Publications by authors named "Yang Jiao"

1,004 Publications

  • Page 1 of 1

Comparison of the Efficacy and Safety of Different Doses of Linaclotide for Patients with Chronic Constipation: A Meta-Analysis and Bayesian Analysis.

Evid Based Complement Alternat Med 2021 14;2021:9923879. Epub 2021 Oct 14.

Department of Gastroenterology, WenChang Road 8, Liuzhou People's Hospital, Liuzhou 545000, Guangxi, China.

Background: It is ambiguous whether a higher dose of linaclotide provides higher efficacy for chronic constipation (CC) patients. The meta-analysis aimed to assess the efficacy and safety of linaclotide doses ranging from 62.5 g to 600 g for CC patients.

Methods: A comprehensive search was conducted, and STATA16 software was used for data analysis.

Results: Seven studies with 4,107 patients were eligible. A significantly enhanced number of completely spontaneous bowel movement (CSBM) responders were found in the extremely low-dose group (OR: 2.94; 95% CI: 1.98-4.34; < 0.001), the low-dose group (OR: 3.24; 95% CI: 2.44-4.31; < 0.001), the medium-dose group (OR: 3.08; 95% CI: 1.46-6.50; =0.003), and high-dose group (OR: 4.79; 95% CI: 3.04-7.54; < 0.001). Bayesian analysis showed the high-dose group obtained the maximum CSBM responder rate (OR: 4.94; 95% credible interval (CrI): 3.22-7.79; probability rank = 0.87) indirectly compared with extremely low-dose, low-dose, and medium-dose groups. However, no significant difference presented in the CSBM responder rate by pairwise comparisons of the different dose groups. Additionally, no more any adverse events occurred in the higher linaclotide dose group (RR: 0.91; 95% CrI: 0.60-1.38) indirectly compared with other dose groups.

Conclusions: High dose of linaclotide could be more effective and safer for CC patients, which need more trials to confirm in the future.
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http://dx.doi.org/10.1155/2021/9923879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531776PMC
October 2021

Targeting PPARα in low ambient temperature exposure-induced cardiac dysfunction and remodeling.

Mil Med Res 2021 Oct 19;8(1):53. Epub 2021 Oct 19.

Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, China.

The present study demonstrates that the down-regulation of peroxisome proliferator-activated receptor-α (PPARα) results in chronic low ambient temperature (LT) exposure-induced cardiac dysfunction and remodeling, emphasizing the therapeutic potential of PPARα activation strategies (e.g. fenofibrate treatment) in LT-associated cardiac injury.
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http://dx.doi.org/10.1186/s40779-021-00347-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524846PMC
October 2021

Case Report: Progressive Cholestasis: Severe Phenotype of MEGDEL Syndrome With SATB2-Associated Syndrome.

Front Pediatr 2021 1;9:713458. Epub 2021 Oct 1.

Department of Neonatology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

MEGDEL syndrome and -associated syndrome (SAS) are both rare congenital disorders with poor prognoses caused by gene mutations. We present the case of a 2-day-old girl with an unexplained abnormal liver function, feeding problem, and dystonia. Using next-generation sequencing, we identified two novel mutations in and a mutation in . Now, she is 15 months old and has the characteristics of SAS, such as downslanting palpebral fissures and delayed primary dentition. Besides the typical phenotypes of MEGDEL syndrome, such as hypertonia, failure to thrive, deafness, and motor regression, she has progressive cholestasis and is prone to high serum lactate after rehabilitation training and hypoglycemia with low ketone under starving conditions. These phenotypes substantially differ from the transient liver function abnormalities and hypoglycemia reported in the literature.
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http://dx.doi.org/10.3389/fped.2021.713458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517520PMC
October 2021

Production of fermented spicy rabbit meat using Lactobacillus paracasei.

Bioprocess Biosyst Eng 2021 Oct 15. Epub 2021 Oct 15.

College of Bioengineering, Sichuan University of Science and Engineering, Number 188, University Town, Lingang District,, Yibin, 644000, Sichuan, People's Republic of China.

Lactobacillus paracasei was used to produce fermented spicy rabbit meat. A series of indexes were determined, including pH value, free amino acid content, true protein content, texture, microstructure and the volatile compounds of fermented spicy rabbit meat and unfermented spicy rabbit meat. The results showed that Lactobacillus paracasei could reduce the pH value of spicy rabbit meat (from 6.85 to 4.65), could degrade the proteins of spicy rabbit meat, could increase the content of free amino acids (from 205.1 mg/100 g to 505.6 mg/100 g), and could improve its textural properties and organoleptic quality of the spicy rabbit meat. The microstructure of the fermented spicy rabbit meat and unfermented spicy rabbit meat was observed by scanning electron microscope. The results showed that the microstructure of the fermented spicy rabbit meat changed obviously, the arrangement of muscle fibers was loose or even seriously broken, and many small pieces were formed, which indicated that the fermentation could improve the tenderness of the rabbit meat. The kinds of volatile flavor compounds after fermentation were increased from 14 to 40 as estimated by solid phase microextraction and GC-MS. Therefore, utilization of microbial fermentation technology can improve the quality, texture, tenderness and flavor of spicy rabbit meat, and enhance the digestion and absorption capacity.
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http://dx.doi.org/10.1007/s00449-021-02642-3DOI Listing
October 2021

Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury.

Crit Care 2021 Oct 12;25(1):356. Epub 2021 Oct 12.

