Publications by authors named "Zhihong Li"

407 Publications

MicroRNA-138 directly targets TNFAIP8 and acts as a tumor suppressor in osteosarcoma.

Exp Ther Med 2021 Dec 4;22(6):1403. Epub 2021 Oct 4.

[This retracts the article DOI: 10.3892/etm.2017.4947.].
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http://dx.doi.org/10.3892/etm.2021.10839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524774PMC
December 2021

A signal-on fluorescent aptasensor by sensitized Tb luminescence for detection of melamine in milk.

Talanta 2022 Jan 3;236:122842. Epub 2021 Sep 3.

Department of Food Quality and Safety, College of Food Science and Engineering, Jilin University, Changchun, 130062, China. Electronic address:

A fluorescent aptasensor based on sensitized terbium(III) luminescence was constructed to detect melamine in milk. Tb as the fluorescence probe can be sensitized by a guanine-rich single-stranded DNA sequence, so the complementary sequence of the polythymidine aptamer (cDNA) was modified with six consecutive guanine bases (G6). In the absence of melamine, melamine aptamer combined with cDNA to form a double helix structure, and G6 hybridized with the extended cytosine bases in the aptamer, resulting in low fluorescence intensity of Tb. In the presence of melamine, cDNA was released due to the specific recognition of melamine to the aptamer, resulting in stronger sensitized fluorescence intensity of Tb. Under the optimum conditions, the linear concentration of melamine in the milk ranged from 1.0 μg/mL to 10.0 μg/mL. This aptasensor can be used for the accurate and rapid detection of melamine in milk with a detection limit of 0.02 μg/mL, and has the advantages of high sensitivity, high efficiency, simple operation and low cost.
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http://dx.doi.org/10.1016/j.talanta.2021.122842DOI Listing
January 2022

Comparative Transcriptomic Analyses of Antibiotic-Treated and Normally Reared Reveals a Possible Gut Self-Immunity Mechanism.

Front Cell Dev Biol 2021 21;9:647604. Epub 2021 Sep 21.

College of Plant Protection, China Agricultural University, Beijing, China.

(Hendel) is a notorious agricultural pest worldwide, and its prevention and control have been widely studied. Bacteria in the midgut of help improve host insecticide resistance and environmental adaption, regulate growth and development, and affect male mating selection, among other functions. Insects have an effective gut defense system that maintains self-immunity and the balance among microorganisms in the gut, in addition to stabilizing the diversity among the gut symbiotic bacteria. However, the detailed regulatory mechanisms governing the gut bacteria and self-immunity are still unclear in oriental fruit flies. In this study, the diversity of the gut symbiotic bacteria in was altered by feeding host fruit flies antibiotics, and the function of the gut bacteria was predicted. Then, a database of the intestinal transcriptome of the host fruit fly was established and analyzed using the Illumina HiSeq Platform. The gut bacteria shifted from Gram negative to Gram positive after antibiotic feeding. Antibiotics lead to a reduction in gut bacteria, particularly Gram-positive bacteria, which ultimately reduced the reproduction of the host flies. Ten immunity-related genes that were differentially expressed in the response to intestinal bacterial community changes were selected for qRT-PCR validation. Peptidoglycan-recognition protein SC2 gene ( was one of the 10 immunity-related genes analyzed. The differential expression of was the most significant, which confirms that may affect immunity of toward gut bacteria.
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http://dx.doi.org/10.3389/fcell.2021.647604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490719PMC
September 2021

Effectiveness comparisons of various therapies for FIGO stage IB2/IIA2 cervical cancer: a Bayesian network meta-analysis.

BMC Cancer 2021 Oct 6;21(1):1078. Epub 2021 Oct 6.

Department of Gynecology, Kunming Tongren Hospital, No. 1099 Guangfu Road, Xishan District, Kunming City, 650100, Yunnan Province, China.

Background: Cervical cancer is a common malignancy of the female genital tract. Treatment options for cervical cancer patients diagnosed at FIGO (2009) stage IB2 and IIA2 remains controversial.

Methods: We perform a Bayesian network meta-analysis to directly or indirectly compare various interventions for FIGO (2009) IB2 and IIA2 disease, in order to improve our understand of the optimal treatment strategy for these women. Three databases were searched for articles published between 1971 and 2020. Data on included study characteristics, outcomes, and risk of bias were abstracted by two reviewers.

Results: Seven thousand four hundred eighty-six articles were identified. Thirteen randomized controlled trials of FIGO (2009) IB2 and IIA2 cervical cancer patients were included in the final analysis. These trials used six different interventions: concomitant chemoradiotherapy (CCRT), radical surgery (RS), radical surgery following chemoradiotherapy (CCRT+RS), neoadjuvant chemotherapy followed by radical surgery (NACT+RS), adjuvant radiotherapy followed by Radical surgery (RT + RS), radiotherapy alone (RT).SUCRA ranking of OS and Relapse identified CCRT+RS and CCRT as the best interventions, respectively. Systematic clustering analysis identified the CCRT group as a unique cluster.

Conclusion: These data suggest that CCRT may be the best approach for improving the clinical outcome of cervical cancer patients diagnosed at FIGO (2009) stage IB2/IIA2. Phase III randomized trials should be performed in order to robustly assess the relative efficacy of available treatment strategies in this disease context.
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http://dx.doi.org/10.1186/s12885-021-08685-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493709PMC
October 2021

Inkjet printing-based fabrication of microscale 3D ice structures.

Microsyst Nanoeng 2020 19;6:89. Epub 2020 Oct 19.

National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Institute of Microelectronics, Peking University, Beijing, 100871 China.

This study proposed a method for fabricating 3D microstructures of ice without a supporting material. The inkjet printing process was performed in a low humidity environment to precisely control the growth direction of the ice crystals. In the printing process, water droplets (volume = hundreds of picoliters) were deposited onto the previously formed ice structure, after which they immediately froze. Different 3D structures (maximum height = 2000 µm) could be formed by controlling the substrate temperature, ejection frequency and droplet size. The growth direction was dependent on the landing point of the droplet on the previously formed ice structure; thus, 3D structures could be created with high degrees of freedom.
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http://dx.doi.org/10.1038/s41378-020-00199-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433306PMC
October 2020

A urine and serum metabolomics study of gastroesophageal reflux disease in TCM syndrome differentiation using UPLC-Q-TOF/MS.

