Publications by authors named "Fan Wang"

1,601 Publications

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Redesign of (R)-Omega-Transaminase and Its Application for Synthesizing Amino Acids with Bulky Side Chain.

Appl Biochem Biotechnol 2021 Aug 4. Epub 2021 Aug 4.

The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310014, People's Republic of China.

ω-Transaminase (ω-TA) is an attractive biocatalyst for stereospecific preparation of amino acids and derivatives, but low catalytic efficiency and unfavorable substrate specificity hamper their industrial application. In this work, to obtain applicable (R)-ω-TA responsible for amination of α-keto acids substrates, the reactivities of eight previously synthesized ω-TAs toward pyruvate using (R)-α-methylbenzylamine ((R)-α-MBA) as amine donor were investigated, and Gibberella zeae TA (GzTA) with the highest (R)-TA activity and stereoselectivity was selected as starting scaffold for engineering. Site-directed mutagenesis around enzymatic active pocket and access tunnel identified three positive mutation sites, S214A, F113L, and V60A. Kinetic analysis synchronously with molecular docking revealed that these mutations afforded desirable alleviation of steric hindrance for pyruvate and α-MBA. Furthermore, the constructed single-, double-, and triple-mutant exhibited varying degrees of improved specificities toward bulkier α-keto acids. Using 2-oxo-2-phenylacetic acid (1d) as substrate, the conversion rate of triple-mutant F113L/V60A/S214A increased by 3.8-fold relative to that of wide-type GzTA. This study provided a practical engineering strategy for improving catalytic efficiency and substrate specificity of (R)-ω-TA. The obtained experience shed light on creating more industrial ω-TAs mutants that can accommodate structurally diverse substrates.
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http://dx.doi.org/10.1007/s12010-021-03616-7DOI Listing
August 2021

Correspondence on "Update on the diagnosis and management of systemic lupus erythematosus" by Fanouriakis .

Ann Rheum Dis 2021 Aug 3. Epub 2021 Aug 3.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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http://dx.doi.org/10.1136/annrheumdis-2021-220897DOI Listing
August 2021

Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of femoral head through miR-206/HIF-1α/BNIP3 axis.

Kaohsiung J Med Sci 2021 Aug 2. Epub 2021 Aug 2.

Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China.

Declining autophagy and rising apoptosis are the main factors driving the development of steroid-induced osteonecrosis of the femoral head (SONFH). Here, we showed that astragalus polysaccharide (APS) improved femoral head necrosis via regulation of cell autophagy and apoptosis through microRNA (miR)-206/hypoxia inducible factor-1 (HIF-1α)/BCL2 interacting protein 3 (BNIP3) axis. The expression of miR-206, HIF-1α, and BNIP3 in SONFH specimens and cell model were measured using qPCR. SONFH cell model was treated with APS. Cell autophagy was evaluated using LC3-immunofluorescence assays. Flow cytometry was conducted to assess cell apoptosis. Apoptosis-related proteins and autophagy-related proteins were determined using western blot. Besides, dual-luciferase reporter assay was employed to investigate the relationship between miR-206 and HIF-1α. Here we showed that miR-206 expression was upregulated in SONFH tissues and cell model. APS promoted autophagy and inhibited apoptosis in SONFH cell model via downregulating miR-206. What is more, HIF-1α was the target of miR-206. Knockdown of HIF-1α reversed the recovery effect of miR-206 inhibitor on SONFH cell model. Furthermore, BNIP3 was the target of HIF-1α. HIF-1α overexpression promoted autophagy and inhibited apoptosis, and knockdown of BNIP3 abolished the recovery effect of HIF-1α overexpression in SONFH cell model. These results provided evidence that APS reduced miR-206 expression, and the downregulated miR-206 increased BNIP3 expression by targeting HIF-1α to promote autophagy and inhibit bone cell apoptosis. Our research proved that APS effectively improved SONFH by regulating cell autophagy and apoptosis.
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http://dx.doi.org/10.1002/kjm2.12426DOI Listing
August 2021

Immediate Resection and Reconstruction of Encephalocele in the Craniofacial Region.

J Craniofac Surg 2021 Jul 27. Epub 2021 Jul 27.

Department of Neurosurgery, Third People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

Introduction: Congenital meningoencephalocele is a herniation of brain and meninges through a skull base defect. It may result not only in neural defects, sensorimotor deficits, neurological morbidities, visual impairment, impaired nasal function, and a potential risk of intracranial infection. Goals of surgery include removal or repositioning of nonfunctional cerebral tissue, closure of the dura, and reconstruction of skeletal and cutaneous structures.

Materials And Methods: The authors present the case of a 4-months-old infant who was found to have a frontoethmoidal encephalomeningocele that was only discovered after birth, the volume increased gradually. After multiple department discussions, the procedures were planned in 2-staged surgical protocol comprising of the first stage urgently performed by neurosurgeon and craniomaxillofacial surgeon, which aimed at removal or repositioning of nonfunctional cerebral tissue, closure of the dura, and reconstruction of skeletal; then second stage was performed by plastic surgeon to correct craniofacial hard and soft tissue deformities.

Results And Conclusions: The surgical procedures for frontoethmoidal encephalomeningocele are complicated, particularly for the infant. In order to achieve the final surgical purpose, it needs multiple department cooperation to make the surgical plans.
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http://dx.doi.org/10.1097/SCS.0000000000007984DOI Listing
July 2021

Are dietary factors involved in the association of methylation and breast cancer risk?

Br J Nutr 2021 Jul 26:1-36. Epub 2021 Jul 26.

Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China.

DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits have been shown to alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell-cell adhesion glycoproteins. We conducted a case-control study (380 newly-diagnosed breast cancers and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL), as well as its combined and interactive effects with dietary factors and lifestyle on BC risk. A case-only study (335 newly-diagnosed breast cancers) was conducted to analyze the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation were detected using quantitative methylation specific PCR (qMSP). Unconditional logistic regressions were used to analyze the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj)= 2.70, 95% confidence interval (CI)= 1.90-3.83, P<0.001). CDH4 hypermethylation also showed significant combined effects with the consumption of <500 g/week vegetables (ORadj=4.33, 95% CI=2.63-7.10), ≤3 times/week allium vegetables (ORadj=7.00, 95% CI=4.17-11.77), <3 times/week fish (ORadj=7.92, 95% CI=3.79-16.53), <3 times/week milk (ORadj=6.30, 95% CI=3.41-11.66), >3 times/week overnight food (ORadj=4.63, 95% CI=2.69-7.99), ≥250 g/week pork (ORadj=5.59, 95% CI=2.94-10.62), and <1 time/month physical activity (ORadj=4.72, 95% CI=2.87-7.76). Moreover, consuming milk ≥ 1 times/month was significantly related with decreased risk of CDH4 methylation (OR=0.61, 95% CI=0.38-0.99) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.
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http://dx.doi.org/10.1017/S0007114521002804DOI Listing
July 2021

The effects of radiotherapy after thoracic and laparoscopic surgery on patients with esophageal cancer and on their prognoses.

Am J Transl Res 2021 15;13(6):6446-6456. Epub 2021 Jun 15.

Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University Hefei, Anhui Province, China.

Objective: This paper aimed to explore the effects of radiotherapy after thoracic and laparoscopic surgery (TLS) in patients with esophageal cancer and on their prognoses.

Methods: Altogether 118 patients with esophageal cancer diagnosed in our hospital were recruited as the study cohort and randomly divided into a postoperative radiotherapy group (59 cases) and a postoperative chemotherapy group (59 cases). All the patients were treated with TLS. In addition to the TLS, the patients in the postoperative radiotherapy group underwent radiotherapy, and the patients in the postoperative chemotherapy group were administered cisplatin and 5-fluorouracil (PF) chemotherapy. Before the treatment and at 6 months after the treatment, the serum carbohydrate antigen 199 (CA199), carbohydrate antigen 153 (CA153), and carcinoembryonic antigen (CEA) levels were measured using immunity transmission turbidity (ITT). The expression levels of Bax and Bcl-2 in the peripheral blood mononuclear cells (PBMCs) were measured using Western blot (WB). The CD4, CD8 and CD3 levels in the peripheral venous blood were measured using a flow cytometer. The two groups were compared in terms of their effective treatment rates, their incidences of complications, and their postoperative survival rates.

Results: After the treatment, the serum CEA, CA153, and CA199 levels in the postoperative radiotherapy group were significantly lower than they were in the postoperative chemotherapy group (P<0.05). After the treatment, the expression level of Bcl-2 was significantly lower in the postoperative radiotherapy group, but the Bax expression level was significantly higher in the postoperative radiotherapy group (P<0.05). After the treatment, there were no statistically significant differences in the CD4, CD3 or CD8 levels between the two groups (P>0.05). After the treatment, the overall response rate (ORR) and the total incidence of adverse reactions were significantly higher in the postoperative radiotherapy group (P<0.05). After the treatment, the 1-year, 3-year, and 5-year survival rates were significantly elevated in the postoperative radiotherapy group (P<0.05).

Conclusion: Compared with the esophageal cancer patients treated with chemotherapy after TLS, the serum CA153, CA199, and CEA levels were significantly improved in the patients treated with radiotherapy. The Bcl-2 and Bax levels in the PBMCs tended close to normal. Therefore, undergoing radiotherapy after TLS is markedly effective in prolonging patients' survival times and improving their prognoses.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290759PMC
June 2021

cFos-ANAB: A cFos-based Web Tool for Exploring Activated Neurons and Associated Behaviors.

Neurosci Bull 2021 Jul 24. Epub 2021 Jul 24.

Medical Information Center, Zhejiang University School of Medicine, Hangzhou, 310058, China.

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database-cFos-ANAB-a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users' purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net .
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http://dx.doi.org/10.1007/s12264-021-00744-2DOI Listing
July 2021

Hypoxic exosomal HIF-1α-stabilizing circZNF91 promotes chemoresistance of normoxic pancreatic cancer cells via enhancing glycolysis.

Oncogene 2021 Jul 22. Epub 2021 Jul 22.

Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Research has indicated that hypoxia profoundly contributes to chemoresistance of pancreatic cancer (PC), while the precise mechanism has not been fully elucidated. In this study, we report a hypoxic exosomal circular RNA (circRNA)-mediated mechanism of conferred chemoresistance in PC cells. Gemcitabine (GEM) resistance was enhanced in normoxic PC cells incubated with exosomes derived from hypoxic PC cells. CircRNA microarray displayed that circZNF91 was remarkably increased in hypoxic exosomes of PC cells compared with normoxic exosomes. Overexpression of circZNF91 obviously stimulated chemoresistance in PC cells, while knockdown of circZNF91 retarded the hypoxic exosome-transmitted chemoresistance. Mechanistically, the hypoxic-induced exosomal circZNF91 transmitted into normoxic PC cells could competitively bind to miR-23b-3p, which deprives the inhibition of miR-23b-3p on expression of deacetylase Sirtuin1 (SIRT1). Consequently, the upregulated SIRT1 enhanced deacetylation-dependent stability of HIF-1α protein, leading to glycolysis and GEM chemoresistance of recipient PC cells. In addition, we revealed that the increased circZNF91 in hypoxic exosome was attributed to the transcriptional regulation by HIF-1α. Coincidently, transmission of hypoxic exosomes into subcutaneous xenografts in nude mice obviously facilitated the chemoresistance of transplanted PC tumor, which could be reversed by depletion of circZNF91 or upregulation of miR-23b-3p. Furthermore, clinical data showed that circZNF91 was significantly upregulated in PC tissues and correlated with overexpression of glycolytic enzymes and short overall survival time. Collectively, exosomal circZNF91 can function as a cargo mediating the signal transmission between hypoxic and normoxic tumor cells to promote GEM chemoresistance of PC and may potentially serve as a therapeutic target.
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http://dx.doi.org/10.1038/s41388-021-01960-wDOI Listing
July 2021

