Publications by authors named "Xiaojuan Li"

461 Publications

Shear strain and inflammation-induced fixed charge density loss in the knee joint cartilage following ACL injury and reconstruction: a computational study.

J Orthop Res 2021 Sep 17. Epub 2021 Sep 17.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland, Yliopistonranta 1, FI, 70210, Kuopio, Finland.

Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage-synovial fluid-interface and decreased towards the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Significance: Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jor.25177DOI Listing
September 2021

Circular RNA hsa_circ_0075542 acts as a sponge for microRNA-1197 to suppress malignant characteristics and promote apoptosis in prostate cancer cells.

Bioengineered 2021 Dec;12(1):5620-5631

Department of Urology, Yuebei People Hospital Affiliated to Medical College of Shantou University, Shaoguan, China.

Numerous differentially expressed circular RNAs (circRNAs) have been identified; however, their roles have not been fully elucidated. Since dysregulated circRNAs may have clinical applications, it is vital to study their expression characteristics, function, and mechanism in prostate cancer cells. The role, regulatory mechanism, and expression of hsa_circ_0075542 were analyzed using quantitative reverse transcription polymerase chain reaction. The results indicated that the expression of hsa_circ_0075542 was downregulated in prostate tumor tissues. The functions of prostate cancer cell lines LNCaP and PC3 cells were assessed using cell counting kit-8 and transwell assays and flow cytometry analysis. The results of the functional experiments showed that overexpression of hsa_circ_0075542 suppressed cell proliferation, reduced migration and invasiveness capabilities, and promoted apoptosis. Moreover, hsa_circ_0075542 targeted the microRNA-1197 (miR-1197) homeobox C11 (HOXC11) axis by sponging miR-1197. Overexpression of miR-1197 played a tumor-promoting role. Overexpression of hsa_circ_0075542 alleviated the tumor-promoting effect of miR-1197 overexpression In conclusion, hsa_circ_0075542 suppressed malignant characteristics and promoted apoptosis in LNCaP and PC3 cells by acting as a competing endogenous RNA of miR-1197. The hsa_circ_0075542/miR-1197 axis might play a role via HOXC11.
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http://dx.doi.org/10.1080/21655979.2021.1967064DOI Listing
December 2021

Integrating a genome-wide association study with transcriptomic data to predict candidate genes and favourable haplotypes influencing Brassica napus seed phytate.

DNA Res 2021 Sep;28(5)

National Key Lab of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Phytate is the storage form of phosphorus in angiosperm seeds and plays vitally important roles during seed development. However, in crop plants phytate decreases bioavailability of seed-sourced mineral elements for humans, livestock and poultry, and contributes to phosphate-related water pollution. However, there is little knowledge about this trait in oilseed rape (Brassica napus). Here, a panel of 505 diverse B. napus accessions was screened in a genome-wide association study (GWAS) using 3.28 × 106 single-nucleotide polymorphisms (SNPs). This identified 119 SNPs significantly associated with phytate concentration (PA_Conc) and phytate content (PA_Cont) and six candidate genes were identified. Of these, BnaA9.MRP5 represented the candidate gene for the significant SNP chrA09_5198034 (27 kb) for both PA_Cont and PA_Conc. Transcription of BnaA9.MRP5 in a low-phytate variety (LPA20) was significantly elevated compared with a high-phytate variety (HPA972). Association and haplotype analysis indicated that inbred lines carrying specific SNP haplotypes within BnaA9.MRP5 were associated with high- and low-phytate phenotypes. No significant differences in seed germination and seed yield were detected between low and high phytate cultivars examined. Candidate genes, favourable haplotypes and the low phytate varieties identified in this study will be useful for low-phytate breeding of B. napus.
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http://dx.doi.org/10.1093/dnares/dsab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435555PMC
September 2021

The QIBA Profile for MRI-based Compositional Imaging of Knee Cartilage.

Radiology 2021 Sep 7:204587. Epub 2021 Sep 7.

From the Department of Radiology, Division of Musculoskeletal Imaging and Intervention, University of Washington, UW Radiology-Roosevelt Clinic, 4245 Roosevelt Way NE, Box 354755, Seattle, WA 98105 (M.C.); Department of Biomedical Engineering, Program of Advanced Musculoskeletal Imaging (PAMI) (X.L.), and Department of Biostatistics (N.A.O.), Cleveland Clinic, Cleveland, Ohio; Department of Radiology, Boston University School of Medicine, Boston, Mass (A.G.); Department of Radiology and Imaging, Hospital for Special Surgery, New York, NY (J.A.C.); Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands (E.H.O.); European Imaging Biomarkers Alliance (E.H.O.); and Department of Radiology and Biomedical Imaging, University of California, San Francisco, Calif (T.M.L.).

