and colorectal adenoma tissues (ADE) were subjected to microarray analysis to identify differentially expressed miRNA. Exosomes from human serum and cell culture medium were separated, quantitated and verified by transmission electronic microscopy and Zetasizer Nano. Luciferase reporter assay, real-time qPCR, western blot, immunoprecipitation, chromatin and re-chromatin immunoprecipitation, migration and invasion assay, PDX mice model, flow cytometry, immunohistochemistry and immunofluorescence staining were employed to explore the regulation among CRC liver metastases, immunosuppression and cell adhesion. In this study, we demonstrated that the hypoxic microenvironment in primary CRC lesions boosted exosome release, selectively initiated a favorable pre-metastatic niche formation in the hepar, but not in other organs. Mechanistically, Kupffer cells (KCs) can phagocytose exosomes contained highly expressed miR-135a-5p from blood circulation into the liver. The exosomal miR-135a-5p initiated LATS2-YAP-MMP7 axis to promote the occurrences of CRC liver metastasis, and CD30-TRAF2-p65-mediated immunosuppression signaling also contributed to this process.

Conclusions: Hypoxia-induced exosomal miR-135a-5p correlates with the development, clinical severity and prognosis of CRC liver metastases through the pre-metastatic niche, and our findings revealed that miR-135a-5p might be a promising target in halting CRC liver metastases.
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http://dx.doi.org/10.1002/hep.32009DOI Listing
June 2021

Lithium metal anodes working at 60 mA·cm-2 and 60 mAh·cm-2 through nanoscale lithium-ion adsorbing.

Angew Chem Int Ed Engl 2021 Jun 9. Epub 2021 Jun 9.

Fudan University, Deptm. of Macromolecular Science, 2205 Songhu Road, 200438, Shanghai, CHINA.

Achieving high-current-density and high-area-capacity operation of Li metal anodes offers promising opportunities for high-performing next-generation batteries. However, high-rate Li deposition suffers from undesired Li-ion depletion especially at the electrolyte-anode interface, which compromises achievable capacity and lifetime. Here, electronegative graphene quantum dots are synthesized and assembled into an ultra-thin overlayer capable of efficient Li-ion adsorbing at the nanoscale on Li metal to fully relieve Li-ion depletion. The protected Li anode achieves long-term reversible Li plating/stripping over 1000 h at both superior current density of 60 mA·cm -2 and areal capacity of 60 mAh·cm -2 . Implementation of the protected anode allows for the construction of Li-air full battery with both enhanced rate capability and cycling performance.
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http://dx.doi.org/10.1002/anie.202106047DOI Listing
June 2021

Estimating mean potential outcome under adaptive treatment length strategies in continuous time.

Biometrics 2021 Jun 4. Epub 2021 Jun 4.

Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York.

An adaptive treatment length strategy is a sequential stage-wise treatment strategy where a subject's treatment begins at baseline and one chooses to stop or continue treatment at each stage provided the subject has been continuously treated. The effects of treatment are assumed to be cumulative and, therefore, the effect of treatment length on clinical endpoint, measured at the end of the study, is of primary scientific interest. At the same time, adverse treatment-terminating events may occur during the course of treatment that require treatment be stopped immediately. Because the presence of a treatment-terminating event may be strongly associated with the study outcome, the treatment-terminating event is informative. In observational studies, decisions to stop or continue treatment depend on covariate history that confounds the relationship between treatment length on outcome. We propose a new risk-set weighted estimator of the mean potential outcome under the condition that time-dependent covariates update at a set of common landmarks. We show that our proposed estimator is asymptotically linear given mild assumptions and correctly specified working models. Specifically, we study the theoretical properties of our estimator when the nuisance parameters are modeled using either parametric or semiparametric methods. The finite sample performance and theoretical results of the proposed estimator are evaluated through simulation studies and demonstrated by application to the Enhanced Suppression of the Platelet Receptor IIb/IIIa with Integrilin Therapy (ESPRIT) infusion trial data.
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http://dx.doi.org/10.1111/biom.13504DOI Listing
June 2021

The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair.

Elife 2021 Jun 4;10. Epub 2021 Jun 4.

Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1 cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1 cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1 cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1 cells further hindered this repair process. Strikingly, intra-articular injection of Gli1 meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.
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http://dx.doi.org/10.7554/eLife.62917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177886PMC
June 2021

Effects of polymorphism of the gene on milk quality traits and its relation to triglyceride metabolism in bovine mammary epithelial cells of dairy cattle.

