Publications by authors named "Yi Ding"

1,128 Publications

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A randomized trial comparing the clinical efficacy and safety of a novel steerable percutaneous kyphoplasty with traditional PKP in osteoporotic vertebral fractures.

Ann Transl Med 2021 Jun;9(12):1024

Department of Sports Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Background: Percutaneous kyphoplasty (PKP) is a highly practical technology to treat osteoporotic vertebral compression fractures (OVCFs). However, the operation time and radiation exposure remain problematic. This study explored the differences in surgical effects and safety between a novel steerable percutaneous kyphoplasty (S-PKP) and traditional PKP in order to achieve better clinical outcomes for OVCF patients. It is also exploring whether the new technology could reduce the radiation exposure.

Methods: This study recruited 72 patients (between March 2019 and January 2020) with OVCFs (single vertebra). The patients were semi-randomly divided these patients into two groups according to ID numbers: a S-PKP group (33 cases) and a PKP group (39 cases). We evaluated the clinical efficacy using the kyphotic Cobb angle, Oswestry disability index (ODI), visual analogue scale (VAS) score, injected cement volume, operation time, intraoperative radiation times, bone cement leakage, and postoperative complications. Patients were followed up once preoperatively, and at 1 day, 6 months, and 1 year postoperatively.

Results: There were no cases of cement leakage or postoperative complications. There were no significant differences in gender, age, Bone mineral density T-score (BMD T) value, Cobb angle between the two groups (P>0.05). Intraoperative bone cement injection was approximately 5.25±1.37 and 5.32±1.29 mL in the PKP and S-PKP groups respectively. The postoperative VAS score and ODI of the two groups at 1 day, 6 months, and 1 year were markedly lower than before (P<0.05). There was a considerable improvement in the Cobb angle postoperatively (P<0.05). However, as the follow-up time extended, the Cobb Angle increased. The operation time and X-ray exposure times of patients in the PKP group were notably higher than those in the S-PKP group. The operation time was 51.59±9.14 min in the PKP group and 30.76±4.82 min in the S-PKP group. The frequency of intraoperative radiation was 105.9±31.93 times in the PKP group and 47.42±11.88 times in the S-PKP group.

Conclusions: Early results showed that S-PKP is a safe and efficient method for the treatment of OVCFs. S-PKP can reduce the operation time and radiation exposure.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2100046727.
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http://dx.doi.org/10.21037/atm-21-1880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267321PMC
June 2021

Building early defenses.

Cell Res 2021 Jul 15. Epub 2021 Jul 15.

T Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

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http://dx.doi.org/10.1038/s41422-021-00535-4DOI Listing
July 2021

Effect of dapagliflozin on diabetic patients with cardiovascular disease via MAPK signalling pathway.

J Cell Mol Med 2021 Jul 14. Epub 2021 Jul 14.

Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.

Clinical studies have shown that dapagliflozin can reduce cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM), but the exact mechanism is unclear. In this study, we used the molecular docking and network pharmacology methods to explore the potential mechanism of dapagliflozin on T2DM complicated with cardiovascular diseases (CVD). Dapagliflozin's potential targets were predicted via the Swiss Target Prediction platform. The pathogenic targets of T2DM and CVD were screened by the Online Mendelian Inheritance in Man (OMIM) and Gene Cards databases. The common targets of dapagliflozin, T2DM and CVD were used to establish a protein-protein interaction (PPI) network; the potential protein functional modules in the PPI network were found out by MCODE. Metascape tool was used for Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A potential protein functional module with the best score was obtained from the PPI network and 9 targets in the protein functional module all showed good binding properties when docking with dapagliflozin. The results of KEGG pathway enrichment analysis showed that the underlying mechanism mainly involved AGE-RAGE signalling pathway in diabetic complications, TNF signalling pathway and MAPK signalling pathway. Significantly, the MAPK signalling pathway was considered as the key pathway. In conclusion, we speculated that dapagliflozin played a therapeutic role in T2DM complicated with CVD mainly through MAPK signalling pathway. This study preliminarily reveals the possible mechanism of dapagliflozin in the treatment of T2DM complicated with CVD and provides a theoretical basis for future clinical research.
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http://dx.doi.org/10.1111/jcmm.16786DOI Listing
July 2021

Manipulated Crystallization and Passivated Defects for Efficient Perovskite Solar Cells via Addition of Ammonium Iodide.

ACS Appl Mater Interfaces 2021 Jul 13. Epub 2021 Jul 13.

Key Laboratory of Photoelectronic Thin Film Devices and Technology of Tianjin, Engineering Research Center of Thin Film Optoelectronics Technology, Ministry of Education, Institute of Photoelectronic Thin Film Devices and Technology of Nankai University, Solar Energy Research Center of Nankai University, #38 Tongyan Road, Jinnan District, Tianjin 300350, China.

Organic-inorganic metal halide perovskite materials have been widely studied as the light absorber for efficient photovoltaics. However, perovskite layers with defective nature are typically prepared with an uncontrollable crystallization process, intrinsically limiting further advance in device performance, and thus require delicate manipulation of crystallization processes and defect density. Here, we demonstrate an ammonium-assisted crystallization of perovskite absorbers during a two-step deposition to fabricate efficient solar cells. Addition of ammonium iodide (NHI) is devised to manipulate the nucleation and crystal growth of perovskite, wherein the formation and transition of intermediate [NH]•[PbI] enables high-quality perovskite layers with an enlarged grain and reduced defect density. As a result, the perovskite solar cells (PSCs) achieve an average efficiency of 21.36% with a champion efficiency of 22.15% and improved environmental stability over 30 days in ambient conditions with varied relative humidity. These results with addition of NHI provide an available and ingenious way to construct high-quality perovskite layers for efficient solar cells and will advance the commercial application of perovskite-based photovoltaics.
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http://dx.doi.org/10.1021/acsami.1c05903DOI Listing
July 2021

A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma.

Biomed Res Int 2021 18;2021:8848227. Epub 2021 Jun 18.

Department of Histology and Embryology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, China.

