Publications by authors named "Lei Tan"

285 Publications

Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis.

Oncogene 2021 Jul 28. Epub 2021 Jul 28.

Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.

Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.
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http://dx.doi.org/10.1038/s41388-021-01971-7DOI Listing
July 2021

Exploratory Metabolomic Analysis Based on Reversed-Phase Liquid Chromatography-Mass Spectrometry to Study an In Vitro Model of Hypoxia-Induced Metabolic Alterations in HK-2 Cells.

Int J Mol Sci 2021 Jul 9;22(14). Epub 2021 Jul 9.

Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Madrid, Spain.

Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography-mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided.
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http://dx.doi.org/10.3390/ijms22147399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304667PMC
July 2021

Thyroid dysfunction following radiofrequency ablation for benign thyroid nodules: more likely to occur within one-week and in high-risk population.

Int J Hyperthermia 2021 ;38(1):1060-1068

Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province Key Laboratory of Hepatology Research Guangzhou, Guangdong, China.

Background: Radiofrequency ablation (RFA) has been recommended as the treatment for benign thyroid nodules (BTNs) by some guidelines. However, detailed follow-up instructions for thyroid function about the timing and affected populations after RFA are lacked due to insufficient researches. This 12-month prospective study aimed to evaluate the incidence and risk factors of thyroid dysfunction at different time points after RFA, especially within 1 week that previous studies didn't concern.

Methods: Seventy-five euthyroid patients who underwent RFA for symptomatic BTNs were enrolled (ChiCTR-INR-16007884). The incidence of thyroid dysfunction within 1 week, at 1, 6, and 12 months after RFA was evaluated. The risk factors for different types of thyroid dysfunction in the different terms were further analyzed.

Results: Within 1 week after RFA, the incidence of thyroid dysfunction was as high as 36.00% unexpectedly, and only overt thyrotoxicosis and subclinical thyrotoxicosis occurred, which were significantly associated with the low-normal baseline thyrotropin (TSH) level ( = 0.001) and high ablation volume ratio ( = 0.008). From 1 to 12 months (the long term), the incidence dropped significantly and remained low (8.00-12.00%); and thyroid dysfunction presented as overt thyrotoxicosis, subclinical thyrotoxicosis, and subclinical hypothyroidism. The long-term thyrotoxicosis group had more cases with diabetes and lower baseline TSH levels. The long-term subclinical hypothyroidism group had more cases with positive thyroid peroxidase antibodies, higher baseline TSH levels, and higher ablation volume ratios.

Conclusions: After the RFA of BTNs, thyroid dysfunction was more likely to occur within 1 week and in populations with risk factors.
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http://dx.doi.org/10.1080/02656736.2021.1950849DOI Listing
January 2021

Acute transient swelling of the thyroid following fine-needle aspiration: A case series.

J Clin Ultrasound 2021 Jul 8. Epub 2021 Jul 8.

Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province Key Laboratory of Hepatology Research, Guangzhou, Guangdong, China.

Acute transient swelling (ATS) of the thyroid is a rare complication following fine-needle aspiration (FNA) of thyroid nodules. We present 31 cases with 35 nodules encountered at our institute and reported in the literature, to provide further information. The incidence rate in our institute was 0.46%. Of these nodules, 74.3% (26/35) were solid, 65.7% (23/35) exhibited hypervascularity, and 77.2% (27/35) were benign or follicular neoplasms. Although most cases (87.1%, 27/31) occurred within 2 h after FNA, four patients experienced delayed ATS after 7 h to 2 days. Therefore, awareness of this complication, especially its delayed occurrence, should be raised.
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http://dx.doi.org/10.1002/jcu.23043DOI Listing
July 2021

Comparison of the protective antigen variabilities of prevalent Newcastle disease viruses in response to homologous/heterologous genotype vaccines.

Poult Sci 2021 Aug 19;100(8):101267. Epub 2021 May 19.

Shanghai Veterinary Research Institute (SHVRI), Chinese Academy of Agricultural Sciences (CAAS), Shanghai 200241, China. Electronic address:

The genotype VII Newcastle disease virus (NDV) vaccine has begun to replace the traditional genotype II NDV vaccine and is widely used in the commercial poultry of China. However, the effect of homologous and heterogeneous anti-NDV serum on the evolution of prevalent NDV is unknown. To understand the effect of genotype II and VII anti-NDV serum on the evolution of genotype VII NDV strains, ZJ1 (waterfowl origin) and CH/SD/2008/128 (ND128; chicken origin) were used for serial passage of 30 generations in DF-1 cells without anti-NDV serum or with genotype II and VII anti-NDV serum independently. The F and HN genes of the 2 viruses were amplified for the 10th, 20th, and 30th generations of each serial passage group and compared with their respective original viruses. We found that there was only one mutation at position 248 in the F gene of ZJ1 due to the serum pressure of genotype VII anti-NDV. Similarly, mutations at residue 527 of the F gene, and position 9 and 319 of the HN gene of ND128 were noted in both anti-NDV serum groups. The results show that the nonsynonymous (NS)-to-synonymous (S) ratio of the F gene of ZJ1 virus was 1.6, and for the HN gene, it was 2.5 in the anti-II serum group. In the anti-VII serum group, the NS/S ratio for the F gene was 2.1, and for the HN gene, it was 2.5. The NS/S ratio of the F gene of the ND128 virus was 0.8, and for the HN gene, it was 3 in the anti-II serum group. Furthermore, the NS/S ratio of the F gene was 0.8, and the HN gene was 2.3 in the anti-VII group. Taken together, our findings highlight that there was no significant difference in the variation of protective antigens in genotype VII NDV under the selection pressure of homologous and heterogeneous genotype NDV inactivated vaccines.
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http://dx.doi.org/10.1016/j.psj.2021.101267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267594PMC
August 2021

N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway.