J Pharm Biomed Anal 2021 Nov 15;206:114369. Epub 2021 Sep 15.

Department of Chemistry, Capital Normal University, No. 105, Xisanhuanbeilu, Haidian District, Beijing 100048, PR China. Electronic address:

Gastroesophageal reflux disease (GERD) is a common, chronic and complex upper gastrointestinal disease. In Traditional Chinese medicine (TCM) theory, GERD is classified into two main types: stagnant heat of liver and stomach (SHLS) and deficient cold of spleen and stomach (DCSS). The discovery and evaluation of potential biomarkers for different syndrome types of GERD may contribute to comprehend specific molecular mechanism and identify new targets for diagnosis and appropriate management. In our study, 60 subjects including 40 GERD patients (20 SHLS and 20 DCSS) and 20 healthy controls were recruited, and the serum and urine metabolic profiles from untargeted liquid chromatography coupled to mass spectrometry (LC-MS) metabolomics approach were obtained. Finally 38 biomarkers associated with disease were identified and 9 metabolic pathways were enriched. The most enriched pathways were amino acid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, sphingolipid metabolism and TCA cycle. According to the area under curve (AUC) value, we propose a cohort of three metabolites from urine and serum samples as promising biomarkers for TCM syndrome differentiation of GERD, which are prolylhydroxyproline, glycitein-4'-O-glucuronide, capsianoside I in urine and neuAcalpha2-3Galbeta-Cer (d18:1/16:0), sphinganine, arachidonic acid in serum. The cumulative AUC value of merged biomarkers in urine and serum was 0.979 (95%CI 0.927-1) and 0.842 (95%CI 0.704-0.980), respectively. The results indicated that LC-MS based metabolomic profiling method might be an effective and promising tool on further pathogenesis discovering of GERD. The findings provided new strategy for the diagnosis of GERD TCM syndrome differentiation in clinic.
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http://dx.doi.org/10.1016/j.jpba.2021.114369DOI Listing
November 2021

[Retracted] MicroRNA‑338‑3p suppresses tumor growth of esophageal squamous cell carcinoma and .

Mol Med Rep 2021 Nov 20;24(5). Epub 2021 Sep 20.

Department of Anesthesiology, The Second Hospital, Jilin University, Changchun, Jilin 130041, P.R. China.

Following the publication of the above article, the authors have requested that it be retracted. After having repeated some of the experiments, the authors were not able to reproduce certain of the results. Furthermore, following a further investigation in the Editorial Office, it came to light that some of the wstern blotting data shown in Fig. 3 and the tumor images in Fig. 5 were strikingly similar to those that had been submitted for publication prior to the receipt of present article. Therefore, this article has been retracted from the Journal; all the authors agree to this retraction. The Editor and the authors would like to apologize for any inconvenience caused. [the original article was published in 12: 3951‑3957, 2015; DOI: 10.3892/mmr.2015.3820].
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http://dx.doi.org/10.3892/mmr.2021.12450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477176PMC
November 2021

Patients' risk factors for periprosthetic joint infection in primary total hip arthroplasty: a meta-analysis of 40 studies.

BMC Musculoskelet Disord 2021 Sep 12;22(1):776. Epub 2021 Sep 12.

Department of Orthopaedics, Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.

Background: Periprosthetic joint infection (PJI) is a catastrophic complication after total hip arthroplasty (THA). Our meta-analysis aimed to identify the individual-related risk factors that predispose patients to PJI following primary THA.

Methods: Comprehensive literature retrieval from Pubmed, Web of Science, and the Cochrane Library was performed from inception to Feb 20th, 2021. Patient-related risk factors were compared as per the modifiable factors (BMI, smoke and alcohol abuse), non-modifiable factors (gender, age), and medical history characteristics, such as diabetes mellitus (DM), avascular necrosis (AVN) of femoral head, femoral neck fracture, rheumatoid arthritis (RA), cardiovascular disease (CVD), and osteoarthritis (OA) etc. The meta-analysis was applied by using risk ratios with 95% corresponding intervals. Sensitivity analysis and publication bias were performed to further assess the credibility of the results.

Results: Overall, 40 studies with 3,561,446 hips were enrolled in our study. By implementing cumulative meta-analysis, higher BMI was found associated with markedly increased PJI risk after primary THA [2.40 (2.01-2.85)]. Meanwhile, medical characteristics including DM [1.64 (1.25-2.21)], AVN [1.65 (1.07-2.56)], femoral neck fracture [1.75 (1.39-2.20)], RA [1.37 (1.23-1.54)], CVD [1.34 (1.03-1.74)], chronic pulmonary disease (CPD) [1.22 (1.08-1.37)], neurological disease [1.19 (1.05-1.35)], opioid use [1.53 (1.35-1.73)] and iron-deficiency anemia (IDA) [1.15 (1.13-1.17)] were also significantly correlated with higher rate of PJI. Conversely, dysplasia or dislocation [0.65 (0.45-0.93)], and OA [0.70 (0.62-0.79)] were protective factors. Of Note, female gender was protective for PJI only after longer follow-up. Besides, age, smoking, alcohol abuse, previous joint surgery, renal disease, hypertension, cancer, steroid use and liver disease were not closely related with PJI risk.

Conclusion: Our finding suggested that the individual-related risk factors for PJI after primary THA included high BMI, DM, AVN, femoral neck fracture, RA, CVD, CPD, neurological disease, opioid use and IDA, while protective factors were female gender, dysplasia/ dislocation and OA.
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http://dx.doi.org/10.1186/s12891-021-04647-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436433PMC
September 2021

The miR-193a-5p/NCX2/AKT axis promotes invasion and metastasis of osteosarcoma.

J Cancer 2021 8;12(19):5903-5913. Epub 2021 Aug 8.

Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Science, Hunan Normal University, Changsha 410081, Hunan, China.