Objective: Autophagy and long noncoding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.

Methods: We downloaded RNA sequencing data and clinical information of melanoma from the Cancer Genome Atlas. The coexpression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate Cox regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.

Results: According to the results of the univariate Cox analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate Cox analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group ( < 0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.

Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNA risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.
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http://dx.doi.org/10.1155/2021/8848227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238568PMC
June 2021

Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-κB/miR-21-5p/PDCD4 Signaling Pathway.

Front Cell Dev Biol 2021 23;9:643525. Epub 2021 Jun 23.

School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.

Tumor growth and metastasis are responsible for breast cancer-related mortality. Andrographolide (Andro) is a traditional anti-inflammatory drug used in the clinic that inhibits NF-κB activation. Recently, Andro has been found in the treatment of various cancers. Andro inhibits breast cell proliferation and invasion and induces apoptosis activating various signaling pathways. Therefore, the underlying mechanisms with regard to the antitumor effects of Andro still need to be further confirmed. Herein, a MMTV-PyMT spontaneous luminal-like breast cancer lung metastatic transgenic tumor model was employed to estimate the antitumor effects of Andro on breast cancer . Andro significantly inhibited tumor growth and metastasis in MMTV-PyMT mice and suppressed the cell proliferation, migration, and invasion of MCF-7 breast cancer cells . Meanwhile, Andro significantly inhibited the expression of NF-κB, and the downregulated NF-κB reduced miR-21-5p expression. In addition, miR-21-5p dramatically inhibited the target gene expression of programmed cell death protein 4 (PDCD4). In the current study, we demonstrated the potential anticancer effects of Andro on luminal-like breast cancer and indicated that Andro inhibits the expression of miR-21-5p and further promotes PDCD4 NF-κB suppression. Therefore, Andro could be an antitumor agent for the treatment of luminal-like breast cancer in the clinic.
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http://dx.doi.org/10.3389/fcell.2021.643525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261247PMC
June 2021

Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways.

Cell Biosci 2021 Jul 7;11(1):126. Epub 2021 Jul 7.

Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands.

Background: Leptin plays a critical role in the regulation of metabolic homeostasis. However, the molecular mechanism and cross talks between leptin and metabolic pathways leading to metabolic homeostasis across different species are not clear. This study aims to explore the effects of leptin in mice and zebrafish larvae by integration of metabolomics and transcriptomics. Different metabolomic approaches including mass spectrometry, nuclear magnetic resonance (NMR) and high-resolution magic-angle-spinning NMR spectrometry were used to investigate the metabolic changes caused by leptin deficiency in mutant ob/ob adult mice and lepb zebrafish larvae. For transcriptome studies, deep RNA sequencing was used.

Results: Thirteen metabolites were identified as common biomarkers discriminating ob/ob mice and lepb zebrafish larvae from their respective wild type controls: alanine, citrulline, ethanolamine, glutamine, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, putrescine, serine and threonine. Moreover, we also observed that glucose and lipid levels were increased in lepb zebrafish larvae compared to the lepb group. Deep sequencing showed that many genes involved in proteolysis and arachidonic acid metabolism were dysregulated in ob/ob mice heads and lepb mutant zebrafish larvae compared to their wild type controls, respectively.

Conclusions: Leptin deficiency leads to highly similar metabolic alterations in metabolites in both mice and zebrafish larvae. These metabolic changes show similar features as observed during progression of tuberculosis in human patients, mice and zebrafish larvae. In addition, by studying the transcriptome, we found similar changes in gene regulation related to proteolysis and arachidonic acid metabolism in these two different in vivo models.
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http://dx.doi.org/10.1186/s13578-021-00642-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265131PMC
July 2021

Anti-RANKL monoclonal antibody and bortezomib prevent mechanical unloading-induced bone loss.

J Bone Miner Metab 2021 Jul 1. Epub 2021 Jul 1.

State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 100850, China.

Introduction: Bone loss is a major health concern for astronauts during long-term spaceflight and for patients during prolonged bed rest or paralysis. It is essential to develop therapeutic strategies to combat the bone loss occurring in people afflicted with disuse atrophy on earth as well as in astronauts in space, especially during prolonged missions. Although several drugs have been demonstrated for treating postmenopausal osteoporosis or bone-related diseases, their effects on microgravity-induced bone loss are still unclear.

Materials And Methods: Here, we employed the hindlimb-unloading (HLU) tail suspension model and compared the preventive efficiencies of five agents including alendronate (ALN), raloxifene (Rox), teriparatide (TPTD), anti-murine RANKL monoclonal antibody (anti-RANKL) and proteasome inhibitor bortezomib (Bzb) on mechanical unloading-induced bone loss. Bone mineral density (BMD) was measured by quantitative computed tomography. The osteoblastic and osteoclastic activity were measured by serum ELISA, histology analysis, and histomorphometric analysis.

Results: Compared to the control, ALN and anti-RANKL antibody could restore bone mass close to sham levels by inhibiting bone resorption. Bzb could increase the whole bone mass and strength by inhibiting bone resorption and promoting bone formation simultaneously. Meanwhile, Rox did not affect bone loss caused by HLU. TPTD stimulated cortical bone formation but the total bone mass was not increased significantly.

Conclusions: We demonstrated for the first time that anti-RANKL antibody and Bzb had a positive effect on preventing mechanical unloading-induced bone loss. This finding puts forward the potential use of anti-RANKL and Bzb on bone loss therapies or prophylaxis of astronauts in spaceflight.
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http://dx.doi.org/10.1007/s00774-021-01246-xDOI Listing
July 2021

Dietary polystyrene nanoplastics exposure alters liver lipid metabolism and muscle nutritional quality in carnivorous marine fish large yellow croaker (Larimichthys crocea).

J Hazard Mater 2021 Jun 24;419:126454. Epub 2021 Jun 24.

Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affair), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao 266003, PR China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao 266003, PR China. Electronic address:

Nanoplastics (NPs) cause various adverse effects on marine fish. However, effects of dietary NPs exposure on liver lipid metabolism and muscle nutritional quality of carnivorous marine fish are not fully understood. In this study, a 21-day feeding test was conducted to simulate the food chain transfer of polystyrene nanoplastics (PS NPs) and then evaluate effects of different dietary PS NPs levels on the survival, growth performance, liver lipid metabolism, and muscle nutritional quality of large yellow croaker Larimichthys crocea. Results indicated that the survival and growth of large yellow croaker decreased with the increase of PS NPs levels. Moreover, PS NPs induced excessive liver lipid accumulation by down-regulating the expression of lipolysis-related genes and inhibiting the AMPK-PPARα signaling pathway. In vitro, PS NPs could be accumulated in hepatocytes, reduce cell viability, and disrupt lipid metabolism of hepatocytes. Also, we found for the first time that PS NPs altered fatty acid composition and texture of fish muscle by enhancing oxidative stress and disrupting lipid metabolism. Overall, this study indicated that PS NPs induced liver lipid deposition by inhibiting lipolysis, and demonstrated that PS NPs altered the nutritional quality of fish, which might cause potential health effects for human consumers.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126454DOI Listing
June 2021

Jahn-Teller Distortion Induced Mn-Rich Cathode Enables Optimal Flexible Aqueous High-Voltage Zn-Mn Batteries.

Adv Sci (Weinh) 2021 Jun 5;8(12):2004995. Epub 2021 May 5.

School of Materials Science & Engineering Key Laboratory of Mobile Materials MOE Jilin University Changchun 130012 China.

Although one of the most promising aqueous batteries, all Zn-Mn systems suffer from Zn dendrites and the low-capacity Mn/Mn process (readily leading to the occurrence of Jahn-Teller distortion, which in turn causes structural collapse and voltage/capacity fading). Here, the Mn reconstruction and disproportionation are exploited to prepare the stable, Mn-rich manganese oxides on carbon-cloth (CMOs) in a discharged state through an inverted design, which promotes reversible Mn/Mn kinetics and mitigates oxygen-related redox activity. Such a 1.65 V Mn-rich cathode enable constructing a 2.2 V Zn-Mn battery, providing a high area capacity of 4.16 mA h cm (25 mA h cm for 10 mL electrolyte) and superior 4000-cycle stability. Moreover, a flexible hybrid 2.7 V Zn-Mn battery is constructed using 2-pH hydrogel electrolytes to demonstrate excellent practicality and stability. A further insight has been gained to the commercial application of aqueous energy storage devices toward low-cost, high safety, and excellent energy density.
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http://dx.doi.org/10.1002/advs.202004995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224442PMC
June 2021

[Result analysis of percutaneous core needle biopsy for bone tumors in upper limbs with pathological fracture].

Zhongguo Gu Shang 2021 Jun;34(6):527-30

Department of Orthopaedic Oncology Surgery, Jishuitan Hospital, Beijing 100035, China.

Objective: To analyze the results of percutaneous core needle biopsy for bone tumors in upper limbs with pathologic fracture and to find the possible factors that could impact the results.

Methods: The including criteria for this study was the patients who had received percutaneous core needle biopsy and definitive surgery, whose tumor was located at upper limb with pathologic fracture. From January 2015 to December 2019, seventy-seven patients were enrolled. There were 55 males and 22 females. The median age was 27 years old (range:5 to 88 years old). The tumor located at humerus in 67 cases, radius in 8 cases and ulna in 2 cases. If the pathologic diagnosis of core needle biopsy was the same with the definitive surgery, it was defined as "correct". If the pathologic diagnosis of biopsy for benign or malignant was right but the exact diagnostic name was not the same with definitive surgery, it was defined as "supportive". If the pathologic diagnosis of biopsy for benign or malignant was not correct, it was defined as "wrong". We retrospectively analyzed the accuracy and impact factors for core needle biopsy.

Results: The result was "correct" in 63 cases(81.8%), "supportive" in 14 cases(18.2%), and "wrong" in 0 cases. We analyzed the gender, age, location, fracture displacement, the destroyed type for bone tumor, soft tissue mass, fluid area in the tumor as the factors. The results showed the rate for "correct" was significantly higher when the tumor had soft tissue mass (< 0.05) and lower when the fluid area existed inside the tumor (<0.05).

Conclusion: The accuracy of percutaneous core needle biopsy for upper limb bone tumor with pathologic is high and acceptable. The biopsy chosen the soft tissue mass area can increase the accuracy.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.06.009DOI Listing
June 2021

Whole Transcriptome Data Analysis Reveals Prognostic Signature Genes for Overall Survival Prediction in Diffuse Large B Cell Lymphoma.

Front Genet 2021 9;12:648800. Epub 2021 Jun 9.

Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Background: With the improvement of clinical treatment outcomes in diffuse large B cell lymphoma (DLBCL), the high rate of relapse in DLBCL patients is still an established barrier, as the therapeutic strategy selection based on potential targets remains unsatisfactory. Therefore, there is an urgent need in further exploration of prognostic biomarkers so as to improve the prognosis of DLBCL.

Methods: The univariable and multivariable Cox regression models were employed to screen out gene signatures for DLBCL overall survival (OS) prediction. The differential expression analysis was used to identify representative genes in high-risk and low-risk groups, respectively, where student test and fold change were implemented. The functional difference between the high-risk and low-risk groups was identified by the gene set enrichment analysis.

Results: We conducted a systematic data analysis to screen the candidate genes significantly associated with OS of DLBCL in three NCBI Gene Expression Omnibus (GEO) datasets. To construct a prognostic model, five genes (, , , , and ) were then screened and tested using the multivariable Cox model and the stepwise regression method. Kaplan-Meier curve confirmed the good predictive performance of this five-gene Cox model. Thereafter, the prognostic model and the expression levels of the five genes were validated by means of an independent dataset. High expression levels of these five genes were significantly associated with favorable prognosis in DLBCL, both in training and validation datasets. Additionally, further analysis revealed the independent value and superiority of this prognostic model in risk prediction. Functional enrichment analysis revealed some vital pathways responsible for unfavorable outcome and potential therapeutic targets in DLBCL.