Front Oncol 2021 8;11:641833. Epub 2021 Jun 8.

Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Most localized human renal clear cell carcinoma (ccRCC)-related deaths result from cancer recurrence and metastasis. However, the precise molecular mechanisms largely remain unknown. In recent years, an increasing number of long noncoding RNAs (lncRNAs) have been shown to be vital regulators of tumorigenesis. In this study, we characterized a lncRNA DUXAP9 and the upregulation of DUXAP9 was analyzed by quantitative real-time PCR in 112 pairs of localized ccRCC tumor tissues compared with adjacent normal tissues. Kaplan-Meier curves showed that patients of localized ccRCC with high DUXAP9 expression had poorer overall survival (P<0.01) and progression-free survival (P<0.05) than cases with low DUXAP9 expression. Multivariate Cox regression analysis also showed that high DUXAP9 expression was an independent risk factor for poor prognosis in localized ccRCC (p<0.05). DUXAP9 knockdown in renal cancer cells inhibited renal cancer cells proliferation and motility capacities and reversed epithelial-mesenchymal transition (EMT), whereas overexpression of DUXAP9 promoted renal cancer cells proliferation and motility capacities and induced EMT. Pull-down, RNA immunoprecipitation and RNA stability assays (involving actinomycin D) showed that DUXAP9 was methylated at N6-adenosine and binds to IGF2BP2, which increases its stability. DUXAP9 activate PI3K/AKT pathway and Snail expression in renal cancer cells. DUXAP9 may be useful as a prognostic marker and/or therapeutic target in localized ccRCC.
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http://dx.doi.org/10.3389/fonc.2021.641833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217835PMC
June 2021

Effects of different anesthetic methods on immune function and oxidative stress in patients undergoing laparoscopic herniorrhaphy.

Wideochir Inne Tech Maloinwazyjne 2021 Jun 22;16(2):329-335. Epub 2021 Apr 22.

Department of Anesthesiology, The First People's Hospital of Suqian, Suqian, China.

Introduction: The influence of anesthetic method on the immune function and oxidative stress in patients receiving laparoscopic herniorrhaphy remains largely unknown.

Aim: To assess the effects of different anesthetic methods on the immune function and oxidative stress in patients undergoing laparoscopic herniorrhaphy.

Material And Methods: A total of 280 eligible patients were randomly divided into two groups to receive total intravenous anesthesia (TIVA group) and inhalation anesthesia (IA group). T lymphocyte subsets, oxidative stress response indices and inflammatory factor levels were measured before anesthesia, at the end of the operation, and 1 and 3 days after the operation. The incidence rates of adverse reactions were compared.

Results: At the end of and 1 day after the operation, CD3 and CD4 T cells and CD4/CD8 decreased in both groups compared with those before anesthesia (p < 0.05). Three days after the operation, CD3 and CD4 T cells decreased in both groups compared with those before anesthesia, which were higher in the TIVA group (p < 0.05). Interleukin-6 and C-reactive protein levels were significantly lower in the TIVA group (p < 0.05). At the end of and 1 and 3 days after the operation, oxidative stress response indices superoxide dismutase, catalase and glutathione peroxidase declined in both groups compared with those before anesthesia, which were higher in the IA group (p < 0.05). The incidence rate of adverse reactions was significantly higher in the IA group (p = 0.002).

Conclusions: Compared with IA, TIVA has less effect on the immune function and oxidative stress of patients undergoing laparoscopic herniorrhaphy, and controls the inflammatory response more effectively, accompanied by a lower incidence rate of adverse reactions.
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http://dx.doi.org/10.5114/wiitm.2021.105528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193758PMC
June 2021

Brachial muscle injury resulting in acute compartment syndrome of the upper arm: a case report and literature review.

BMC Musculoskelet Disord 2021 Jun 14;22(1):545. Epub 2021 Jun 14.

Department of Orthopedic Trauma, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, 130021, Jilin, China.

Background: Acute compartment syndrome (ACS) is a potentially devastating condition. ACS is rare in the upper arm.

Case Presentation: We report a case of acute compartment syndrome of the anterior compartment of the upper arm due to brachial muscle injury. The patient experienced abnormal progressive swelling and pain in his right upper arm, and passive pulling pain of the right wrist and right hand. It was highly suspected to be right upper arm compartment syndrome, and was confirmed by surgery. The patient transferred to the emergency operating room for fasciotomy that was performed under general anesthesia using the anterolateral approach. The brachial muscle was found to be heavily swollen and had the greatest tension. The brachial muscle fibers were split lengthwise, and a large amount of hematoma was cleared. The brachial muscles were injured and partly ruptured. After full decompression, a negative pressure drainage device was used to cover the wound in the first stage. Ten days after injury, the swelling of the affected limb subsided and the wound was sutured. The patient's limbs completely recovered to normal. The shoulder and elbow joints could move freely and the patient resumed normal farming work ability.

Conclusion: Clinicians should fully recognize the fact that acute compartment syndrome can occur in the upper arm, rather than only the forearm and leg, and therefore avoid serious consequences caused by missed diagnosis and misdiagnosis.
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http://dx.doi.org/10.1186/s12891-021-04318-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204510PMC
June 2021

Caspase-Dependent Cleavage of DDX21 Suppresses Host Innate Immunity.

mBio 2021 06 14;12(3):e0100521. Epub 2021 Jun 14.

Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.

