Publications by authors named "Chen Ding"

378 Publications

METTL3-mediated mA RNA methylation promotes the anti-tumour immunity of natural killer cells.

Nat Commun 2021 Sep 17;12(1):5522. Epub 2021 Sep 17.

Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China.

Natural killer (NK) cells exert critical roles in anti-tumor immunity but how their functions are regulated by epitranscriptional modification (e.g., N-methyladenosine (mA) methylation) is unclear. Here we report decreased expression of the mA "writer" METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein expression levels of METTL3 and effector molecules in NK cells. Deletion of Mettl3 in NK cells alters the homeostasis of NK cells and inhibits NK cell infiltration and function in the tumor microenvironment, leading to accelerated tumor development and shortened survival in mice. The gene encoding SHP-2 is mA modified, and its protein expression is decreased in METTL3-deficient NK cells. Reduced SHP-2 activity renders NK cells hyporesponsive to IL-15, which is associated with suppressed activation of the AKT and MAPK signaling pathway in METTL3-deficient NK cells. These findings show that mA methylation safeguards the homeostasis and tumor immunosurveillance function of NK cells.
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http://dx.doi.org/10.1038/s41467-021-25803-0DOI Listing
September 2021

TRIM21 regulates pyroptotic cell death by promoting Gasdermin D oligomerization.

Cell Death Differ 2021 Sep 11. Epub 2021 Sep 11.

Department of Neurology, Huashan Hospital and Institute of Neurology, State Key Laboratory of Genetic Engineering, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, China.

Gasdermin-D (GSDMD), the executioner of pyroptotic cell death when it is cleaved by inflammatory caspases, plays a crucial role in host defense and the response to danger signals. So far, there are no known mechanisms, other than cleavage, for regulating GSDMD. Here, we show that tripartite motif protein TRIM21 acts as a positive regulator of GSDMD-dependent pyroptosis. TRIM21 interacted with GSDMD via its PRY-SPRY domain, maintaining GSDMD stable expression in resting cells yet inducing the N-terminus of GSDMD (GSDMD-N) aggregation during pyroptosis. TRIM21-deficient cells displayed a reduced cell death in response to NLRP3 or NLRC4 inflammasome activation. Genetic ablation of TRIM21 in mice conferred protection from LPS-induced inflammation and dextran sulfate sodium-induced colitis. Therefore, TRIM21 plays an essential role in GSDMD-mediated pyroptosis and may be a viable target for controlling and treating inflammation-associated diseases.
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http://dx.doi.org/10.1038/s41418-021-00867-zDOI Listing
September 2021

H2O2 gel bleaching induces cytotoxicity and pain conduction in dental pulp stem cells via intracellular reactive oxygen species on enamel/dentin disc.

PLoS One 2021 10;16(9):e0257221. Epub 2021 Sep 10.

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

Background: Bleaching is widely accepted for improving the appearance of discolored teeth; however, patient compliance is affected by bleaching-related complications, especially bleaching sensitivity. This study aimed to investigate the role of reactive oxygen species (ROS) in cytotoxicity and pain conduction activated by experimental tooth bleaching.

Methods: Dental pulp stem cells with or without N-acetyl-L-cysteine (NAC), an ROS scavenger, were cultured on the dentin side of the enamel/dentin disc. Subsequently, 15% (90 min) and 40% (30 min) bleaching gels were painted on the enamel surface. Cell viability, intracellular ROS, Ca2+, adenosine triphosphate (ATP), and extracellular ATP levels were evaluated using the Cell Counting Kit-8 assay, 2',7'-dichlorodihydrofluorescein diacetate, CellROX, fura-3AM fluorescence assay, and ATP measurement kit. The rat incisor model was used to evaluate in vivo effects after 0, 1, 3, 7, and 30 days of bleaching. Changes in gene and protein expression of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNFα), transient receptor potential ankyrin 1 (TRPA1), and Pannexin1 (PANX1) in dental pulp stem cells and pulp tissue were detected through RT-PCR, western blotting, and immunofluorescence.

Results: The bleaching gel suppressed dental pulp stem cell viability and extracellular ATP levels and increased intracellular ROS, Ca2+, and intracellular ATP levels. The mRNA and protein expression of IL-6, TNFα, TRPA1, and PANX1 were up-regulated in vitro and in vivo. Furthermore, the 40% gel had a stronger effect than the 15% gel, and NAC ameliorated the gel effects.

Conclusions: Our findings suggest that bleaching gels induce cytotoxicity and pain conduction in dental pulp stem cells via intracellular ROS, which may provide a potential therapeutic target for alleviating tooth bleaching nociception.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257221PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432789PMC
September 2021

Proteomic Analysis of Copper Toxicity in Human Fungal Pathogen .

Front Cell Infect Microbiol 2021 12;11:662404. Epub 2021 Aug 12.

Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China.

is an invasive human fungal pathogen that causes more than 181,000 deaths each year. Studies have demonstrated that pulmonary infection induces innate immune responses involving copper, and copper detoxification in  improves its fitness and pathogenicity during pulmonary infection. However, the molecular mechanism by which copper inhibits  proliferation is unclear. We used a metallothionein double-knockout mutant that was highly sensitive to copper to demonstrate that exogenous copper ions inhibit fungal cell growth by inducing reactive oxygen species generation. Using liquid chromatography-tandem mass spectrometry, we found that copper down-regulated factors involved in protein translation, but up-regulated proteins involved in ubiquitin-mediated protein degradation. We propose that the down-regulation of protein synthesis and the up-regulation of protein degradation are the main effects of copper toxicity. The ubiquitin modification of total protein and proteasome activity were promoted under copper stress, and inhibition of the proteasome pathway alleviated copper toxicity. Our proteomic analysis sheds new light on the antifungal mechanisms of copper.
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http://dx.doi.org/10.3389/fcimb.2021.662404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415117PMC
August 2021

LncRNA ZNFTR functions as an inhibitor in pancreatic cancer by modulating ATF3/ZNF24/VEGFA pathway.

Cell Death Dis 2021 Sep 3;12(9):830. Epub 2021 Sep 3.

Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

The majority of long non-coding RNAs (lncRNAs) have been discovered to be overexpressed in pancreatic cancer (PC) and served as promoters in the tumorigenesis of PC, while the inhibitory functions of lncRNAs in the development of PC have not been fully elucidated yet. LncRNA microarray was adopted to analyze the differential expression of lncRNAs in PC tissues and that in normal peritumoral (NP) tissues. Functional role of lncRNA BM466146.1 on PC was evaluated by gain- and loss-of-function experiments in vivo and in vitro. RNA pull-down, RNA immunoprecipitation, luciferase reporter, and Chromatin-immunoprecipitation assays were performed to assess the mechanism of ZNFTR, respectively. The correlation between the expression of ZNFTR and various clinicopathological characteristics was accessed in PC specimens. This study displayed lncRNA BM466146.1 was downregulated in PC tissues and functioned as a suppressor through regulating the expression of adjacent gene Zinc finger protein 24 (ZNF24), which was assigned as ZNFTR. Mechanistically, ZNFTR interacted with activating transcription factor 3 (ATF3) and sequestered ATF3 away from the ZNF24 promoter, which consequently increased the expression of ZNF24. Further, ZNF24 inhibited the proliferative, metastatic, and pro-angiogenic abilities of PC cells by suppressing transcription of vascular endothelial growth factor A (VEGFA). Therefore, the downregulation of ZNFTR in PC led to the decreased expression of ZNF24, which further resulted in the upregulation of VEGFA to facilitate the development of PC. Meanwhile, ZNFTR was transcriptionally inhibited by the HIF-1α/HDAC1 complex-mediated deacetylation. Clinical results further demonstrated that the low expression of ZNFTR was associated with poor overall survival time. Taken together, our results implicated that ZNFTR was a hypoxia-responsive lncRNA, and functioned as an inhibitor by modulating ATF3/ZNF24/VEGFA pathway in PC.
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http://dx.doi.org/10.1038/s41419-021-04119-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417266PMC
September 2021

TRPA1 triggers hyperalgesia and inflammation after tooth bleaching.

Sci Rep 2021 Aug 31;11(1):17418. Epub 2021 Aug 31.

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

Hyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P < 0.0001), and proliferation factors [PCNA (P < 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.
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http://dx.doi.org/10.1038/s41598-021-97040-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408176PMC
August 2021

Pre-service Teachers Learning to Teach English as a Foreign Language to Preschool Learners in Macau: A Longitudinal Study.

Front Psychol 2021 10;12:720660. Epub 2021 Aug 10.

Faculty of Education, University of Macau, Macao, China.

Language teacher beliefs have received increasing research attention for the past few decades. However, little is known about the beliefs of pre-service teachers in the pre-primary English as a foreign language (EFL) education context. This qualitative case study extends this line of inquiry by investigating the trajectory of student teachers' beliefs about teaching English to pre-primary learners in Macau within a teacher education course. The participants included 60 pre-service teachers taking an course in their third year of a 4-year Bachelor of pre-primary education program. The data comprised written reflections collected at three points in time during the 16-week course: at the beginning of the course, mid-way through the course, and at the end of the course. The findings showed five broad themes, constituted from 15 subthemes, regarding (1) learners and learning, (2) teaching, (3) subject, (4) self, and (5) learning to teach. The major themes have been documented in the literature, but several subthemes were identified for the first time in the context of pre-primary EFL teacher education. More importantly, the findings revealed that some of the subthemes were newly shaped and several subthemes were reshaped as a consequence of taking the course. The findings were interpreted in relation to the content of the course, the experiential learning opportunities, the pre-service teachers' prior experiences of language learning and teaching, and the local language teaching and learning context. Implications for pre-service teacher education programs are discussed.
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http://dx.doi.org/10.3389/fpsyg.2021.720660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382846PMC
August 2021

Biochemical identification of a hyperthermostable l-ribulose 3-epimerase from Labedella endophytica and its application for d-allulose bioconversion.

Int J Biol Macromol 2021 Aug 21;189:214-222. Epub 2021 Aug 21.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu 214122, China.

Currently, low sugar and low energy have become an important trend in the food industries. Therefore, the bioconversion of the functional low-calorie rare sugars attracts more and more attention. l-Ribulose 3-epimerase (LREase) belongs to the ketose 3-epimerase (KEase) family, which could not only efficiently catalyze the reversible C-3 epimerization between l-ribulose and l-xylulose but also between d-fructose and d-allulose. In this paper, a hyperthermostable LREase from Labedella endophytica was identified and characterized. It exhibited maximum catalytic activity at pH 6.0 and 80 °C with 1 mM Ni. In the presence of Co, the t values at 60, 65, and 70 °C were 37.7, 9.0, and 4.6 h, respectively, and T value was 80.9 °C. From 500 g/L d-fructose, it could produce 154.2 g/L d-allulose with a conversion rate of 30.8% in 10 h. In view of its strong thermostability and high catalytic efficiency, L. endophytica LREase might be a good potential alternative for d-allulose industrial production.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.131DOI Listing
August 2021

Is there a difference in the outcomes of anterior cervical discectomy and fusion among female patients with different menopausal statuses?

J Orthop Surg Res 2021 Aug 20;16(1):518. Epub 2021 Aug 20.

Department of Orthopaedic Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.

Background: The surgical outcomes of anterior cervical discectomy and fusion (ACDF) in female patients according to menopausal status remain unclear. The objective of this study was to investigate the differences in these outcomes among female patients with different menopausal statuses.

Methods: Ninety-one patients undergoing single-level or consecutive two-level ACDF with a minimum 12-month postoperative follow-up were included in this study. There were 38 patients in the premenopausal group, 28 patients in the early postmenopausal group, and 25 patients in the late postmenopausal group. The clinical outcomes were evaluated by means of the neck disability index (NDI) scores, Japanese Orthopedic Association (JOA) scores, and visual analog scale (VAS) scores. Radiological parameters included cervical lordosis (CL), the functional spinal unit (FSU) angle, range of motion (ROM) of the total cervical spine, ROM of the FSU, anterior and posterior FSU height, implant subsidence, adjacent segment degeneration (ASD), and Hounsfield unit (HU) values.