MRI-based cartilage compositional analysis shows biochemical and microstructural changes at early stages of osteoarthritis before changes become visible with structural MRI sequences and arthroscopy. This could help with early diagnosis, risk assessment, and treatment monitoring of osteoarthritis. Spin-lattice relaxation time constant in rotating frame (T1ρ) and T2 mapping are the MRI techniques best established for assessing cartilage composition. Only T2 mapping is currently commercially available, which is sensitive to water, collagen content, and orientation of collagen fibers, whereas T1ρ is more sensitive to proteoglycan content. Clinical application of cartilage compositional imaging is limited by high variability and suboptimal reproducibility of the biomarkers, which was the motivation for creating the Quantitative Imaging Biomarkers Alliance (QIBA) Profile for cartilage compositional imaging by the Musculoskeletal Biomarkers Committee of the QIBA. The profile aims at providing recommendations to improve reproducibility and to standardize cartilage compositional imaging. The QIBA Profile provides two complementary claims (summary statements of the technical performance of the quantitative imaging biomarkers that are being profiled) regarding the reproducibility of biomarkers. First, cartilage T1ρ and T2 values are measurable at 3.0-T MRI with a within-subject coefficient of variation of 4%-5%. Second, a measured increase or decrease in T1ρ and T2 of 14% or more indicates a minimum detectable change with 95% confidence. If only an increase in T1ρ and T2 values is expected (progressive cartilage degeneration), then an increase of 12% represents a minimum detectable change over time. The QIBA Profile provides recommendations for clinical researchers, clinicians, and industry scientists pertaining to image data acquisition, analysis, and interpretation and assessment procedures for T1ρ and T2 cartilage imaging and test-retest conformance. This special report aims to provide the rationale for the proposed claims, explain the content of the QIBA Profile, and highlight the future needs and developments for MRI-based cartilage compositional imaging for risk prediction, early diagnosis, and treatment monitoring of osteoarthritis.
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http://dx.doi.org/10.1148/radiol.2021204587DOI Listing
September 2021

Mogroside V reduce OVA-induced pulmonary inflammation based on lung and serum metabolomics.

Phytomedicine 2021 Aug 21:153682. Epub 2021 Aug 21.

Department of Pharmacy, Guilin Medical University, Guilin 541199, PR China. Electronic address:

Background: Mogroside V, the main ingredient of Siraitia grosvenorii, has been proved to have therapeutic effects on pulmonary diseases. The specific mechanism still remains to be clarified, which hinders the potence of its medicinal value.

Purpose: Serum and lung metabolomics based on LC-MS analysis were applied to explore the mechanism of mogroside V against lung inflammation.

Method: In this study, balb/c mice were divided into control, model, mogeoside V and SH groups. We evaluated the protective effects of mogroside V on lung inflammation in asthmatic mice. Suhuang Zhike Jiaonang was used as positive drug. Metabolic profiles of serum and lung samples of mice in control, model and mogroside V groups were analyzed by LC-MS.

Results: Administration of mogroside V effectively relieved the expression of biochemical cytokines and lung inflammatory infiltration of asthmatic mice caused by ovalbumin (OVA). And visceral index of mice treated with mogroside V was close to control group. These results indicated that mogroside V ameliorated OVA-induced lung inflammation. LC-MS based metabolomics analysis demonstrated 6 main pathways in asthmatic mice including Vitamin B6 metabolism, Taurine and hypotaurine metabolism, Ascorbate and aldarate metabolism, Histidine metabolism, Pentose and glucuronate interconversions, Citrate cycle (TCA cycle) were regulated after using mogroside V.

Conclusion: The study firstly elucidates the metabolic pathways regulated by mogroside V on lung inflammation through metabolomics, providing a theoretical basis for more sufficient utilization and compatibility of mogroside V.
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http://dx.doi.org/10.1016/j.phymed.2021.153682DOI Listing
August 2021

The sequence structure and phylogenetic analysis by complete mitochondrial genome of kohlrabi ( var. L.).

Mitochondrial DNA B Resour 2021 18;6(9):2714-2716. Epub 2021 Aug 18.

Qinghai University (Qinghai Academy of Agriculture and Forestry Sciences), Xining, PR China.

Kohlrabi ( var. L.) is an important dietary rhizome vegetable in the Brassicaceae family. However, to date, few mitochondrial genomic resources have been reported for kohlrabi. In this study, we obtained the complete mitochondrial DNA sequence of 219,964 bp from an individual green kohlrabi. A total of 61 genes were annotated, including 33 protein-coding genes, 23 transfer RNA genes, three ribosomal RNA genes, and two pseudo genes. In addition, 1,001 open reading frames and five RNA editing sites were annotated. Relative synonymous codon usage analysis revealed significant difference in usage frequency of synonymous codon. Phylogenetic inference showed that kohlrabi is closely related to var. This study provides a good foundation for further understanding the relationship and evolutionary origins among Brassicaceae crops.
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http://dx.doi.org/10.1080/23802359.2021.1966341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382015PMC
August 2021

Hsa-miR-4277 Decelerates the Metabolism or Clearance of Sorafenib in HCC Cells and Enhances the Sensitivity of HCC Cells to Sorafenib by Targeting .

Front Oncol 2021 26;11:735447. Epub 2021 Jul 26.

Chinese People's Liberation Army (PLA) Medical School, Beijing, China.

Increasing evidence has shown that the metabolism and clearance of molecular targeted agents, such as sorafenib, plays an important role in mediating the resistance of HCC cells to these agents. Metabolism of sorafenib is performed by oxidative metabolism, which is initially mediated by CYP3A4. Thus, targeting CYP3A4 is a promising approach to enhance the sensitivity of HCC cells to chemotherapeutic agents. In the present work, we examined the association between CYP3A4 and the prognosis of HCC patients receiving sorafenib. Using the online tool miRDB, we predicted that has-microRNA-4277 (miR-4277), an online miRNA targets the 3'UTR of the transcript of . Furthermore, overexpression of miR-4277 in HCC cells repressed the expression of CYP3A4 and reduced the elimination of sorafenib in HCC cells. Moreover, miR-4277 enhanced the sensitivity of HCC cells to sorafenib and . Therefore, our results not only expand our understanding of CYP3A4 regulation in HCC, but also provide evidence for the use of miR-4277 as a potential therapeutic in advanced HCC.
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http://dx.doi.org/10.3389/fonc.2021.735447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350395PMC
July 2021

[Clinical and genetic analysis of a family with autosomal dominant-familial Mediterranean fever].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Aug;38(8):719-722

Department of Paediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.