DEAD (Glu-Asp-Ala-Glu) box RNA helicases have been proven to contribute to antiviral innate immunity. The DDX21 RNA helicase was identified as a nuclear protein involved in rRNA processing and RNA unwinding. DDX21 was also proven to be the scaffold protein in the complex of DDX1-DDX21-DHX36, which senses double-strand RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes caspase-dependent cleavage after virus infection and treatment with RNA/DNA ligands, especially for RNA virus and ligands. Caspase-3/6 cleaves DDX21 at D126 and promotes its translocation from the nucleus to the cytoplasm in response to virus infection. The cytoplasmic cleaved DDX21 negatively regulates the interferon beta (IFN-β) signaling pathway by suppressing the formation of the DDX1-DDX21-DHX36 complex. Thus, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immune response to virus. Innate immunity serves as the first barrier against virus infection. DEAD (Glu-Asp-Ala-Glu) box RNA helicases, originally considered to be involved in RNA processing and RNA unwinding, have been shown to play an important role in antiviral innate immunity. The precise regulation of innate immunity is critical for the host because the aberrant production of cytokines leads to unexpected pathological consequences. Here, we identified that DDX21 was cleaved at D126 by virus infection and treatment with RNA/DNA ligands via the caspase-3/6-dependent pathway. The cytoplasmic cleaved DDX21 negatively regulates the IFN-β signaling pathway by suppressing the formation of the DDX1-DDX21-DHX36 complex. In sum, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immune response to virus.
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http://dx.doi.org/10.1128/mBio.01005-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262918PMC
June 2021

Single-Atom Catalysis for Efficient Sonodynamic Therapy of Methicillin-Resistant -Infected Osteomyelitis.

ACS Nano 2021 06 4;15(6):10628-10639. Epub 2021 Jun 4.

School of Materials Science & Engineering, the Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China, Tianjin University, Tianjin 300072, China.

Osteomyelitis, as a severe bone disease caused by bacterial infection, can result in lifelong disability or fatal sepsis. Considering that the infection is stubborn and deep-sited in bone tissue, and rapid treatments for osteomyelitis remain a significant challenge. Herein, we prepare an ultrasound (US)-activated single-atom catalyst that consists of a Au nanorod (NRs)-actuated single-atom-doped porphyrin metal-organic framework ([email protected]) and red cell membrane (RBC), which can efficiently treat methicillin-resistant (MRSA)-infected osteomyelitis under US. Besides the outstanding performance in the field of photocatalysis, we find that single atoms (such as Pt, Au, Cu) also improve the sonocatalytic ability of the sonosensitizer. Due to the strong electron-trapping and oxygen adsorption capacity, the Pt single atom endows [email protected] with an excellent sonocatalytic activity. It shows an excellent antibacterial performance with an antibacterial efficiency of 99.9% toward MRSA under 15 min of US irradiation. Meanwhile, the [email protected] can be propelled directionally under US and thus dynamically neutralize the secreted toxins. The MRSA-infected osteomyelitis in rat tibia was successfully treated, which shows negligible bone loss, reduced inflammation response, and great biocompatibility. This work presents an efficient sonodynamic therapy for the treatment of deep tissue infections a multifunctional single-atom catalyst.
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http://dx.doi.org/10.1021/acsnano.1c03424DOI Listing
June 2021

Influence of swimming exercise on the expression of apoptotic gene caspase-3 in chondrocytes in osteoarthritis.

Am J Transl Res 2021 15;13(4):2511-2517. Epub 2021 Apr 15.

Department of Traumatic Orthopedics, The First Hospital of Jilin University Changchun, Jilin, China.

Objective: To study swimming exercise's effect on caspase-3 expression in chondrocytes in osteoarthritis (OA).

Methods: 36 SD rats were randomly separated into normal group (n = 12), OA model group (n = 12) and swimming exercise group (n = 12). After modeling, rats received no intervention in model group and swimming exercise once a day (15 min/time) for 4 consecutive weeks in swimming exercise group. After intervention for 4 weeks, specimens were taken to analyze tissue morphology by H&E staining, caspase-3 expression by Western blot and qPCR, chondrocytes apoptosis by TUNEL assay.

Results: HE staining revealed abnormal bone tissue morphology in model group and swimming exercise group with improved morphology after swimming exercise. Model group and swimming exercise group all showed significantly higher Caspase-3 protein level than normal group with lower level after swimming exercise (P < 0.05). Consistently, qPCR showed similar expression profile of caspase-3 mRNA level to the protein level.

Conclusion: Swimming exercise can inhibit caspase-3 level and chondrocytes apoptosis in OA, thus improving the joint morphology.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129308PMC
April 2021

Utility of Fusion Imaging for Percutaneous Thermal Ablation of Hepatocellular Carcinoma in the Caudate Lobe.

J Vasc Interv Radiol 2021 Aug 17;32(8):1209-1214. Epub 2021 May 17.

Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

The treatment outcomes of ultrasound-guided percutaneous thermal ablation of hepatocellular carcinoma in the caudate lobe with and without fusion imaging (FI) assistance were evaluated and compared. Twenty-six patients with 28 tumors in the FI group and 8 patients with 8 tumors in the non-FI group were included. Although a higher number of tumors measured >20 mm in the FI group, the technique efficacy and local tumor progression were similar between the 2 groups (P > .99 and P = .45, respectively). FI aided in the detection, guidance, and treatment monitoring of thermal ablation for caudate lobe hepatocellular carcinomas, especially for tumors measuring >20 mm.
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http://dx.doi.org/10.1016/j.jvir.2021.04.028DOI Listing
August 2021

Mechanisms of polymyxin resistance induced by Salmonella typhimurium in vitro.

Vet Microbiol 2021 Jun 1;257:109063. Epub 2021 Apr 1.