Department of Anesthesiology and Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: Polymorphonuclear neutrophils (PMNs) play an important role in sepsis-related acute lung injury (ALI). Accumulating evidence suggests PMN-derived exosomes as a new subcellular entity acting as a fundamental link between PMN-driven inflammation and tissue damage. However, the role of PMN-derived exosomes in sepsis-related ALI and the underlying mechanisms remains unclear.

Methods: Tumor necrosis factor-α (TNF-α), a key regulator of innate immunity in sepsis-related ALI, was used to stimulate PMNs from healthy C57BL/6J mice in vitro. Exosomes isolated from the supernatant were injected to C57BL/6J wild-type mice intraperitoneally (i.p.) and then examined for lung inflammation, macrophage (Mϕ) polarization and pyroptosis. In vitro co-culture system was applied where the mouse Raw264.7 macrophages or bone marrow-derived macrophages (BMDMs) were co-cultured with PMN-derived exosomes to further confirm the results of in vivo animal study and explore the potential mechanisms involved.

Results: Exosomes released by TNF-α-stimulated PMNs (TNF-Exo) promoted M1 macrophage activation after in vivo i.p. injection or in vitro co-culture. In addition, TNF-Exo primed macrophage for pyroptosis by upregulating NOD-like receptor 3 (NLRP3) inflammasome expression through nuclear factor κB (NF-κB) signaling pathway. Mechanistic studies demonstrated that miR-30d-5p mediated the function of TNF-Exo by targeting suppressor of cytokine signaling (SOCS-1) and sirtuin 1 (SIRT1) in macrophages. Furthermore, intravenous administration of miR-30d-5p inhibitors significantly decreased TNF-Exo or cecal ligation and puncture (CLP)-induced M1 macrophage activation and macrophage death in the lung, as well as the histological lesions.

Conclusions: The present study demonstrated that exosomal miR-30d-5p from PMNs contributed to sepsis-related ALI by inducing M1 macrophage polarization and priming macrophage pyroptosis through activating NF-κB signaling. These findings suggest a novel mechanism of PMN-Mϕ interaction in sepsis-related ALI, which may provide new therapeutic strategies in sepsis patients.
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http://dx.doi.org/10.1186/s13054-021-03775-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507252PMC
October 2021

Evaluation of the prognostic ability of serum uric acid for elderly acute coronary syndrome patients with diabetes mellitus: a prospective cohort study.

J Zhejiang Univ Sci B 2021 Oct;22(10):856-865

Senior Department of Cardiology, the Sixth Medical Center of PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China.

Objectives: This study evaluated the prognostic power of serum uric acid (UA) in predicting adverse events in elderly acute coronary syndrome (ACS) patients with diabetes mellitus (DM).

Methods: The analysis involved 718 ACS patients ‍>80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012. These patients were classified into two groups based on DM status, and then followed up after discharge. The Kaplan-Meier method was used for major adverse cardiac event (MACE) rates and all-cause mortality. Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis. Receiver operating characteristic (ROC) curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM. There were 242 and 476 patients in the DM and non-DM (NDM) groups, respectively, and the follow-up time after discharge was 40‒120 months (median, 63 months; interquartile range, 51‒74 months).

Results: The all-cause mortality, cardiac mortality, and MACE rates in both DM and NDM patients were higher than those in the control group (=0.001). All-cause mortalities, cardiac mortalities, and MACE rates in DM patients with moderate and high UA levels were significantly higher than those in the NDM group (=0.001). Long-term survival rates decreased significantly with increased UA levels in the ACS groups (=0.001). UA (odds ratio (OR)=2.106, 95% confidence interval (CI)=1.244‒3.568, =0.006) was found to be an independent risk factor for all-cause mortality and MACE in elderly ACS patients with DM. The cutoff value of UA was 353.6 μmol/L (sensitivity, 67.4%; specificity, 65.7%).

Conclusions: Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.
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http://dx.doi.org/10.1631/jzus.B2000637DOI Listing
October 2021

Disulfiram Alone Functions as a Radiosensitizer for Pancreatic Cancer Both and .

Front Oncol 2021 23;11:683695. Epub 2021 Sep 23.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China.

The prognosis of pancreatic cancer remains very poor worldwide, partly due to the lack of specificity of early symptoms and innate resistance to chemo-/radiotherapy. Disulfiram (DSF), an anti-alcoholism drug widely used in the clinic, has been known for decades for its antitumor effects when simultaneously applied with copper ions, including pancreatic cancer. However, controversy still exists in the context of the antitumor effects of DSF alone in pancreatic cancer and related mechanisms, especially in its potential roles as a sensitizer for cancer radiotherapy. In the present study, we focused on whether and how DSF could facilitate ionizing radiation (IR) to eliminate pancreatic cancer. DSF alone significantly suppressed the survival of pancreatic cancer cells after exposure to IR, both and . Additionally, DSF treatment alone caused DNA double-strand breaks (DSBs) and further enhanced IR-induced DSBs in pancreatic cancer cells. In addition, DSF alone boosted IR-induced cell cycle G2/M phase arrest and apoptosis in pancreatic cancer exposed to IR. RNA sequencing and bioinformatics analysis results suggested that DSF could trigger cell adhesion molecule (CAM) signaling, which might be involved in its function in regulating the radiosensitivity of pancreatic cancer cells. In conclusion, we suggest that DSF alone may function as a radiosensitizer for pancreatic cancer, probably by regulating IR-induced DNA damage, cell cycle arrest and apoptosis, at least partially through the CAM signaling pathway.
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http://dx.doi.org/10.3389/fonc.2021.683695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494980PMC
September 2021

Extended Mulliken-Hush Method with Applications to the Theoretical Study of Electron Transfer.