Objective: To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF).

Methods: A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and Sanger sequencing was conducted. The impact of detected variants were predicted and validated by bioinformatics.

Results: A missense variant c.2229C>G (p.Phe743Leu) in MEFV gene was identified in the proband and his family members including his mother, sister and brother. This variant had not been reported in China previously, but the locus of it had already been reported in Arabic patient with AD-FMF (PS1). This variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on Mutationtaster, PROVEAN and PolyPhen-2. In addition, the change of amino acid, locating in 743 locus of pyrin protein, encoding by MEFV gene, was found to cause SPRY_PRY_TRIM20 and SPRY_superfamily domain destroyed and finally influenced the fuction of pyrin protein. On the other hand, using UCSF chimera software, we find the variant c.2229C>G (p.Phe743Leu) can induce serious influence to the spatial structure of pyrin protein and loss of protein fuction (PP3). According to the ACMG variant classification guideline, the variant c.2229C>G (p.Phe743Leu) in MEFV gene was classified as likely pathogenic (PS1+PM2+PP3).

Conclusion: The condition of this AD-FMF family may be attributed to the missense variant c.2229C>G (p.Phe743Leu) in MEFV gene. The recurrent aseptic meningitis was a very rare manifestation in AD-FMF patients and had not been reported in China previously. The clinical and genetic findings of the present study are helpful for the further understanding of AD-FMF.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200318-00175DOI Listing
August 2021

RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25-mediated K63-linked polyubiquitination.

Elife 2021 07 27;10. Epub 2021 Jul 27.

Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

Upon viral RNA recognition, the RIG-I signalosome continuously generates IFNs and cytokines, leading to neutrophil recruitment and inflammation. Thus, attenuation of excessive immune and inflammatory responses is crucial to restore immune homeostasis and prevent unwarranted damage, yet few resolving mediators have been identified. In the present study, we demonstrated that RTN3 is strongly upregulated during RNA viral infection and acts as an inflammation-resolving regulator. Increased RTN3 aggregates on the endoplasmic reticulum and interacts with both TRIM25 and RIG-I, subsequently impairing K63-linked polyubiquitination and resulting in both IRF3 and NF-κB inhibition. Rtn3 overexpression in mice causes an obvious inflammation resolving phenomenon when challenged with VSV, Rtn3-overexpressing mice display significantly decreased neutrophil numbers and inflammatory cell infiltration, which is accompanied by reduced tissue edema in the liver and thinner alveolar interstitium. Taken together, our findings identify RTN3 as a conserved negative regulator of immune and inflammatory responses and provide insights into the negative feedback that maintains immune and inflammatory homeostasis.
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http://dx.doi.org/10.7554/eLife.68958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315805PMC
July 2021

Predictive Value of C-Reactive Protein-to-Albumin Ratio for Neonatal Sepsis.

J Inflamm Res 2021 13;14:3207-3215. Epub 2021 Jul 13.

General Hospital of Taiyuan Steel (Group) Co., Ltd., Taiyuan, 030000, People's Republic of China.

Purpose: Previous studies have reported that C-reactive protein-to-albumin ratio (CAR) was a risk factor for sepsis in adults. However, little is known regarding the role of CAR in neonates with sepsis. The aim of this study was to explore the relationship between CAR and neonatal sepsis.

Patients And Methods: In this research, from January 2016 to February 2020, a total of 1076 neonates were enrolled at Henan Children's Hospital in China. Complete clinical and laboratory data were collected. To identify the potential independent risk factor for neonatal sepsis, multivariate logistic regression analysis was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of CAR in identifying neonatal sepsis.

Results: CAR levels were higher in neonates with sepsis and showed a gradual increase among the control group, mild sepsis group and severe sepsis group. The prevalence of neonates with overall sepsis, mild sepsis and severe sepsis increased significantly from CAR tertile 1 to tertile 3. Multiple logistic regression analysis showed that CAR was an independent risk factor for the presence of sepsis (OR = 10.144, 95% CI 4.151-24.790, P < 0.001) and severe sepsis (OR = 1.876, 95% CI 1.562-2.253, P < 0.001). ROC curve analysis showed that CAR had a well discriminatory power in predicting sepsis (area under curve (AUC) = 0.74, 95% CI, 0.71-0.77, P < 0.001) and severe sepsis (AUC = 0.70, 95% CI, 0.67-0.74, P < 0.001).

Conclusion: CAR was an independent predictor for the presence and severity of neonatal sepsis.
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http://dx.doi.org/10.2147/JIR.S321074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286121PMC
July 2021

First Report of Oxacillin Susceptible A-Positive in a Children's Hospital in Kunming, China.

Infect Drug Resist 2021 6;14:2597-2606. Epub 2021 Jul 6.

Department of Clinical Laboratory, Kunming Children's Hospital, Kunming, Yunnan, People's Republic of China.

Purpose: The present study investigated the prevalence characteristics of oxacillin susceptible A-positive (OS-MRSA) in a children's hospital in Kunming from January 2019 to December 2020.

Methods: A total of 499 strains were included in the study and tested for oxacillin susceptibility using the VITEK 2 Compact automated antimicrobial susceptibility test system. All oxacillin-susceptible strains were detected A and C by polymerase chain reaction (PCR). E-test was used to compare the minimum inhibitory concentration (MIC) values of methicillin-susceptible (MSSA), methicillin-resistant (MRSA), and OS-MRSA for oxacillin, cefoxitin, penicillin, vancomycin, erythromycin, and clindamycin. Molecular typing of OS-MRSA was performed by MLST and SCC typing. Toxin genes were detected by PCR.