Arch Anim Breed 2021 29;64(1):35-44. Epub 2021 Jan 29.

College of Animal Science, Jilin University, Changchun, Jilin 130062, PR China.

Mitochondrial glycerol-3-phosphate acyltransferase () catalyses the initial and rate-regulated first-stage pathway of glycerol lipid synthesis and helps to allocate acyl-CoA (acyl-coenzyme A) to triglyceride (TG) synthesis and away from degradation pathways in animal lipometabolism-related pathways. In this study, RNA interference (RNAi) and gene overexpression were used to examine the correlation between the expression of and adipogenesis in bovine mammary epithelial cells (bMECs). Additionally, three novel polymorphisms were identified within the bovine key functional domain of with Sanger sequencing. The relationship between variants of the gene and milk quality traits of Chinese Holstein cows was then analysed using statistical methods. The results showed that knockdown of the gene significantly reduced the synthesis of triglycerides in the bMECs (    0.05), whereas the overexpression of the gene significantly increased the synthesis of TG (    0.05). In Chinese Holstein dairy cattle, the polymorphic locus of the gene E20-3386G   A was significantly correlated with fat, protein and somatic cell count (    0.05); I18-652A   G was significantly correlated with fat, total fat content, protein, dry matter and somatic cell count (    0.05); and I18-726A   G was significantly correlated with protein, milk yield, dry matter and somatic cell count (    0.05). Specifically, individuals with the AA genotype of the I18-652A   G and E20-3386G   A polymorphic loci had a higher milk fat percentage (    0.05). In summary, plays a pivotal role in the intracellular regulation of triglyceride, and its mutations could work as a competent molecular marker for selective breeding in dairy cattle.
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http://dx.doi.org/10.5194/aab-64-35-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161264PMC
January 2021

Long-Term Effect of Salt Substitute on All-Cause and Cardiovascular Disease Mortality: An Exploratory Follow-Up of a Randomized Controlled Trial.

Front Cardiovasc Med 2021 17;8:645902. Epub 2021 May 17.

Department of Clinical Epidemiology and Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.

Salt substitute, a strategy for salt reduction, has been shown to decrease blood pressure and the incidence of hypertension. However, whether its hypotensive effect will reduce long-term mortality remains unclear. Our study reported an exploratory follow-up of mortality outcomes from previous randomized controlled trial to assess the long-term effect of low-sodium salt on total and cardiovascular disease (CVD) mortality. Participants who completed a previous 3-year double-blind randomized controlled trial were followed up from 2009 to 2019 to collect mortality data. Multivariable Cox regression models were used to evaluate the association between low-sodium salt intervention and all-cause and CVD mortality. Four hundred and forty participants completed the intervention trial, of which 428 participants had death outcome data recorded after 10 years follow-up: 209 in a salt substitute group and 219 in a normal salt group. Fifty participants died during follow-up, 25 died due to CVD. No significant differences in relative risks were found for all-cause mortality [HR = 0.81, 95% confidence interval (CI): 0.46-1.42] and CVD mortality (HR = 0.58, 95% CI: 0.26-1.32) in unadjusted analyses. After adjusted with age and alcohol drinking status, there were significant reductions for stroke mortality among all participants (HR = 0.26, 95% CI: 0.08-0.84) and for CVD mortality (HR = 0.38, 95% CI: 0.16-0.92) and stroke mortality (HR = 0.25, 95% CI: 0.08-0.82) among hypertensive participants. Compared to normal salt, salt substitute might reduce the risk of CVD death, especially stroke among hypertensive patients. Our exploratory follow-up results provide potential evidence that low-sodium salt may be an accessible and effective strategy for prevention of CVD events, but definitive randomized controlled trials are warranted.
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http://dx.doi.org/10.3389/fcvm.2021.645902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165103PMC
May 2021

Large scale RNA-binding proteins/LncRNAs interaction analysis to uncover lncRNA nuclear localization mechanisms.

Brief Bioinform 2021 May 31. Epub 2021 May 31.