Incidence and risk factors for early mortality in adults with skin Merkel cell carcinoma: A SEER-based study.

J Am Acad Dermatol 2021 Jul 19. Epub 2021 Jul 19.

Department of Dermatology and Venerology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China; Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu 610041, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.07.020DOI Listing
July 2021

Enhanced Microwave Absorbing Ability of Carbon Fibers with Embedded FeCo/CoFeO Nanoparticles.

ACS Appl Mater Interfaces 2021 Aug 22;13(30):36182-36189. Epub 2021 Jul 22.

College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, P. R. China.

In the face of increasingly severe electromagnetic (EM) wave pollution, the research of EM wave absorbing materials is an effective solution. To reduce the density of traditional absorbing materials, in this work, FeCo/CoFeO/carbon nanofiber composites were successfully prepared by electrospinning for the EM wave attenuation application. Benefiting from the loss ability of interface polarization, dipole polarization, and magnetic loss, the composites obtained a bandwidth of 5.0 GHz at a 1.95 mm thickness and an absorption peak of -52.3 dB. More importantly, the radar cross section (RCS) reduction of composite coatings calculated by ANSYS Electronics Desktop 2018 (HFSS) can reach 34.5 dBm, and the RCS value is almost less than -10 dBm when the incident angle is greater than 20°, demonstrating great scattering ability of the material coating to EM waves. This work, combined with the exploration of the mechanism and the simulation analysis of the absorbing coating, will be of significance for the development of absorbing materials.
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http://dx.doi.org/10.1021/acsami.1c09430DOI Listing
August 2021

A novel biliopancreatic duct endoscope combined optical coherence tomography with intraductal ultrasonography for exploring the bile duct: a diagnostic study in a porcine model.

Gastrointest Endosc 2021 Jul 15. Epub 2021 Jul 15.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Clinical Center and Key Lab of Intestinal and Colorectal Diseases of Hubei Province 430071, Wuhan, China. Electronic address:

Background And Aims: There are many deficiencies of existing biliopancreatic duct endoscopy in the examination of early biliary and pancreatic tumors. This study aimed to evaluate the usefulness and feasibility of a novel ultrafine separable biliopancreatic duct endoscopy device with dual modalities of intraductal ultrasonography (IDUS) and optical coherence tomography (OCT) for the in vivo assessment of biliopancreatic duct system during ERCP.

Methods: Five Bama miniature pigs were selected to probe their common bile duct and branches by using this novel equipment during ERCP. The feasibility of the procedure was evaluated by clear, clinically interpretable images obtained by using spiral scanning with pull-back method. The clinical usefulness of the novel product was evaluated by postoperative choledochoscopy and assessment of the animal's general condition.

Results: One hundred forty-one pairs of images from 5 Bama miniature pigs were acquired. Both OCT and IDUS's visualization of the bile duct was characterized by a differentiated 3-layer architecture, whereas IDUS shows with poor clarity than OCT. Postoperative choledochoscopy showed there was no local lesion in the bile duct wall, and the general condition of animals was normal.

Conclusions: This prospective evaluation indicates the feasibility and potential clinical value of the novel ultrafine separable biliopancreatic duct endoscopy device. The fusion of the 2 imaging modalities can shed light on the early diagnosis of biliary and pancreatic tumors. Further studies shall be carried out to establish the diagnosis criteria with the dual-modality imaging using animal pathological model and human clinic study.
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http://dx.doi.org/10.1016/j.gie.2021.07.009DOI Listing
July 2021

Asymmetric epigenetic modification and homoeolog expression bias in the establishment and evolution of allopolyploid Brassica napus.

New Phytol 2021 Jul 15. Epub 2021 Jul 15.

College of Life Sciences, Wuhan University, Wuhan, 430072, China.

This study explores how allopolyploidization reshapes the biased expression and asymmetric epigenetic modification of homoeologous gene pairs, and examines the regulation types and epigenetic basis of expression bias. We analyzed the gene expression and four epigenetic modifications (DNA methylation, H3K4me3, H3K27me3 and H3K27ac) of 29 976 homoeologous gene pairs in resynthesized, natural allopolyploid Brassica napus and an in silico 'hybrid'. We comprehensively elucidated the biased gene expression, asymmetric epigenetic modifications and the generational transmission characteristics of these homoeologous gene pairs in B. napus. We analyzed cis/trans effects and the epigenetic basis of homoeolog expression bias. There was a significant positive correlation between two active histone modifications and biased gene expression. We revealed that parental legacy was the dominant principle in the remodeling of homoeolog expression bias and asymmetric epigenetic modifications in B. napus, and further clarified that this depends on whether there were differences in the expression/epigenetic modifications of gene pairs in parents/progenitors. The maternal genome was dominant in the homoeolog expression bias of resynthesized B. napus, and this phenomenon was attenuated in natural B. napus. Furthermore, cis rather than trans effects were dominant when epigenetic modifications potentially affected biased expression of gene pairs in B. napus.
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http://dx.doi.org/10.1111/nph.17621DOI Listing
July 2021

Prevalence and Characteristics of spp. from a Pig Farm in Shanghai, China.