Conclusion: We developed a five-gene Cox model for the clinical outcome prediction of DLBCL patients. Meanwhile, potential drug selection using this model can help clinicians to improve the clinical practice for the benefit of patients.
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http://dx.doi.org/10.3389/fgene.2021.648800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220154PMC
June 2021

Bioinformatics Analysis of Autophagy-related lncRNAs in Esophageal Carcinoma.

Comb Chem High Throughput Screen 2021 Jun 24. Epub 2021 Jun 24.

Department of Anesthesiology, Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China.

Background: Esophageal carcinoma (ESCA) is a malignant tumor with high invasiveness and mortality. Autophagy has multiple roles in the development of cancer; however, there are limited data on autophagy genes associated with long non-coding RNAs (lncRNAs) in ESCA. The purpose of this study was to screen potential diagnostic and prognostic molecules and to identify gene co-expression networks associated with autophagy in ESCA.

Methods: We downloaded transcriptome expression profiles from The Cancer Genome Atlas and autophagy-related gene data from the Human Autophagy Database and analyzed the co-expression of mRNAs and lncRNAs. In addition, the diagnostic and prognostic value of autophagy-related lncRNAs was analyzed by multivariate Cox regression. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was carried out for high-risk patients, and enriched pathways were analyzed by gene set enrichment analysis.

Results: The results showed that genes of high-risk patients were enriched in protein export and spliceosome. Based on Cox stepwise regression and survival analysis, we identified seven autophagy-related lncRNAs with prognostic and diagnostic value, with the potential to be used as a combination to predict the prognosis of patients with ESCA. Finally, a co-expression network related to autophagy was constructed.

Conclusion: These results suggest that autophagy-related lncRNAs and the spliceosome play important parts in the pathogenesis of ESCA. Our findings provide new insight into the molecular mechanism of ESCA and suggest a new method for improving its treatment.
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http://dx.doi.org/10.2174/1386207324666210624143452DOI Listing
June 2021

COVID-19 vaccine development from the perspective of cancer patients.

Hum Vaccin Immunother 2021 Jun 25:1-7. Epub 2021 Jun 25.

Department of Radiation Oncology, Rutgers-Cancer Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Currently, many companies around the world are actively developing COVID-19 vaccines. Fourteen vaccines with reliable safety and effectiveness are being successfully distributed to the public. However, there is no specific clinical trial data of the vaccines currently on the market on cancer patients at various stages, so the safety and effectiveness on cancer patients is unknown. This mini-review aims to discuss the impact of COVID-19 on cancer patients, and the urgent need of COVID-19 vaccines for cancer patients. In this review, we described the current status of the COVID-19 vaccine usages in cancer patients, as well as discussed potential problems in the use of vaccine. In addition, we included an original survey of the acceptance of the COVID-19 vaccines in 209 cancer patients and their family members. COVID-19 vaccine can provide cancer patients with social and medical benefits; therefore, clinical trials of vaccines on cancer patients are in great need.
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http://dx.doi.org/10.1080/21645515.2021.1943988DOI Listing
June 2021

Keratin-A6ACA NPs for gastric ulcer diagnosis and repair.

J Mater Sci Mater Med 2021 Jun 12;32(6):66. Epub 2021 Jun 12.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China.

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http://dx.doi.org/10.1007/s10856-021-06537-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197711PMC
June 2021

Efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for acute myeloid leukemia: A protocol for a Bayesian network meta-analysis.

Medicine (Baltimore) 2021 Jun;100(23):e26098

Affiliated Hospital of Shandong University of Traditional Chinese Medicine.

Background: Acute myeloid leukemia (AML) is the most common malignant tumor of the hematopoietic system, which seriously threatens the lives of patients. Most AML patients have acute onset, severe condition, and poor prognosis. The present study aimed to comprehensively evaluate the effectiveness and safety of chemotherapy combined with different doses of interleukin-2 (IL-2) maintenance treatments in AML by Bayesian network meta-analysis (NMA).

Methods: From its inception until October 2021, we will search PubMed, Cochrane Library, CNKI, Embase, and other databases to comprehensively collect randomized controlled trials (RCTs) of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. Two independent researchers will complete the literature screening and data extraction according to the inclusion and exclusion criteria, and then independently conduct a bias risk assessment of all the evidence. Bayesian NMA was used to evaluate all the evidence comprehensively. Use STATA16.0 and WinBUGS1.4.3 software to process and analyze all data, and classify the quality of evidence in NMA according to grading of recommendations assessment, development, and evaluation .

Results: The study will evaluate the efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for AML.

Conclusion: The study will provide a basis for the efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. We hope that this study can provide meaningful support for clinicians and patients.

Protocol Registration Number: INPLASY202140106.

Ethical Approval: Since the study is based on published or registered RCTs, ethical approval and patient informed consent are abandoned.
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http://dx.doi.org/10.1097/MD.0000000000026098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202562PMC
June 2021

Rectal Douching and Anal Human Papillomavirus Among Young Men Who Have Sex With Men in China.

Sex Transm Dis 2021 Aug;48(8):550-556

Department of AIDS/STD Control and Prevention, Chongqing Center for Disease Control and Prevention, Chongqing.

Background: Young men who have sex with men (YMSM) are particularly at increased risk for human papillomavirus (HPV) infection and related malignancies. Rectal douching, commonly practiced among MSM, has been associated with HIV, chlamydia, gonorrhea, and viral hepatitis in cross-sectional studies. We conducted this study to understand the association between self-reported rectal douching and anal HPV among YMSM in China.

Methods: Between September 2018 and March 2019, MSM aged 15 to 24 years who ever engaged in receptive anal intercourse over the last 3 months were recruited via community-based organizations and centers for disease control located in 4 cities in China. Participants were asked to complete an online survey. We performed multivariate logistic regression adjusted for potential confounders to examine the association between self-reported rectal douching and anal HPV.