Department of Orthaepedics and Traumatology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Long non-coding RNAs (lncRNAs) are key regulators of major biological processes and their functional modes are dictated by their subcellular localization. Relative nuclear enrichment of lncRNAs compared to mRNAs is a prevalent phenomenon but the molecular mechanisms governing their nuclear retention in cells remain largely unknown. Here in this study, we harness the recently released eCLIP data for a large number of RNA-binding proteins (RBPs) in K562 and HepG2 cells and utilize multiple bioinformatics methods to comprehensively survey the roles of RBPs in lncRNA nuclear retention. We identify an array of splicing RBPs that bind to nuclear-enriched lincRNAs (large intergenic non-coding RNAs) thus may act as trans-factors regulating their nuclear retention. Further analyses reveal that these RBPs may bind with distinct core motifs, flanking sequence compositions, or secondary structures to drive lincRNA nuclear retention. Moreover, network analyses uncover potential co-regulatory RBP clusters and the physical interaction between HNRNPU and SAFB2 proteins in K562 cells is further experimentally verified. Altogether, our analyses reveal previously unknown factors and mechanisms that govern lincRNA nuclear localization in cells.
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http://dx.doi.org/10.1093/bib/bbab195DOI Listing
May 2021

Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation.

J Clin Invest 2021 May 27. Epub 2021 May 27.

Department of Medicine, University of California San Diego, La Jolla, United States of America.

Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in one of three genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2 and KLF4-dependent elevation of eNOS in CCM endothelium. The increased brain endothelial production of NO stabilized HIF-1a in astrocytes, resulting in increased VEGF production and expression of a "hypoxic" program under normoxic conditions. We showed that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1a target gene and a known component of the hypoxic program, contributed to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevented the progression of CCM lesions. Thus, non-cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.
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http://dx.doi.org/10.1172/JCI139570DOI Listing
May 2021

Muscle regeneration controlled by a designated DNA dioxygenase.

Cell Death Dis 2021 May 25;12(6):535. Epub 2021 May 25.

Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 20023, China.

Tet dioxygenases are responsible for the active DNA demethylation. The functions of Tet proteins in muscle regeneration have not been well characterized. Here we find that Tet2, but not Tet1 and Tet3, is specifically required for muscle regeneration in vivo. Loss of Tet2 leads to severe muscle regeneration defects. Further analysis indicates that Tet2 regulates myoblast differentiation and fusion. Tet2 activates transcription of the key differentiation modulator Myogenin (MyoG) by actively demethylating its enhancer region. Re-expressing of MyoG in Tet2 KO myoblasts rescues the differentiation and fusion defects. Further mechanistic analysis reveals that Tet2 enhances MyoD binding by demethylating the flanking CpG sites of E boxes to facilitate the recruitment of active histone modifications and increase chromatin accessibility and activate its transcription. These findings shed new lights on DNA methylation and pioneer transcription factor activity regulation.
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http://dx.doi.org/10.1038/s41419-021-03817-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149877PMC
May 2021

Anticancer Effect of Biodegradable Magnesium on Hepatobiliary Carcinoma: An and Study.

ACS Biomater Sci Eng 2021 06 24;7(6):2774-2782. Epub 2021 May 24.

Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110001, China.

Biliary-stent implantation has become an effective treatment for patients with malignant obstructive jaundice caused by hepatobiliary carcinoma. Stent restenosis due to tumor ingrowth is a common problem. In this study, we assessed a biodegradable form of magnesium (Mg) for its anticancer effect on hepatobiliary carcinoma, compared to the conventional stent material of titanium (Ti). The results showed that a Mg extract inhibited proliferation and induced apoptosis in human cholangiocarcinoma cells, while a Mg plate inhibited cell adhesion and destroyed the cytoskeleton in the process of biodegradation. In animal experiments with H22 tumor-bearing mice, Mg wires implanted in tumors exhibited an inhibitory effect on their growth compared with Ti wires. Fifteen days after implantation of metal wires, the mean tumor volume and weight in the Mg group were significantly smaller than in the Ti group. We observed the dynamic-degradation process of Mg wires in tumors and generation of H gas via soft X-ray photography and scanning electron microscopy. Histopathological analyses showed that apoptosis of tumor cells around Mg wires significantly increased, expression of carbonic anhydrase 9 significantly decreased, and the upstream protein hypoxia-inducible factor 1-alpha also decreased to some extent. Taken together, these results indicated that biodegradable Mg had antitumor properties both and , suggesting its potential application as a novel material for biodegradable biliary stents.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00288DOI Listing
June 2021

Editorial: Imaging and Mechanism of Leukocyte Recruitment and Function in Inflammation and Infections.

Front Cell Dev Biol 2021 7;9:690003. Epub 2021 May 7.

