Publications by authors named "Jia Guo"

804 Publications

MiR-138 plays an important role in diabetic nephropathy through SIRT1-p38-TTP regulatory axis.

J Cell Physiol 2021 Apr 12. Epub 2021 Apr 12.

Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and is one of the most common and serious complications of diabetes mellitus (DM). Sirtuin 1 (SIRT1) and tristetraprolin (TTP) are two important protective factors in DN; however, the regulatory relationship between SIRT1 and TTP, and the underneath mechanism are interesting but still unclear. Identifying the key factors that regulate SIRT1 or TTP may be of great value to the understanding and treatment of the DN. In this study, through systematic experimental methods, we found that the expression of miR-138 was significantly upregulated in DN clinical patient samples, and our experimental results suggested that miR-138 could bind the 3'-UTR of SIRT1 and inhibit its expression in both cultured podocytes and db/db mice kidney tissues. Furthermore, our in vitro and in vivo experiments also indicated miR-138 could target SIRT1 and affect TTP through p38 pathway. And downregulation of miR-138 attenuated podocyte injury and showed some extent of therapeutic effects in DN mice models. Our findings revealed that the regulatory axis of miR-138-SIRT1-p38-TTP might play a key role in DN. We believe that these findings may be of some value for deepening the understanding of DN and may serve as a reference for future treatment of this disease.
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http://dx.doi.org/10.1002/jcp.30238DOI Listing
April 2021

Factors associated with diabetes distress among adolescents with type 1 diabetes.

J Clin Nurs 2021 Apr 7. Epub 2021 Apr 7.

Xiangya School of Nursing, Central South University, Changsha, China.

Aims: To describe the specific domains of diabetes distress and factors associated with these domains.

Background: Diabetes distress is a common problem but not well recognised in adolescents by healthcare providers or adolescents themselves. There is insufficient evidence on how specific domains of diabetes distress exist in adolescents, making it challenging to select precise components to alleviate diabetes stress.

Design: A quantitative, descriptive and cross-sectional study.

Methods: Data were collected on socio-demographic and clinical characteristics, diabetes distress, perceived stress, self-efficacy and diabetes self-management using established questionnaires. Multivariate linear regression was conducted to examine the associations between specific factors and four domains in diabetes distress. STROBE checklist was used as the guideline for this study.

Results: A total of 100 adolescents with type 1 diabetes aged 12 to 18 years participated in this study. Adolescents experienced the highest levels of distress in the regimen-related distress [2.41 (SD =0.82)] and physician-related distress [2.40 (SD =0.80)] domains. Older age, female gender, more diabetes problem-solving and higher levels of perceived stress were associated with higher regimen-related distress (β = 0.21 ~ 0.45, p < 0.05). Older age, female gender, a lower degree of endorsement of relevant diabetes-related goals and higher levels of perceived stress were associated with higher physician-related distress (β = -0.29 ~ 0.34, p < 0.05).

Conclusions: Diabetes distress was reported more on regimen-related and physician-related domains among adolescents with type 1 diabetes in China, associating with older age, female, increased perceived stress and poor diabetes-related problem-solving.

Relevance To Clinical Practice: Nurses need to screen the specific domains of diabetes distress among adolescents with type 1 diabetes, especially for the older adolescents and girls. This study highlighted the importance of incorporating diabetes-related problem-solving support and stress management strategies into diabetes management for adolescents with type 1 diabetes, which could help relieve diabetes distress.
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http://dx.doi.org/10.1111/jocn.15742DOI Listing
April 2021

Phase Tailoring of Ruddlesden-Popper Perovskite at Fixed Large Spacer Cation Ratio.

Small 2021 Apr 4:e2100560. Epub 2021 Apr 4.

Joint Key Laboratory of the Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Avenida da Universidade, Taipa, Macao, 999078, China.

Ruddlesden-Popper (RP) metal halide perovskites are considered as promising optoelectronic materials due to their good environmental stability and desirable optoelectronic properties. However, the phase composition and ordering in the deposited film, with a fixed ratio of large organic spacer cation in the precursor solution, are hard to be further tailored for specific optoelectronic applications. Herein, it is shown that even with a fixed spacer cation ratio, the phase composition and ordering can still be largely regulated by utilizing different crystallization kinetics of various cations with the inorganic octahedral lead halide. By using two different short cations to compete with the large spacer cation, the phase composition can be continuously tailored from thin multiple quantum wells (MQWs) dominated to 3D perovskite dominated. The phase ordering can be reversed from small n phases' prior to large n phases' prior near the substrate. Finally, with the same amount of large spacer cation protection, the perovskite can be tailored for both high-performance electroluminescence and photovoltaics with favorable energetic landscape for the corresponding desired first-order excitonic recombination and second-order free electron-hole recombination, respectively. This exploration substantially contributes to the understanding of precise phase engineering in RP perovskite and may provide a new insight into the design of multiple functional devices.
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http://dx.doi.org/10.1002/smll.202100560DOI Listing
April 2021

Instrument Context Relevance Evaluation, Translation, and Psychometric Testing of the Diabetes Eating Problem Survey-Revised (DEPS-R) among People with Type 1 Diabetes in China.