Foodborne Pathog Dis 2021 Jul;18(7):477-488

Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.

spp. is a major foodborne pathogen that is distributed among most pork production chains worldwide. This study aimed to investigate the dynamic changes in spp. along the pig breeding process monthly from April 2018 to March 2019 in a pig farm in Shanghai, China, and identify the potential critical control points during the production. In total, 239 spp. isolates were obtained from 1389 samples, in which were detected from 26.3% (222/843) of fecal samples, 7.1% (17/240) of feed samples, and 0.0% (0/306) of both water and insect samples. Seven different serotypes were identified, with the predominant serotype being Salmonella Derby (21.8%), followed by Typhimurium (18.8%), Rissen (16.3%), Mbandaka (12.6%), and 1,4,[5],12:i:- (11.8%). Most probable number (MPN) analysis revealed that the load of spp. gradually increased along the pig production chain, while the highest number of spp. isolates was at the fattening stage (MPN value, 11-15 MPN/g). The pulsed-field gel electrophoresis showed that both Typhimurium and Derby isolates were grouped to six clusters. The antimicrobial resistance analyzed demonstrated that 80.0% of the isolates were of multidrug resistance and resistant to sulfamethoxazole (84.5%), lincomycin (89.4%), ampicillin (96.9%), oxytetracycline (93.8%), and tetracycline (95.1%). We further evaluated the spp. Resistance to quaternary ammonium compounds (QACs) showed an increasing trend along with the testing period indicating that the use of QACs could induce the resistance of spp. to QACs. Our study confirmed the dynamic changes in spp. over time and space in this pig farm and identified feed and the fattening house as the key points for the prevention and control of spp. contamination.
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http://dx.doi.org/10.1089/fpd.2021.0018DOI Listing
July 2021

The Use of Oseltamivir as Adjunctive Therapy for the Treatment of Hand-Food-and-Mouth Disease: A Meta-Analysis of Randomized Clinical Trials.

Front Pharmacol 2021 25;12:653691. Epub 2021 Jun 25.

School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.

Hand-foot-and-mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Oseltamivir (OS), a neuraminidase inhibitor, has been frequently used as an adjunctive therapy for the treatment of HFMD. Solid evidence, however, is lacking regarding the efficacy of such adjunctive therapy. This work is to conduct a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy of oseltamivir for HFMD in children. Eligible studies from inception to October 10, 2020 were identified by searching six databases (PubMed, Embase, CENTRAL, CNKI, Wanfang, and VIP database). Quality of evidence was assessed using the Cochrane Collaboration tool. Of a total of 91 entries, 11 RCTs involving 977 HFMD children were included in the final analysis. The results showed that the therapy combined with oseltamivir was more effective, with higher effective rate (RR, 0.84; 95% CI, 0.80 to 0.87; < 0.01), shorter fever clearance time (days) (SMD, -0.74; 95% CI, -1.12 to -0.35; < 0.01), shorter rash regression time (days) (MD, -0.89; 95% CI, -1.05 to -0.72; < 0.01) and shorter clinical cure time (SMD, -1.08; 95% CI, -1.55 to -0.61; < 0.01). No significant difference was observed in the risk of adverse reactions between the groups with and without oseltamivir. The use of oseltamivir as adjunctive therapy shows effectiveness and no increased risk of adverse reactions for the treatment of HFMD in children.
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http://dx.doi.org/10.3389/fphar.2021.653691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267410PMC
June 2021

Increased glycolysis in skeletal muscle coordinates with adipose tissue in systemic metabolic homeostasis.

J Cell Mol Med 2021 Jul 6. Epub 2021 Jul 6.

State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China.

Insulin-independent glucose metabolism, including anaerobic glycolysis that is promoted in resistance training, plays critical roles in glucose disposal and systemic metabolic regulation. However, the underlying mechanisms are not completely understood. In this study, through genetically manipulating the glycolytic process by overexpressing human glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) in mouse skeletal muscle, we examined the impact of enhanced glycolysis in metabolic homeostasis. Enhanced glycolysis in skeletal muscle promoted accelerated glucose disposal, a lean phenotype and a high metabolic rate in mice despite attenuated lipid metabolism in muscle, even under High-Fat diet (HFD). Further study revealed that the glucose metabolite sensor carbohydrate-response element-binding protein (ChREBP) was activated in the highly glycolytic muscle and stimulated the elevation of plasma fibroblast growth factor 21 (FGF21), possibly mediating enhanced lipid oxidation in adipose tissue and contributing to a systemic effect. PFKFB3 was critically involved in promoting the glucose-sensing mechanism in myocytes. Thus, a high level of glycolysis in skeletal muscle may be intrinsically coupled to distal lipid metabolism through intracellular glucose sensing. This study provides novel insights for the benefit of resistance training and for manipulating insulin-independent glucose metabolism.
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http://dx.doi.org/10.1111/jcmm.16698DOI Listing
July 2021

Supertransport of excitons in atomically thin organic semiconductors at the 2D quantum limit.

Light Sci Appl 2020 Jul 6;9(1):116. Epub 2020 Jul 6.

Research School of Electrical, Energy and Materials Engineering, College of Engineering and Computer Science, The Australian National University, Canberra, ACT, 2601, Australia.