Department of Immunology, School of Medicine, UConn Health, Farmington, CT, United States.

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http://dx.doi.org/10.3389/fcell.2021.690003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138456PMC
May 2021

Particle-Phase Photoreactions of HULIS and TMIs Establish a Strong Source of HO and Particulate Sulfate in the Winter North China Plain.

Environ Sci Technol 2021 Jun 21;55(12):7818-7830. Epub 2021 May 21.

Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Department of Environmental Science and Engineering, Institute of Atmospheric Sciences, Fudan University, Shanghai 200438, China.

During haze periods in the North China Plain, extremely high NO concentrations have been observed, commonly exceeding 1 ppbv, preventing the classical gas-phase HO formation through HO recombination. Surprisingly, HO mixing ratios of about 1 ppbv were observed repeatedly in winter 2017. Combined field observations and chamber experiments reveal a photochemical in-particle formation of HO, driven by transition metal ions (TMIs) and humic-like substances (HULIS). In chamber experiments, steady-state HO mixing ratios of 116 ± 83 pptv were observed upon the irradiation of TMI- and HULIS-containing particles. Correspondingly, HO formation rates of about 0.2 ppbv h during the initial irradiation periods are consistent with the HO rates observed in the field. A novel chemical mechanism was developed explaining the in-particle HO formation through a sequence of elementary photochemical reactions involving HULIS and TMIs. Dedicated box model studies of measurement periods with relative humidity >50% and PM ≥ 75 μg m agree with the observed HO concentrations and time courses. The modeling results suggest about 90% of the particulate sulfate to be produced from the SO reaction with OH and HSO oxidation by HO. Overall, under high pollution, the HO-caused sulfate formation rate is above 250 ng m h, contributing to the sulfate formation by more than 70%.
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http://dx.doi.org/10.1021/acs.est.1c00561DOI Listing
June 2021

Per- and polyfluoroalkyl substances (PFASs) in the soil-plant system: Sorption, root uptake, and translocation.

Environ Int 2021 May 15;156:106642. Epub 2021 May 15.

State Key Laboratory of Organic Geochemistry and Guangdong-Hong Kong-Macao Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; CAS Center for Excellence in Deep Earth Science, Guangzhou, 510640, China.

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in the environment but pose potential risks to ecosystems and human health. The soil-plant system plays an important role in the bioaccumulation of PFASs. Because most PFASs in the natural environment are anionic and amphiphilic (both lipophilic and hydrophilic), their sorption and accumulation behaviors differ from those of neutral organic and common ionic compounds. In this review, we discuss processes affecting the availability of PFASs in soil after analyzing the potential mechanisms underlying the sorption and uptake of PFASs in the soil-plant system. We also summarize the current knowledge on root uptake and translocation of PFASs in plants. We found that the root concentration factor of PFASs for plants grown in soil was not significantly correlated with hydrophobicity, whereas the translocation factor was significantly and negatively correlated with PFAS hydrophobicity regardless of whether plants were grown hydroponically or in soil. Further research on the cationic, neutral, and zwitterionic forms of diverse PFASs is urgently needed to comprehensively understand the environmental fates of PFASs in the soil-plant system. Additional research directions are suggested, including the development of more accurate models and techniques to evaluate the bioavailability of PFASs, the effects of root exudates and rhizosphere microbiota on the bioavailability and plant uptake of PFASs, and the roles of different plant organelles, lipids, and proteins in the accumulation of PFASs by plants.
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http://dx.doi.org/10.1016/j.envint.2021.106642DOI Listing
May 2021

Genome-Wide Detection of Runs of Homozygosity in Laiwu Pigs Revealed by Sequencing Data.

Front Genet 2021 29;12:629966. Epub 2021 Apr 29.

Department of Animal Science, College of Animal Sciences, Zhejiang University, Hangzhou, China.