Results: Among 273 MSM with a median age of 20 years (interquartile range, 19-21 years) included in this study, 130 (47.6%) practiced rectal douching during the preceding 3 months and 96 (36.2%) were infected with anal HPV. Self-reported rectal douching was found to be associated with increased odds of anal HPV infection (odds ratio, 2.16; 95% confidence interval, 1.22-3.82) among YMSM, after adjusting for age, sexual debut, sex with alcohol or drugs, and HIV testing history.

Conclusions: Self-reported rectal douching is associated with higher odds of anal HPV infection independent of sexual behaviors among YMSM. More prospective studies to ascertain this association are needed. Health education materials should inform men of the potential risk of rectal douching. Research on safer rectal douching procedures is warranted.
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http://dx.doi.org/10.1097/OLQ.0000000000001392DOI Listing
August 2021

An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke.

Sci Transl Med 2021 06;13(597)

Translational Research Institute of Brain and Brain-Like Intelligence and Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai 200434, China.

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Therefore, finding a common and critical therapeutic target for both ischemic and hemorrhagic stroke is appealing. Here, we report that the expression of myeloid differentiation protein 2 (MD2), which is traditionally regarded to be expressed only in microglia in the normal brain, was markedly increased in cortical neurons after stroke. We synthesized a small peptide, Trans-trans-activating (Tat)-cold-inducible RNA binding protein (Tat-CIRP), which perturbed the function of MD2 and strongly protected neurons against excitotoxic injury in vitro. In addition, systemic administration of Tat-CIRP or genetic deletion of MD2 induced robust neuroprotection against ischemic and hemorrhagic stroke in mice. Tat-CIRP reduced the brain infarct volume and preserved neurological function in rhesus monkeys 30 days after ischemic stroke. Tat-CIRP efficiently crossed the blood-brain barrier and showed a wide therapeutic index for stroke because no toxicity was detected when high doses were administered to the mice. Furthermore, we demonstrated that MD2 elicited neuronal apoptosis and necroptosis via a TLR4-independent, Sam68-related cascade. In summary, Tat-CIRP provides robust neuroprotection against stroke in rodents and gyrencephalic nonhuman primates. Further efforts should be made to translate these findings to treat both ischemic and hemorrhagic stroke in patients.
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http://dx.doi.org/10.1126/scitranslmed.abb6716DOI Listing
June 2021

MRI Evaluation of Complete Response of Locally Advanced Rectal Cancer After Neoadjuvant Therapy: Current Status and Future Trends.

Cancer Manag Res 2021 1;13:4317-4328. Epub 2021 Jun 1.

Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.

Complete tumor response can be achieved in a certain proportion of patients with locally advanced rectal cancer, who achieve maximal response to neoadjuvant therapy (NAT). For these patients, a watch-and-wait (WW) or nonsurgical strategy has been proposed and is becoming widely practiced in order to avoid unnecessary surgical complications. Therefore, a non-invasive, reliable diagnostic tool for accurately evaluating complete tumor response is needed. Magnetic resonance imaging (MRI) plays a crucial role in both primary staging and restaging tumor response to NAT in rectal cancer without relying on resected specimen. In recent years, numerous efforts have been made to research the value of MRI in predicting and evaluating complete response in rectal cancer. Current MRI evaluation is mainly based on morphological and functional images. Morphologic MRI yields high soft tissue resolution, multiplanar images, and provides detailed depictions of rectal cancer and its surrounding structures. Functional MRI may help to distinguish residual tumor from fibrosis, therefore improving the diagnostic performance of morphologic MRI in identifying complete tumor response. Both morphologic and functional MRI have several promising parameters that may help accurately evaluate and/or predict complete response of rectal cancer. However, these parameters still have limitations and the results remain inconsistent. Recent development of new techniques, such as textural analysis, radiomics analysis and deep learning, demonstrate great potential based on MRI-derived parameters. This article aimed to review and help better understand the strengths, limitations, and future trends of these MRI-derived methods in evaluating complete response in rectal cancer.
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http://dx.doi.org/10.2147/CMAR.S309252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179813PMC
June 2021

Detection of BCOR gene rearrangement in Ewing-like sarcoma: an important diagnostic tool.

Diagn Pathol 2021 Jun 8;16(1):50. Epub 2021 Jun 8.

Department of Pathology, Beijing Jishuitan Hospital, The Fourth Medical College of Peking University, Beijing, People's Republic of China.

Background: BCOR-CCNB3 sarcoma (BCS) is a group of undifferentiated small round cell sarcomas harboring the BCOR gene rearrangement which shares morphology with the Ewing sarcoma family as well as other malignant round blue cell tumors, thus making them difficult to diagnose. The aim of this study was to explore the role of molecular techniques in the diagnosis of BCS.

Methods: Twenty-three cases of EWSR1 rearrangement-negative undifferentiated small round cell sarcomas (Ewing-like sarcoma) were analyzed for the presence of BCOR gene rearrangement by Fluorescence in situ hybridization (FISH) and Reverse Transcription -Polymerase Chain Reaction (RT-PCR). The clinicopathological features of the positive cases were also reviewed. Fifteen additional cases were used as negative controls.

Results: Eight cases were found with BCOR gene rearrangement by FISH and reappraised as BCS. The patients ranged in age from 8 to 20 years old, with a male predominance (M:F = 6:2). All tumors were located in the lower extremities. The tumor locations were more common in bone (n = 6) than deep soft tissue (n = 2). Histologically, 7 of 8 tumors were predominately composed of spindle or ovoid cells. The tumor cells were usually arranged in solid hypercellular sheets without a distinct architectural pattern. IHC showed expression of TLE1 (100%), CCNB3 (88%), BCOR (71%). RT-PCR for BCOR-CCNB3 fusion transcript was positive in 7 of 8 cases. Pre-operative chemotherapy resulted in eradication of tumors in 5 patients after a follow-up of 7 to 42 months.