Long-range and fast transport of coherent excitons is important for the development of high-speed excitonic circuits and quantum computing applications. However, most of these coherent excitons have only been observed in some low-dimensional semiconductors when coupled with cavities, as there are large inhomogeneous broadening and dephasing effects on the transport of excitons in their native states in materials. Here, by confining coherent excitons at the 2D quantum limit, we first observed molecular aggregation-enabled 'supertransport' of excitons in atomically thin two-dimensional (2D) organic semiconductors between coherent states, with a measured high effective exciton diffusion coefficient of ~346.9 cm/s at room temperature. This value is one to several orders of magnitude higher than the values reported for other organic molecular aggregates and low-dimensional inorganic materials. Without coupling to any optical cavities, the monolayer pentacene sample, a very clean 2D quantum system (~1.2 nm thick) with high crystallinity (J-type aggregation) and minimal interfacial states, showed superradiant emission from Frenkel excitons, which was experimentally confirmed by the temperature-dependent photoluminescence (PL) emission, highly enhanced radiative decay rate, significantly narrowed PL peak width and strongly directional in-plane emission. The coherence in monolayer pentacene samples was observed to be delocalised over ~135 molecules, which is significantly larger than the values (a few molecules) observed for other organic thin films. In addition, the supertransport of excitons in monolayer pentacene samples showed highly anisotropic behaviour. Our results pave the way for the development of future high-speed excitonic circuits, fast OLEDs, and other optoelectronic devices.
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http://dx.doi.org/10.1038/s41377-020-00347-yDOI Listing
July 2020

ABCnet: Adversarial bias correction network for infant brain MR images.

Med Image Anal 2021 08 18;72:102133. Epub 2021 Jun 18.

Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Automatic correction of intensity nonuniformity (also termed as the bias correction) is an essential step in brain MR image analysis. Existing methods are typically developed for adult brain MR images based on the assumption that the image intensities within the same brain tissue are relatively uniform. However, this assumption is not valid in infant brain MR images, due to the dynamic and regionally-heterogeneous image contrast and appearance changes, which are caused by the underlying spatiotemporally-nonuniform myelination process. Therefore, it is not appropriate to directly use existing methods to correct the infant brain MR images. In this paper, we propose an end-to-end 3D adversarial bias correction network (ABCnet), tailored for direct prediction of bias fields from the input infant brain MR images for bias correction. The "ground-truth" bias fields for training our network are carefully defined by an improved N4 method, which integrates manually-corrected tissue segmentation maps as anatomical prior knowledge. The whole network is trained alternatively by minimizing generative and adversarial losses. To handle the heterogeneous intensity changes, our generative loss includes a tissue-aware local intensity uniformity term to reduce the local intensity variation in the corrected image. Besides, it also integrates two additional terms to enhance the smoothness of the estimated bias field and to improve the robustness of the proposed method, respectively. Comprehensive experiments with different sizes of training datasets have been carried out on a total of 1492 T1w and T2w MR images from neonates, infants, and adults, respectively. Both qualitative and quantitative evaluations on simulated and real datasets consistently demonstrate the superior performance of our ABCnet in both accuracy and efficiency, compared with popularly available methods.
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http://dx.doi.org/10.1016/j.media.2021.102133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316417PMC
August 2021

Genomic insights into the fast growth of paulownias and the formation of Paulownia witches' broom.

Mol Plant 2021 Jun 29. Epub 2021 Jun 29.

Institute of Paulownia, Henan Agricultural University, Zhengzhou, Henan, 450002, China; College of Forestry, Henan Agricultural University, Zhengzhou, Henan, 450002, China. Electronic address:

Paulownias are among the fastest growing trees in the world, but often suffer tremendous loss of wood production due to infection by Paulownia witches' broom (PaWB) phytoplasmas. Here, we have sequenced and assembled a high-quality nuclear genome of Paulownia fortunei, a commonly cultivated paulownia species. The assembled genome of P. fortunei, 511.6 Mb in size, with 93.2% of the sequences being anchored to 20 pseudo-chromosomes, contains 31,985 protein-coding genes. Phylogenomic analyses show that the family Paulowniaceae is sister to a clade composed of Phrymaceae and Orobanchaceae. Higher photosynthetic efficiency is achieved through integrating C3 photosynthesis and the crassulacean acid metabolism pathway, which may have contributed to the extremely fast growth habit of paulownia trees. Comparative transcriptome analyses reveals modules related to cambial growth and development, photosynthesis, and defense responses. Additional genome sequencing of PaWB phytoplasma, combined with functional analyses, indicates that the effector PaWB-SAP54 directly interacts with Paulownia PfSPLa, which in turn causes the degradation of PfSPLa by the ubiquitin-mediated pathway and leads to the formation of witches' broom. Our data provide significant insights into the biology of paulownias and the regulatory mechanism for the formation of PaWB.
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http://dx.doi.org/10.1016/j.molp.2021.06.021DOI Listing
June 2021

Influences of Psychological Intervention on Negative Emotion, Cancer-Related Fatigue and Level of Hope in Lung Cancer Chemotherapy Patients Based on the PERMA Framework.

Iran J Public Health 2021 Apr;50(4):728-736

Department of Nursing, Wuhan No.4 Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Psychological status is a decisive factor for regulating the lung cancer chemotherapy patients' levels of fatigue and hope. Using the PERMA (Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment) framework. We aimed to explore the influences of the psychological intervention on the patients' negative emotion, cancer-related fatigue, and level of hope.

Method: A total of 100 lung cancer chemotherapy patients admitted in Wuhan No.4 Hospital, China, from Jan 2018 to Aug 2019 were enrolled as research objects divided into the control group and observation group. Positive psychological intervention using the PERMA framework was given to the observation group. The scores of Post-Traumatic Growth Inventory (PTGI), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Cancer Fatigue Scale (CFS), and Herth Hope Index (HHI) were evaluated and compared in the two groups.