Laiwu pigs, distinguished by their high intramuscular fat of 7-9%, is an indigenous pig breed of China, and recent studies also found that Laiwu pigs showed high resistance to Porcine circovirus type 2. However, with the introduction of commercial varieties, the population of Laiwu pigs has declined, and some lineages have disappeared, which could result in inbreeding. Runs of homozygosity (ROH) can be used as a good measure of individual inbreeding status and is also normally used to detect selection signatures so as to map the candidate genes associated with economically important traits. In this study, we used data from Genotyping by Genome Reducing and Sequencing to investigate the number, length, coverage, and distribution patterns of ROH in 93 Chinese Laiwu pigs and identified genomic regions with a high ROH frequency. The average inbreeding coefficient calculated by pedigree was 0.021, whereas that estimated by all detected ROH segments was 0.133. Covering 13.4% of the whole genome, a total of 7,508 ROH segments longer than 1 Mb were detected, whose average length was 3.76 Mb, and short segments (1-5 Mb) dominated. For individuals, the coverage was in the range between 0.56 and 36.86%. For chromosomes, SSC6 had the largest number ( = 688), and the number of ROH in SSC12 was the lowest ( = 215). Thirteen ROH islands were detected in our study, and 86 genes were found within those regions. Some of these genes were correlated with economically important traits, such as meat quality (, , , , and ), immunity capacity (, , , , and ), production (, , and ), and reproduction ( and ). A total of six significant Gene Ontology terms and nine significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, most of which were correlated with disease resistance and biosynthesis processes, and one KEGG pathway was related to lipid metabolism. In addition, we aligned all of the ROH islands to the pig quantitative trait loci (QTL) database and finally found eight QTL related to the intramuscular fat trait. These results may help us understand the characteristics of Laiwu pigs and provide insight for future breeding strategies.
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http://dx.doi.org/10.3389/fgene.2021.629966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116706PMC
April 2021

Infrared broadband enhancement of responsivity in Ge photodetectors decorated with Au nanoparticles.

Opt Express 2021 Apr;29(9):12941-12949

A broadband, high-performance infrared Ge photodetector decorated with Au nanoparticles (NPs) is proposed. Photoelectronic characterization demonstrated that the responsivity of devices decorated with Au NPs is as high as 3.95 A/W at a wavelength of 1550 nm. Compared with a Ge photodetector without Au NPs, the responsivity of a device decorated with Au NPs is significantly increased, i.e., by more than 10 times in the entire range of infrared communication wavelengths, including the O, E, S, C, L, and U bands. The increase is ascribed to type-II energy-band alignment between Ge covered with Au NPs and bare Ge, instead of the localized surface-plasmon-resonance effect. The type-II energy-band alignment enhances the spatial electron-hole separation and restrains the electron-hole recombination, thus a larger photocurrent is observed. These results reflect the potential of this approach for achieving broadband, high-performance Ge photodetectors operating in the near-infrared communication band.
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http://dx.doi.org/10.1364/OE.423899DOI Listing
April 2021

A novel photothermal, self-healing and anti-reflection water evaporation membrane.

Soft Matter 2021 May;17(18):4730-4737

The Key Laboratory of Synthetic and Biotechnology Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China.

For the solar water evaporation system, there are no reports on the self-healing support, which is crucial for the sustainable use of solar evaporation membrane. In this work, a self-healing hydrogel is prepared via free radical copolymerization with covalent cross-linking and coordination cross-linking and is used as a photothermal water evaporation support. The photothermal material is then introduced into the hydrogel by physically doping acetylene carbon black. At the same time, inverted micro-pyramids are fabricated on the surface of the hydrogel by soft imprint to increase the utilization efficiency of incident light. The water evaporation rate of the composite membrane can reach 1.58 kg m-2 h-1, and the breaking elongation is 1580%. It can self-heal after it is completely broken, and can still be stretched 3 times its original length. The design of this self-healing photothermal membrane will provide a new idea for its application in a harsh outdoor environment.
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http://dx.doi.org/10.1039/d1sm00030fDOI Listing
May 2021

Inhibition of the HEG1-KRIT1 interaction increases KLF4 and KLF2 expression in endothelial cells.

FASEB Bioadv 2021 May 18;3(5):334-355. Epub 2021 Feb 18.

Department of Medicine University of California San Diego La Jolla CA USA.