Results: All groups showed significant improvements in their JOA, VAS, and NDI scores (P < 0.05). The differences in preoperative and final follow-up CL, ROM of C2-7, FSU angle, and ROM of FSU were not statistically significant among the three groups (P > 0.05). The anterior FSU height loss rate showed a significant difference (P = 0.043), while there was no difference in the posterior FSU height loss rate (P = 0.072). The fusion rates in the early and late postmenopausal groups were consistently lower than those in the premenopausal group during the follow-up period. All patients had satisfactory outcomes at the final follow-up.

Conclusion: There were no significant differences in clinical or other related outcomes of single-level or consecutive two-level ACDF in the long term among female patients with different menopausal statuses. However, the early bony fusion rates and anterior FSU height loss rates were poorer in late postmenopausal patients than in premenopausal or early postmenopausal patients. Hence, importance should be attached to the protection of late postmenopausal patients in the early postoperative period to guarantee solid bony fusion.
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http://dx.doi.org/10.1186/s13018-021-02673-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377952PMC
August 2021

Comparison of Clinical and Imaging Outcomes of Cervical Disc Replacement in Patients with Different Hounsfield Units.

World Neurosurg 2021 Aug 12. Epub 2021 Aug 12.

Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Objective: To compare clinical and imaging outcomes after cervical disc replacement (CDR) in patients with different Hounsfield units (HU).

Methods: We performed a retrospective study of patients with cervical degenerative disc disease treated by 1-level and 2-level Prestige-LP arthroplasty. The patients were divided into group A (HU <320), group B (HU 320-347), and group C (HU >347) according to the results of cervical vertebral HU measurement in the literature, and the clinical and radiographic results were compared among the 3 groups.

Results: A total of 127 patients were reviewed, comprising 13 patients in group A, 31 patients in group B, and 83 patients in group C. The clinical parameters were significantly improved postoperatively in the 3 groups (P < 0.05). However, no significant differences were found among the 3 groups at the final follow-up (P > 0.05). The mean postoperative intervertebral space height (ISH) was 4.76 ± 0.45 mm, 5.23 ± 0.81 mm, and 6.26 ± 1.12 mm in the 3 groups, respectively. The postoperative ISH in group C was significantly higher than those in the other groups at the final follow-up (P < 0.001). One patient in group A and 1 patient in group B had implant subsidence, and degeneration at the inferiorly adjacent level was radiographically identified in 30.77% patients in group A, 16.13% patients in group B, and 9.64% patients in group C. However, there were only significant differences between group A and group C in subsidence (P = 0.011) and occurrence of adjacent level degeneration (P = 0.032).

Conclusions: The HU value has a large variation range among the patients with T-score ≥ -2.5. We found significantly increased rates of implant subsidence, loss of ISH, and adjacent segment degeneration in patients with lower HU value undergoing CDR. However, these radiographic complications did not predispose patients with lower HU value to worse clinical outcomes. Routine application of HU combined with dual-energy X-ray absorptiometry measurement to evaluate bone quality may help to screen the optimal candidates for CDR and reduce the implant-related complications.
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http://dx.doi.org/10.1016/j.wneu.2021.08.021DOI Listing
August 2021

Ultralow Ru Incorporated Amorphous Cobalt-Based Oxides for High-Current-Density Overall Water Splitting in Alkaline and Seawater Media.

Small 2021 Aug 12:e2102777. Epub 2021 Aug 12.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, 430070, China.

Realizing efficiency and stable hydrogen production by water electrolysis under high current densities is essential to the forthcoming hydrogen economy. However, its industrial breakthrough is seriously limited by bifunctional catalysts with slow hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) electrocatalytic processes. Herein, an ultralow Ru incorporated amorphous cobalt-based oxide (Ru-CoO /NF), effectively driving the electrolysis of water at high current densities in alkaline water and seawater, is designed and constructed. In 1 m KOH, to reach the current density of 1000 mA cm for HER and OER, it only needs 252 and 370 mV overpotentials, respectively, beyond commercial Pt/C and RuO catalysts. At the high current density, it also presents outstanding electrochemical stability. Then the electrolyzer apparatus assembled with Ru-CoO /NF, just requires the ultra-low voltage of 2.2 and 2.62 V to support the current density of 1000 mA cm in alkaline water and seawater electrolysis, respectively, for hydrogen production, better than that of the commercial Pt/C and RuO catalysts. This work demonstrates that Ru-CoO /NF is one of the most promising catalysts for industrial applications and provides a possibility for exploration of high-current-density water electrocatalysis by changing the crystallinity of the catalyst.
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http://dx.doi.org/10.1002/smll.202102777DOI Listing
August 2021

Proteome-Wide Profiling of Readers for DNA Modification.

Adv Sci (Weinh) 2021 Aug 5:e2101426. Epub 2021 Aug 5.

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.

DNA modifications, represented by 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), play important roles in epigenetic regulation of biological processes. The specific recognition of DNA modifications by the transcriptional protein machinery is thought to be a potential mechanism for epigenetic-driven gene regulation, and many modified DNA-specific binding proteins have been uncovered. However, the panoramic view of the roles of DNA modification readers at the proteome level remains largely unclear. Here, a recently developed concatenated tandem array of consensus transcription factor (TF) response elements (catTFREs) approach is employed to profile the binding activity of TFs at DNA modifications. Modified DNA-binding activity is quantified for 1039 TFs, representing 70% of the TFs in the human genome. Additionally, the modified DNA-binding activity of 600 TFs is monitored during the mouse brain development from the embryo to the adult stages. Readers of these DNA modifications are predicted, and the hierarchical networks between the transcriptional protein machinery and modified DNA are described. It is further demonstrated that ZNF24 and ZSCAN21 are potential readers of 5fC-modified DNA. This study provides a landscape of TF-DNA modification interactions that can be used to elucidate the epigenetic-related transcriptional regulation mechanisms under physiological conditions.
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http://dx.doi.org/10.1002/advs.202101426DOI Listing
August 2021

Establishment of an Immune Cell Infiltration Score to Help Predict the Prognosis and Chemotherapy Responsiveness of Gastric Cancer Patients.