MiR-193a-5p has been observed to have oncogenic or tumor suppressive functions in different kinds of cancers, but its role and molecular mechanism in osteosarcoma are elusive. Na/Ca exchangers (NCX1, NCX2 and NCX3) normally extrude Ca from the cell, and deregulation of the intracellular Ca homeostasis is related to several kinds of diseases, including cancer. The present study demonstrated that miR-193a-5p was upregulated in osteosarcoma tissues compared with the corresponding adjacent noncancerous tissues, and promoted colony formation, migration, invasion and epithelial-mesenchymal transition (EMT) in osteosarcoma cells (SaOS-2 and U-2OS), as well as metastasis in a murine xenograft model. Tandem mass tag-based quantitative proteomics analysis identified NCX2 as a potential target of miR-193a-5p. Luciferase activity assays and Western blotting further confirmed that miR-193a-5p recognized the 3'-untranslated region of NCX2 mRNA, and negatively regulated NCX2 expression. NCX2 was downregulated in osteosarcoma tissues, and its expression was negatively correlated with miR-193a-5p levels. Ectopic expression of NCX2 in osteosarcoma cells could reverse the oncogenicity of miR-193a-5p, indicating that miR-193a-5p exerted its effects by targeting NCX2. Further study demonstrated that NCX2 suppresses Ca-dependent Akt phosphorylation by decreasing intracellular Ca concentration, and then inhibited EMT process. Treatment with the antagomir against miR-193a-5p sensitized osteosarcoma to the Akt inhibitor afuresertib in a murine xenograft model. In conclusion, a miR-193a-5p/NCX2/AKT signaling axis contributes to the progression of osteosarcoma, which may provide a new therapeutic target for osteosarcoma treatment.
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http://dx.doi.org/10.7150/jca.60969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408106PMC
August 2021

Circ_0003732 promotes osteosarcoma progression through regulating miR-377-3p/CPEB1 axis and Wnt/β-catenin signaling pathway.

Anticancer Drugs 2021 Aug 16. Epub 2021 Aug 16.

Department Of Orthopedics, The Second Xiangya Hospital Of Central South University, China.

Osteosarcoma is a prevalent malignant bone cancer. This study aimed to explore the biologic role and potential mechanism of circ_0003732 in osteosarcoma carcinogenesis. Quantitative real-time PCR was implemented to detect the RNA expression of circ_0003732, microRNA-377-3p (miR-377-3p) and cytoplasmic polyadenylation element-binding protein 1 (CPEB1). Cell proliferation was evaluated by cell counting kit-8 assay and colony formation assay. Transwell, wound healing and flow cytometry assays were employed to assess cell migration, invasion and apoptosis. In addition, the interaction between miR-377-3p and circ_0003732 or CPEB1 was validated by dual-luciferase reporter assay. The protein expression was detected by western blot assay or immunohistochemistry assay. Xenograft tumor assay was performed to explore the regulation of circ_0003732 on osteosarcoma tumor growth in vivo. Circ_0003732 was upregulated in osteosarcoma tissues and cells. Knockdown of circ_0003732 suppressed osteosarcoma cell proliferation, migration, invasion and triggered cell apoptosis in vitro, as well as reduced osteosarcoma tumor growth in vivo. Meanwhile, miR-377-3p could bind to circ_0003732 and CPEB1 and miR-377-3p inhibitor could reverse the effects of circ_0003732 silence on osteosarcoma cell progression. Furthermore, CPEB1 overexpression could overturn the suppressive impacts of miR-377-3p on osteosarcoma progression. In addition, circ_0003732 silence restrained Wnt/β-catenin signaling pathway via regulating miR-377-3p in osteosarcoma cells. Circ_0003732 might play a positive role in the malignant progression of osteosarcoma by regulating the miR-377-3p/CPEB1 axis and activating the Wnt/β-catenin signaling pathway, which might provide new insights for osteosarcoma therapy.
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http://dx.doi.org/10.1097/CAD.0000000000001206DOI Listing
August 2021

Research trends of platelet-rich plasma application in orthopaedics from 2002 to 2020: a bibliometric analysis.

Int Orthop 2021 Aug 2. Epub 2021 Aug 2.

Department of Orthopedic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Background: Platelet-rich plasma (PRP) has been widely used to treat various orthopaedic diseases, and there are a large number of studies on the matter. However, there have been no bibliometric reports on the publications in this field. Bibliometrics is an excellent method to systematically evaluate the current research status of a specific field. In this study, CiteSpace 5.7.R2 software was used to analyse the status, hotspots, and frontiers of PRP in the treatment of orthopaedic diseases in the past 19 years.

Methods: All articles about the application of PRP in orthopaedics from 2002 to 2020 were searched from the Web of Science Core Collection. The author, country, institution, journal, cited journal, and keywords were retrieved, and the bibliometric analysis was done in CiteSpace 5.7.R2.

Results: A total of 321 articles were retrieved. The analysis showed that the number of publications increased in the past 19 years, and the most productive author in this field was Brian J. Cole. The most productive country and the most productive institution were the US and the Hospital for Special Surgery in New York, respectively. The journals with the highest output and the highest citation frequency were the Journal of Orthopaedic Research and the American Journal of Sports Medicine, respectively. From the keyword analysis, we observed that the primary research hotspots were the study of the PRP composition, growth factors, and the combination of PRP and mesenchymal stem cells. The frontiers of PRP were in vivo experiments, the treatment of rotator cuff and cartilage injury, and the comparison of clinical efficacy between PRP and hyaluronic acid.

Conclusion: The efficacy of PRP in treating orthopaedic diseases remains controversial. There are still some problems with the experimental methods, such as insufficient sample size, low level of evidence, confusion of system naming, lack of standardisation of preparation methods and application programs, and lack of in-depth basic scientific research. The research status shown by co-occurrence and cluster maps and the analysis of hotspots and frontiers may help solve present problems and explore new directions.
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http://dx.doi.org/10.1007/s00264-021-05163-6DOI Listing
August 2021

Performance Evaluation of Warfarin Dose Prediction Algorithms and Effects of Clinical Factors on Warfarin Dose in Chinese Patients.

Ther Drug Monit 2021 08;43(4):527-535

School of Pharmacy, Shanxi Medical University, Taiyuan, China; and.

Background: The clinical utility of warfarin dose prediction algorithms remains controversial, our purpose is to evaluate the performance of warfarin dose prediction algorithms and the effects of clinical factors on warfarin dose in Chinese patients.

Methods: Clinical data of 217 patients who received warfarin treatment were used to assess 6 warfarin dose prediction algorithms (OHNO, IWPC [International Warfarin Pharmacogenetics Consortium], HUANG, KIM, BRESS, and MIAO). The predicted dose (PD) was compared with the warfarin optimal dose (WOD, defined as the dose that maintains the international normalized ratio within the target range of 2.0-3.0). A multiple regression analysis with WOD as the dependent variable was performed to evaluate the effects of clinical factors on warfarin dose.