J Chem Theory Comput 2021 Oct 4. Epub 2021 Oct 4.

The State Key Laboratory of Physical Chemistry of Solid Surfaces, Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, China.

A novel adiabatic-to-diabatic (ATD) transformation strategy, namely, the extended MullikenHush (XMH) method, is proposed to evaluate diabatic properties including electronic couplings, potential energy surfaces, and their crossings. The XMH method is developed by adopting our recently proposed ATD transformation formula of a general vectorial physical observable, in which a useful ATD transformation is further determined by using an auxiliary dipole between localized frontier orbitals as a simple approximation of the diabatic transition dipole. The XMH method is simple and practical that provides a flexible way to construct diabatic states. To some extent, it can be regarded as an extension of the generalized MullikenHush (GMH) method since the latter takes a stronger approximation, in which the diabatic transition dipole is assumed to be vanishing. Test calculations on the HeH system show that the electronic couplings predicted by the XMH method are closer to the ones calculated by the valence bond block-diagonalization approach than the GMH ones since the XMH method takes into account both the magnitude and direction of the diabatic transition dipole, which is consistent with the properties of this molecule. In the study of electron transfer in the two kinds of donor-bridge-acceptor systems, the XMH method maintains the simplicity of the GMH method and gives reasonable results even when the latter fails, wherein the diabatic transition dipole is nearly perpendicular to the difference of the initial and final adiabatic dipoles. More importantly, the XMH method can be easily combined with high-level electronic structure methods, in which the properties of the ground and excited states may be more accurately calculated, and hence, one may expect that further development of the XMH method would result in a general computational model for studying electron transfer reactions.
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http://dx.doi.org/10.1021/acs.jctc.1c00603DOI Listing
October 2021

Synergic adhesive chemistry-based fabrication of BMP-2 immobilized silk fibroin hydrogel functionalized with hybrid nanomaterial to augment osteogenic differentiation of rBMSCs for bone defect repair.

Int J Biol Macromol 2021 Sep 28;192:407-416. Epub 2021 Sep 28.

Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, PR China.. Electronic address:

Bone defect repair and tissue engineering is specifically challenging process because of the distinctive morphological and structural behaviours of natural bone with complex healing and biochemical mechanisms. In the present investigation, we designed dopamine adhesive chemistry-based fabrication of silk fibroin hydrogel (SFD) with incorporation of nano-hydroxyapatite (nHA)-graphene oxide (GO) hybrid nanofillers with well-arranged porous morphology immobilized with bone morphogenic protein-2 (BMP-2) for the effective in vitro rabbit bone marrow derived mesenchymal stem cells loading compatibility and in vivo new bone regrowth and collagen deposition ability. We have achieved bone-specific hydrogel scaffolds with upgraded structural features, mechanical properties and particularly promoted in vitro osteogenic differentiation and compatibility of rabbit bone marrow mesenchymal stem cells (rBMSCs). Structural and microscopic analyses established greater distributions of components and well-ordered and aligned porous structure of the hydrogel network. In vivo result of new bone regrowth was promisingly higher in the [email protected] hydrogel (85%) group as compared to the other treatment groups of nHG-SFD (77%) and nH-SFD (64%) hydrogel. Overall, we summarized that morphologically improved hydrogel material with immobilization of BMP-2 could be have more attentions for new generation bone regeneration therapies.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.036DOI Listing
September 2021

Deoxycholic acid-modified microporous SiOnanofibers mimicking colorectal microenvironment to optimize radiotherapy-chemotherapy combined therapy.

Biomed Mater 2021 Oct 12;16(6). Epub 2021 Oct 12.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Textiles, Donghua University, Shanghai 201620, People's Republic of China.

Radiotherapy and chemotherapy remain the main therapeutics for colorectal cancer. However, due to their inevitable side effects on nomal tissues, it is necessary to evaluate the toxicity of radio-/chemotherapy regimens. The newly developedhigh throughput strategy is promising for these assessments. Nevertheless, the currently monolayer culture condition adopted in the preclinical screening processeshas been proved not so efficient assince its poor physiological similarity tomicroenvironment. Herein, we fabricated microporous SiOnanofiber mats and further bioactivated with deoxycholic acid (DCA) to mimic the chemical signals in the colorectal cancer microenvironment forregimen assessment of radiotherapy and chemotherapy. The colorectal cancer cells contacted with the DCA-modified SiOnanofiber (SiO-DCA NF) mats spatially, and the human intestinal epithelial cell on SiO-DCA NF mats exhibited better x-ray and cisplatin tolerance. The distinguishable irradiation and drug tolerance of cells on SiO-DCA NF mats indicated that the actual microenvironment of intestine might instruct colorectal cancer differently compared with the common biological experiments. The presented DCA-modified microporous SiOnanofibrous mats endowing a better mimicry of colorectal micro-environment, would provide a promising platform forassessment of radio-/chemotherapy regimens.
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http://dx.doi.org/10.1088/1748-605X/ac2bbbDOI Listing
October 2021

A flexible, stretchable system for simultaneous acoustic energy transfer and communication.

Sci Adv 2021 Oct 29;7(40):eabg2507. Epub 2021 Sep 29.

AML, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abg2507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480923PMC
October 2021

vdW-DF-ahcx: a range-separated van der Waals density functional hybrid.

J Phys Condens Matter 2021 Sep 29. Epub 2021 Sep 29.

Microtechnology and Nanoscience - MC2, Chalmers University of Technology, Kemivägen 9, Goteborg, 412 96, SWEDEN.