Front Oncol 2021 9;11:650673. Epub 2021 Jul 9.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

The immune microenvironment plays a critical role in tumor biology. The molecular profiles of immune components and related genes are of tremendous value for the study of primary resistance to immune checkpoint blockers (ICBs) for gastric cancer (GC) and serve as prognostic biomarkers to predict GC survival. Recent studies have revealed that tumor immune cell infiltration (ICI) is an indicator of the survival and responsiveness to chemotherapy in GC patients. Here, we describe the immune cell landscape based on the ESTIMATE and CIBERSORT algorithms to help separate GC into 3 ICI clusters using the unsupervised clustering method. Further in-depth analyses, such as differential expression gene (DEG) analysis and principal component analysis (PCA), help to establish an ICI scoring system. A low ICI score is characterized by an increased tumor mutation burden (TMB). The combination of the ICI score and TMB score better predicts the survival of GC patients. Analyses based on public and our own database revealed that the ICI scoring system could also help predict the survival and chemotherapy responsiveness of GC patients. The present study demonstrated that the ICI score may be an effective prognostic biomarker and predictive indicator for chemotherapy and immunotherapy.
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http://dx.doi.org/10.3389/fonc.2021.650673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299334PMC
July 2021

News recommender system: a review of recent progress, challenges, and opportunities.

Artif Intell Rev 2021 Jul 21:1-52. Epub 2021 Jul 21.

Ryerson University, Toronto, Canada.

Nowadays, more and more news readers read news online where they have access to millions of news articles from multiple sources. In order to help users find the right and relevant content, news recommender systems (NRS) are developed to relieve the information overload problem and suggest news items that might be of interest for the news readers. In this paper, we highlight the major challenges faced by the NRS and identify the possible solutions from the state-of-the-art. Our discussion is divided into two parts. In the first part, we present an overview of the recommendation solutions, datasets, evaluation criteria beyond accuracy and recommendation platforms being used in the NRS. We also talk about two popular classes of models that have been successfully used in recent years. In the second part, we focus on the deep neural networks as solutions to build the NRS. Different from previous surveys, we study the effects of news recommendations on user behaviors and try to suggest possible remedies to mitigate those effects. By providing the state-of-the-art knowledge, this survey can help researchers and professional practitioners have a better understanding of the recent developments in news recommendation algorithms. In addition, this survey sheds light on the potential new directions.
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http://dx.doi.org/10.1007/s10462-021-10043-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294232PMC
July 2021

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

Oncogene 2021 Sep 22;40(36):5505-5517. Epub 2021 Jul 22.

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

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

Preliminary results in anterior cervical discectomy and fusion with the uncovertebral joint fusion cage in a goat model.

BMC Musculoskelet Disord 2021 Jul 17;22(1):628. Epub 2021 Jul 17.

Department of Operation Room and Anesthesia Center, West China Hospital, Sichuan University, No. 37 Guo Xue Rd, Chengdu, 610041, China.

Objective: To preliminarily evaluate the safety and efficacy of the uncovertebral joint fusion cage in a goat model of cervical spine interbody fusion.

Methods: Twenty-four healthy adult goats were randomly assigned to one of the two following groups: Group A, goats were implanted with an uncovertebral joint fusion cage combined with a local autograft and Group B, goats were implanted with a non-profile cage filled with a local autograft. The goats were prospectively evaluated for 24 weeks and then were sacrificed for evaluation. X-rays, CT and micro-CT scanning, and undecalcified bone histological analysis were used for the evaluation of fusion.

Results: 75.0% (9/12) of the goats in Group A were evaluated as having fusion at 12 weeks, compared to 41.7% (5/12) in Group B. 83.3% (10/12) of the goats in Group A were evaluated as having fusion at 24 weeks compared to 58.3% (7/12) in Group B. The fusion grading scores in Group A were significantly higher than that in Group B both at 12 weeks and 24 weeks (P < 0.05). Micro-CT scanning and undecalcified bone histological analysis showed that new bone formation can be obviously found in the bilateral uncovertebral joint. The bone volume fraction (BV/ TV) in Group A (23.59 ± 4.43%) was significantly higher than Group B (16.16 ± 4.21%), with P < 0.05.

Conclusions: Preliminary results of this study demonstrated that uncovertebral joint fusion cage is effective for achieving early bone formation and fusion without increase of serious complications.
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http://dx.doi.org/10.1186/s12891-021-04412-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286593PMC
July 2021

Risk factors and biofilm formation analyses of hospital-acquired infection of Candida pelliculosa in a neonatal intensive care unit.

BMC Infect Dis 2021 Jun 29;21(1):620. Epub 2021 Jun 29.

Department of Laboratory Medicine of Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, China.

Background: Candida pelliculosa is an ecological fungal species that can cause infections in immunocompromised individuals. Numerous studies globally have shown that C. pelliculosa infects neonates. An outbreak recently occurred in our neonatal intensive care unit; therefore, we aimed to evaluate the risk factors in this hospital-acquired fungal infection.

Methods: We performed a case-control study, analysing the potential risk factors for neonatal infections of C. pelliculosa so that infection prevention and control could be implemented in our units. Isolated strains were tested for drug resistance and biofilm formation, important factors for fungal transmission that give rise to hospital-acquired infections.

Results: The use of three or more broad-spectrum antimicrobials or long hospital stays were associated with higher likelihoods of infection with C. pelliculosa. The fungus was not identified on the hands of healthcare workers or in the environment. All fungal isolates were susceptible to anti-fungal medications, and after anti-fungal treatment, all infected patients recovered. Strict infection prevention and control procedures efficiently suppressed infection transmission. Intact adhesin-encoding genes, shown by genome analysis, indicated possible routes for fungal transmission.