Results: After the intervention, PTGI score in the observation group is higher than that in the control group, whereas the SAS and SDS scores are lower in the observation group than in the control group, and the differences are statistically significant (<0.05). Score of each CFS dimension and total CFS score in the observation group are all lower than those in the control group, with statistically significant differences (<0.05). Score of each HHI dimension and total HHI score are higher than those in the control group, and the differences are statistically significant (<0.05).

Conclusion: Positive psychological intervention using the PERMA framework can improve the emotional and fatigue state of lung cancer chemotherapy patients and elevate their level of hope.
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http://dx.doi.org/10.18502/ijph.v50i4.5997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219625PMC
April 2021

[Execution, assessment and improvement methods of motor imagery for brain-computer interface].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Jun;38(3):434-446

School of Information Engineering and Automation, Kunming University of Science and Technology, Kunming 650500, P.R.China.

Motor imagery (MI) is an important paradigm of driving brain computer interface (BCI). However, MI is not easy to control or acquire, and the performance of MI-BCI depends heavily on the performance of the subjects' MI. Therefore, the correct execution of MI mental activities, ability evaluation and improvement methods play important and even critical roles in the improvement and application of MI-BCI system's performance. However, in the research and development of MI-BCI, the existing researches mainly focus on the decoding algorithm of MI, but do not pay enough attention to the above three aspects of MI mental activities. In this paper, these problems of MI-BCI are discussed in detail, and it is pointed out that the subjects tend to use visual motor imagery as kinesthetic motor imagery. In the future, we need to develop some objective, quantitatively visualized MI ability evaluation methods, and develop some effective and less time-consumption training methods to improve MI ability. It is also necessary to solve the differences and commonness of MI problems between and within individuals and MI-BCI illiteracy to a certain extent.
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http://dx.doi.org/10.7507/1001-5515.202101037DOI Listing
June 2021

Deubiquitination of MITF-M Regulates Melanocytes Proliferation and Apoptosis.

Front Mol Biosci 2021 9;8:692724. Epub 2021 Jun 9.

College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Microphthalmia-associated transcription factor-M (MITF-M) is the key gene in the proliferation and differentiation of melanocytes, which undergoes an array of post-translation modifications. As shown in our previous study, deubiquitinase USP13 is directly involved in melanogenesis. However, it is still ambiguous that the effect of USP13-mediated MITF-M expression on melanocytes proliferation and apoptosis. Herein, we found that MITF-M overexpressing melanocytes showed high cell proliferation, reduced apoptosis, and increased melanin levels. Besides, melanin-related genes, TYR, DCT, GPNMB, and PMEL, were significantly up-regulated in MITF-M overexpressing melanocytes. Furthermore, Exogenous USP13 significantly upregulated the endogenous MITF-M protein level, downregulated USP13 significantly inhibited MITF-M protein levels, without altering MITF-M mRNA expression. In addition, USP13 upregulation mitigated the MITF-M degradation and significantly increased the half-life of MITF-M. Also, USP13 stabilized the exogenous MITF protein levels. In conclusion, the MITF-M level was regulated by USP13 deubiquitinase in melanocytes, affecting melanocytes proliferation and apoptosis. This study provides the theoretical basis for coat color transformation that could be useful in the development of the new breed in fur animals.
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http://dx.doi.org/10.3389/fmolb.2021.692724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221579PMC
June 2021

Editorial: Recent Advances in Fluorescent Probes for Super-Resolution Microscopy.

Front Chem 2021 11;9:698531. Epub 2021 Jun 11.

School of Basic Sciences, Indian Institute of Technology, Mandi, India.

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http://dx.doi.org/10.3389/fchem.2021.698531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225944PMC
June 2021

Three-dimensional comparative evaluation of customized bone-anchored vs tooth-borne maxillary protraction in patients with skeletal Class III malocclusion.

Am J Orthod Dentofacial Orthop 2021 Jun 22. Epub 2021 Jun 22.

Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China. Electronic address:

Introduction: The aim of this prospective study was to assess the 3-dimensional skeletal and dental effects induced by a new maxillary protraction approach using customized miniplates for anchorage compared with a control group of traditional tooth-borne maxillary protraction.

Methods: Forty-one growing patients at prepubescent stage with skeletal Class III malocclusion participated in this study. These patients were randomly split into 2 groups. In group 1 (n = 20), patients underwent maxillary protraction anchored with customized miniplates. The miniplates were individually designed and inserted using the surgical templates. In group 2 (n = 21), patients underwent tooth-borne maxillary protraction. Pretreatment and posttreatment cone-beam computed tomography scans were obtained, and 30 measurements of cone-beam computed tomography images were acquired and calculated. The changes after treatment and the comparison of the 2 groups were assessed.

Results: After maxillary protraction, group 1 showed a greater forward movement of the maxilla than group 2. The maxilla length increased more in group 1 than in group 2. The rotations of the palatal and mandibular planes in group 1 were less than those in group 2. In group 1, the maxillary incisors proclined less, the mandibular incisors retroclined less, and the maxillary first molars extruded less.

Conclusions: Compared with tooth-borne maxillary protraction, customized miniplates anchored maxillary protraction produced more maxillary growth, fewer dental changes, and less maxillary and mandibular plane rotation.
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http://dx.doi.org/10.1016/j.ajodo.2020.04.034DOI Listing
June 2021

NADPH is superior to NADH or edaravone in ameliorating metabolic disturbance and brain injury in ischemic stroke.