Hybrid density functionals replace a fraction of an underlying generalized-gradient approximation (GGA) exchange description with a Fock-exchange component. Range-separated hybrids (RSHs) also effectively screen the Fock-exchange component and thus open the door for characterizations of metals and adsorption at metal surfaces. The RSHs are traditionally based on a robust GGA, such as PBE [PRL 77, 3865 (1996)], for example, as implemented in the HSE design [JCP 118, 8207 (2003)]. Here we define an analytical-hole (AH) [JCP 128, 194105 (2008)] consistent-exchange (AHCX) RSH extension to the van der Waals density functional (vdW-DF) method [ROPP 78, 066501 (2015)], launching vdW-DF-ahcx. We characterize the GGA-type exchange in the vdW-DF-cx version [PRB 89, 035412 (2014)], isolate the short-ranged exchange component, and define the new vdW-DF hybrid. We find that the performance vdW-DF-ahcx compares favorably to (dispersion-corrected) HSE for descriptions of bulk (broad molecular) properties. We also find that it provides accurate descriptions of noble-metal surface properties, including CO adsorption.
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http://dx.doi.org/10.1088/1361-648X/ac2ad2DOI Listing
September 2021

NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury.

Front Oncol 2021 23;11:680058. Epub 2021 Aug 23.

State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.

Radiation-induced skin injury (RISI) commonly occur in cancer patients who received radiotherapy and is one of the first clinical symptoms after suffering from nuclear exposure. Oxidative damage is the major causes of RISI. Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a key mediator of the cellular antioxidant response. However, whether Nrf2 can alleviate RISI after high-dose irradiation remains unknown. In this study, we demonstrated that Nrf2-deficient ( ) mice were susceptible to high-dose irradiation and adenovirus-mediated overexpression of Nrf2 (ad-Nrf2) protected against radiation in skin cells. Overexpression of Nrf2 attenuated the severity of skin injury after high-dose electron beam irradiation. To uncover the mechanisms of Nrf2 involved in RISI, mRNA sequencing technology was performed to analyze the mRNA expression profiles of Ad-Nrf2 skin cells following radiation. The results revealed that a total of 127 genes were significantly changed, 55 genes were upregulated, and 72 genes were downregulated after Nrf2 overexpression. GSEA showed that Nrf2 was associated with positive regulation of genes involved in the reactive oxygen species pathway after radiation. Taken together, this study illustrated the role of Nrf2 in RISI and provided potentially strategies for ameliorating RISI.
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http://dx.doi.org/10.3389/fonc.2021.680058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461566PMC
August 2021

Embryo-Engineered Nonhuman Primate Models: Progress and Gap to Translational Medicine.

Research (Wash D C) 2021 21;2021:9898769. Epub 2021 Aug 21.

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.

Animal models of human diseases are vital in better understanding the mechanism of pathogenesis and essential for evaluating and validating potential therapeutic interventions. As close relatives of humans, nonhuman primates (NHPs) play an increasingly indispensable role in advancing translational medicine research. In this review, we summarized the progress of NHP models generated by embryo engineering, analyzed their unique advantages in mimicking clinical patients, and discussed the remaining gap between basic research of NHP models to translational medicine.
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http://dx.doi.org/10.34133/2021/9898769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404551PMC
August 2021

Osteoblast Response to Copper-Doped Microporous Coatings on Titanium for Improved Bone Integration.

Nanoscale Res Lett 2021 Sep 20;16(1):146. Epub 2021 Sep 20.

Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China.

Due to their excellent mechanical properties and good biocompatibility, titanium alloys have become a popular research topic in the field of medical metal implants. However, the surface of the titanium alloy does not exhibit biological activity, which may cause poor integration between the interface of the titanium implant and the interface of the bone tissue and subsequently may cause the implant to fall off. Therefore, surface biological inertness is one of the problems that titanium alloys must overcome to become an ideal orthopedic implant material. Surface modification can improve the biological properties of titanium, thereby enhancing its osseointegration effect. Copper is an essential trace element for the human body, can promote bone formation and plays an important role in maintaining the physiological structure and function of bone and bone growth and development. In this study, a microporous copper-titanium dioxide coating was prepared on the surface of titanium by microarc oxidation. Based on the evaluation of its surface characteristics, the adhesion, proliferation and differentiation of MC3T3-E1 cells were observed. A titanium rod was implanted into the rabbit femoral condyle, and the integration of the coating and bone tissue was evaluated. Our research results show that the microporous copper-titanium dioxide coating has a nearly three-dimensional porous structure, and copper is incorporated into the coating without changing the structure of the coating. In vitro experiments found that the coating can promote the adhesion, proliferation and differentiation of MC3T3-E1 cells. In vivo experiments further confirmed that the titanium copper-titanium dioxide microporous coating can promote the osseointegration of titanium implants. In conclusion, copper-titanium dioxide microporous coatings can be prepared by microarc oxidation, which can improve the biological activity and biocompatibility of titanium, promote new bone formation and demonstrate good osteoinductive properties. Therefore, the use of this coating in orthopedics has potential clinical application.
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http://dx.doi.org/10.1186/s11671-021-03602-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452820PMC
September 2021

Effective treatment of progressive nodular histiocytosis by intermediate-dose cytarabine: a case report and literature review.

Am J Transl Res 2021 15;13(8):9040-9047. Epub 2021 Aug 15.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.

Background: Progressive nodular histiocytosis (PNH) is a rare, clinically distinct non-Langerhans cell histiocytic neoplasm affecting the skin and mucous membranes with no signs of spontaneous regression of the lesions. Patients typically have hundreds of lesions of superficial xanthomatous papules to nodules and deep larger fibrous nodules, which can be life-threatening if laryngeal mucosa was involved. So far, few cases of PNH have been reported and no effective treatment has been shown to reverse the progressive clinical course.