Results: The mean absolute error analysis ranked the predictive accuracies of the algorithms as OHNO > IWPC > HUANG > KIM > BRESS > MIAO. Stratified analysis indicated that HUANG most accurately predicted that patients required lower WODs (≤3 mg/d), whereas OHNO was the most effective in predicting medium WODs (3-5 mg/d). KIM was effective in predicting high WODs (>5 mg/d). Multiple linear regression analysis showed that VKORC1 (rs9923231) and body mass index were significantly positively correlated with WOD, whereas concurrent atrial fibrillation status, CYP2C9*3 (rs1057910), and sex were significantly negatively correlated with WOD.

Conclusions: In Chinese patients, OHNO should be given priority during the prediction and selection of warfarin dose. When using OHNO to predict warfarin dose (≤3 mg/d or >5 mg/d), HUANG or KIM algorithms can provide precise predictions. At the same time, physicians should pay close attention to clinical factors, such as VKORC1 (rs9923231), concurrent atrial fibrillation status, CYP2C9*3 (rs1057910), body mass index, and sex, to improve warfarin dose adjustment strategies in Chinese patients.
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http://dx.doi.org/10.1097/FTD.0000000000000880DOI Listing
August 2021

All-optical laser-ultrasonic technology for width and depth gauging of rectangular surface-breaking defects.

Rev Sci Instrum 2021 May;92(5):054901

State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou 310027, People's Republic of China.

In this paper, the width and depth of rectangular surface-breaking defects were successfully gauged using an all-optical laser-ultrasonic system. The finite element method was used to simulate propagating paths of defect-induced reflected and transmitted Rayleigh waves. It is observed that most Rayleigh waves with wavelengths less than the depth of the defect are reflected by the defect. A small part of the Rayleigh waves with wavelengths greater than the depth of the defect directly transmits through the bottom edge of the defect without acting on the left edge of the defect. Based on the simulation results, a three-step detection method of width and depth gauging of rectangular surface-breaking defects is proposed. In the first step, the pulsed laser and detection laser are irradiated on one side of the defect. In the second step, the sample is moved to a certain distance to ensure that both lasers reach the other side of the defect. In the third step, two lasers are irradiated on both sides of the defect. The width and depth of the defect are calculated according to the arrival time of the incident, reflected, and transmitted Rayleigh waves, as well as the movement distance of the sample. Experimental results are consistent with the reference-results measured by using a digital microscope. The proposed three-step detection method is proved to be feasible in simultaneous measurement of the width and depth of rectangular surface-breaking defects. Furthermore, it may be potentially useful for measuring other types of defect structures.
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http://dx.doi.org/10.1063/5.0026174DOI Listing
May 2021

Exosomes: A Friend or Foe for Osteoporotic Fracture?

Front Endocrinol (Lausanne) 2021 21;12:679914. Epub 2021 Jun 21.

Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, China.

The clinical need for effective osteoporotic fracture therapy and prevention remains urgent. The occurrence and healing of osteoporotic fracture are closely associated with the continuous processes of bone modeling, remodeling, and regeneration. Accumulating evidence has indicated a prominent role of exosomes in mediating multiple pathophysiological processes, which are essential for information and materials exchange and exerting pleiotropic effects on neighboring or distant bone-related cells. Therefore, the exosomes are considered as important candidates both in the occurrence and healing of osteoporotic fracture by accelerating or suppressing related processes. In this review, we collectively focused on recent findings on the diagnostic and therapeutic applications of exosomes in osteoporotic fracture by regulating osteoblastogenesis, osteoclastogenesis, and angiogenesis, providing us with novel therapeutic strategies for osteoporotic fracture in clinical practice.
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http://dx.doi.org/10.3389/fendo.2021.679914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256167PMC
June 2021

Complementary Photo-Synapses Based on Light-Stimulated Porphyrin-Coated Silicon Nanowires Field-Effect Transistors (LPSNFET).

Small 2021 07 29;17(30):e2101434. Epub 2021 Jun 29.

Key Laboratory of Microelectronic Devices and Circuits (MOE), Institute of Microelectronics, Peking University, Beijing, 100871, China.

Neuromorphic computing has emerged as the high-energy-efficiency and intelligent solution for processing sensory data. As a potential alternative to neuromorphic computing, photo-excited synaptic systems can integrate the functions of optoelectronic sensing and synaptic computing to realize the low-power and high-performance visual perception. However, one major challenge in high-efficient photo-excited synaptic system is to realize the complementarily enhanced and inhibited synaptic behaviors with small hardware cost as possible. Another challenge is to fabricate the photo-synapse devices with complementary metal oxide semiconductor (CMOS)-compatible process to achieve high enough integration density for practical application. Here, a CMOS-compatible Light-stimulated Porphyrin-coated Silicon Nanowire Field Effect Transistor (LPSNFET) technology is proposed and developed to form the complementary photo-synapses with only two CMOS-like transistors. LPSNFET exhibits fivefold improvement in photo-sensitivity compared to the bare silicon nanowire (SiNW) devices, and can still show obvious responses when incident illumination power is as low as 0.1 mW cm . Moreover, it enables tunable dynamic synaptic plasticity and versatile synaptic functions. Especially, the complementarily enhanced and inhibited behaviors can be realized by modulating SiNW/porphyrin interface via simply changing the MOS type of LPSNFET, which acts like the photonic counterpart of CMOS technology to provide the basic brick for building complex neuromorphic circuits efficiently and economically. Finally, the CMOS process compatibility of LPSNFET provides potential application in future large scale in-sensor computing.
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http://dx.doi.org/10.1002/smll.202101434DOI Listing
July 2021

TMSB4 Overexpression Enhances the Potency of Marrow Mesenchymal Stromal Cells for Myocardial Repair.

Front Cell Dev Biol 2021 9;9:670913. Epub 2021 Jun 9.

Department of the Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Objective: The actin-sequestering proteins, thymosin beta-4 (Tβ4) and hypoxia-inducible factor (HIF)-1α, are known to be associated with angiogenesis after myocardial infarction (MI). Herein, we aimed to identify the mechanism of HIF-1α induction by Tβ4 and investigate the effects of bone marrow mesenchymal stromal cells (BMMSCs) transfected with the Tβ4 gene () in a rat model of MI.