Conclusions: The use of three or more broad-spectrum antimicrobials or a lengthy hospital stay is theoretically associated with the risk of infection with C. pelliculosa. Strains that we isolated are susceptible to anti-fungal medications, and these were eliminated by treating all patients with an antifungal. Transmission is likely via adhesion to the cell surface and biofilm formation.
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http://dx.doi.org/10.1186/s12879-021-06295-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244135PMC
June 2021

Deep Dive on the Proteome of Human Body Fluids: A Valuable Data Resource for Biomarker Discovery.

Cancer Genomics Proteomics 2021 Jul-Aug;18(4):549-568

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China;

Background/aim: Body fluids are considered to be a rich source of disease biomarkers. Proteins in many body fluids have potential clinical applications for disease diagnostic and prognostic purposes. The aim of this study was to establish an in-depth multi-body fluid proteome.

Materials And Methods: Ten body fluids associated with 8 types of cancers collected from 23 patients involved in 19 common diseases underwent liquid chromatography tandem mass spectrometry (MS) analysis after gel-based protein separation (SDS-PAGE) or peptide-based fractionations. Bioinformatic analysis, including principal component analysis (PCA), consensus clustering, and hierarchical clustering analysis were also performed. The biological function was determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID).

Results: We profiled the proteome of ten body fluids, including ascites, bile, cerebrospinal fluid (CSF), hydrothorax, knee joint fluid (KJF), plasma, saliva, serum, tears, and urine. A total of 3,396 nonredundant proteins were identified, of which 304 were shared among ten body fluids, with common functions in focal adhesion and complement/coagulation cascades. A total of 41.5% (1,409) of the proteins were detected in only one body fluid and were closely related to their adjacent tissues by function. The functional analysis of the remaining 1,683 proteins showed that similar functions might be shared among different body fluids, which further highlighted the close connection of body fluids in the human body.

Conclusion: A deep proteome of multi-body fluids originated from patients diagnosed with 19 common diseases provides a valuable data resource, and might indicate the potential application of body fluids for biomarker discovery.
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http://dx.doi.org/10.21873/cgp.20280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404731PMC
March 2021

Assessment of the self-reported dysphagia in patients undergoing one-level versus two-level cervical disc replacement with the Prestige-LP prosthesis.

Clin Neurol Neurosurg 2021 08 11;207:106759. Epub 2021 Jun 11.

Department of Orthopedic Surgery, West China Hospital, Sichuan University, China.

Objectives: Cervical disc replacement (CDR) has been established as an alternative to anterior cervical discectomy and fusion (ACDF) for treating cervical degenerative pathologies over the past decade. However, swallowing difficulties challenge patient safety due to the increased risk of malnutrition, dehydration and aspiration pneumonia after CDR. Currently, there are limited studies focusing on the incidences, severity and associated risk factors for dysphagia after CDR. This paucity, therefore, necessitated this retrospective study on post-operative dysphagia after one- and two-level CDR.

Patients And Methods: One hundred and fourteen patients underwent one-level CDR and forty eight patients underwent two-level CDR were recruited with a mean follow-up of 21 months (ranging from 14 to 30 months). The prevalence and severity of dysphagia was evaluated by the Bazaz grading system during the follow-up time. Regression analyses were done to identify risk factors associated with post-operative dysphagia after CDR.

Results: The overall dysphagia occurrences in the one- and two-level CDR groups were 17.54% and 35.41% at week one, 12.28% and 25% after one month, 9.65% and 18.75% after three months, 6.14% and 14.58% after six months, 4.39% and 6.25% after one year, and 3.51% and 4.17% at the final follow-up, respectively. The identified risk factors for dysphagia after CDR were advanced age, C4/5 surgery, two-level surgery, dC2-C7 angle ≥ - 5° and ≥ 6 mm changes in the prevertebral soft tissue swelling (dPSTS).

Conclusion: The patients who experienced two-level CDR may have poor swallowing functions in the early post-operative term. However, these patients also can recover well with increasing length of follow-up. In addition, patients with advanced age, C4/5 surgery, dC2-C7 angle ≥ - 5° and ≥ 6 mm changes in dPSTS may prone to occur dysphagia after CDR.
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http://dx.doi.org/10.1016/j.clineuro.2021.106759DOI Listing
August 2021

Anion Modulation of Pt-Group Metals and Electrocatalysis Applications.

Chemistry 2021 Aug 9;27(48):12257-12271. Epub 2021 Jul 9.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, 430070, P. R. China.

Pt-group metal (PGM) electrocatalysts with unique electronic structures and irreplaceable comprehensive properties play crucial roles in electrocatalysis. Anion engineering can create a series of PGM compounds (such as RuP , IrP , PtP , RuB , Ru B , RuS , etc.) that provide a promising prospect for improving the electrocatalytic performance and use of Pt-group noble metals. This review seeks the electrochemical activity origin of anion-modulated PGM compounds, and systematically analyzes and summarizes their synthetic strategies and energy-relevant applications in electrocatalysis. Orientation towards the sustainable development of nonfossil resources has stimulated a blossoming interest in the design of advanced electrocatalysts for clean energy conversion. The anion-modulated strategy for Pt-group metals (PGMs) by means of anion engineering possesses high flexibility to regulate the electronic structure, providing a promising prospect for constructing electrocatalysts with superior activity and stability to satisfy a future green electrochemical energy conversion system. Based on the previous work of our group and others, this review summarizes the up-to-date progress on anion-modulated PGM compounds (such as RuP , IrP , PtP , RuB , Ru B , RuS , etc.) in energy-related electrocatalysis from the origin of their activity and synthetic strategies to electrochemical applications including hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), hydrogen oxidation reaction (HOR), N reduction reaction (NRR), and CO reduction reaction (CO RR). At the end, the key problems, countermeasures and future development orientations of anion-modulated PGM compounds toward electrocatalytic applications are proposed.
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http://dx.doi.org/10.1002/chem.202101645DOI Listing
August 2021

Change in the postoperative intervertebral space height and its impact on clinical and radiological outcomes after ACDF surgery using a zero-profile device: a single-Centre retrospective study of 138 cases.