Conclusions: Efficient diagnosis of BCOR rearranged sarcomas is achieved by the using a combination of FISH and RT-PCR assays.
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http://dx.doi.org/10.1186/s13000-021-01114-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185946PMC
June 2021

Academic procrastination precedes problematic mobile phone use in Chinese adolescents: A longitudinal mediation model of distraction cognitions.

Addict Behav 2021 10 23;121:106993. Epub 2021 May 23.

Department of Experimental and Applied Psychology, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.

Cross-sectional studies have documented a positive association between academic procrastination and problematic mobile phone use (PMPU). However, the specific predictive direction has remained controversial and the potential mechanisms underlying the association have not been rigorously evaluated. According to Davis's cognitive-behavioral model, Brand et al.'s I-PACE model, and procrastination-related theories, academic procrastination and PMPU might have a reciprocal relationship and distraction cognitions might play a mediating role in this process. A total of 633 secondary school students completed three self-report questionnaires at three 6-month intervals over the course of 1.5 years. The cross-lagged panel model results showed that earlier academic procrastination positively predicted subsequent PMPU over time, but the reverse prediction was not stable. Furthermore, distraction cognitions played a mediating role in linking earlier academic procrastination and subsequent PMPU. These findings indicate that academic procrastination precedes PMPU with distraction cognitions as a potential mediator, which contributes to clarifying the controversial relationship and explicating the underlying mechanism. Overall, interventions for academic procrastination may be effective in reducing maladaptive cognitions associated with mobile phones and preventing adolescents from developing PMPU.
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http://dx.doi.org/10.1016/j.addbeh.2021.106993DOI Listing
October 2021

[Effect of electroacupuncture at Neiguan (PC 6) on pulmonary function during one-lung ventilation in patients with lobectomy].

Zhongguo Zhen Jiu 2021 Jun;41(6):598-602

Department of Anesthesiology, First Affiliated Hospital of Guangxi University of CM, Nanning 530023, China.

Objective: To observe the protective effect of electroacupuncture (EA) at Neiguan (PC 6) on pulmonary function during one-lung ventilation (OLV) in patients with lobectomy, and explore its action mechanism.

Methods: Sixty patients with lobectomy were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with general anesthesia, and OLV was given when surgery began; when the surgery finished, air was removed from the thoracic cavity and two-lung ventilation was performed. On the basis of the treatment in the control group, the patients in the observation group were treated with EA (disperse-dense wave, 2 Hz/100 Hz of frequency) at Neiguan (PC 6) 30 min before anesthesia induction until the end of the surgery. The pulmonary function indexes [arterial partial pressure of oxygen (PaO), oxygenation index (OI), compliance of lung (CL), respiratory index (RI)] and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were observed before surgery (T), 30 min into OLV (T), 60 min into OLV (T) and after operation (T). The total incidence of complications, pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay were compared between the two groups.

Results: Compared with T, the PaO, OI, CL and serum SOD at T, T and T in the two groups were decreased (<0.05), and those in the observation group were higher than those in the control group (<0.05). The RI and serum levels of MDA, IL-6, TNF-α at T, T and T in the two groups were increased, and those in the observation group were lower than those in the control group (<0.05). The total incidence of complications in the observation group was lower than that in the control group [3.3% (1/30) vs 23.3% (7/30), <0.05]. The pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay in the observation group were less than those in the control group (<0.05).

Conclusion: EA at Neiguan (PC 6) has protective effects on lung injury induced by OLV after lobectomy, and its mechanism may be related to the improvement of oxidative stress and inflammatory response.
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http://dx.doi.org/10.13703/j.0255-2930.20201125-0004DOI Listing
June 2021

Ultrafast non-volatile flash memory based on van der Waals heterostructures.

Nat Nanotechnol 2021 Jun 3. Epub 2021 Jun 3.

State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Shanghai, China.

Flash memory has become a ubiquitous solid-state memory device widely used in portable digital devices, computers and enterprise applications. The development of the information age has demanded improvements in memory speed and retention performance. Here we demonstrate an ultrafast non-volatile flash memory based on MoS/hBN/multilayer graphene van der Waals heterostructures, which achieves an ultrafast writing/erasing speed of 20 ns through two-triangle-barrier modified Fowler-Nordheim tunnelling. Using detailed theoretical analysis and experimental verification, we postulate that a suitable barrier height, gate coupling ratio and clean interface are the main reasons for the breakthrough writing/erasing speed of our flash memory devices. Because of its non-volatility this ultrafast flash memory could provide the foundation for the next generation of high-speed non-volatile memory.
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http://dx.doi.org/10.1038/s41565-021-00921-4DOI Listing
June 2021

Essential Role of CRIM1 on Endometrial Receptivity in Goat.

Int J Mol Sci 2021 May 18;22(10). Epub 2021 May 18.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

In domestic ruminants, endometrial receptivity is related to successful pregnancy and economic efficiency. Despite several molecules having been reported in the past regarding endometrial receptivity regulation, much regarding the mechanism of endometrial receptivity regulation remains unknown due to the complex nature of the trait. In this work, we demonstrated that the cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1 (CRIM1) served as a novel regulator in the regulation of goat endometrial receptivity in vitro. Our results showed that hormones and IFN-τ increased the expression of CRIM1 in goat endometrial epithelial cells (EECs). Knockdown of CRIM1 via specific shRNA hindered cell proliferation, cell adhesion and prostaglandins (PGs) secretion and thus derailed normal endometrial receptivity. We further confirmed that receptivity defect phenotypes due to CRIM1 interference were restored by ATG7 overexpression in EECs while a loss of ATG7 further impaired receptivity phenotypes. Moreover, our results showed that changing the expression of ATG7 affected the reactive oxygen species (ROS) production. Moreover, mR-143-5p was shown to be a potential upstream factor of CRIM1-regulated endometrial receptivity in EECs. Overall, these results suggest that CRIM1, as the downstream target of miR-143-5p, has effects on ATG7-dependent autophagy, regulating cell proliferation, cell adhesion and PG secretion, and provides a new target for the diagnosis and treatment of early pregnancy failure and for improving the success rates of artificial reproduction.
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http://dx.doi.org/10.3390/ijms22105323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158520PMC
May 2021

Molecular characteristics and tumorigenicity of ascites-derived tumor cells: mitochondrial oxidative phosphorylation as a novel therapy target in ovarian cancer.