Methods: Rat BMMSCs were isolated, cultured, and transfected with the gene by using the lentivirus-mediated method. Rats with surgically induced MI were randomly divided into three groups ( = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ), or medium (MI). The fourth group of animals ( = 9) underwent all surgical procedures necessary for MI induction except for the ligation step (Sham). Four weeks after the injection, heart function was measured using transthoracic echocardiography. Infarct size was calculated by TTC staining, and collagen volume was measured by Masson staining. Angiogenesis in the infarcted heart area was evaluated by CD31 immunofluorescence histochemistry. experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).

Results: experiments showed that vascular density 4 weeks after treatment was about twofold higher in BMMSC-TMSB4 -treated animals than in BMMSC-TMSB4 -treated animals ( < 0.05). The cardiac function and infarct size significantly improved in both cell-treatment groups compared to controls. Notably, the cardiac function and infarct size were most prominent in BMMSC-TMSB4 -treated animals (both < 0.05). HIF-1α and phosphorylated HIF-1α (p-HIF-1α) were significantly enhanced by exogenous Tβ4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1). The expression of prolyl hydroxylase domain proteins (PHD) was decreased upon treatment with Tβ4 and further decreased with the combined treatment of Tβ4 and FG-4497 (a specific PHD inhibitor).

Conclusion: TMSB4-transfected BMMSCs might significantly improve recovery from myocardial ischemia and promote the generation of HIF-1α and p-HIF-1α the AKT pathway, and inhibit the degradation of HIF-1α the PHD and FIH pathways.
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http://dx.doi.org/10.3389/fcell.2021.670913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221609PMC
June 2021

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma.

Cancer Cell Int 2021 Jun 15;21(1):313. Epub 2021 Jun 15.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, No 139 Middle Renmin Road, Changsha, 410011, Hunan, China.

Osteosarcoma is a common and highly malignant bone tumor among children, adolescents and young adults. However, the underlying molecular mechanisms remain largely unexplored. LncRNAs are transcripts with no or limited protein-coding capacity in human genomes, and have been demonstrated to play crucial functions in initiation, progression, therapeutic resistance, recurrence and metastasis of tumor. Considerable studies revealed a dysregulated lncRNA expression pattern in osteosarcoma, which may act as oncogenes or suppressors to regulate osteosarcoma progression. Wnt signaling pathway is an important cascade in tumorigenesis by modulation of pleiotropic biological functions including cell proliferation, apoptosis, differentiation, stemness, genetic stability and chemoresistance. Hyperactivation or deficiency of key effectors in Wnt cascade is a common event in many osteosarcoma patients. Recently, increasing evidences have suggested that lncRNAs could interplay with component of Wnt pathway, and thereby contribute to osteosarcoma onset, progression and dissemination. In this review, we briefly summarize Wnt signaling-related lncRNAs in osteosarcoma progression, aiming to gain insights into their underlying crosstalk as well as clinical application in osteosarcoma therapeutic modalities.
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http://dx.doi.org/10.1186/s12935-021-02013-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207720PMC
June 2021

Interaction between valproic acid and carbapenems: decreased plasma concentration of valproic acid and liver injury.

Ann Palliat Med 2021 May;10(5):5417-5424

Department of Pharmacy, Shanxi Bethune Hospital/Shanxi Academy of Medical Sciences, Taiyuan, China.

Background: Several case reports and retrospective studies have indicated that carbapenems decrease the plasma concentration of valproic acid (VPA). This retrospective study examines the effect of carbapenems on VPA levels, and explores whether the drug-drug interaction can influence the liver function of patients.

Methods: The data of 141 patients were collected from the Department of Neurosurgery at Shanxi Bethune Hospital from January 2018 to December 2019. We compared the VPA levels between the VPA monotherapy group and VPA + carbapenem group to evaluate the influence of carbapenem antibiotics on the plasma concentration of VPA. We also compared the liver injury rate of the VPA monotherapy group, VPA + meropenem group, and VPA + imipenem group to evaluate the influence of concomitant use of VPA with carbapenem antibiotics on liver function.

Results: The VPA serum concentration in the VPA + meropenem group was 22.32±21.77 µg/mL, which was markedly lower than that in the VPA monotherapy group (i.e., without carbapenems) (65.17±21.49 µg/mL) (P<0.01). The rate of liver injury was significantly different between the VPA monotherapy, VPA + meropenem, and VPA + imipenem groups (χ2=30.13, P<0.01). Further comparisons showed that the liver injury rate of the VPA + meropenem group (35.42%) was higher than that of the VPA + imipenem (3.7%) and VPA monotherapy (1.52%) groups (P<0.01). Although no significant differences in liver injury rate were observed between the VPA + imipenem (3.7%) and VPA monotherapy (1.52%) groups, the alanine aminotransferase (ALT) value of the VPA + imipenem group after co-administration (65.22±48.01 U/L) was notably higher than before (40.48±24.97 U/L) (P<0.01).

Conclusions: In this study, the interaction between VPA and carbapenems resulted in decreased plasma concentrations of VPA as well as possible liver injury. Clinicians should be aware of this potential interaction, and closely monitor VPA concentrations and liver function. Different carbapenems combined with VPA showed different effects on both VPA concentration and liver function, indicating that the mechanisms of these two effects might be related.
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http://dx.doi.org/10.21037/apm-21-795DOI Listing
May 2021

Capturing the Catalytic Proton of Dihydrofolate Reductase: Implications for General Acid-Base Catalysis.

ACS Catal 2021 May 28;11(9):5873-5884. Epub 2021 Apr 28.

Department of Pharmacology and Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, United States.

Acid-base catalysis, which involves one or more proton transfer reactions, is a chemical mechanism commonly employed by many enzymes. The molecular basis for catalysis is often derived from structures determined at the optimal pH for enzyme activity. However, direct observation of protons from experimental structures is quite difficult; thus, a complete mechanistic description for most enzymes remains lacking. Dihydrofolate reductase (DHFR) exemplifies general acid-base catalysis, requiring hydride transfer and protonation of its substrate, DHF, to form the product, tetrahydrofolate (THF). Previous X-ray and neutron crystal structures coupled with theoretical calculations have proposed that solvent mediates the protonation step. However, visualization of a proton transfer has been elusive. Based on a 2.1 Å resolution neutron structure of a pseudo-Michaelis complex of DHFR determined at acidic pH, we report the direct observation of the catalytic proton and its parent solvent molecule. Comparison of X-ray and neutron structures elucidated at acidic and neutral pH reveals dampened dynamics at acidic pH, even for the regulatory Met20 loop. Guided by the structures and calculations, we propose a mechanism where dynamics are crucial for solvent entry and protonation of substrate. This mechanism invokes the release of a sole proton from a hydronium (HO) ion, its pathway through a narrow channel that sterically hinders the passage of water, and the ultimate protonation of DHF at the N5 atom.
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http://dx.doi.org/10.1021/acscatal.1c00417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154319PMC
May 2021

Inhibition of the Oxygen-Sensing Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-Inducible Factor: A Potential Hypoxia Response Modulating Strategy.