Case Presentation: Here we describe a case of PNH presenting as diffuse, progressively enlarging papules, nodules and even leonine appearance in a young woman. The diagnosis was confirmed by histological and immunohistochemical findings. Next-generation sequencing (NGS) showed identical missense mutation in and in-frame deletion in . Since ERK inhibitor has not been on the market yet, the patient received chemotherapy instead. Traditional chemotherapy with intermediate-dose of cytarabine (500 mg/m cytarabine by 3-hour infusion every 12 hours for 3 days every 5 weeks) achieved favorable therapeutic effect as confirmed by clinical symptoms and PET/CT imaging.

Conclusions: PNH is a rare, proliferative disorder with disfiguring lesions and deteriorative quality of life. Mutations in , may play crucial roles in the pathogenesis of PNH. Intermediate-dose cytarabine can be considered as a promising treatment option for PNH patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430172PMC
August 2021

Characterization of N-Terminal Glutamate Cyclization in Monoclonal Antibody and Bispecific Antibody Using Charge Heterogeneity Assays and Hydrophobic Interaction Chromatography.

J Pharm Sci 2021 Sep 10. Epub 2021 Sep 10.

Analytical Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878.

N-terminal glutamate (E) cyclization to form pyroglutamate (pE) generates charge heterogeneities for mAbs and proteins. Thus far, pE formation rate in lyophilized formulation as compared to in liquid formulation has not been reported. Impact of pE on antibody biological activity has only been predicted or assessed using stressed samples that may contain other confounding degradations besides pE. Additionally, application of hydrophobic interaction chromatography (HIC) to separate pE has not been reported. In our study, N-terminal E cyclization was identified as the major degradation pathway in lyophilized formulation at elevated temperature for both monoclonal antibody (mAb-A) and IgG-like bispecific antibody (bsAb-A). pE was enriched in salt-gradient ion exchange chromatography (IEC) as pre-peak and in HIC as post-peak for both mAb-A and bsAb-A. Structure-function studies with pE-enriched IEC and HIC fractions confirmed that pE did not affect binding activities for mAb-A and bsAb-A. In vitro incubation of bsAb-A in serum and PBS revealed that the serum matrix may play a role in pE conversion in human serum, in contrast to the chemical reaction mechanism reported. These techniques can help in characterization of N-terminal E-to-pE cyclization and quality attribute severity assessment during therapeutic protein product development.
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http://dx.doi.org/10.1016/j.xphs.2021.09.006DOI Listing
September 2021

A Distinct Clinicopathological Feature and Prognosis of Young Gastric Cancer Patients Aged ≤ 45 Years Old.

Front Oncol 2021 26;11:674224. Epub 2021 Aug 26.

Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China.

Purpose: The aim of this retrospective study was to probe into clinicopathological features and prognosis of early-onset gastric cancer (EOGC) patients aged ≤ 45 years old.

Methods: This study selected 154 young gastric cancer patients aged ≤ 45 years old and 158 elderly gastric cancer patients aged > 50 years old admitted to West China Hospital of Sichuan University in 2009-2019 as the research object. These patients were further divided into two groups according to whether tumor can be resected radically. The following parameters were analyzed: age, gender, helicobacter pylori (HP) infection status, Her-2 status, pathological type and stage, chemotherapy, tumor differentiation degree, overall survival (OS).

Results: More than 3,000 patients with gastric carcinoma were screened, and 154 young gastric cancer patients aged ≤ 45 years old were identified as EOGC. Among them, the number of female patients in EOGC group was significantly higher than that of males, accounting for 63.6%. In addition, EOGC were associated with diffuse Laur´en type and poorly differentiated tumors. Interestingly, the Kaplan-Meier method showed that the OS of unresectable EOGC group was significantly lower than that of unresectable LOGC group ( = 0.0005) and chemotherapy containing paclitaxel tended to be more effective in the young people ( = 0.0511). Nevertheless, there was no significant difference in OS between young and elderly patients with gastric cancer in the radical resection group ( = 0.3881).

Conclusion: EOGC patients have a worse prognosis than late-onset gastric cancer (LOGC) patients with advanced unresectable gastric cancer. Palliative surgery or chemotherapy containing paclitaxel may improve the OS of unresectable young individuals with gastric cancer. Additional randomized controlled trials are required for guiding clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.674224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426597PMC
August 2021

Recent advances and challenges of biosensing in point-of-care molecular diagnosis.

Sens Actuators B Chem 2021 Dec 3;348:130708. Epub 2021 Sep 3.

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.

Molecular diagnosis, which plays a major role in infectious disease screening with successful understanding of the human genome, has attracted more attention because of the outbreak of COVID-19 recently. Since point-of-care testing (POCT) can expand the application of molecular diagnosis with the benefit of rapid reply, low cost, and working in decentralized environments, many researchers and commercial institutions have dedicated tremendous effort and enthusiasm to POCT-based biosensing for molecular diagnosis. In this review, we firstly summarize the state-of-the-art techniques and the construction of biosensing systems for POC molecular diagnosis. Then, the application scenarios of POCT-based biosensing for molecular diagnosis were also reviewed. Finally, several challenges and perspectives of POC biosensing for molecular diagnosis are discussed. This review is expected to help researchers deepen comprehension and make progresses in POCT-based biosensing field for molecular diagnosis applications.
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http://dx.doi.org/10.1016/j.snb.2021.130708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424413PMC
December 2021

Impact of left atrial geometric remodeling on late atrial fibrillation recurrence after catheter ablation.