BMC Musculoskelet Disord 2021 Jun 14;22(1):543. Epub 2021 Jun 14.

Department of Orthopedic Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang Rd, Chengdu, 610041, Sichuan, China.

Background: The effects of postoperative intervertebral height (IH) changes on the clinical and radiological outcomes after anterior cervical decompression and fusion (ACDF) surgery using a zero-profile device remain unclear.

Methods: We retrospectively reviewed patients who had undergone ACDF using a zero-profile device from March 2012 to February 2016 at our institution. Based on the postoperative IH variation, the patients were divided into group A with postoperative IH 0 to 2 mm, group B with postoperative IH 2 to 4 mm, and group C with postoperative IH greater than 4 mm. Clinical efficacy was evaluated using JOA, VAS, and NDI scores in the groups. Imaging parameters including the IH, cervical lordosis, fusion rate, intervertebral foramen (IVF) diameter and complications such as subsidence, dysphagia, and ASD were also compared across the three groups.

Results: The average IH increased significantly from 6.72 mm preoperatively to 10.46 mm 1 week after surgery, and then gradually decreased to 7.48 mm at the final follow-up. The fusion rate was 61.90% in group A, 63.23% in group B, 53.57% in group C at 3 months, 73.81% in group A, 79.41% in group B, 67.86% in group C at 6 months, 90.48% in group A, 95.59% in group B, 92.86% in group C 1 year after surgery, and at the last follow-up, the fusion rate of three groups was all 100%. The IVF diameter was 6.52 ± 1.80 mm in group A, 9.55 ± 2.36 mm in group B, and 9.34 ± 1.62 mm in group C. ASD at the superior and inferior levels affected 11.90 and 16.67% patients in group A, 5.88 and 7.38% in group B, and 14.28 and 10.71% in group C. Regarding the 3 groups, the subsidence rates were 7.14, 4.41, and 14.29%, respectively.

Conclusions: No clear correlation was found between IH changes and clinical efficacy within a year of surgery. However, the IH may affect various complications after ACDF. If postoperative IH changes are maintained at 2 to 4 mm after a year, a satisfactory imaging parameters and relatively low complications may be achieved after ACDF surgery using a zero-profile device.
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http://dx.doi.org/10.1186/s12891-021-04432-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204480PMC
June 2021

Quantum-Inspired Support Vector Machine.

IEEE Trans Neural Netw Learn Syst 2021 Jun 10;PP. Epub 2021 Jun 10.

Support vector machine (SVM) is a particularly powerful and flexible supervised learning model that analyzes data for both classification and regression, whose usual algorithm complexity scales polynomially with the dimension of data space and the number of data points. To tackle the big data challenge, a quantum SVM algorithm was proposed, which is claimed to achieve exponential speedup for least squares SVM (LS-SVM). Here, inspired by the quantum SVM algorithm, we present a quantum-inspired classical algorithm for LS-SVM. In our approach, an improved fast sampling technique, namely indirect sampling, is proposed for sampling the kernel matrix and classifying. We first consider the LS-SVM with a linear kernel, and then discuss the generalization of our method to nonlinear kernels. Theoretical analysis shows our algorithm can make classification with arbitrary success probability in logarithmic runtime of both the dimension of data space and the number of data points for low rank, low condition number, and high dimensional data matrix, matching the runtime of the quantum SVM.
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http://dx.doi.org/10.1109/TNNLS.2021.3084467DOI Listing
June 2021

Identification and assessment of pulmonary Cryptococcus neoformans infection by blood serum surface-enhanced Raman spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 20;260:119978. Epub 2021 May 20.

College of Life and Health Sciences, Northeastern University, Shenyang 110169, China. Electronic address:

Cryptococcus neoformans (C. neoformans) is a causative agent for acute pulmonary infection, which can further develop to lethal meningoencephalitis if untreated. The meningoencephalitis infection can be prevented, if timely treatment on pulmonary cryptococcal infection can be implemented based on its early diagnosis and accurate assessment. In this study, blood serum surface-enhanced Raman spectroscopy (SERS) method was investigated on identification and assessment of pulmonary C. neoformans infection. The serum SERS measurements were collected from the mice infected with C. neoformans and the healthy mice, in which the infected mice were further divided into four subgroups according to the duration of infection. Based on those SRES measurements, biochemical differences were analyzed among those different groups to investigate the potential biomarkers for identifying and assessing the pulmonary C. neoformans infection. Furthermore, partial least square (PLS) analysis followed by linear discriminant analysis (LDA) model was employed to identify pulmonary cryptococcal infection and to assess the degrees of infection with the accuracies of 96.7% and 85.3%, respectively. Therefore, our study has demonstrated the great clinical potential of using serum SERS technique for an accurate identification and assessment of pulmonary cryptococcal infection.
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http://dx.doi.org/10.1016/j.saa.2021.119978DOI Listing
November 2021

Demethylation of the Promoter Drives Gastric Cancer Progression via the Wnt Pathway.

Mol Cancer Res 2021 Sep 20;19(9):1454-1464. Epub 2021 May 20.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Wnt signaling is believed to be an important contributor to tumor development and has been reported to be modulated by secreted frizzled-related proteins (SFRP). Nevertheless, the role of secreted frizzled-related protein 4 (SFRP4) in tumorigenesis remains controversial. We aim to explore its biological function in gastric cancer. Genomes analysis based on the Gene Expression Omnibus (GEO) dataset was used to find the differential gene expression between different tumor-node-metastasis (TNM) stages of gastric cancer. IHC was used to determine the relationship between SFRP4 expression and clinicopathologic characteristics in patients with gastric cancer. The influence of SFRP4 on tumor progression was evaluated by CCK-8, colony formation, cell apoptosis, and cell cycle , as well as xenograft model . The methylation status of SFRPs was examined in gastric cancer specimens by quantitative methylation analysis. SFRP4 was most upregulated in advanced gastric cancer. High intratumoral SFRP4 expression, which was associated with tumor invasion and metastasis, was also a poor prognostic indicator for patients with gastric cancer. and studies revealed that SFRP4 could promote tumor growth; however, IWR-1 could suppress tumor growth mediated by SFRP4 overexpression. Mechanistic exploration found that SFRP4 was overexpressed by the decrease of promoter methylation and thus could competitively antagonize the inhibitory effect of SFRP1 on Wnt pathway activation and tumor progression in gastric cancer. IMPLICATIONS: In gastric cancer, the expression of SFRP4 was upregulated by decreased methylation. High intratumoral SFRP4 expression could activate the Wnt pathway to promote tumor progression and predict poor survival of patients with gastric cancer.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0933DOI Listing
September 2021

Risk factors evaluation of post-transplant lymphoproliferative disorders after allogeneic haematopoietic stem cell transplantation with comparison between paediatric and adult.