J Med Chem 2021 06 24;64(11):7189-7209. Epub 2021 May 24.

Jiangsu Key Laboratory of Drug Design and Optimization, and Department of Chemistry, China Pharmaceutical University, Nanjing 211198, China.

Factor inhibiting hypoxia-inducible factor (FIH) is a JmjC domain 2-oxogluarate and Fe(II)-dependent oxygenase that catalyzes hydroxylation of specific asparagines in the C-terminal transcriptional activation domain of hypoxia-inducible factor alpha (HIF-α) isoforms. This modification suppresses the transcriptional activity of HIF by reducing its interaction with the transcriptional coactivators p300/CBP. By contrast with inhibition of the HIF prolyl hydroxylases (PHDs), inhibitors of FIH, which accepts multiple non-HIF substrates, are less studied; they are of interest due to their potential ability to alter metabolism (either in a HIF-dependent and/or -independent manner) and, provided HIF is upregulated, to modulate the course of the HIF-mediated hypoxic response. Here we review studies on the mechanism and inhibition of FIH. We discuss proposed biological roles of FIH including its regulation of HIF activity and potential roles of FIH-catalyzed oxidation of non-HIF substrates. We highlight potential therapeutic applications of FIH inhibitors.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00415DOI Listing
June 2021

Significantly improving the thermostability of a hyperthermophilic GH10 family xylanase XynAF1 by semi-rational design.

Appl Microbiol Biotechnol 2021 Jun 20;105(11):4561-4576. Epub 2021 May 20.

Key Laboratory of Microbial Resources Collection and Preservation, Ministry of Agriculture, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, People's Republic of China.

Xylanases have a broad range of applications in industrial biotechnologies, which require the enzymes to resist the high-temperature environments. The majority of xylanases have maximum activity at moderate temperatures, which limited their potential applications in industries. In this study, a thermophilic GH10 family xylanase XynAF1 from the high-temperature composting strain Aspergillus fumigatus Z5 was characterized and engineered to further improve its thermostability. XynAF1 has the optimal reaction temperature of 90 °C. The crystal structure of XynAF1 was obtained by X-ray diffraction after heterologous expression, purification, and crystallization. The high-resolution X-ray crystallographic structure of the protein-product complex was obtained by soaking the apo-state crystal with xylotetraose. Structure analysis indicated that XynAF1 has a rigid skeleton, which helps to maintain the hyperthermophilic characteristic. The homologous structure analysis and the catalytic center mutant construction of XynAF1 indicated the conserved catalytic center contributed to the high optimum catalytic temperature. The amino acids in the surface of xylanase XynAF1 which might influence the enzyme thermostability were identified by the structure analysis. Combining the rational design with the saturation mutation at the high B-value regions, the integrative mutant XynAF1-AC with a 6-fold increase of thermostability was finally obtained. This study efficiently improved the thermostability of a GH10 family xylanase by semi-rational design, which provided a new biocatalyst for high-temperature biotechnological applications. KEY POINTS: • Obtained the crystal structure of GH10 family hyperthermophilic xylanase XynAF1. • Shed light on the understanding of the GH10 family xylanase thermophilic mechanism. • Constructed a 6-fold increased thermostability recombinant xylanase.
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http://dx.doi.org/10.1007/s00253-021-11340-9DOI Listing
June 2021

Yeast-based nucleotide supplementation in mother sows modifies the intestinal barrier function and immune response of neonatal pigs.

Anim Nutr 2021 Mar 5;7(1):84-93. Epub 2021 Jan 5.

Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, Hunan 410125, China.

In the present study, we aimed to evaluate the effects of maternal yeast-based nucleotide (YN) supplementation on the intestinal immune response and barrier function in neonatal pigs, as well as the diarrhoea rate and growth performance in suckling piglets. Sixty-four late-gestation sows were assigned to the following groups: the CON (fed a basal diet) and YN groups (fed a basal diet with 4 g YN/kg diet). The experiment started on d 85 of gestation and ended on d 20 of lactation. Diarrhoea rate and average daily gain of the piglets were recorded, and samples of blood and intestines from neonatal piglets were collected before they consumed colostrum during farrowing. Compared with the CON group, maternal YN supplementation increased the weaning weight of litter and decreased the diarrhoea rate ( < 0.01). In addition, maternal YN supplementation promoted the ileal villus development in the neonates compared with that in the CON group ( < 0.01). Maternal YN supplementation also increased the ileal secretory immunoglobulin A (sIgA) level compared with that in the CON group ( < 0.05). The real-time PCR results showed that maternal dietary YN supplementation increased the jejunal and ileal expression of interleukin (), , , and tumor necrosis factor ()- α in the neonates compared with that in the CON group ( < 0.05). Overall, maternal nucleotide supplementation improved the villus development and innate immunity of neonatal piglets during late pregnancy. This may be associated with the decrease in diarrhoea and the increase in weaning weight of the litter of suckling piglets.
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http://dx.doi.org/10.1016/j.aninu.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110885PMC
March 2021

Knowledge map and global trends in extreme weather research from 1980 to 2019: a bibliometric analysis.

Environ Sci Pollut Res Int 2021 Sep 3;28(36):49755-49773. Epub 2021 May 3.

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.