J Cardiovasc Med (Hagerstown) 2021 Sep 9. Epub 2021 Sep 9.

Department of Medical Imaging, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei, China.

Aims: To quantitatively investigate the impact of left atrial geometric remodeling on atrial fibrillation recurrence after catheter ablation.

Methods: A retrospective analysis of 105 patients with atrial fibrillation who underwent coronary computed tomographic angiography before catheter ablation. Risk factors for atrial fibrillation recurrence were identified by multivariable logistic regression analysis and used to create a nomogram.

Results: After at least 12 months of follow-up, 30 patients (29%) developed recurrent atrial fibrillation. Patients with recurrence had higher left atrial volume, left atrial sphericity, and lower left atrial ejection fraction (LAEF) (P < 0.05). There was no significant difference in asymmetry index between the two groups (P = 0.121). Multivariable regression analysis showed that left atrial minimal volume index (LAVImin) [odds ratio (OR): 1.026, 95% confidence interval (CI): 1.002-1.050, P = 0.034], left atrial sphericity (OR: 1.222, 95% CI: 1.040-1.435, P = 0.015) and CHADS2 score (OR: 1.511, 95% CI: 1.024-2.229, P = 0.038) were independent predictors of atrial fibrillation recurrence. The combined model of the left atrial sphericity to the LAVImin substantially increased the predictive power for atrial fibrillation recurrence [area under the curve (AUC) = 0.736, 95% CI: 0.627-0.844, P < 0.001], with a sensitivity of 80% and a specificity of 61%. A nomogram was generated based on the contribution weights of the risk factors; the AUC was 0.772 (95% CI: 0.670-0.875) and had good internal validity.

Conclusion: The CHADS2 score, left atrial sphericity, and LAVImin were significant and independent predictors of atrial fibrillation recurrence after catheter ablation. Furthermore, the nomogram had a better predictive capacity for atrial fibrillation recurrence.
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http://dx.doi.org/10.2459/JCM.0000000000001255DOI Listing
September 2021

Echocardiographic characteristics of pediatric preexcitation cardiomyopathy.

Echocardiography 2021 Sep 9. Epub 2021 Sep 9.

Department of Ultrasound, Beijing Children's Hospital, Capital Medical University, National Center for children's Health, Beijing, China.

Preexcitation cardiomyopathy is a rare cardiac anomaly but it can be life threatening. It may occur in type B preexcitation syndrome. A patients with this condition typically has an enlarged left ventricle and reduced systolic function without tachycardia-associated cardiomyopathy. Echocardiography plays an important role in diagnosis in identifying this condition by revealing the "rebounce" movement of the inter-ventricular septum (IVS). We report echocardiographic findings of five pediatric patients with preexcitation cardiomyopathy. All of them had a radiofrequency catheter ablation (RFCA) and recovered during the follow-up.
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http://dx.doi.org/10.1111/echo.15181DOI Listing
September 2021

A facile one-pot room-temperature growth of self-supported ultrathin rhodium-iridium nanosheets as high-efficiency electrocatalysts for hydrogen evolution reaction.

J Colloid Interface Sci 2021 Aug 24;606(Pt 2):1707-1714. Epub 2021 Aug 24.

College of Geography and Environmental Sciences, College of Chemistry and Life Sciences, Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Zhejiang Normal University, Jinhua 321004, China. Electronic address:

The development of low-cost and high-efficiency electrocatalysts is very important for electrocatalytic hydrogen evolution reaction (HER) in water splitting system. Herein, ultrathin rhodium-iridium nanosheets were facilely in-situ grown on nickel foam (RhIr NSs/NF) by a one-pot aqueous strategy at room temperature. The sheet-like structures with the film thickness of 78 nm were identified by scanning electron microscopy and transmission electron microscopy. The catalyst showed greatly high HER features in both 1.0 M KOH and 0.5 M HSO with the overpotentials of 15 and 14 mV to achieve 10 mA cm, respectively, surpassing most Pt-free catalysts. Also, the RhIr NSs/NF exhibited amazing catalytic stability during the long-term operation. This study offers a facile and rational pathway for design and synthesis of advanced HER electrocatalysts for energy conversion devices.
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http://dx.doi.org/10.1016/j.jcis.2021.08.144DOI Listing
August 2021

Molybdenum doped induced amorphous phase in cobalt acid nickel for supercapacitor and oxygen evolution reaction.

J Colloid Interface Sci 2021 Aug 26;606(Pt 2):1695-1706. Epub 2021 Aug 26.

College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua 321004, China. Electronic address:

Reasonable structural design and metal-doping play significant roles in the optimization of electrochemical energy storage and conversion. Herein, in situ growth of Molybdenum-doped amorphous cobalt acid nickel nanoneedles on Ni foam (Mo-NiCoO/NF) has been successfully synthesized by a simple hydrothermal-annealing strategy. Benefiting from the unique hierarchical nanostructures and doping-optimized electronic structural configuration, the cross-link network structure of Mo-doped amorphous NiCoO with large specific surface areas exhibit excellent supercapacitor performance and electrocatalytic activity. As expected, the optimized Mo-doped NiCoO samples possess a specific capacitance of 3970 mF cm at 1 mA cm and remarkable rate performance. The assembled hybrid supercapacitor obtains a maximum energy density of 35 Wh kg (420 W kg) and keeps a capacitance retention of 107% after 5000 cycles. As an electrocatalyst, Mo-NiCoO/NF shows a rapid self-reconstruction process during oxygen evolution reaction (OER) that produces rich oxygen vacancies and thus exhibits remarkable long-term stability. The nanocomposites exhibit small overpotential (280 mV at 10 mA cm) and Tafel slope (43 mV dec). These results strongly demonstrate that both local amorphous phase and porous hierarchical structure design from Mo dopant provide superiorities for the synthesis of efficient and stable multifunctional electrode materials for energy storage and conversion.
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http://dx.doi.org/10.1016/j.jcis.2021.08.151DOI Listing
August 2021

PPFIBP1 induces glioma cell migration and invasion through FAK/Src/JNK signaling pathway.