J Clin Pathol 2021 May 19. Epub 2021 May 19.

Pathology, Peking University People's Hospital, Beijing, China.

To describe the clincopathological features and evaluate risk factors of post-transplant lymphoproliferative disorder (PTLD) after allogeneic haematopoietic stem cell transplants (allo-HSCT), with comparison between paediatric and adult .Clinicopathological features of 81 cases of PTLD after allo-HSCT were analysed by histopatholgy, immunohistochemistry and in situ hybridisatioin.The cases included 58 males and 23 females with a median age of 26.7 years (range 6-55 years) and the PTLDs developed 1-60 months post-transplant (mean 5.9 months). The histological types indicated 10 cases of non-destructive PTLD, including 4 of plasmacytic hyperplasia, 5 of infectious mononucleosis and 1 of florid follicular hyperplasia. Fifty-six cases were polymorphic PTLD, and 15 were monomorphic PTLD, including thirteen of diffuse large B cell lymphoma, 1 of extranodal nasal type natural killer (NK)/T cell lymphoma and 1 of plasmablastic lymphoma. Foci and sheets of necrosis were observed in 31 cases. The infected ratio of Epstein-Barr virus (EBV) was 91.4%. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion or anti-CD20 monoclonal rituximab. Thirty-three cases died. Compared with that of adult, overall survival of paediatric recipient may be better.The first half year after allo-HSCT is very important for the development of PTLD. Type of PTLD, EBV infection and graft-versus-host disease are risk factors. The prognosis of PTLD is poor, and PTLD after allo-HSCT exhibits some features different from that after solid organ transplantation and some differences existing between adult and paediatric recipients.
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http://dx.doi.org/10.1136/jclinpath-2021-207492DOI Listing
May 2021

High energy density and extremely stable supercapacitors based on carbon aerogels with 100% capacitance retention up to 65,000 cycles.

Proc Natl Acad Sci U S A 2021 May;118(21)

Institute of Materials, Ningbo University of Technology, 315016 Ningbo, People's Republic of China;

In terms of ideal future energy storage systems, besides the always-pursued energy/power characteristics, long-term stability is crucial for their practical application. Here, we report a facile and sustainable strategy for the scalable fabrication of carbon aerogels with three-dimensional interconnected nanofiber networks and rationally designed hierarchical porous structures, which are based on the carbonization of bacterial cellulose assisted by the soft template of Zn-1,3,5-benzenetricarboxylic acid. As binder-free electrodes, they deliver a fundamentally enhanced specific capacitance of 352 F ⋅ g at 1 A ⋅ g in a wide potential window (1.2 V, 6 M KOH) in comparison with those of bacterial cellulose-derived carbons (178 F ⋅ g) and most activated carbons (usually lower than 250 F ⋅ g). The as-assembled supercapacitors exhibit an ultrahigh capacitance of 297 F ⋅ g at 1 A ⋅ g, remarkable energy density (14.83 Wh ⋅ kg at 0.60 kW ⋅ kg), and extremely high stability, with 100% capacitance retention for up to 65,000 cycles at 6 A ⋅ g, representing their superior energy storage performance when compared with that of state-of-the-art supercapacitors of commercial activated carbons and biomass-derived analogs.
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http://dx.doi.org/10.1073/pnas.2105610118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166133PMC
May 2021

E3 ligase TRIM25 ubiquitinates RIP3 to inhibit TNF induced cell necrosis.

Cell Death Differ 2021 May 5. Epub 2021 May 5.

State Key Laboratory of Genetic Engineering, Department of Neurology, School of Life Sciences and Huashan Hospital, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, 200438, China.

Receptor interacting protein kinase 3 (RIP3 or RIPK3), the critical executor of cell programmed necrosis, plays essential roles in maintaining immune responses and appropriate tissue homeostasis. Although the E3 ligases CHIP and PELI1 are reported to promote RIP3 degradation, however, how post-translational modification regulates RIP3 activity and stability is poorly understood. Here, we identify the tripartite motif protein TRIM25 as a negative regulator of RIP3-dependent necrosis. TRIM25 directly interacts with RIP3 through its SPRY domain and mediates the K48-linked polyubiquitination of RIP3 on residue K501. The RING domain of TRIM25 facilitates the polyubiquitination chain on RIP3, thereby promoting proteasomal degradation of RIP3. Also, TRIM25 deficiency inhibited the ubiquitination of RIP3, thus promoting TNF-induced cell necrosis. Our current finding reveals the regulating mechanism of polyubiquitination on RIP3, which might be a potential therapeutic target for the intervention of RIP3-dependent necrosis-related diseases.
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http://dx.doi.org/10.1038/s41418-021-00790-3DOI Listing
May 2021

Does Early Postoperative T1 Slope Change Affect Clinical Results of Patients With Single-level ACDF?

Clin Spine Surg 2021 Apr 28. Epub 2021 Apr 28.

Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Study Design: This was a retrospective study.

Objective: The main question of this study is whether the change of postoperative T1 slope will affect the clinical and imaging recovery of patients with single-level anterior cervical discectomy and fusion (ACDF).

Summary Of Background Data: The T1 slope after ACDF is different from that preoperatively, however, the clinical significance of this change has not been reported.