Pharmacology and Toxicology Laboratory, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230026, PR China; Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei, Anhui 230036, PR China. Electronic address:

The increase incidence of multi-drug resistant (MDR) Salmonella has become a major global health concern. Polymyxin, an ancient polypeptide antibiotic, has been given renewed attention over recent years, resulting in resistance of Gram-negative bacteria to polymyxin, but its resistance mechanism is not completely clear. Thus, it is important to study its resistance mechanisms. In this study, an in vitro induced polymyxin-resistant strain of Salmonella typhimurium in the laboratory were constructed to investigate the mechanism of resistance of Salmonella to polymyxin. Gradual induction of Salmonella typhimurium ATCC13311 (AT) by concentration increment was used to screen for a highly polymyxin-resistant strain AT-P128. The broth dilution technique was used to compare the sensitivity of the two strains to different antimicrobial drugs. Single nucleotide polymorphisms (SNPs) were then identified by whole genome sequencing, and differences in gene expression between the two strains were compared by transcriptome sequencing and reverse transcription-quantitative PCR (RT-qPCR). Finally, for the first time, the CRISPR/Cas9 gene-editing system was used to construct gene deletion mutants in Salmonella to knock out the phoP gene of AT-P128. The results showed that strain AT-P128 was significantly more resistant to amoxicillin, ceftiofur, ampicillin, fluphenazine, and chloramphenicol and significantly less resistant to sulfamethoxazole than the parental strain AT. The growth curve results showed no significant change in the growth rate between AT-P128 and AT. Motility and biofilm formation assays showed a significant decrease in AT-P128. Additionally, the WGS results showed that AT-P128 had mutations in 9 genes involving 14 SNPs. RNA-seq and RT-qPCR results showed increased expression of phoPQ. The loss of the phoP gene decreased AT-P128ΔphoP resistance to polymyxin by 32-fold. These results suggested that polymyxin resistance affected the biology, genome components, and gene expression levels of Salmonella and that the PhoPQ two-component system played a key role in polymyxin resistance in Salmonella, providing insights into the diversity and complexity of polymyxin resistance in Salmonella.
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http://dx.doi.org/10.1016/j.vetmic.2021.109063DOI Listing
June 2021

The relationship between the clearance of HBsAg and the remodeling of B cell subsets in CHB patients treated with Peg-IFN-α.

Ann Transl Med 2021 Mar;9(5):414

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: The seroconversion of the hepatitis B antigen is the ideal outcome for long-acting interferon-pegylated interferon-α (Peg-IFN-α) treatment among patients with chronic hepatitis B (CHB). B-cell response plays an important role in the process of hepatitis B antigen clearance, but the specific mechanism by which B-cell improve hepatitis B virus (HBV) is still unclear.

Methods: A total of 103 CHB patients participated in this study. The patients received 24 weeks of Peg-IFN-α treatment. Flow cytometry was used to detect B-cell surface markers' cluster of differentiation cluster of differentiation CD19, CD24, and CD27 in the peripheral blood mononuclear cells (PBMCs) of CHB patients before and after 24 weeks of Peg-IFN-α treatment.

Results: After 24 weeks of Peg-IFN-α treatment, the content of memory B cells (CD19CD27) and effector B cells (CD19CD38) increased significantly. Further analysis showed that the clearance of the hepatitis B antigen was correlated with the change value, ΔT, of plasma cells before and after treatment. The B-cell subsets (CD19CD24; CD19CD40; CD19CD40; CD19CD80), was also tested and the results showed that CD19CD24 and CD19CD80 content also increased significantly after treatment.

Conclusions: After Peg-IFN-α treatment, the B-cell subsets of CHB patients are remodeled. Thus, Peg-IFN-α treatment appears to play an important role in the remodeling of B cell subsets and the clearance of HBV antigens. The results of this study provide a theoretical basis and guidance for the clinical treatment of CHB.
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http://dx.doi.org/10.21037/atm-21-409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033293PMC
March 2021

Detecting SARS-CoV-2 in the Breath of COVID-19 Patients.

Front Med (Lausanne) 2021 17;8:604392. Epub 2021 Mar 17.

Commune of Scientific Engineers, Institute of Physics, Chinese Academy of Sciences, Beijing, China.

In the COVID-19 outbreak year 2020, a consensus was reached on the fact that SARS-CoV-2 spreads through aerosols. However, finding an efficient method to detect viruses in aerosols to monitor the risk of similar infections and enact effective control remains a great challenge. Our study aimed to build a swirling aerosol collection (SAC) device to collect viral particles in exhaled breath and subsequently detect SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR). Laboratory tests of the SAC device using aerosolized SARS-CoV-2 pseudovirus indicated that the SAC device can produce a positive result in only 10 s, with a collection distance to the source of 10 cm in a biosafety chamber, when the release rate of the pseudovirus source was 1,000,000 copies/h. Subsequent clinical trials of the device showed three positives and 14 negatives out of 27 patients in agreement with pharyngeal swabs, and 10 patients obtained opposite results, while no positive results were found in a healthy control group ( = 12). Based on standard curve calibration, several thousand viruses per minute were observed in the tested exhalations. Furthermore, referring to the average tidal volume data of adults, it was estimated that an exhaled SARS-CoV-2 concentration of approximately one copy/mL is detectable for COVID-19 patients. This study validates the original concept of breath detection of SARS-CoV-2 using SAC combined with RT-PCR.
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http://dx.doi.org/10.3389/fmed.2021.604392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010128PMC
March 2021

Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer.

Front Cell Dev Biol 2021 18;9:646982. Epub 2021 Mar 18.