Results: Forty-five OS-MRSA strains were detected, for an overall rate of 9.02% (45/499). The MICs of MSSA, OS-MRSA, and MRSA against oxacillin were concentrated at 0.38, 0.38, and 12 μg/mL, respectively; the cefoxitin MICs of MSSA and MRSA were concentrated at 2 and 32 μg/mL respectively; and MICs of OS-MRSA were concentrated at 2 and 8 μg/mL; penicillin, vancomycin and erythromycin MICs against MSSA, OS-MRSA, and MRSA showed same centralized points and were 32, 1, and 256 μg/mL, respectively; the MICs of clindamycin against MSSA were 0.5 μg/mL, while that against OS-MRSA and MRSA were concentrated at 256 μg/mL. Molecular typing of OS-MRSA was dominated by ST59-SCCmec IV. The carrier rates of hemolysin genes () and fibrinogen-binding clumping factor genes (A, B) were 100% in OS-MRSA, followed by 40% (18/45) for enterotoxin genes ().

Conclusion: OS-MRSA has a high detection rate in children, and main molecular typing is ST59-SCCIV in Kunming. The identification ability of automated antibacterial drug sensitivity test detection systems for OS-MRSA is very limited. A combination of phenotypic analysis and molecular detection should be used to improve OS-MRSA identification.
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http://dx.doi.org/10.2147/IDR.S317670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275014PMC
July 2021

The International Workshop on Osteoarthritis Imaging Knee MRI Segmentation Challenge: A Multi-Institute Evaluation and Analysis Framework on a Standardized Dataset.

Radiol Artif Intell 2021 May 10;3(3):e200078. Epub 2021 Feb 10.

Departments of Radiology (A.D.D., G.E.G., B.A.H., A.S.C.) and Electrical Engineering (A.D.D., B.A.H.), Stanford University, Lucas Center for Imaging, 1201 Welch Rd, PS 055B, Stanford, CA 94305; Department of Radiology, University of California, San Francisco, San Francisco, Calif (F.C., C. Iriondo, V.P.); Berkeley Joint Graduate Group in Bioengineering, University of California, Berkeley, Berkeley, Calif (C. Iriondo); Department of Computer Science, University of Central Florida, Orlando, Fla (A.M., U.B.); Department of Radiology, Northwestern University, Chicago, Ill (U.B.); Department of Radiology, Columbia University, New York, NY (S.J.); Department of Computer Science, University of Copenhagen, Copenhagen, Denmark (M.P., C. Igel, E.B.D.); Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio (S.G., M.Y., X.L.); Department of Radiology, New York University Langone Health, New York, NY (C.M.D., R.R.); and Department of Biomedical Imaging and Image-guided Therapy, High-Field MR Centre, Medical University of Vienna, Vienna, Austria (V.J.).

Purpose: To organize a multi-institute knee MRI segmentation challenge for characterizing the semantic and clinical efficacy of automatic segmentation methods relevant for monitoring osteoarthritis progression.

Materials And Methods: A dataset partition consisting of three-dimensional knee MRI from 88 retrospective patients at two time points (baseline and 1-year follow-up) with ground truth articular (femoral, tibial, and patellar) cartilage and meniscus segmentations was standardized. Challenge submissions and a majority-vote ensemble were evaluated against ground truth segmentations using Dice score, average symmetric surface distance, volumetric overlap error, and coefficient of variation on a holdout test set. Similarities in automated segmentations were measured using pairwise Dice coefficient correlations. Articular cartilage thickness was computed longitudinally and with scans. Correlation between thickness error and segmentation metrics was measured using the Pearson correlation coefficient. Two empirical upper bounds for ensemble performance were computed using combinations of model outputs that consolidated true positives and true negatives.

Results: Six teams ( - ) submitted entries for the challenge. No differences were observed across any segmentation metrics for any tissues ( = .99) among the four top-performing networks ( , , , ). Dice coefficient correlations between network pairs were high (> 0.85). Per-scan thickness errors were negligible among networks - ( = .99), and longitudinal changes showed minimal bias (< 0.03 mm). Low correlations (ρ < 0.41) were observed between segmentation metrics and thickness error. The majority-vote ensemble was comparable to top-performing networks ( = .99). Empirical upper-bound performances were similar for both combinations (P = .99).

Conclusion: Diverse networks learned to segment the knee similarly, where high segmentation accuracy did not correlate with cartilage thickness accuracy and voting ensembles did not exceed individual network performance.See also the commentary by Elhalawani and Mak in this issue. Cartilage, Knee, MR-Imaging, Segmentation © RSNA, 2020
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http://dx.doi.org/10.1148/ryai.2021200078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231759PMC
May 2021

The Difficulties and Mental Health Intervention Need of Doctors and Nurses in Biological Emergencies: A Qualitative Study.

Front Psychiatry 2021 18;12:696823. Epub 2021 Jun 18.

Department of Pharmacy, Changsha Stomatological Hospital, Changsha, China.