There is an increasing number of studies focusing on extreme weather all over the world, but global trends and research topics related to extreme weather are still unclear. This study aimed to explore the current situation, research themes, and future trends in the field of extreme weather. Publications published from 1980 to 2019 were identified and retrieved from the Web of Science Core Collection databases by using keywords on May 5, 2020. Excel 2019, VOSviewer, R, and CiteSpace were used for scientific analysis. The results showed that (1) the number of publications on extreme weather research has rapidly increased and expanded continually, shifting from core disciplines to interdisciplinary fields; (2) the International Journal of Climatology was the most productive journal, and climate and environment were the most popular subject categories. Most studies were carried out in the USA, China, Germany, and other nations, and the Chinese Academy of Sciences was the most productive institution; (3) the main research topics were summarized as (a) climate change; (b) variability; (c) trends; (d) rainfall; (e) temperature; and (f) maximum. At the same time, (4) keyword bursts analysis showed that the domain focused on changes to atmospheric rivers, the impacts of global nitrogen content on extreme weather, and the relationship between water quality, soil moisture content, and extreme weather. Based on the in-depth analysis of extreme weather research, this paper developed a further understanding of the developments in this field over the past 39 years and also provided a reference for future research.
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http://dx.doi.org/10.1007/s11356-021-13825-6DOI Listing
September 2021

High Child-Pugh and CRUB65 scores predict mortality of decompensated cirrhosis patients with COVID-19: A 23-center, retrospective study.

Virulence 2021 12;12(1):1199-1208

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

: COVID-19 has rapidly become a major health emergency worldwide. The characteristic, outcome, and risk factor of COVID-19 in patients with decompensated cirrhosis remain unclear.: Medical records were collected from 23 Chinese hospitals. Patients with decompensated cirrhosis and age- and sex-matched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling.: There were more comorbidities with higher Chalson Complication Index (p < 0.001), higher proportion of patients having gastrointestinal bleeding, jaundice, ascites, and diarrhea among those patients (p < 0.05) and in decompensated cirrhosis patients. Mortality (p < 0.05) and the proportion of severe ill (p < 0.001) were significantly high among those patients. Patients in severe ill subgroup had higher mortality (p < 0.001), MELD, and CRUB65 score but lower lymphocytes count. Besides, this subgroup had larger proportion of patients with abnormal (PT), activated partial thromboplatin time (APTT), D-Dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) and Creatinine (Cr) (p < 0.05). Multivariate logistic regression for severity shown that MELD and CRUB65 score reached significance. Higher Child-Pugh and CRUB65 scores were found among non-survival cases and multivariate logistic regression further inferred risk factors for adverse outcome. Receiver Operating Characteristic (ROC) curves also provided remarkable demonstrations for the predictive ability of Child-Pugh and CRUB65 scores.: COVID-19 patients with cirrhosis had larger proportion of more severely disease and higher mortality. MELD and CRUB65 score at hospital admission may predict COVID-19 severity while Child-Pugh and CRUB65 score were highly associated with non-survival among those patients.
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http://dx.doi.org/10.1080/21505594.2021.1909894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078510PMC
December 2021

CPA-seq reveals small ncRNAs with methylated nucleosides and diverse termini.

Cell Discov 2021 Apr 19;7(1):25. Epub 2021 Apr 19.

School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

High-throughput sequencing reveals the complex landscape of small noncoding RNAs (sRNAs). However, it is limited by requiring 5'-monophosphate and 3'-hydroxyl in RNAs for adapter ligation and hindered by methylated nucleosides that interfere with reverse transcription. Here we develop Cap-Clip acid pyrophosphatase (Cap-Clip), T4 polynucleotide kinase (PNK) and AlkB/AlkB(D135S)-facilitated small ncRNA sequencing (CPA-seq) to detect and quantify sRNAs with terminus multiplicities and nucleoside methylations. CPA-seq identified a large number of previously undetected sRNAs. Comparison of sRNAs with or without AlkB/AlkB(D135S) treatment reveals nucleoside methylations on sRNAs. Using CPA-seq, we profiled the sRNA transcriptomes (sRNomes) of nine mouse tissues and reported the extensive tissue-specific differences of sRNAs. We also observed the transition of sRNomes during hepatic reprogramming. Knockdown of mesenchymal stem cell-enriched U1-5' snsRNA promoted hepatic reprogramming. CPA-seq is a powerful tool with high sensitivity and specificity for profiling sRNAs with methylated nucleosides and diverse termini.
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http://dx.doi.org/10.1038/s41421-021-00265-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053708PMC
April 2021

Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2'3'-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation.

J Immunol 2021 05 7;206(9):2061-2074. Epub 2021 Apr 7.

The Center for Microbes, Development and Health, Chinese Academy of Sciences Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China;

The recently identified anion channel LRRC8 volume-regulated anion channels (VRACs) are heteromeric hexamers constituted with the obligate LRRC8A subunit paired with at least one of the accessory LRRC8B to LRRC8E subunits. In addition to transport chloride, taurine, and glutamate, LRRC8 VRACs also transport the anticancer agent cisplatin and STING agonists 2'3'-cyclic GMP-AMP (cGAMP) and cyclic dinucleotides; hence, they are implicated in a variety of physiological and pathological processes, such as cell swelling, stroke, cancer, and viral infection. Although the subunit composition largely determines VRAC substrate specificity, the opening of various VRAC pores under physiological and pathological settings remains enigmatic. In this study, we demonstrated that VRACs comprising LRRC8A and LRRC8E (LRRC8A/E-containing VRACs), specialized in cGAMP transport, can be opened by a protein component present in serum under resting condition. Serum depletion ablated the tonic activity of LRRC8A/E-containing VRACs, decreasing cGAMP transport in various human and murine cells. Also, heating or proteinase K treatment abolished the ability of serum to activate VRAC. Genetic analyses revealed a crucial role for cGAMP synthase (cGAS) in serum/TNF-promoted VRAC activation. Notably, the presence of cGAS on the plasma membrane, rather than its DNA-binding or enzymatic activity, enabled VRAC activation. Moreover, phospholipid PIP2 seemed to be instrumental in the membrane localization of cGAS and its association with VRACs. Corroborating a role for LRRC8A/D-containing VRACs in cisplatin transport, serum and TNF markedly potentiated cisplatin uptake and killing of cancer cells derived from human or mouse. Together, these observations provide new insights into the complex regulation of VRAC activation and suggest a novel approach to enhance the efficacy of cGAMP and cisplatin in treating infection and cancer.
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http://dx.doi.org/10.4049/jimmunol.2000989DOI Listing
May 2021

Phylogenomic resolution of the Ceratitis FARQ complex (Diptera: Tephritidae).

Mol Phylogenet Evol 2021 08 29;161:107160. Epub 2021 Mar 29.