Department of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Immune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data set and identified 161 messenger RNAs (mRNAs) as differentially expressed immunity genes (DEIGs). Using the LASSO Cox regression model, an eight-mRNA-based risk signature was built. We validated the prognostic and predictive accuracy of this immune-related risk signature in 348 metastatic urothelial cancer (mUC) samples treated with anti-PD-L1 (atezolizumab) from IMvigor210. We built an immune-related risk signature based on the eight mRNAs: ANXA1, IL22, IL9R, KLRK1, LRP1, NRG3, SEMA6D, and STAP2. The eight-mRNA-based risk signature successfully categorizes patients into high-risk and low-risk groups. Overall survival was significantly different between these groups, regardless if the initial TCGA training set, the internal TCGA testing set, all TCGA set, or the ICI treatment set. The hazard ratio (HR) of the high-risk group to the low-risk group was 3.65 ( < 0.0001), 2.56 ( < 0.0001), 3.36 ( < 0.0001), and 2.42 ( = 0.0009). The risk signature was an independent prognostic factor for prediction survival. Moreover, the risk signature was related to immunity characteristics. In different tumor mutational burden (TMB) subgroups, it successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome. Our eight-mRNA-based risk signature is a stable biomarker for urothelial cancer and might be able to predict which patients benefit from ICI treatment. It might play a role in precision individualized immunotherapy.
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http://dx.doi.org/10.3389/fcell.2021.646982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012532PMC
March 2021

Newcastle Disease Virus Induced Pathologies Severely Affect the Exocrine and Endocrine Functions of the Pancreas in Chickens.

Genes (Basel) 2021 03 29;12(4). Epub 2021 Mar 29.

Shanghai Veterinary Research Institute (SHVRI), Chinese Academy of Agricultural Sciences (CAAS), Shanghai 200241, China.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry. ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease in egg production high morbidity and mortality. Although significant advances have been made in the vaccine development, outbreaks are reported in vaccinated birds. In this study, we report the damage caused by NDV infection in the pancreatic tissues of vaccinated and specific-pathogen-free chickens. The histopathological examination of the pancreas showed severe damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of the pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone and somatostatin were observed in NDV-infected chicken at three- and five- days post infection (DPI). A slight decrease in the plasma concentrations of insulin was noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection decreased the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in the pancreas, decreases the activity and expression of pancreatic enzymes, and increases plasma corticosterone and somatostatin. These findings provide new insights that a defective pancreas may be one of the reasons for decreased growth performance after NDV infection in chickens.
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http://dx.doi.org/10.3390/genes12040495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067305PMC
March 2021

Thermal ablation of medium-sized hepatocellular carcinomas using intraoperative ultrasound fusion imaging: A propensity score-matched analysis.

Clin Res Hepatol Gastroenterol 2021 Mar 21;45(5):101581. Epub 2021 Mar 21.

Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025, Shennanzhong Road, Shenzhen, 518033, PR China. Electronic address:

Objective: To explore the value of ultrasound fusion imaging for the thermal ablation of medium-sized hepatocellular carcinomas (HCCs).

Materials And Methods: From December 2010 to June 2018, patients with medium-sized (3.1-5.0 cm) HCCs who underwent radiofrequency ablation (RFA) or microwave ablation (MWA) with the assistance of ultrasound fusion imaging were enrolled in this retrospective study. Technical efficacy, local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), tumor-free survival (TFS) and major complications were evaluated during the follow-up period. The therapeutic outcomes were compared between the RFA/MWA combined with trans-arterial chemoembolization (TACE) group and the RFA/MWA alone group with propensity-score matching (PSM) analysis.

Results: A total of 112 patients with 115 medium-sized HCCs were finally enrolled in this study. The median duration of follow-up was 33 months (range, 2-104 months). The technique efficacy was 100% (115/115). The 1-, 3-, 5-year OS rates and TFS rates were 95.5%, 76.7%, 71.5% and 74.1%, 48.7%, 41.8%, respectively. The corresponding LTP rates and IDR rates were 5.4%, 7.3%, 7.3% and 21.8%, 46.9%, 50.3%, respectively. The incidence of major complications was 5.4% (6/112). After PSM analysis (19 patients in each group), the therapeutic outcomes, including the OS, TFS, and LTP rates, were comparable in the two groups (P > 0.05).

Conclusions: With the assistance of ultrasound fusion imaging, thermal ablation of medium-sized HCC could achieve a satisfactory local control rate and long-term survival. The outcomes were comparable in the stratified analysis between the RFA/MWA alone group and the RFA/MWA + TACE group after PSM analysis.
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http://dx.doi.org/10.1016/j.clinre.2020.11.011DOI Listing
March 2021

The topological criticality in disordered non-Hermitian system.

J Phys Condens Matter 2021 Apr 23;33(18). Epub 2021 Apr 23.

Institute of Theoretical Physics, Lanzhou University, Lanzhou 730000, People's Republic of China.

Disorders have a rich influence on topological and localized properties. Here, we explore the effects of different type of disorders (intracell and intercell) on the non-Hermitian system. We first exhibit the phase diagram and find that the intracell disorder and intercell disorder can broaden and narrow the topological region, respectively. Moreover, the skin effect, which is unique in the non-Hermitian system, is broken by disorders. Furthermore, we propose the generalized localization length to settle the issue of how to determine the topological phase boundary explicitly in the disordered non-Hermitian system. Significantly, the rationality of this definition can be verified by similarity transformation, in which we prove that the topological invariant remains invariant. Finally, a byproduct of our definition is that one can analytically get the criticality of topology in the clean-limit non-Hermitian system.
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http://dx.doi.org/10.1088/1361-648X/abee3dDOI Listing
April 2021

Inhibition of anti-viral stress granule formation by coronavirus endoribonuclease nsp15 ensures efficient virus replication.

PLoS Pathog 2021 02 26;17(2):e1008690. Epub 2021 Feb 26.

Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China.