When a biological public health event breaks out, due to the characteristics of their work, doctors and nurses must face risks directly when the situation is unknown. Their difficulties and psychological pressure are unimaginable. However, few studies have investigated the difficulties encountered by those doctors and nurses and their requirements for psychological interventions. This study aimed to explore the difficulties and psychological intervention needs of doctors and nurses during the new biological public health events in China in 2019. We carried out a qualitative study using a phenomenological approach. We used convenience sampling to identify participants who provided direct care and treatment for patients with biological events such as coronavirus disease 2019 (COVID-19). They participated in semi-structured, in-depth face-to-face interviews. The interviews were transcribed and analyzed using Colaizzi's seven-step method. Analysis of this study was divided into the difficulties encountered by doctors and nurses and their mental health need. The difficulties encountered by doctors and nurses included four themes: being worried about the impact on others, lack of knowledge and skills, difficult patients, being socially isolated, and the feeling of uncertainty. The mental health need was summarized into two parts, needs expressed by doctors and nurses and needs observed by researchers. Doctors and nurses mostly did not feel that they needed any psychological support, but the researchers noticed several signs of stress or potential mental health problems among interviewees. Doctors and nurses faced significant complex and multidimensional difficulties. Many denied needing psychological support, even though the researchers noted signs that it might be helpful. Interventions and support strategies that involve mental health promotion activities should consider individual needs related to doctors and nurses' situation.
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http://dx.doi.org/10.3389/fpsyt.2021.696823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249915PMC
June 2021

Follicle-stimulating hormone level and changes in bone mass and body composition in older women and men.

J Clin Endocrinol Metab 2021 Jul 2. Epub 2021 Jul 2.

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Context: Follicle-stimulating hormone (FSH) may have independent actions on bone remodeling and body fat regulation. Cross-sectionally, we have shown that serum FSH is associated with bone mineral density (BMD) and body fat in older postmenopausal women, but it remains unknown whether FSH predicts bone and fat changes.

Objective: We examined whether baseline FSH level is associated with subsequent bone loss or body composition changes in older adults.

Setting, Design, Participants: We studied 162 women and 158 men (mean age 82 ±4 years) from the AGES-BMA cohort, a substudy of the AGES-Reykjavik Study of community-dwelling older adults. Skeletal health and body composition were characterized at baseline and 3 years later.

Main Outcomes: Annualized change in BMD and body composition by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Models were adjusted for serum estradiol and testosterone levels.

Results: There was no evidence for an association between baseline FSH level and change in BMD or body composition by DXA or QCT. For femoral neck areal BMD, adjusted mean difference (95% CI) per SD increase in FSH was 1.3 (-0.7, 3.3) mg/cm 2/year in women, and -0.2 (-2.6, 2.2) mg/cm 2/year in men. For visceral fat, adjusted mean difference (95% CI) per SD increase in FSH was 1.80 (-0.03, 3.62) cm 2/year in women, and -0.33 (-3.73, 3.06) cm 2/year in men.

Conclusions: Although cross-sectional studies and studies in perimenopausal women have demonstrated associations between FSH and BMD and body composition, in older adults, FSH level is not associated with bone mass or body composition changes.
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http://dx.doi.org/10.1210/clinem/dgab481DOI Listing
July 2021

Photocatalyzed Radical Relayed Regio- and Stereoselective Trifluoromethylthiolation-Boration.

Org Lett 2021 Jul 28;23(14):5410-5414. Epub 2021 Jun 28.

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, 210023 Nanjing, People's Republic of China.

Vinylboronates and alkylboronates are key components in variegated transformations in all aspects of chemical science. This work describes a sequential radical difunctionalization strategy for the construction of fluorine-containing vinylboronates and alkylboronates with the integrated redox-active reagent -trifluoromethylthiophthalimide. This multifunctional N-S precursor offers a scalable and practical protocol for the trifluoromethylthiolation-borylation of unsaturated hydrocarbons in a highly regio- and stereoselective fashion, which can be further converted into valuable synthons via boryl migration.
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http://dx.doi.org/10.1021/acs.orglett.1c01737DOI Listing
July 2021

Delayed stillbirth by hysterectomy following early-term uterine rupture with fetal demise in secundigravida.

Radiol Case Rep 2021 Aug 8;16(8):2081-2085. Epub 2021 Jun 8.

Department of Obstetrics in hospital of Xinjiang Uygur Autonomous Region.

Uterine rupture and postterm pregnancy pose a number of life-threatening complications to both mother and child, including severe intra-abdominal bleeding and peritonitis, birth injury, hypoxia, and fetal loss. This report presents a rare case of a 20-year-old female experiencing fetal demise at 60 weeks of pregnancy, with uterine rupture and bone tissue discharge from her vagina without severe intra-abdominal bleeding and peritonitis. The mild clinical course despite complete uterine rupture was due to the firm adhesion of the amniotic sac to the uterus caused by inflammation. The adhesion of the intestines to the rupture site prevented dehiscence of the ruptured wound. Suppuration and bone tissue discharge relieved the pressure on the patient's abdominal cavity and prevented subsequent occurrence of severe peritonitis. Radiologists mistakenly regarded the thick amniotic sac wall on the right side of the uterine wall as a right cornual pregnancy with uterine rupture caused by chronic inflammation. This report aims to bring awareness of this rare condition to medical students and radiologists.
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http://dx.doi.org/10.1016/j.radcr.2021.04.085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203557PMC
August 2021

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients.

Front Genet 2021 28;12:663098. Epub 2021 May 28.

BGI-Shenzhen, Shenzhen, China.

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.
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http://dx.doi.org/10.3389/fgene.2021.663098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194351PMC
May 2021

HJURP promotes proliferation in prostate cancer cells through increasing CDKN1A degradation via the GSK3β/JNK signaling pathway.

Cell Death Dis 2021 06 7;12(6):583. Epub 2021 Jun 7.