Mol Oncol 2021 Jun 1. Epub 2021 Jun 1.

Department of Gynecology, University Medical Center Hamburg-Eppendorf, Germany.

Ovarian cancer disseminates primarily intraperitoneally. Detached tumor cell aggregates (spheroids) from the primary tumor are regarded as 'metastatic units' that exhibit a low sensitivity to classical chemotherapy, probably due to their unique molecular characteristics. We have analyzed the cellular composition of ascites from OvCa patients, using flow cytometry, and studied their behavior in vitro and in vivo. We conclude that ascites-derived cultured cells from OvCa patients give rise to two subpopulations: adherent cells and non-adherent cells. Here, we found that the AD population includes mainly CD90 cells with highly proliferative rates in vitro but no tumorigenic potential in vivo, whereas the NAD population contains principally tumor cell spheroids (EpCAM /CD24 ) with low proliferative potential in vitro. Enriched tumor cell spheroids from the ascites of high-grade serous OvCA patients, obtained using cell strainers, were highly tumorigenic in vivo and their metastatic spread pattern precisely resembled the tumor dissemination pattern found in the corresponding patients. Comparative transcriptome analyses from ascites-derived tumor cell spheroids (n = 10) versus tumor samples from different metastatic sites (n = 30) revealed upregulation of genes involved in chemoresistance (TGM1, HSPAs, MT1s), cell adhesion and cell-barrier integrity (PKP3, CLDNs, PPL), and the oxidative phosphorylation process. Mitochondrial markers (mass and membrane potential) showed a reduced mitochondrial function in tumoroids from tumor tissue compared with ascites-derived tumor spheroids in flow cytometry analysis. Interestingly, response to OXPHOS inhibition by metformin and IACS010759 in tumor spheroids correlated with the extent of mitochondrial membrane potential measured by fluorescence-activated cell sorting. Our data contribute to a better understanding of the biology of ovarian cancer spheroids and identify the OXPHOS pathway as new potential treatment option in advanced ovarian cancer.
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http://dx.doi.org/10.1002/1878-0261.13028DOI Listing
June 2021

Investigation of the Multi-Target Mechanism of Guanxin-Shutong Capsule in Cerebrovascular Diseases: A Systems Pharmacology and Experimental Assessment.

Front Pharmacol 2021 13;12:650770. Epub 2021 May 13.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Guanxin-Shutong capsule (GXSTC), a combination of Mongolian medicines and traditional herbs, has been clinically proven to be effective in treating cerebrovascular diseases (CBVDs). However, the underlying pharmacological mechanisms of GXSTC in CBVDs remain largely unknown. In this study, a combination of systems pharmacology and experimental assessment approach was used to investigate the bioactive components, core targets, and possible mechanisms of GXSTC in the treatment of CBVDs. A total of 15 main components within GXSTC were identified using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) and a literature research. Fifty-five common genes were obtained by matching 252 potential genes of GXSTC with 462 CBVD-related genes. Seven core components in GXSTC and 12 core genes of GXSTC on CBVDs were further determined using the protein-protein interaction (PPI) and component-target-pathway (C-T-P) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results predicted that the molecular mechanisms of GXSTC on CBVDs were mainly associated with the regulation of the vascular endothelial function, inflammatory response, and neuronal apoptosis. Molecular docking results suggested that almost all of core component-targets have an excellent binding activity (affinity < -5 kcal/mol). More importantly, in middle cerebral artery occlusion (MCAO) -injured rats, GXSTC significantly improved the neurological function, reduced the infarct volume, and decreased the percentage of impaired neurons in a dose-dependent manner. Western blotting results indicated that GXSTC markedly upregulated the expression of vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS), while downregulating the expression of cyclooxygenase-2 (COX-2) and transcription factor AP-1 (c-Jun) in MCAO-injured rats. These findings confirmed our prediction that GXSTC exerts a multi-target synergetic mechanism in CBVDs by maintaining vascular endothelial function, inhibiting neuronal apoptosis and inflammatory processes. The results of this study may provide a theoretical basis for GXSTC research and the clinical application of GXSTC in CBVDs.
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http://dx.doi.org/10.3389/fphar.2021.650770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155632PMC
May 2021

Proteomic analysis reveals that naturally produced citral can significantly disturb physiological and metabolic processes in the rice blast fungus Magnaporthe oryzae.

Pestic Biochem Physiol 2021 Jun 27;175:104835. Epub 2021 Mar 27.

Institute of Plant Protection, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China.

Rice blast (Magnaporthe oryzae), a major fungal disease in rice producing areas all over the world as well as in China, seriously affects the safety of rice production. Citral, a mixture of Z/E and trans isomers, is a natural acycloid monoterpene compound with good bacteriostatic effect on rice blast. To further investigate the underlying molecular mechanism, a comparative proteomics analysis was conducted between citral-treated and non-treated M. oryzae spores through two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Our analysis identified 1600-1800 proteins from M. oryzae ZB15, of which 147 were differentially expressed in 100 μg/mL citral-treated samples relative to the control group. Among these differentially expressed proteins (DEPs), 40 proteins showed significantly different expression. GO enrichment and NCBI conserved domains database analysis showed that the main groups of the cellular component were cytoplasm (23.33%), and the major molecular function categories were ion binding (31.37%), and the major categories of biological processes included small molecule metabolic process (22.22%) and transport (13.89%). Further analysis found that down-regulated proteins included the tubulin α chain, ATP synthase subunit β and malate dehydrogenase, while the tubulin β, enolase were upregulated. These DEPs could possibly limit the availability of energy required for many cellular processes and result in various physiological adaptions of M. oryzae. This study represents the first proteomic analysis of M. oryzae treated by citral and will help to uncover the mode-of-action of this biologically active compound against M. oryzae. These findings have practical implications with respect to the use of citral for fungal disease control.
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http://dx.doi.org/10.1016/j.pestbp.2021.104835DOI Listing
June 2021

The cytokine FAM3B/PANDER is an FGFR ligand that promotes posterior development in .