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs exert anti-viral functions due to their involvement in protein synthesis shut off and recruitment of innate immune signaling intermediates. The largest RNA viruses, coronaviruses, impose great threat to public safety and animal health; however, the significance of SGs in coronavirus infection is largely unknown. Infectious Bronchitis Virus (IBV) is the first identified coronavirus in 1930s and has been prevalent in poultry farm for many years. In this study, we provided evidence that IBV overcomes the host antiviral response by inhibiting SGs formation via the virus-encoded endoribonuclease nsp15. By immunofluorescence analysis, we observed that IBV infection not only did not trigger SGs formation in approximately 80% of the infected cells, but also impaired the formation of SGs triggered by heat shock, sodium arsenite, or NaCl stimuli. We further demonstrated that the intrinsic endoribonuclease activity of nsp15 was responsible for the interference of SGs formation. In fact, nsp15-defective recombinant IBV (rIBV-nsp15-H238A) greatly induced the formation of SGs, along with accumulation of dsRNA and activation of PKR, whereas wild type IBV failed to do so. Consequently, infection with rIBV-nsp15-H238A strongly triggered transcription of IFN-β which in turn greatly affected rIBV-nsp15-H238A replication. Further analysis showed that SGs function as an antiviral hub, as demonstrated by the attenuated IRF3-IFN response and increased production of IBV in SG-defective cells. Additional evidence includes the aggregation of pattern recognition receptors (PRRs) and signaling intermediates to the IBV-induced SGs. Collectively, our data demonstrate that the endoribonuclease nsp15 of IBV interferes with the formation of antiviral hub SGs by regulating the accumulation of viral dsRNA and by antagonizing the activation of PKR, eventually ensuring productive virus replication. We further demonstrated that nsp15s from PEDV, TGEV, SARS-CoV, and SARS-CoV-2 harbor the conserved function to interfere with the formation of chemically-induced SGs. Thus, we speculate that coronaviruses employ similar nsp15-mediated mechanisms to antagonize the host anti-viral SGs formation to ensure efficient virus replication.
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http://dx.doi.org/10.1371/journal.ppat.1008690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946191PMC
February 2021

Current Status and Challenge of Pseudorabies Virus Infection in China.

Virol Sin 2021 Feb 22. Epub 2021 Feb 22.

Laboratory of Animal Disease Prevention and Control and Animal Model, Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, College of Veterinary Medicine, Hunan Agricultural University (HUNAU), Changsha, 410128, China.

Pseudorabies (PR), also called Aujeszky's disease, is a highly infectious disease caused by pseudorabies virus (PRV). Without specific host tropism, PRV can infect a wide variety of mammals, including pig, sheep, cattle, etc., thereby causing severe clinical symptoms and acute death. PRV was firstly reported in China in 1950s, while outbreaks of emerging PRV variants have been documented in partial regions since 2011, leading to significant economic losses in swine industry. Although scientists have been devoting to the design of diagnostic approaches and the development of vaccines during the past years, PR remains a vital infectious disease widely prevalent in Chinese pig industry. Especially, its potential threat to human health has also attracted the worldwide attention. In this review, we will provide a summary of current understanding of PRV in China, mainly focusing on PRV history, the existing diagnosis methods, PRV prevalence in pig population and other susceptible mammals, molecular characteristics, and the available vaccines against its infection. Additionally, promising agents including traditional Chinese herbal medicines and novel inhibitors that may be employed to treat this viral infection, are also discussed.
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http://dx.doi.org/10.1007/s12250-020-00340-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897889PMC
February 2021

The universal dual-mode aptasensor for simultaneous determination of different bacteria based on naked eyes and microfluidic-chip together with magnetic DNA encoded probes.

Talanta 2021 Apr 29;225:122062. Epub 2020 Dec 29.

Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, Faculty of Materials Science and Chemical Engineering, Ningbo University, 315211, PR China. Electronic address:

It was critically important to develop some sensitive, convenient and on-site methods for simultaneous assay of different pathogenic bacteria in foods. In this work, a dual-mode aptasensor was established for fulfilling above aims combing colorimetry with microfluidic chip. This as-prepared dual-mode aptasensor not only realized rapid screening by naked eye on-site, but also the simultaneous quantification of multiple bacteria. Namely, the presence of pathogenic bacteria was firstly judged by naked eyes with Salmonella typhimurium (S.T) and Vibrio parahaemolyticus (V.P) as models. And then, S.T and V.P in positive samples were simultaneously quantified by microfluidic chip. In order to obtain the multiple signals, a series of magnetic DNA encoded-probes (MDEs) was fabricated containing rolling cycle amplified long DNA chain (RCA-DNA) rich in G-quadruplex sequences. They can combine with hemin as DNAzyme to catalyze 3,3'-5,5'-Tetramethyl benzidine (TMB)-HO system for color development and be cleaved by EcoRV endonuclease to produce DNA fragments with different lengths. The microfluidic chip was employed to separate and quantify the fragments for quantifying S.T and V.P simultaneously. For this protocol, 100 CFU·mL of V.P or S.T could be observed by the naked eye and as low as 32 S.T and 30 CFU·mL V.P could be detected by the chip within 3 min. The dual-mode aptasensor could quickly screen positive samples, and simultaneously perform quantitative detection of the bacteria in positive samples. Our protocol demonstrated its potential in on-site qualification & simultaneous quantification of foodborne bacteria in foods.
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http://dx.doi.org/10.1016/j.talanta.2020.122062DOI Listing
April 2021

Anterior Controllable Antedisplacement and Fusion (ACAF) vs Posterior Laminoplasty for Multilevel Severe Cervical Ossification of the Posterior Longitudinal Ligament: Retrospective Study Based on a Two-Year Follow-up.

Orthop Surg 2021 Apr 31;13(2):474-483. Epub 2021 Jan 31.

Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Objectives: To compare the clinical outcomes of anterior controllable antedisplacement fusion (ACAF), a new surgical technique, with laminoplasty for the treatment of multilevel severe cervical ossification of the posterior longitudinal ligament (OPLL) based on a 2-year follow-up.