Cell Death Dis 2021 09 3;12(9):827. Epub 2021 Sep 3.

School of Biomedical Engineering (Suzhou), Division of Life Sciences and Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor, with a 5-year survival ratio <5%. Invasive growth is a major determinant of the poor prognosis in GBM. In this study, we demonstrate that high expression of PPFIA binding protein 1 (PPFIBP1) correlates with remarkable invasion and poor prognosis of GBM patients. Using scratch and transwell assay, we find that the invasion and migration of GBM cells are promoted by overexpression of PPFIBP1, while inhibited by knockdown of PPFIBP1. Then, we illustrate that overexpression of PPFIBP1 facilitates glioma cell infiltration and reduces survival in xenograft models. Next, RNA-Seq and GO enrichment analysis reveal that PPFIBP1 regulates differentially expressed gene clusters involved in the Wnt and adhesion-related signaling pathways. Furthermore, we demonstrate that PPFIBP1 activates focal adhesion kinase (FAK), Src, c-Jun N-terminal kinase (JNK), and c-Jun, thereby enhancing Matrix metalloproteinase (MMP)-2 expression probably through interacting with SRCIN1 (p140Cap). Finally, inhibition of phosphorylation of Src and FAK significantly reversed the augmentation of invasion and migration caused by PPFIBP1 overexpression in GBM cells. In conclusion, these findings uncover a novel mechanism of glioma invasion and identify PPFIBP1 as a potential therapeutic target of glioma.
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http://dx.doi.org/10.1038/s41419-021-04107-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417031PMC
September 2021

HbA combined with glycated albumin or 1,5-anhydroglucitol improves the efficiency of diabetes screening in a Chinese population.

Diabet Med 2021 Sep 2:e14685. Epub 2021 Sep 2.

Department of Endocrinology, School of Medicine, Zhongda Hospital, Institute of Diabetes, Southeast University, Nanjing, China.

Aims: This study aimed to evaluate the ability of HbA combined with glycated albumin (GA) or 1,5-anhydroglucitol (1,5-AG) to detect diabetes in residents of Jiangsu, China.

Methods: The oral glucose tolerance test (OGTT) was performed on 2184 people in Jiangsu. HbA , GA, 1,5-AG and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA , GA and 1,5-AG according to the Youden index.

Results: (1) The optimal thresholds of HbA , GA and 1,5-AG for the screening of diabetes were ≥45 mmol/mol (6.3%), ≥13.0% and ≤23.0 μg/ml, respectively. (2) The sensitivities of HbA combined with GA and 1,5-AG were both 85%, higher than that of HbA (70%, p < 0.001).

Conclusions: This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA combined with GA or 1,5-AG can improve the sensitivity of diabetes screening, reduce the miss rate and save the use of OGTT. GA and 1,5-AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5-AG enhances the detection in those with hyperuricaemia.
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http://dx.doi.org/10.1111/dme.14685DOI Listing
September 2021

Effect of long-term exposure to acrylamide on endoplasmic reticulum stress and autophagy in rat cerebellum.

Ecotoxicol Environ Saf 2021 Aug 24;224:112691. Epub 2021 Aug 24.

Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, China. Electronic address:

Acrylamide (ACR) is a widely used chemical compound that has neurotoxicity in human, but whether ACR could impair the cerebellum and the related mechanism were still unknown. This study aimed to observe the changes in behavioral performance and cerebellar morphology caused by chronic ACR exposure, and to evaluate its influence on apoptosis, endoplasmic reticulum stress (ERS) and autophagy. Rats were treated with 0, 0.5 and 5 mg/kg ACR by drinking water for 12 months. Results showed that 5 mg/kg ACR treatment damaged the gait, balance ability, hindlimb muscle strength and motor coordination ability of rats. The results of hematoxylin and eosin and Nissl staining indicated that ACR impaired the structures of all three layers of the cerebellum, especially the Purkinje cell layer, showing abnormal morphology with nucleus condensation and pyknosis. Accumulation of autophagosomes, dilated endoplasmic reticulum and swollen mitochondria were observed in neurons under transmission electron microscopy. The enhanced apoptotic rates and the increased Bax expression indicated the elevated level of apoptosis. The results of Western blot showed that ACR treatment elevated protein levels of Beclin1, LC3-II/LC3-I, p-PERK/t-PERK, ATF4 and CHOP, indicating the initiation of autophagy, the activation of PERK pathway in ERS. This work helps to demonstrate the ACR neurotoxicity on cerebellum under chronic treatment and its underlying mechanism.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112691DOI Listing
August 2021

Cu-Co Co-Doped Microporous Coating on Titanium with Osteogenic and Antibacterial Properties.

J Biomed Nanotechnol 2021 Jul;17(7):1435-1447

Department of Stomatology, The 7th Medical Center, Chinese PLA General Hospital, Beijing 100700, China.