Proc Natl Acad Sci U S A 2021 May;118(20)

Institute of Neuroscience, Translational Medicine Institute, Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, China;

Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior-posterior (A-P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals. However, the molecular mechanism of FAM3B action in these processes remains poorly understood, largely because its receptor is still unidentified. Here we uncover an unexpected role of FAM3B acting as a FGF receptor (FGFR) ligand in embryos. messenger RNA (mRNA) is initially expressed maternally and uniformly in the early embryo and then in the epidermis at neurula stages. Overexpression of mRNA inhibited cephalic structures and induced ectopic tail-like structures. Recombinant human FAM3B protein was purified readily from transfected tissue culture cells and, when injected into the blastocoele cavity, also caused outgrowth of tail-like structures at the expense of anterior structures, indicating FGF-like activity. Depletion of by specific antisense morpholino oligonucleotides in resulted in macrocephaly in tailbud tadpoles, rescuable by FAM3B protein. Mechanistically, FAM3B protein bound to FGFR and activated the downstream ERK signaling in an FGFR-dependent manner. In embryos, FGFR activity was required epistatically downstream of Fam3b to mediate its promotion of posterior cell fates. Our findings define a FAM3B/FGFR/ERK-signaling pathway that is required for axial patterning in embryos and may provide molecular insights into FAM3B-associated human diseases.
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http://dx.doi.org/10.1073/pnas.2100342118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158011PMC
May 2021

YTHDF2 is a potential target of AML1/ETO-HIF1α loop-mediated cell proliferation in t(8;21) AML.

Oncogene 2021 Jun 6;40(22):3786-3798. Epub 2021 May 6.

Department of Hematology, Chinese PLA General Hospital, Beijing, China.

The t(8;21) fusion product, AML1/ETO, and hypoxia-inducible factor 1α (HIF1α) form a feed-forward transcription loop that cooperatively transactivates the DNA methyltransferase 3a gene promoter that leads to DNA hypermethylation and drives leukemia cell growth. Suppression of the RNA N-methyladenosine (mA)-reader enzyme YTH N-methyladenosine RNA binding protein 2 (YTHDF2) specifically compromises cancer stem cells in acute myeloid leukemia (AML) but promotes hematopoietic stem cell expansion without derailing normal hematopoiesis. However, the relevance of expression between AML1/ETO-HIF1α loop and YTHDF2, and its functional relationship with t(8;21) AML have not been documented. Here, we show that YTHDF2 is highly expressed in t(8;21) AML patients and associated with a higher risk of relapse and inferior relapse-free survival. Knockdown of YTHDF2 in leukemia cells causes an impaired cell proliferation rate in vitro and in mice. Mechanistically, HIF1α is able to bind to the hypoxia-response elements of the 5'-untranslated region of the YTHDF2 gene and promotes the transactivity of the YTHDF2 promoter. Knockdown and overexpression of either AML1/ETO or HIF1α resulted in decreased and increased YTHDF2 protein and mRNA expression in t(8;21) AML cells. In particular, knockdown of YTHDF2 resulted in increased global mRNA mA levels in t(8;21) AML cells, accompanied by increased TNF receptor superfamily member 1b (TNFRSF1b) mRNA and protein expression levels. Last, we demonstrated that the mA methylation and expression levels of the TNFRSF1b gene were both negatively correlated with HIF1α expression levels. In conclusion, YTHDF2 is a downstream target of the AML1/ETO-HIF1α loop and promotes cell proliferation probably by modulating the global mA methylation in t(8;21) AML.
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http://dx.doi.org/10.1038/s41388-021-01818-1DOI Listing
June 2021

A meta-analysis and cost-minimization analysis of bivalirudin versus heparin in high-risk patients for percutaneous coronary intervention.

Pharmacol Res Perspect 2021 May;9(3):e00774

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

This meta-analysis was performed to compare the safety, efficacy, and pharmacoeconomic of bivalirudin versus heparin in high-risk patients for percutaneous coronary interventions (PCI). Earlier meta-analysis comparing bivalirudin and heparin during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. However, little data were available on the safety of bivalirudin versus heparin in high-risk patients for PCI. Thus, we performed a meta-analysis to evaluate the efficacy and safety in the "high-risk" patients. A systematic search of electronic databases was conducted up to July 30, 2020. The Cochrane Risk of Bias assessment tool was used to assess the quality of included studies. The primary outcomes were all-cause death and major adverse cardiac events (MACE); secondary outcomes were major and minor bleeding, followed by a cost-minimization analysis comparing bivalirudin and heparin using a local drug and medical costs reported in China. Subgroup analysis was based on the type of disease of the high-risk population. Finally, a total of 10 randomized controlled trials involved 42,699 patients were collected. The Cochrane Risk of Bias Tool was employed to appraise the research quality. No significant difference was noted between bivalirudin and heparin regarding all-cause death and MACE. However, subgroup analysis showed that bivalirudin caused less major bleeding in female (OR:0.65, 95% CI:0.53-0.79), diabetes (OR:0.55, 95%CI:0.42-0.73), and CKD (OR:0.59, 95%CI:0.63-1.65). The scatterers of the included literature were approximately symmetrical, and no research was outside the funnel plot. Additionally, cost-minimization analysis showed that heparin was likely to represent a cost-effective option compared with bivalirudin in China, with potential savings of 2129.53 Chinese Yuan (CNY) per patient for one PCI. Overall, the meta-analysis showed that although bivalirudin appeared to have a lower risk of major bleeding rate, the overall effectiveness and safety between the two groups showed no significant difference in high-risk patients for PCI. But the results of the cost-minimization analysis showed that heparin could be a potential cost-saving drug than bivalirudin in patients for PCI in China.
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http://dx.doi.org/10.1002/prp2.774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092421PMC
May 2021