Int J Environ Res Public Health 2021 Mar 26;18(7). Epub 2021 Mar 26.

School of Nursing, Yale University, New Haven, CT 06520, USA.

Background: People with type 1 diabetes are susceptible to disordered eating behaviors. The American Diabetes Association recommends using the Diabetes Eating Problem Survey-Revised (DEPS-R) to screen them. There is no validated diabetes-specific screening measure in China. The objectives were to adapt DEPS-R into Mandarin Chinese and to test its psychometric properties among youths and adults with type 1 diabetes in China, respectively.

Methods: This study was conducted in two phases. Phase 1 included context relevance evaluation and instrument translation. Phase 2 was psychometric testing of reliability and construct validity among 89 youths (8~17 years old) and 61 adults with type 1 diabetes.

Result: The Context Relevance Index and Translation Validity Index of this instrument were good. Strong internal consistency reliability correlations and convergent validity were demonstrated among youths and adults.

Discussion: The Chinese version of the DEPS-R is a valid and reliable tool for screening disordered eating behaviors in Chinese youths and adults with type 1 diabetes. The Context Relevance Index is advocated to evaluate the difference between the context in which an instrument was originally developed and the target context.
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http://dx.doi.org/10.3390/ijerph18073450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037186PMC
March 2021

Erratum: The Role of CHK1 Varies with the Status of Oestrogen-receptor and Progesterone-receptor in the Targeted Therapy for Breast Cancer : Erratum.

Int J Biol Sci 2021 20;17(3):911-912. Epub 2021 Feb 20.

Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.

[This corrects the article DOI: 10.7150/ijbs.41627.].
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http://dx.doi.org/10.7150/ijbs.58372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975706PMC
February 2021

Structural insights into the lipid and ligand regulation of serotonin receptors.

Nature 2021 Mar 24. Epub 2021 Mar 24.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter that activates the largest subtype family of G-protein-coupled receptors. Drugs that target 5-HT, 5-HT, 5-HT and other 5-HT receptors are used to treat numerous disorders. 5-HT receptors have high levels of basal activity and are subject to regulation by lipids, but the structural basis for the lipid regulation and basal activation of these receptors and the pan-agonism of 5-HT remains unclear. Here we report five structures of 5-HT receptor-G-protein complexes: 5-HT in the apo state, bound to 5-HT or bound to the antipsychotic drug aripiprazole; 5-HT bound to 5-HT; and 5-HT in complex with a 5-HT- and 5-HT-selective agonist, BRL-54443. Notably, the phospholipid phosphatidylinositol 4-phosphate is present at the G-protein-5-HT interface, and is able to increase 5-HT-mediated G-protein activity. The receptor transmembrane domain is surrounded by cholesterol molecules-particularly in the case of 5-HT, in which cholesterol molecules are directly involved in shaping the ligand-binding pocket that determines the specificity for aripiprazol. Within the ligand-binding pocket of apo-5-HT are structured water molecules that mimic 5-HT to activate the receptor. Together, our results address a long-standing question of how lipids and water molecules regulate G-protein-coupled receptors, reveal how 5-HT acts as a pan-agonist, and identify the determinants of drug recognition in 5-HT receptors.
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http://dx.doi.org/10.1038/s41586-021-03376-8DOI Listing
March 2021

Measurement of the sound velocity of shock compressed water.

Sci Rep 2021 Mar 17;11(1):6116. Epub 2021 Mar 17.

Shanghai Institute of Laser Plasma, China Academy of Engineering Physics, ShangHai, 201102, China.