Methods: Clinical data of 53 patients (21 by ACAF and 32 by laminoplasty) who have accepted surgery for treatment of cervical myelopathy caused by multilevel severe OPLL (occupying rate ≥ 50%) from March 2015 to March 2017 were retrospectively reviewed and compared between ACAF group and laminoplasty group. Operative time, blood loss, and complications of the two groups were recorded. Radiographic parameters were evaluated pre- and postoperatively: cervical lordosis on X-ray, space available for the cord (SAC) and the occupying ratio (OR) on computed tomography (CT), and the anteroposterior (AP) diameter of the spinal cord at the narrowest level and the spinal cord curvature on magnetic resonance imaging (MRI). Japanese Orthopaedic Association (JOA) scoring was used to evaluate neurologic recovery. Statistical analysis was conducted to analyze the differences between two groups. The Mann-Whitney U test and chi square test were used to compare categorical variables. unpaired t test was used to compare continuous data.

Results: All patients were followed up for at least 24 months. The operative time was longer in ACAF group (286.5 vs 178.2 min, P < 0.05). The blood loss showed no significant difference (291.6 vs 318.3 mL, P > 0.05). Less complications were observed in ACAF group than in laminoplasty group (one case [4.7%] of C5 palsy and one case [4.7%] of cerebrospinal fluid [CSF] leakage in ACAF group; four cases [12.5%] of C5 palsy, two cases [6.3%] of CSF leakage, and four cases [12.5%] of axial symptoms in laminoplasty group). The mean JOA score at last follow-up (14.6 vs 12.8, P < 0.05) and the improvement rate (IR) (63.8% vs 47.8%, P < 0.05) in ACAF group were superior to those in laminoplasty group significantly. The postoperative OR (16.7% vs 40.9%, P < 0.05), SAC (150.8 vs 110.5 mm , P < 0.05), AP spinal cord diameter (5.5 vs 4.2 mm, P < 0.05), and cervical lordosis (12.7° vs 4.7°, P < 0.05) were improved more considerably in ACAF group, with significant differences between two groups. Notably, the spinal cord on MRI showed a better curvature in ACAF group.

Conclusions: This study showed that ACAF is considered superior to laminoplasty for the treatment of multilevel severe OPLL as anterior direct decompression and better curvature of the spinal cord led to satisfactory neurologic outcomes and low complication rate.
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http://dx.doi.org/10.1111/os.12856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957409PMC
April 2021

A panel of eight autophagy-related long non-coding RNAs is a good predictive parameter for clear cell renal cell carcinoma.

Genomics 2021 Mar 28;113(2):740-754. Epub 2021 Jan 28.

Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Institute of Precision Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

Clear-cell renal cell carcinoma (ccRCC) carries a variable prognosis. Prognostic biomarkers can stratify patients according to risk, and can provide crucial information for clinical decision-making. We screened for an autophagy-related long non-coding lncRNA (lncRNA) signature to improve postoperative risk stratification in The Cancer Genome Atlas (TCGA) database. We confirmed this model in ICGC and SYSU cohorts as a significant and independent prognostic signature. Western blotting, autophagic-flux assay and transmission electron microscopy were used to verify that regulation of expression of 8 lncRNAs related to autophagy affected changes in autophagic flow in vitro. Our data suggest that 8-lncRNA signature related to autophagy is a promising prognostic tool in predicting the survival of patients with ccRCC. Combination of this signature with clinical and pathologic parameters could aid accurate risk assessment to guide clinical management, and this 8-lncRNAs signature related to autophagy may serve as a therapeutic target.
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http://dx.doi.org/10.1016/j.ygeno.2021.01.016DOI Listing
March 2021

Feasibility of 3D US/CEUS-US/CEUS fusion imaging-based ablation planning in liver tumors: a retrospective study.

Abdom Radiol (NY) 2021 06 23;46(6):2865-2874. Epub 2021 Jan 23.

Department of Ultrasound, Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China.

Purpose: To assess the feasibility of ablation planning based on fusion imaging of three-dimensional ultrasound/contrast-enhanced ultrasound (3D US/CEUS) with real-time US/CEUS for liver tumor thermal ablation.

Materials And Methods: Between January 2017 and December 2018, 85 hepatic tumors from 82 patients who underwent percutaneous ablation were included. First, intraprocedural 3D US/CEUS imaging was performed for ablation planning. Then, fusion imaging of 3D US/CEUS with real-time US/CEUS was used to guide the implementation of the plan, immediately evaluate the technical success and indicate the need for supplemental ablation. In addition, contrast-enhanced CT/MR imaging was performed 1 month after the procedure to evaluate the presence of residual tumors, and follow-up scans were repeated every 3 months.

Results: The average liver tumor diameter was 28 ± 9 mm (range, 10-55 mm). 3D US/CEUS-based planning was successfully conducted in all 85 tumors with a 100% technical success rate of planning. The immediate evaluation by 3D CEUS/US-CEUS fusion imaging showed a 100% technical success rate of ablation. The 1-month CT/MR scans found a residual tumor in one intrahepatic cholangiocarcinoma patient; the technique efficacy rate was 98.8%. The median follow-up period was 21.5 months (IQR: 4-36 months). During the follow-up period, the local tumor progression rate was 5.9% (5/84), and no major procedure-related complications occurred.

Conclusions: Ablation planning based on 3D US/CEUS-US/CEUS fusion imaging is feasible for liver tumors.
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http://dx.doi.org/10.1007/s00261-020-02909-5DOI Listing
June 2021

Upregulation of DUSP6 impairs infectious bronchitis virus replication by negatively regulating ERK pathway and promoting apoptosis.

Vet Res 2021 Jan 11;52(1). Epub 2021 Jan 11.

Waterfowl Viral Infectious Diseases Team, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P. R. China.