Acta Pharmacol Sin 2021 Jun 24. Epub 2021 Jun 24.

Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

Our previous studies confirm that exogenous reduced nicotinamide adenine dinucleotide phosphate (NADPH) exerts a neuroprotective effect in animal models of ischemic stroke, and its primary mechanism is related to anti-oxidative stress and improved energy metabolism. However, it is unknown whether nicotinamide adenine dinucleotide (NADH) also plays a neuroprotective role and whether NADPH is superior to NADH against ischemic stroke? In this study we compared the efficacy of NADH, NADPH, and edaravone in ameliorating brain injury and metabolic stress in ischemic stroke. Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) mouse model and in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model were established. The mice were intravenously administered the optimal dose of NADPH (7.5 mg/kg), NADH (22.5 mg/kg), or edaravone (3 mg/kg) immediately after reperfusion. We showed that the overall efficacy of NADPH in ameliorating ischemic injury was superior to NADH and edaravone. NADPH had a longer therapeutic time window (within 5 h) after reperfusion than NADH and edaravone (within 2 h) for ischemic stroke. In addition, NADPH and edaravone were better in alleviating the brain atrophy, while NADH and NADPH were better in increasing the long-term survival rate. NADPH showed stronger antioxidant effects than NADH and edaravone; but NADH was the best in terms of maintaining energy metabolism. Taken together, this study demonstrates that NADPH exerts better neuroprotective effects against ischemic stroke than NADH and edaravone.
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http://dx.doi.org/10.1038/s41401-021-00705-5DOI Listing
June 2021

Fabricating Silicon Nanotubes by Electrochemical Exfoliation and Reduction of Layer-Structured CaSiO in Molten Salt.

ACS Appl Mater Interfaces 2021 Jul 24;13(26):30668-30677. Epub 2021 Jun 24.

School of Resource and Environmental Sciences, Hubei International Scientific and Technological Cooperation Base of Sustainable Resource and Energy, Wuhan University, Wuhan 430072, P. R. China.

Silicon nanotubes (SNTs) are very attractive in the fields of energy, catalysis, and sensors, but a facile template- and/or catalyst-free preparation method is still absent. Herein, we study a controllable and cost-effective approach for preparing SNTs by electrochemically reducing layer-structured calcium silicate (CaSiO) in molten CaCl/NaCl without any template and catalyst. The underlying mechanism of the SNT formation is uncovered: the layer-structured CaSiO is first electrochemically exfoliated into SiO (0 < < 2) sheets while releasing CaO into the molten salts, and then the SiO sheets are electrochemically reduced and simultaneously crimped into SNTs. The diameter (120-312 nm) and wall thickness (∼40 nm) of the SNTs can be tailorable by manipulating the reduction potential between -1.28 and -1.48 V (vs Ag/AgCl). Lastly, the electrolytic SNTs show a high lithium storage capacity of 3737 mAh g at 0.2 A g, a high rate capability of 1371 mA h g at 10 A g, and stable cycling with a capacity of 974 mAh g after 600 cycles at 1 A g. Overall, the template- and catalyst-free electrochemical method provides a straightforward and facile way to prepare SNTs with a brand-new mechanism that can be applied to other tubular structure materials.
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http://dx.doi.org/10.1021/acsami.1c07031DOI Listing
July 2021

Targeting HSPA8 inhibits proliferation via downregulating BCR-ABL and enhances chemosensitivity in imatinib-resistant chronic myeloid leukemia cells.

Exp Cell Res 2021 Aug 19;405(2):112708. Epub 2021 Jun 19.

Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, PR China.

The resistance to tyrosine kinase inhibitors is currently a major problem for chronic myeloid leukemia (CML) treatment and HSPA8 is highly expressed and a hallmark of poor prognosis in several human cancers. However, its role in imatinib-resistant CML (IR-CML) cells remains undetermined. Here, we determined HSPA8 was overexpressed in IR-CML cells and associated with imatinib resistance. HSPA8 ablation could downregulate BCR-ABL/STAT5 and BCR-ABL/AKT signaling pathways, dramatically induce proliferation inhibition, autophagy, G0/G1 phase cell cycle arrest but not apoptosis in IR-CML cells. Significantly, HSPA8 ablation enhanced the antitumor activity of imatinib via promoting apoptosis in vitro and vivo. These findings unraveled that HSPA8 ablation inhibits proliferation via downregulating BCR-ABL and enhances chemosensitivity of imatinib in IR-CML cells, which investigate the role and molecular mechanism of HSPA8 in IR-CML cells and suggest that HSPA8 may be a potential target for IR-CML treatment.
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http://dx.doi.org/10.1016/j.yexcr.2021.112708DOI Listing
August 2021

Discovery of hydroxytyrosol as thioredoxin reductase 1 inhibitor to induce apoptosis and G/S cell cycle arrest in human colorectal cancer cells via ROS generation.

Exp Ther Med 2021 Aug 3;22(2):829. Epub 2021 Jun 3.

School of Pharmacy, Wannan Medical College, Wuhu, Anhui 241000, P.R. China.

Colorectal cancer (CRC) is one of the most common cancer types and a leading cause of cancer-associated mortality in China. Increased thioredoxin reductase 1 (TrxR1) levels have been previously identified as possible target for CRC. The present study revealed that the natural product hydroxytyrosol (HT), which exhibits a polyphenol scaffold, is a potent inhibitor of TrxR1. Inhibition of TrxR1 was indicated to result in accumulation of reactive oxygen species, inhibit proliferation and induce apoptosis and G/S cell cycle arrest of CRC cells. Using a C-terminal mutant TrxR1 enzyme activity assay, TrxR1 RNA interference assay and HT binding model assay, the present study demonstrated the core character of the selenocysteine residue in the interaction between HT and TrxR1. HT can serve as polyphenol scaffold to develop novel TrxR1 inhibitors for CRC treatment in the future.
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http://dx.doi.org/10.3892/etm.2021.10261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200807PMC
August 2021

Occurrence, accumulation, and risk assessment of trace metals in tea (Camellia sinensis): A national reconnaissance.