The transmembrane protein heart of glass1 (HEG1) directly binds to and recruits Krev interaction trapped protein 1 (KRIT1) to endothelial junctions to form the HEG1-KRIT1 protein complex that establishes and maintains junctional integrity. Genetic inactivation or knockdown of endothelial HEG1 or KRIT1 leads to the upregulation of transcription factors Krüppel-like factors 4 and 2 (KLF4 and KLF2), which are implicated in endothelial vascular homeostasis; however, the effect of acute inhibition of the HEG1-KRIT1 interaction remains incompletely understood. Here, we report a high-throughput screening assay and molecular design of a small-molecule HEG1-KRIT1 inhibitor to uncover acute changes in signaling pathways downstream of the HEG1-KRIT1 protein complex disruption. The small-molecule HEG1-KRIT1 inhibitor 2 (HKi2) was demonstrated to be a bona fide inhibitor of the interaction between HEG1 and KRIT1 proteins, by competing orthosterically with HEG1 through covalent reversible interactions with the FERM (4.1, ezrin, radixin, and moesin) domain of KRIT1. The crystal structure of HKi2 bound to KRIT1 FERM revealed that it occupies the same binding pocket on KRIT1 as the HEG1 cytoplasmic tail. In human endothelial cells (ECs), acute inhibition of the HEG1-KRIT1 interaction by HKi2 increased KLF4 and KLF2 mRNA and protein levels, whereas a structurally similar inactive compound failed to do so. In zebrafish, HKi2 induced expression of klf2a in arterial and venous endothelium. Furthermore, genome-wide RNA transcriptome analysis of HKi2-treated ECs under static conditions revealed that, in addition to elevating KLF4 and KLF2 expression, inhibition of the HEG1-KRIT1 interaction mimics many of the transcriptional effects of laminar blood flow. Furthermore, HKi2-treated ECs also triggered Akt signaling in a phosphoinositide 3-kinase (PI3K)-dependent manner, as blocking PI3K activity blunted the Akt phosphorylation induced by HKi2. Finally, using an in vitro colocalization assay, we show that HKi6, an improved derivative of HKi2 with higher affinity for KRIT1, significantly impedes recruitment of KRIT1 to mitochondria-localized HEG1 in CHO cells, indicating a direct inhibition of the HEG1-KRIT1 interaction. Thus, our results demonstrate that early events of the acute inhibition of HEG1-KRIT1 interaction with HKi small-molecule inhibitors lead to: (i) elevated and gene expression; and (ii) increased Akt phosphorylation. Thus, HKi's provide new pharmacologic tools to study acute inhibition of the HEG1-KRIT1 protein complex and may provide insights to dissect early signaling events that regulate vascular homeostasis.
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http://dx.doi.org/10.1096/fba.2020-00141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103725PMC
May 2021

Urinary involvement in Erdheim-Chester disease: computed tomography imaging findings.

Abdom Radiol (NY) 2021 May 10. Epub 2021 May 10.

Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Purpose: To describe the urological manifestations of Erdheim-Chester disease (ECD) and their computed tomography (CT) findings.

Methods: We retrospectively reviewed 48 patients diagnosed with ECD at Peking Union Medical College Hospital from January 2014 to January 2020. Twenty-four patients exhibited urological manifestations. Their CT findings, including appearances of the involved area (e.g., perirenal space, renal sinus, ureters, renal arteries, and adrenal glands), occurrence rate of ECD involvement in each area, signal enhancement pattern after CT contrast agent administration, disease progression, and causes of hydronephrosis were discussed.

Results: In 24 patients with evidence of ECD urological involvement, the most common manifestation was perirenal infiltration, appearing as "hairy kidney" on unenhanced CT scans and moderate signal enhancement on enhanced CT scans (17/24, 70.8%). Other manifestations included renal sinus infiltration (16/24, 66.7%), proximal ureter involvement (14, 58.3%), renal artery sheath (10, 41.7%), hydronephrosis (14, 58.3%), and adrenal glands involvement (8, 33.3%). The histiocytic infiltrate was mostly bilateral, starting from the perirenal space and spreading to the renal sinus and ureters. Hydronephrosis was usually associated with infiltration of ureters.

Conclusion: Kidneys are the most common visceral organs affected by ECD. CT scanning is not only advantageous in early diagnosis, but also critical for designing the treatment regime for patients with ECD.
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http://dx.doi.org/10.1007/s00261-021-03106-8DOI Listing
May 2021

The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes.

Cell Discov 2021 May 4;7(1):31. Epub 2021 May 4.

Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and The Research Units of West China, Chinese Academy of Medical Sciences, Chengdu, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 pandemic. How SARS-CoV-2 regulates cellular responses to escape clearance by host cells is unknown. Autophagy is an intracellular lysosomal degradation pathway for the clearance of various cargoes, including viruses. Here, we systematically screened 28 viral proteins of SARS-CoV-2 and identified that ORF3a strongly inhibited autophagic flux by blocking the fusion of autophagosomes with lysosomes. ORF3a colocalized with lysosomes and interacted with VPS39, a component of the homotypic fusion and protein sorting (HOPS) complex. The ORF3a-VPS39 interaction prohibited the binding of HOPS with RAB7, which prevented the assembly of fusion machinery, leading to the accumulation of unfused autophagosomes. These results indicated the potential mechanism by which SARS-CoV-2 escapes degradation; that is, the virus interferes with autophagosome-lysosome fusion. Furthermore, our findings will facilitate strategies targeting autophagy for conferring potential protection against the spread of SARS-CoV-2.
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http://dx.doi.org/10.1038/s41421-021-00268-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096138PMC
May 2021

Structure and Expression Analysis of Sucrose Phosphate Synthase, Sucrose Synthase and Invertase Gene Families in .

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Shaanxi Engineering Research Center for Vegetables/College of Horticulture, Northwest A & F University, Yangling 712100, China.

Sucrose phosphate synthase (SPS), sucrose synthase (SUS) and invertase (INV) are all encoded by multigene families. In tomato (), a comprehensive analysis of structure characteristics of these family genes is still lacking, and the functions of individual isoforms of these families are mostly unclear under stress. Here, the structure characteristics of the three families in tomato were analyzed; moreover, as a first step toward understanding the functions of isoforms of these proteins under stress, the tissue expression pattern and stress response of these genes were also investigated. The results showed that four genes, six genes and nineteen genes were identified in tomato. The subfamily differentiation of and might have completed before the split of monocotyledons and dicotyledons. The conserved motifs were mostly consistent within each protein family/subfamily. These genes demonstrated differential expressions among family members and tissues, and in response to polyethylene glycerol, NaCl, HO, abscisic acid or salicylic acid treatment. Our results suggest that each isoform of these families may have different functions in different tissues and under environmental stimuli. , , , , , and demonstrated consistent expression responses and may be the major genes responding to exogenous stimuli.
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http://dx.doi.org/10.3390/ijms22094698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124378PMC
April 2021

cIAP1/2 are involved in the radiosensitizing effect of birinapant on NSCLC cell line in vitro.

J Cell Mol Med 2021 May 3. Epub 2021 May 3.

Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Tumour radioresistance is a major problem for cancer radiation therapy. To identify the underlying mechanisms of this resistance, we used human non-small cell lung cancer (NSCLC) cell lines and focused on the Inhibitor of Apoptosis Protein (IAP) family, which contributes to tumourigenesis and chemoresistance. We investigated the possible correlation between radioresistance in six NSCLC cell lines and IAP protein levels and tested the radiosensitizing effect of birinapant in vitro, a molecule that mimics the second mitochondria-derived activator of caspase. We found that birinapant-induced apoptosis and inhibited the proliferation of NSCLC cells after exposure to radiation. These effects were induced by birinapant downregulation of cIAP protein levels and changes of cIAP gene expression. Overall, birinapant can inhibit tumour growth of NSCLC cell lines to ironizing radiation and act as a promising strategy to overcome radioresistance in NSCLC.
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http://dx.doi.org/10.1111/jcmm.16526DOI Listing
May 2021

Anisotropic Synthetic Allomelanin Materials via Solid State Polymerization of Self-Assembled 1,8-Dihydroxynaphthalene Dimers.

Angew Chem Int Ed Engl 2021 Apr 28. Epub 2021 Apr 28.

Northwestern University, Chemistry, 2145 Sheridan Road, 6000, Evanston, UNITED STATES.

Melanosomes have diverse morphologies in nature, including spheres, rods, and platelets. By contrast, shapes of synthetic melanins have been almost entirely limited to spherical nanoparticles with few exceptions produced by complex templated synthetic methods. Here, we report a non-templated method to access synthetic melanins with a variety of architectures including spheres, sheets, and platelets. Three 1,8-dihydroxynaphthalene dimers (4-4', 2-4' and 2-2') were used as self-assembling synthons. These dimers pack to form well-defined structures of varying morphologies depending on the isomer. Specifically, distinctive ellipsoidal platelets can be obtained using 4-4' dimers. Solid-state polymerization of the preorganized dimers generates polymeric synthetic melanins while maintaining the initial particle morphologies. This work provides a new route to anisotropic synthetic melanins, where the building blocks are preorganized into specific shapes, followed by solid-state polymerization.
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http://dx.doi.org/10.1002/anie.202103447DOI Listing
April 2021