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

Genes with cross-cancer aberrations are most likely to be functional genes or potential therapeutic targets. Here, we found a total of 137 genes were ectopically expressed in eight cancer types, of which Holliday junction recognition protein (HJURP) was significantly upregulated in prostate cancer (PCa). Moreover, patients with higher HJURP mRNA and protein levels had poorer outcomes, and the protein levels served as an independent prognosis factor for the overall survival of PCa patients. Functionally, ectopic HJURP expression promoted PCa cells proliferation in vitro and in vivo. Mechanistically, HJURP increased the ubiquitination of cyclin-dependent kinase inhibitor 1 (CDKN1A) via the GSK3β/JNK signaling pathway and decreased its stability. This study investigated the role of HJURP in PCa proliferation and may provide a novel prognostic and therapeutic target for PCa.
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http://dx.doi.org/10.1038/s41419-021-03870-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184824PMC
June 2021

BRLF1-dependent viral and cellular transcriptomes and transcriptional regulation during EBV primary infection in B lymphoma cells.

Genomics 2021 Jul 1;113(4):2591-2604. Epub 2021 Jun 1.

Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong 510080, China. Electronic address:

The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.039DOI Listing
July 2021

Genetic alteration of Chinese patients with rectal mucosal melanoma.

BMC Cancer 2021 May 27;21(1):623. Epub 2021 May 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Fucheng Road No.52, Haidian District, Peking, 100142, Beijing, People's Republic of China.

Background: Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy.

Methods: 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance.

Results: BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735-34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305-97.300), P = 0.005].

Conclusions: This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.
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http://dx.doi.org/10.1186/s12885-021-08383-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161925PMC
May 2021

Ab initio dynamics simulation of laser-induced photodissociation of phenol.

Phys Chem Chem Phys 2021 Jun 26;23(22):12718-12730. Epub 2021 May 26.

College of Physical, Sichuan University, Chengdu 610065, China.

We theoretically investigated the photodissociation dynamics of phenol molecules steered by a sequence of temporally shaped femtosecond laser pulses with high intensity and ultrashort duration, via the real-time Time-Dependent Density Functional Theory (rt-TDDFT) combined with a Molecular Dynamics (MD) simulation. The principal findings of this research are that the phenol photodissociation can take place in 50 fs; the bonds broke sequentially; the degree of phenol molecular dissociation has a strong linear correlation with the intensity. For an incident laser being 800 nm-40 fs (wavelength-pulse duration), the threshold intensity is 7 × 10 W cm and the products are hydrogen from OH1 (phenolic hydroxyl group) and CHO-fragments. More fragments will be found at stronger intensity, shorter wavelengths, and longer pulse duration. More accurately, we estimated the critical values of bond cleavage of an isolated phenol molecule are 1.779 Å for O-H1 and 2.184 Å for C-Hs via Electron localization function (ELF) analysis. The photodissociation of the phenol molecule was triggered via the excitation of electrons and the dissociation process of phenol here is in good agreement with the characteristics of field-assisted dissociation (FAD) theory. Orthogonal tests with an L (3) matrix and threshold intensity decrease tests were conducted to confirm the mechanism. Our research gives an insight into the photodissociation experiment of phenol and provides a simple yet effective way to understand the photochemical experiments of more complex organic pollutants with toxicity.
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http://dx.doi.org/10.1039/d1cp00290bDOI Listing
June 2021

In vitro and in vivo anti-metastatic effect of the alkaliod matrine from Sophora flavecens on hepatocellular carcinoma and its mechanisms.

Phytomedicine 2021 Jul 27;87:153580. Epub 2021 Apr 27.

Department of Pharmacy, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Boulevard (North), Guangzhou 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Backgrounds: Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancer with high metastasis and recurrence rates. Hypoxia-induced miRNAs and HIF-1α are demonstrated to play essential roles in tumor metastasis. Matrine (CHNO), an alkaloid extracted from Sophora flavescens Aiton, has been used as adjuvant therapy for liver cancer in China. The anti-metastasis effects of matrine on HCC and the underlying mechanisms remain poorly understood.

Purpose: We aimed to investigate the effects of matrine on metastasis of HCC both in vitro and in vivo, and explored whether miR-199a-5p and HIF-1α are involved in the action of matrine.

Methods: MTT method, colony formation, wound healing and matrigel transwell assays were performed to evaluate the effects of matrine on cell proliferation, migration and invasion. Nude mice xenograft model and immunohistochemistry (IHC) assay were employed to investigate the anti-metastatic action of matrine in vivo. Quantitative real-time PCR, western blot and dual luciferase reporter assay were conducted to determine the underlying mechanisms of matrine.

Results: Matrine exerted stronger anti-proliferative action on Bel7402 and SMMC-7721 cells under hypoxia than that in normoxia. Both matrine and miR-199a-5p exhibited significant inhibitory effects on migration, invasion and EMT in Bel7402 and SMMC-7721 cells under hypoxia. Further study showed that miR-199a-5p was downregulated in HCC cell lines, and this microRNA was identified to directly target HIF-1α, resulting in decreased HIF-1α expression. Matrine induced miR-199a-5p expression, decreased HIF-1α expression and inhibited metastasis of Bel7402 and SMMC-7721 cells, while miR-199a-5p knockdown reversed the inhibitory effects of matrine on cell migration, invasion, EMT and HIF-1α expression. In vivo, matrine showed significant anti-metastatic activity in the nude mouse xenograft model. H&E and IHC analysis indicated that lung and liver metastasis nodules were reduced, and the protein expression of HIF-1α and Vimentin were significantly decreased by i.p injection of matrine.