Elucidating virus-cell interactions is fundamental to understanding viral replication and identifying targets for therapeutic control of viral infection. The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate pathogenesis during many viral infections, but its role during coronavirus infection is undetermined. Infectious bronchitis virus is the representative strain of Gammacoronavirus, which causes acute and highly contagious diseases in the poultry farm. In this study, we investigated the role of ERK1/2 signaling pathway in IBV infection. We found that IBV infection activated ERK1/2 signaling and the up-regulation of phosphatase DUSP6 formed a negative regulation loop. Pharmacological inhibition of MEK1/2-ERK1/2 signaling suppressed the expression of DUSP6, promoted cell death, and restricted virus replication. In contrast, suppression of DUSP6 by chemical inhibitor or siRNA increased the phosphorylation of ERK1/2, protected cells from apoptosis, and facilitated IBV replication. Overexpression of DUSP6 decreased the level of phospho-ERK1/2, promoted apoptosis, while dominant negative mutant DUSP6-DN lost the regulation function on ERK1/2 signaling and apoptosis. In conclusion, these data suggest that MEK-ERK1/2 signaling pathway facilitates IBV infection, probably by promoting cell survival; meanwhile, induction of DUSP6 forms a negative regulation loop to restrict ERK1/2 signaling, correlated with increased apoptosis and reduced viral load. Consequently, components of the ERK pathway, such as MEK1/2 and DUSP6, represent excellent targets for the development of antiviral drugs.
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http://dx.doi.org/10.1186/s13567-020-00866-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798014PMC
January 2021

Ultrasonic Interfacial Engineering of Red Phosphorous-Metal for Eradicating MRSA Infection Effectively.

Adv Mater 2021 Feb 22;33(5):e2006047. Epub 2020 Dec 22.

School of Materials Science & Engineering, The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China, Tianjin University, Tianjin, 300072, China.

Sonodynamic therapy (SDT) is considered to be a potential treatment for various diseases including cancers and bacterial infections due to its deep penetration ability and biosafety, but its SDT efficiency is limited by the hypoxia environment of deep tissues. This study proposes creating a potential solution, sonothermal therapy, by developing the ultrasonic interfacial engineering of metal-red phosphorus (RP), which has an obviously improved sonothermal ability of more than 20 °C elevation under 25 min of continuous ultrasound (US) excitation as compared to metal alone. The underlying mechanism is that the mechanical energy of the US activates the motion of the interfacial electrons. US-induced electron motion in the RP can efficiently transfer the US energy into phonons in the forms of heat and lattice vibrations, resulting in a stronger US absorption of metal-RP. Unlike the nonspecific heating of the cavitation effect induced by US, titanium-RP can be heated in situ when the US penetrates through 2.5 cm of pork tissue. In addition, through a sonothermal treatment in vivo, bone infection induced by multidrug-resistant Staphylococcus aureus (MRSA) is successfully eliminated in under 20 min of US without tissue damage. This work provides a new strategy for combating MRSA by strong sonothermal therapy through US interfacial engineering.
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http://dx.doi.org/10.1002/adma.202006047DOI Listing
February 2021

Crosstalk between the COX2-PGE2-EP4 signaling pathway and primary cilia in osteoblasts after mechanical stimulation.

J Cell Physiol 2021 Jun 4;236(6):4764-4777. Epub 2020 Dec 4.

Department of Orthopedic Trauma, The First Hospital of Jilin University, Changchun, China.

Primary cilia have been found to function as mechanosensors in low-magnitude high-frequency vibration (LMHFV)-induced osteogenesis. The PGE2 also regulates bone homeostasis and mechanical osteogenesis through its receptor EP4 signaling, but its involvement in LMHFV-induced or in primary cilia-induced osteogenesis has not been investigated. We hypothesized that LMHFV stimulates osteoblast (OB) differentiation by activating the COX2-PGE2-EP pathway in a manner dependent on primary cilia and that primary cilia are also affected by the PGE2 pathway. In this study, through western blot analysis, RNA interference, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and cytochemical staining, we observed that COX2, mPGES-1, and PGE2 levels were markedly elevated in cells treated with LMHFV and were greatly decreased in LMHFV-treated cells following IFT88 silencing. EP4 expression was significantly increased in OBs following LMHFV treatment, but IFT88 silencing significantly blocked this increase. EP4 localized to the bases of primary cilia. LMHFV reduced the length and abundance of primary cilia, but the cells could self-repair their primary cilia after mechanical damage. EP4 antagonism significantly blocked the LMHFV-induced increase in IFT88 expression and blocked the recovery of primary cilia length and the proportion of cells with primary cilia. In addition, COX2 or EP4 antagonism disrupted LMHFV-induced osteogenesis. These results demonstrate the integration of and crosstalk between primary cilia and the COX2-PGE2-EP4 signaling pathway under mechanical stimulation.
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http://dx.doi.org/10.1002/jcp.30198DOI Listing
June 2021

Engineered probiotics biofilm enhances osseointegration via immunoregulation and anti-infection.

Sci Adv 2020 Nov 13;6(46). Epub 2020 Nov 13.

School of Materials Science and Engineering, the Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China, Tianjin University, Tianjin 300072, China.

Preventing multidrug-resistant bacteria-related infection and simultaneously improving osseointegration are in great demand for orthopedic implants. However, current strategies are still limited to a combination of non-U.S. Food and Drug Administration-approved antibacterial and osteogenic agents. Here, we develop a food-grade probiotic-modified implant to prevent methicillin-resistant (MRSA) infection and accelerate bone integration. is cultured on the surface of alkali heat-treated titanium (Ti) substrates and inactivated by ultraviolet irradiation to avoid sepsis induced by viable bacteria. This inactivated biofilm shows excellent 99.98% antibacterial effectiveness against MRSA due to the production of lactic acid and bacteriocin. In addition, the polysaccharides in the biofilm stimulate macrophages to secrete abundant osteogenic cytokines such as oncostatin M and improve osseointegration of the Ti implant. Inactivated probiotics modification can be a promising strategy to endow implants with both excellent self-antibacterial activity and osteointegration ability.
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http://dx.doi.org/10.1126/sciadv.aba5723DOI Listing
November 2020
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