Department of Entomology and MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing 100193, China. Electronic address:

The Ceratitis FARQ complex (formerly FAR complex) includes four frugivorous tephritids, Ceratitis fasciventris, C. anonae, C. rosa and C. quilicii, the latter two causing important agricultural losses in Africa. Although FARQ species can be identified on the basis of subtle morphological differences, they cannot be resolved as monophyletic when trying phylogenetic tree reconstructions based on mitochondrial or nuclear gene fragments except for microsatellites. In this study, we used mitogenome and genome-wide SNPs to investigate the phylogenetic relationship within the complex as well as between all four Ceratitis subgenera. The analysis of 13 species supported the monophyly of the Ceratitis subgenera Ceratitis, Ceratalaspis, Pardalaspis, and recovered Pterandrus as paraphyletic but could not properly resolve species within the FARQ complex. Conversely, gene and species tree reconstructions based on 785,484 genome-wide SNPs could consistently resolve the FARQ taxa and provide insights into their phylogenetic relationships. Gene flow was detected by TreeMix analysis from C. quilicii to C. fasciventris, suggesting the existence of introgression events in the FARQ complex. Our results suggest that genome-wide SNPs represent a suitable tool for the molecular diagnosis of FARQ species and could possibly be used to develop rapid diagnostic methods or to trace the origins of intercepted samples.
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http://dx.doi.org/10.1016/j.ympev.2021.107160DOI Listing
August 2021

Correction to: Survivorship and prognostic factors for pleomorphic liposarcoma: a population-based study.

J Orthop Surg Res 2021 Mar 29;16(1):228. Epub 2021 Mar 29.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, 139 Renming Road, Changsha, 410011, Hunan, People's Republic of China.

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http://dx.doi.org/10.1186/s13018-021-02369-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006338PMC
March 2021

Liraglutide Protects Nucleus Pulposus Cells Against High-Glucose Induced Apoptosis by Activating PI3K/Akt/ mTOR/Caspase-3 and PI3K/Akt/GSK3β/Caspase-3 Signaling Pathways.

Front Med (Lausanne) 2021 19;8:630962. Epub 2021 Feb 19.

Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Diabetes mellitus (DM) is reportedly a significant risk factor for intervertebral disc degeneration (IDD). Incretin system and particularly glucagon-like peptide 1 (GLP-1) because of its glucose-lowering effects has become an important target in therapeutic strategies of type 2 diabetes (T2D). Liraglutide is a GLP-1 receptor (GLP-1R) agonist with glucoregulatory and insulinotropic functions as well as regulatory functions on cell proliferation, differentiation, and apoptosis. However, little is known on the roles and signaling pathways of apoptosis protecting effects of liraglutide in IDD. This study aimed to investigate the potential protective effects of liraglutide against high glucose-induced apoptosis of nucleus pulposus cells (NPCs) and the possible involved signaling pathways. The human NPCs were incubated with 100 nM liraglutide alone or in combination with LY294002 (PI3K inhibitor), rapamycin (mTOR inhibitor), and SB216763 (GSK3β inhibitor) in a high glucose culture for 48 h. The four groups were assessed further for apoptosis and genes expressions. The apoptotic effect was evaluated by flow cytometry and further confirmed by cell death detection enzyme-linked immunoassay plus (ELISAPLUS). The gene and protein expression levels were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting techniques. The results were comparatively assessed between the four groups. The results confirmed the presence of GLP-1R in the NPCs indicating that liraglutide inhibited the high glucose-induced apoptosis, which was blocked by silencing GLP-1R with siRNA. Moreover, liraglutide stimulated the phosphorylation of Akt, mTOR and GSK3β. Treatment with LY294002 significantly increased the apoptosis of NPCs and reduced the levels of their downstream substrates (p-AKT, p-mTOR, and p-GSK3β). Further assessments revealed that activation of mTOR and GSK3β was almost completely inhibited by rapamycin and SB216763, respectively, which significantly increased the caspase-3 levels. Liraglutide could protect NPCs against high glucose-induced apoptosis by activating the PI3K/AKT/mTOR/caspase-3 and PI3K/AKT/GSK3β/caspase-3 signaling pathways.
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http://dx.doi.org/10.3389/fmed.2021.630962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933515PMC
February 2021

Survivorship and prognostic factors for pleomorphic liposarcoma: a population-based study.

J Orthop Surg Res 2021 Mar 4;16(1):175. Epub 2021 Mar 4.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, 139 Renming Road, Changsha, 410011, Hunan, People's Republic of China.

Background: Pleomorphic liposarcoma is the least common but most aggressive subtype of liposarcoma. Very few studies have presented data on pleomorphic liposarcoma specifically, often including a limited number of cases and short-term follow-up. As a result, the survivorship and prognostic characteristics of this tumor remain incompletely identified.

Study Design And Setting: Cross-sectional analysis of the Surveillance Epidemiology and End Results database (1996-2015).

Results: Overall survival for the entire series was 54% (95% confidence interval [CI], 49-58%) and 40% (95% CI, 35-45%) at 5 and 10 years, respectively. Disease-specific survival for the entire series was 60% (95% CI, 56-65%) and 53% (95% CI, 48-58%) at 5 and 10 years, respectively. Patients who survived 10 years or more were more likely to die of events unrelated to pleomorphic liposarcoma. Univariate and multivariate analysis demonstrated that not receiving cancer-directed surgery was an independent poor prognostic factor. Older age (≥ 65 years old) was associated with worse overall survival but not disease-specific survival. Tumor stage and radiotherapy showed different impact on survival depending on tumor size. In comparison to localized staged tumors, regional stage only predicts poor survival in patients with tumor size less than 5 cm, while distant stage is an independent worse prognosis factor. Radiotherapy only benefits patients with tumor size larger than 10 cm. These results were confirmed in competing risk analysis.

Conclusion: Survival rates of patients with pleomorphic liposarcoma has not changed over the past 20 years. Patients with distant stage have poor prognosis; regional stage indicates worse survival in patients with tumor size less than 5 cm. Receiving surgery could prolong the survival, while radiotherapy only benefits patients with large tumor size (> 10 cm). Older age is associated with poor overall survival but not disease-specific survival. Routine patient surveillance following initial diagnosis should at least be 10 years for pleomorphic liposarcoma.
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http://dx.doi.org/10.1186/s13018-021-02327-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931523PMC
March 2021
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