Conclusions: Matrine exhibits significant anti-metastatic effect on HCC, which is attributed to enhanced miR-199a-5p expression and subsequently impaired HIF-1α signaling and EMT. These findings suggest that miR-199a-5p is a potential therapeutic target of HCC, and matrine may represent a promising anti-metastatic medication for HCC therapy.
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http://dx.doi.org/10.1016/j.phymed.2021.153580DOI Listing
July 2021

Concealed Wireless Warning Sensor Based on Triboelectrification and Human-Plant Interactive Induction.

Research (Wash D C) 2021 29;2021:9870936. Epub 2021 Apr 29.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

With the continuous development of artificial intelligence, the demand for sensors with simple preparation and strong concealment continues to increase. However, most of the high-sensitivity sensors have complex manufacturing methods, high costs, and single functions. In this paper, a sensitive motion sensor based on the triboelectric interaction between a living plant and the human body was designed to detect the real-time movements of human beings and provide danger warning. A certain relationship exists between the triboelectric signal and the distance between the plant and the human body, with effective signals being detected in the range of 1.8 m. In addition, the triboelectric signal generated by each person is unique like a fingerprint, which can be used for biometrics. On the basis of the triboelectric signal, a wireless character entry warning system is designed. This sensor can not only send out a wireless warning signal at a specific distance but also allow one to receive the warning information synchronously on a mobile phone in real time. The wireless movement sensor receives signals through a living plant, and it has the characteristics of convenient use, strong concealment, and shielding difficulty. This sensor has the potential to be widely used in person recognition, danger warning, and motion monitoring.
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http://dx.doi.org/10.34133/2021/9870936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106444PMC
April 2021

Vitamin D receptor gene polymorphisms and its interactions with environmental factors on renal cell carcinoma risk.

Genes Environ 2021 May 18;43(1):19. Epub 2021 May 18.

Department of Urology, Linyi cancer hospital, No.6 Lingyuan East Street, Lanshan District, Shandong Province, Linyi CIty, China.

Aims: We designed a case-control study to investigate the effect of vitamin D receptor gene (VDR) gene single nucleotide polymorphisms (SNPs) and possible gene- environment interaction on the susceptibility of renal cell carcinoma (RCC).

Methods: Generalized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between SNPs and environmental factors, including gene- gene synergy and gene environment synergy effect. Logistic regression was used to analyze the correlation between the four SNPs in VDR gene and RCC, and the significant interaction combinations found by GMDR model were analyzed by hierarchical analysis.

Results: The genotype distribution of the control group was in accordance with Hardy- Weinberg equilibrium. Logistic regression analysis showed that the risk of RCC in VDR-rs7975232 A allele carriers was significantly higher than that of CC genotype carriers (CA + AA vs. CC), adjusted OR (95 % CI) = 1.75 (1.26-2.28). We used GMDR model to screen the best synergistic model between the four SNPs of VDR gene and smoking and drinking. We found a significant two locus model (P = 0.0010) involving rs7975232 and smoking. The cross- validation consistency of the two- locus model was 10/ 10, and the accuracy was 60.72 %. Compared with non-smokers with rs7975232 -CA or AA genotype, smokers with rs7975232 -CC genotype had the highest risk of RCC, or (95 % CI) = 2.23 (1.42-3.09), after adjustment for covariates.

Conclusions: We found that the A allele of rs7975232 within VDR gene, interaction between rs7975232 and smoking were all associated with increased RCC risk.
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http://dx.doi.org/10.1186/s41021-021-00185-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130296PMC
May 2021

Plant multiscale networks: charting plant connectivity by multi-level analysis and imaging techniques.

Sci China Life Sci 2021 Sep 12;64(9):1392-1422. Epub 2021 Mar 12.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, 100083, China.

In multicellular and even single-celled organisms, individual components are interconnected at multiscale levels to produce enormously complex biological networks that help these systems maintain homeostasis for development and environmental adaptation. Systems biology studies initially adopted network analysis to explore how relationships between individual components give rise to complex biological processes. Network analysis has been applied to dissect the complex connectivity of mammalian brains across different scales in time and space in The Human Brain Project. In plant science, network analysis has similarly been applied to study the connectivity of plant components at the molecular, subcellular, cellular, organic, and organism levels. Analysis of these multiscale networks contributes to our understanding of how genotype determines phenotype. In this review, we summarized the theoretical framework of plant multiscale networks and introduced studies investigating plant networks by various experimental and computational modalities. We next discussed the currently available analytic methodologies and multi-level imaging techniques used to map multiscale networks in plants. Finally, we highlighted some of the technical challenges and key questions remaining to be addressed in this emerging field.
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http://dx.doi.org/10.1007/s11427-020-1910-1DOI Listing
September 2021

Cell Wall and Hormone Interplay Controls Growth Asymmetry.

Trends Plant Sci 2021 07 3;26(7):665-667. Epub 2021 May 3.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China. Electronic address:

Plant cell elongation and expansion require the biosynthesis and remodeling of cell wall composition. Recently, Aryal et al. reported how feedback between the cell wall and the auxin response controls differential growth in apical hook development.
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http://dx.doi.org/10.1016/j.tplants.2021.04.003DOI Listing
July 2021

Xiaoyaosan Improves Antibiotic-Induced Depressive-Like and Anxiety-Like Behavior in Mice Through Modulating the Gut Microbiota and Regulating the NLRP3 Inflammasome in the Colon.

Front Pharmacol 2021 16;12:619103. Epub 2021 Apr 16.

Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

Disturbance of the gut microbiota plays an essential role in mental disorders such as depression and anxiety. Xiaoyaosan, a traditional Chinese medicine formula, has a wide therapeutic spectrum and is used especially in the management of depression and anxiety. In this study, we used an antibiotic-induced microbiome-depleted (AIMD) mouse model to determine the possible relationship between imbalance of the intestinal flora and behavioral abnormalities in rodents. We explored the regulatory effect of Xiaoyaosan on the intestinal flora and attempted to elucidate the potential mechanism of behavioral improvement. We screened NLRP3, ASC, and CASPASE-1 as target genes based on the changes in gut microbiota and explored the effect of Xiaoyaosan on the colonic NLRP3 pathway. After Xiaoyaosan intervention, AIMD mice showed a change in body weight and an improvement in depressive and anxious behaviors. Moreover, the gut flora diversity was significantly improved. Xiaoyaosan increased the abundance of Lachnospiraceae in AIMD mice and decreased that of Bacteroidaceae, the main lipopolysaccharide (LPS)-producing bacteria, resulting in decreased levels of LPS in feces, blood, and colon tissue. Moreover, serum levels of the inflammatory factor, IL-1β, and the levels of NLRP3, ASC, and CASPASE-1 mRNA and DNA in the colon were significantly reduced. Therefore, Xiaoyaosan may alleviate anxiety and depression by modulating the gut microbiota, correcting excessive LPS release, and inhibiting the immoderate activation of the NLRP3 inflammasome in the colon.
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http://dx.doi.org/10.3389/fphar.2021.619103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087337PMC
April 2021

Traditional Chinese Formula Xiaoyaosan Alleviates Depressive-Like Behavior in CUMS Mice by Regulating PEBP1-GPX4-Mediated Ferroptosis in the Hippocampus.

Neuropsychiatr Dis Treat 2021 6;17:1001-1019. Epub 2021 Apr 6.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.

Background: At present, the pathogenesis of depression is not fully understood, and nearly half of depression patients experience no obvious effects during treatment. This study aimed to establish a depression mouse model to explore the possible role of ferroptosis in the pathogenesis of depression, and observe the effects of Xiaoyaosan on PEBP1-GPX4-mediated ferroptosis in the hippocampus.

Methods: Forty-eight male C57BL/6 mice were randomly divided into a control group, CUMS group, Xiaoyaosan group and fluoxetine group, and the model was established by chronic unpredictable mild stress (CUMS) for a successive 6 weeks. The medication procedure was performed from the 4th to the 6th week of modeling. The behavioral evaluations were measured to evaluate depressive-like behaviors. The expressions of GPX4, FTH1, ACSL4 and COX2 were detected as ferroptosis-related indicators. Then, the total iron and ferrous content in the hippocampus were measured. The levels of PEBP1 and ERK1/2 were observed, and the expressions of GFAP and IBA1 were also detected to measure the functions of astrocytes and microglia in the hippocampus.

Results: Eight herbs of Xiaoyaosan had 133 active ingredients which could regulate the 43 ferroptosis-related genes in depression. After 6 weeks of modeling, the data showed that mice in the CUMS group had obvious depressive-like behaviors, and medication with Xiaoyaosan or fluoxetine could significantly improve the behavioral changes. The expressions of GPX4, FTH1, ACSL4, COX2, PEBP1, ERK1/2, GFAP and IBA1 changed in the CUMS group mice, while the total iron and ferrous content also changed. Xiaoyaosan and fluoxetine had obvious curative effects that could significantly alleviate the above changes in the hippocampus.

Conclusion: Our results revealed that the activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.
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http://dx.doi.org/10.2147/NDT.S302443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039849PMC
April 2021

Circ_001569 regulates FLOT2 expression to promote the proliferation, migration, invasion and EMT of osteosarcoma cells through sponging miR-185-5p.

Open Life Sci 2020 10;15(1):476-487. Epub 2020 Jul 10.

Department of Orthopaedic, Second People's Hospital of Gansu Province, No. 1 Hezheng West Street, Chengguan District, Lanzhou City, Gansu Province, 730000, China.

Osteosarcoma (OS) is a common malignant tumor in the world. Circular RNAs are endogenous non-coding RNAs that have been linked to the development of cancer. However, the role of circ_001569 in OS progression is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_001569, microRNA-185-5p (miR-185-5p) and flotillin-2 (FLOT2). The abilities of cell proliferation, migration and invasion were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2--tetrazolium bromide (MTT) and Transwell assays, respectively. Also, western blot analysis was performed to assess the levels of epithelial-mesenchymal transition (EMT)-related proteins and FLOT2 protein. Besides, the dual-luciferase reporter assay was used to verify the interactions among circ_001569, miR-185-5p and FLOT2. Circ_001569 expression was increased in OS tissues and cells, and its knockdown reduced the proliferation, migration, invasion and EMT of OS cells. MiR-185-5p could interact with circ_001569. Inhibition of miR-185-5p could recover the suppression effects of silenced-circ_001569 on the proliferation and metastasis of OS cells. Furthermore, FLOT2 was a target of miR-185-5p. Overexpressed FLOT2 could restore the inhibition effects of miR-185-5p mimic on the proliferation and metastasis of OS cells. Also, FLOT2 expression was regulated by circ_001569 and miR-185-5p. In addition, circ_001569 knockdown also reduced the OS tumor growth . Circ_001569 might act as an oncogene in OS progression by regulating the miR-185-5p/FLOT2 axis, which provided a reliable new approach for the treatment of OS patients.
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http://dx.doi.org/10.1515/biol-2020-0050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874578PMC
July 2020
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