Sci Total Environ 2021 Jun 9;792:148354. Epub 2021 Jun 9.

Department of Tea Science, Zhejiang University, Hangzhou 310058, China. Electronic address:

Accumulation of potentially toxic elements in soil and tea leaves is a particular concern for tea consumers worldwide. However, the contents of potentially toxic elements and their potential health and ecological risks in Chinese tea gardens have rarely been investigated on the national scale. In this study, we collected 225 paired soil and tea plant samples from 45 tea gardens in 15 provinces of China to survey the current risk of potentially toxic element accumulation in Chinese tea gardens. The results suggest that the average contents of most trace metals in rhizosphere soils meet the risk control standard for agricultural land in China. However, the mean contents of As, Cr, Cd, Zn, Cu, and Ni in rhizosphere soils were 1.94, 2.14, 1.23, 1.15, 1.18, and 1.19 times their corresponding background soil values in China. Cd had the highest geo-accumulation index, followed by As, Zn, Cr, Ni, Cu, Pb, and Mn in rhizosphere soils. Nearly 2.22% and 4.44% of soils were moderately to heavily contaminated with As and Cd, respectively. The risk index ranged from 18.0 to 292, with an average value of 90.0, indicating low to moderate ecological risk in Chinese tea gardens. This is the first national-scale reconnaissance of trace metals in tea across China. Our findings provide a useful reference for ensuring the quality and safety of tea production and mitigating the risk of toxic element accumulation in tea.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148354DOI Listing
June 2021

Anti-inflammatory role and mechanism of microRNA-92b-3p in the progression of hypoxic pulmonary hypertension.

Life Sci 2021 Jun 16:119725. Epub 2021 Jun 16.

Department of Respiratory, Linyi People's Hospital, Linyi 276000, PR China. Electronic address:

Aims: Pulmonary hypertension (PH) is a serious lung disease that caused by cellular proliferation, vascular wall inflammation and fibrosis. MicroRNAs (miRNAs) have been known to participate in the pathogenesis of PH and could be used to treat PH. In this study, we investigated the molecular mechanism of a miRNA candidate and its roles in the process of hypoxic PH.

Main Methods: The hypoxic PH model was established in SD rats treated with 10% O for 21 days. The change of body weight, the hemodynamic index, the right ventricular remodeling index and the pulmonary artery remodeling were monitored during treatments. CCK8 and Transwell assay were applied for detection of the primary pulmonary artery smooth muscle cells (PASMCs) activity and migration.

Key Findings: High expression of HIF-1α and low expression of miR-92b-3p were found in pulmonary artery and primary PASMCs of hypoxia-treated rats. Overexpression of miR-92b-3p or suppression of HIF-1α inhibited hypoxia-induced pulmonary remodeling, inflammatory cytokines and proliferation/migration of primary PASMCs. RIP and luciferase reporter gene assay suggested a direct interaction between miR-92b-3p and HIF-1α, and overexpression of miR-92b-3p could inhibit the expression of HIF-1α, RhoA and ROCK activity. Upregulated miR-92b-3p partially reduced inflammatory cytokines, inhibited pulmonary remodeling, and thus alleviating the hypoxic PH. miR-92b-3p could alleviate the hypoxia-induced PH.

Significances: Our findings offer basis for better understanding the role of miRNAs in PH.
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http://dx.doi.org/10.1016/j.lfs.2021.119725DOI Listing
June 2021

An Integrin-αβ/αβ-Bitargeted Probe for the SPECT Imaging of Pancreatic Adenocarcinoma in Preclinical and Primary Clinical Studies.

Bioconjug Chem 2021 Jul 17;32(7):1298-1305. Epub 2021 Jun 17.

Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Pancreatic adenocarcinoma (PA) is one of the deadliest human malignancies. However, early detection, prediction of surgical resectability, and prognosis of PA are challenging with current conventional imaging technologies in the clinic. Molecular imaging technologies combined with novel imaging probes could be useful for early detection and accurate staging of PA. Integrin αβ and αβ are found to be overexpressed in PA. In this study, integrin αβ/αβ-bitargeted probes Tc-HYNIC-isoDGR (Tc-isoDGR) and Tc-HYNIC-PEG-PisoDGR2 (Tc-3PisoDGR2) were prepared and evaluated in the BxPC-3 human pancreatic tumor model. Both subcutaneous and BxPC-3 tumors could be clearly visualized by Tc-isoDGR nanoScan SPECT/CT imaging with a high ratio of tumor to background. The blocking study with excess nonradioactive peptide showed a significantly reduced tumor uptake, which confirmed the specificity of Tc-isoDGR. Biodistribution results confirmed the imaging results. The dimer tracer Tc-3PisoDGR2 significantly enhanced tumor uptake compared with Tc-isoDGR, and the spontaneous PA lesion in the mouse model could be clearly visualized by Tc-3PisoDGR2. The primary clinical study also verified the ability of Tc-3PisoDGR2 for detection of PA. Therefore, SPECT/CT imaging using the integrin αβ/αβ-bitargeted Tc-3PisoDGR2 provided a potential approach for the noninvasive detection of PA.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00296DOI Listing
July 2021
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