Materials And Methods: A retrospective analysis was conducted on 87 patients with single-level ACDF. Visual Analogue Scale was used to compare neck and upper limb pain before and after surgery. Neurological improvement was assessed by the Japanese Orthopaedic Association Scores and Neck Disability Index. Preoperative and postoperative T1 slope, occipital-C2 angle, C2-C7 overall curvature and functional spinal unit curvature were measured and analyzed by lateral cervical spine x-ray.

Results: All patients were followed up for 23.98±12.17 months. The Japanese Orthopaedic Association, Visual Analogue Scale, and Neck Disability Index scores as well as the overall curvature and change of C2-C7 and functional spinal unit were significantly improved in the last postoperative follow-up. At 12 months after surgery and the last follow-up, patients with increased T1 slope had more severe neck pain symptoms than those with decreased T1 slope (P<0.05). The overall curvature and change of C2-C7 in patients with increased T1 slope were better than those with decreased T1 slope (P<0.05).

Conclusion: For patients with increased postoperative T1 slope after single-level ACDF, the degree of postoperative neck pain was more severe, suggesting that some clinical intervention is needed.
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http://dx.doi.org/10.1097/BSD.0000000000001145DOI Listing
April 2021

Polypeptide N-acetylgalactosaminyltransferase 18 retains in endoplasmic reticulum depending on its luminal regions interacting with ER resident UGGT1, PLOD3 and LPCAT1.

Glycobiology 2021 Sep;31(8):947-958

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

Mucin-type O-glycosylation is initiated by the polypeptide: N-acetylgalactosaminyltransferase (ppGalNAc-T) family of enzymes, which consists of 20 members in humans. Among them, unlike other ppGalNAc-Ts located in Golgi apparatus, ppGalNAc-T18 distributes primarily in the endoplasmic reticulum (ER) and non-catalytically regulates ER homeostasis and O-glycosylation. Here, we report the mechanism for ppGalNAc-T18 ER localization and the function of each structural domain of ppGalNAc-T18. By using ppGalNAc-T18 truncation mutants, we revealed that the luminal stem region and catalytic domain of ppGalNAc-T18 are essential for ER localization, whereas the lectin domain and N-glycosylation of ppGalNAc-T18 are not required. In the absence of the luminal region (i.e., stem region, catalytic and lectin domains), the conserved Golgi retention motif RKTK within the cytoplasmic tail combined with the transmembrane domain ensure ER export and Golgi retention, as observed for other Golgi resident ppGalNAc-Ts. Results from coimmunoprecipitation assays showed that the luminal region interacts with ER resident proteins UGGT1, PLOD3 and LPCAT1. Furthermore, flow cytometry analysis showed that the entire luminal region is required for the non-catalytic O-GalNAc glycosylation activity of ppGalNAc-T18. The findings reveal a novel subcellular localization mechanism of ppGalNAc-Ts and provide a foundation to further characterize the function of ppGalNAc-T18 in the ER.
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http://dx.doi.org/10.1093/glycob/cwab031DOI Listing
September 2021

[Effect of modified lateral mass screws implantation strategy on axial symptoms in cervical expansive open-door laminoplasty].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Apr;35(4):445-452

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.

Objective: To investigate the effect of modified lateral mass screws implantation strategy on axial symptoms in cervical expansive open-door laminoplasty.

Methods: A clinical data of 166 patients, who underwent cervical expansive open-door laminoplasty between August 2011 and July 2016 and met the selection criteria, was retrospective analyzed. Among them, 81 patients were admitted before August 2014 using the traditional mini-plate placement and lateral mass screws implantation strategy (control group), and 85 patients were admitted after August 2014 using modified lateral mass screws implantation strategy (modified group). There was no significant difference in the gender composition, age, clinical diagnosis, disease duration, diseased segment, and preoperative Japanese Orthopaedic Association (JOA) score, pain visual analogue scale (VAS) score, Neck Disability Index (NDI), cervical curvature and range of motion, spinal canal diameter and cross-sectional areas, and Pavlov's value between the two groups ( >0.05). The operation time, intraoperative blood loss, the number of facet joints penetrated by lateral mass screws, effectiveness evaluation indexes (JOA score and improvement rate, VAS score, NDI), imaging evaluation indexes (cervical curvature and range of motion, spinal canal diameter and cross-sectional areas, Pavlov's value, and lamina open angle), and complications were recorded and compared between the two groups.

Results: The modified group had shorter operation time and lower intraoperative blood loss than the control group ( <0.05). There were 121 (29.9%, 121/405) and 10 (2.4%, 10/417) facet joints penetrated by lateral mass screws in control and modified groups, respectively; and the difference in incidence was significant ( =115.797, =0.000). Eighteen patients in control group had 3 or more facet joints penetrated while no patients in modified group suffered 3 or more facet joint penetrated. The difference between the two groups was significant ( =0.000). All patients were followed up, the follow-up time was (28.7±4.9) months in modified group and (42.4±10.7) months in control group, showing significant difference ( =10.718, =0.000). The JOA score, VAS score, and NDI at last follow-up of the two groups were significantly improved compared with preoperative ( <0.05); there was no significant difference in JOA score and improvement rate and VAS score between the two groups ( >0.05), but the NDI was significantly lower in modified group than in control group ( <0.05). There were significant differences in cervical curvature and range of motion, spinal canal diameter, Pavlov's value, and cross-sectional areas at last follow-up when compared with those before operation in both groups ( <0.05). There was no significant difference in the above indicators and lamina open angle between the two groups ( >0.05). The modified group has a relative lower axial symptom rate (23/85, 27.1%) than the control group (27/81, 33.3%), but the difference was not significant ( =-1.446, =0.148). There was no significant differences between the two groups in the incidences of C nerve root palsy, cerebrospinal fluid leakage, wound infection, and lung or urinary tract infection ( >0.05).

Conclusion: In the cervical expansive open-door laminoplasty, the modified lateral mass screws implantation strategy can effectively reduce the risk of lateral mass screw penetrated to the cervical facet joints, and thus has a positive significance in avoiding the axial symptoms caused by facet joint destruction.
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http://dx.doi.org/10.7507/1002-1892.202010024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171624PMC
April 2021
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