Titanium (Ti) and its alloys are widely used in bone surgery by virtue of their excellent mechanical properties and good biocompatibility; however, complications such as loosening and sinking have been reported post-implantation. Herein we deposited a copper-cobalt (Cu-Co) co-doped titanium dioxide (TUO) coating on the surface of Ti implants by microarc oxidation. The osteogenic and antimicrobial properties of the coating were evaluated by experiments, and we also assessed -catenin expression levels on different sample surfaces. Our results revealed that the coating promoted the adhesion, proliferation, and differentiation of MG63 osteoblasts, and TUO coating promoted -catenin expression; moreover, the proliferation of was inhibited. To summarize, we report that Cu-Co co-doping can enhance the osteogenic and antibacterial activities of orthopedic Ti implants, leading to potentially improved clinical performance.
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http://dx.doi.org/10.1166/jbn.2021.3120DOI Listing
July 2021

Available acid consumption capacity of sediments in six water bodies in the Yangtze River Basin in China.

Water Res 2021 Sep 16;203:117565. Epub 2021 Aug 16.

Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China. Electronic address:

Acid-base reactivity is a fundamental property of sediments and is responsible for sediments' multiple roles in aquatic ecosystems. However, little information currently exists about the composition, magnitude, and change of the available acid consumption capacity (AACC) of sediments. To optimize reaction conditions, we developed operational procedures to determine AACC using base titration to recover surplus acid in suspensions. We characterized the sediment AACC of Dianchi Lake (DL), Daduhe River (DR), Tuojiang River (TR), Honghu Lake (HL), Wuhan Donghu Lake (DhL), and Taihu Lake (TL) in the Yangtze River Basin, China. The procedure demonstrated that reacting 40 mL 0.1 M HCl with fresh sediments equivalent to 1.0 g dry weight for 4 h and recovering surplus acid in the suspension by NaOH titration to an endpoint pH of 3.0 could determine sediment AACC. Sediment AACC in the Yangtze River Basin had high regional variability. The mean magnitude of AACC among sites was ranked DL > DR > DhL > TR > HL > TL, which is extremely similar to their geographical location from the upper to lower reaches of the Yangtze River Basin. Qualitative results from acid titration curves showed that more components contributed to AACC in DL, DR, TR, and DhL sediments than to those in HL and TL sediments. The correlation between AACC and the total amount of multivalent cations released indicated that AACC depended significantly on labile acid-soluble minerals that contain multivalent cations (Fe, Fe, Ca, Al, Mg, and Mn) (p < 0.01). Based on the contribution percentages of multivalent cations to AACC, sediment AACC of six water bodies were divided into two types: Ca-Mg dominated (DL, DR, and TR) and Fe-Al dominated (HL, DhL, and TL). We suggest that sediment AACC complexing with pH can contribute to a better description of the acid-base characteristics of sediments.
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http://dx.doi.org/10.1016/j.watres.2021.117565DOI Listing
September 2021

Formation of Moiré Superlattices via Surfactant/Nanosheet-Co-mediated Crystallization.

J Phys Chem Lett 2021 Aug 12;12(33):7901-7907. Epub 2021 Aug 12.

Key Lab for Magnetism and Magnetic Materials of MOE, School of Physical Science and Technology, Lanzhou University, Lanzhou 730000, P. R. China.

Moiré superlattices (MSLs) of two-dimensional (2D) van der Waals materials have attracted considerable attention in recent years; however, studies of bottom-up growth of twisted MSL structures via solution-processed crystallization are rarely reported. Through facile one-pot solvothermal synthesis, here we demonstrate a nonclassical surfactant/nanosheet-co-mediated crystallization pathway for formation of MSL structures with two models of SnS and SnSe. Our experimental results reveal that attractive interactions between 2D inorganic building blocks and surfactant organic molecules during the initial stage of crystallization are crucial to drive surfactant-covered nanosheets to crystallize into molecule-intercalated nanosheet aggregates. Under the high-pressure condition, further crystallograpic fusion can occur if the reaction time is prolonged, which alters the interactions of adjacent layers during the coalescence of small-grain-size 2D domains due to insertion of foreign molecules, leading to interlayer rotations. This work uncovers an interesting organic-inorganic cocrystallization growth mode and provides a novel pathway for large-scale fabrication of MSLs.
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http://dx.doi.org/10.1021/acs.jpclett.1c01735DOI Listing
August 2021

Construction and analysis of the abnormal lncRNA-miRNA-mRNA network in hypoxic pulmonary hypertension.

Biosci Rep 2021 Aug;41(8)

First Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

The incidence of hypoxic pulmonary hypertension (HPH) is increasing. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in HPH, but the functions and mechanism have yet to be fully elucidated. In the present study, we established a HPH rat model with 8 h of hypoxia exposure (10% O2) per day for 21 days. High-throughput sequencing identified 60 differentially expressed (DE) lncRNAs, 20 DE miRNAs and 695 DE mRNAs in rat lung tissue. qRT-PCR verified the accuracy of the results. The DE mRNAs were significantly enriched in immune response, inflammatory response, leukocyte migration, cell cycle, cellular response to interleukin-1, IL-17 signalling pathway, cytokine-cytokine receptor interaction and Toll-like receptor signalling pathway. According to the theory of competing endogenous RNA (ceRNA) networks, lncRNA-miRNA-mRNA network was constructed by Cytoscape software, 16 miRNAs and 144 mRNAs. The results suggested that seven DE lncRNAs (Ly6l, AABR07038849.2, AABR07069008.2, AABR07064873.1, AABR07001382.1, AABR07068161.1 and AABR07060341.2) may serve as molecular sponges of the corresponding miRNAs and play a major role in HPH.
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http://dx.doi.org/10.1042/BSR20210021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390787PMC
August 2021
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