The sound velocities of water in the Hugoniot states are investigated by laser shock compression of precompressed water in a diamond anvil cell. The obtained sound velocities in the off-Hugoniot region of liquid water at precompressed conditions are used to test the predictions of quantum molecular dynamics (QMD) simulations and the SESAME equation-of-state (EOS) library. It is found that the prediction of QMD simulations agrees with the experimental data while the prediction of SESAME EOS library underestimates the sound velocities probably due to its improper accounting for the ionization processes.
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http://dx.doi.org/10.1038/s41598-021-84978-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969927PMC
March 2021

Cerebrovascular reactivity measurements using simultaneous O-water PET and ASL MRI: Impacts of arterial transit time, labeling efficiency, and hematocrit.

Neuroimage 2021 Mar 11;233:117955. Epub 2021 Mar 11.

Department of Radiology, Stanford University, Stanford, CA, United States. Electronic address:

Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p<0.01, paired t-test). Changes in ATT pre- and post-acetazolamide was the principal factor affecting ASL-based CVR quantification. Variations in labeling efficiency and blood T1 had negligible effects.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117955DOI Listing
March 2021

Entropy-Driven Quick Loading of Functional Proteins in Nanohydrogels for Highly Efficient Tumor Targeting Therapy.

ACS Appl Mater Interfaces 2021 Mar 14;13(11):12888-12898. Epub 2021 Mar 14.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, Shanghai 200438, P. R. China.

With the gradual deep understanding of the tumorigenesis and development process, nanodrug are thought to have great prospects for individualized treatment of tumors. To deliver adequate concentration of active ingredients to targeted tissues, proteins are usually used as carriers to avoid clearance by the immune system. Herein, a new strategy is developed for preparation of the protein-functionalized targeting nanodrugs; different kinds of proteins (albumin, horseradish, transferrin, and ricin) can be quickly loaded in polyacrylic acid nanohydrogels (PAA-NGs) without discrimination within 1 min under the strong driving force of entropy; and the loading efficiency can reach 99% with about 50% loading content. Meanwhile, the activity of the released protein can be well retained. After oriented binding of the targeting agent on the surface of the nanocarriers by a unique and facile technique, the protein-loaded nanodrug exhibits excellent tumor cell uptake and targeting effect. The excellent targeting ability from the oriented binding is further proved by comparing with the non-oriented targeting system. With quick loading of the anti-tumor protein of ricin and oriented binding of transferrin protein (Tf), the targeting nanodrug (PAA-BB@Ricin/Tf) shows a remarkable anti-tumor effect. This study proves a new universal delivery and targeting strategy for improving the nanodelivery system, which has great potentials for clinical application.
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http://dx.doi.org/10.1021/acsami.0c23124DOI Listing
March 2021

Importance of NLRP3 Inflammasome in Abdominal Aortic Aneurysms.

J Atheroscler Thromb 2021 Mar 6. Epub 2021 Mar 6.

School of Health Science, Faculty of Medicine, Kagoshima University.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory degenerative aortic disease, which particularly affects older people. Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome is a multi-protein complex and mediates inflammatory responses by activating caspase 1 for processing premature interleukin (IL)-1β and IL-18. In this review, we first summarize the principle of NLRP3 inflammasome activation and the functionally distinct classes of small molecule NLRP3 inflammasome inhibitors. Next, we provide a comprehensive literature review on the expression of NLRP3 inflammasome effector mediators (IL-1β and IL-18) and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3) in clinical and experimental AAAs. Finally, we discuss the influence of genetic deficiency or pharmacological inhibition of individual effector mediators and components of NLRP3 inflammasome on experimental AAAs. Accumulating clinical and experimental evidence suggests that NLRP3 inflammasome may be a promise therapeutic target for developing pharmacological strategies for clinical AAA management.
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http://dx.doi.org/10.5551/jat.RV17048DOI Listing
March 2021

, An AP2/ERF Transcription Factor, Is Positively Involved in Wheat Resistance to f. sp. .

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling 712100, China.

AP2 transcription factors play a crucial role in plant development and reproductive growth, as well as response to biotic and abiotic stress. However, the role of , in the interaction between wheat and the stripe fungus, f. sp. (), remains elusive. In this study, we isolated and characterized its function during the interaction. TaAP2-15 was localized in the nucleus of wheat and . Silencing of by barley stripe mosaic virus (BSMV)-mediated VIGS (virus-induced gene silencing) increased the susceptibility of wheat to accompanied by enhanced growth of the pathogen (number of haustoria, haustorial mother cells and hyphal length). We confirmed by quantitative real-time PCR that the transcript levels of pathogenesis-related genes ( and ) were down-regulated, while reactive oxygen species (ROS)-scavenging genes ( and ) were induced accompanied by reduced accumulation of HO. Furthermore, we found that TaAP2-15 interacted with a zinc finger protein (TaRZFP34) that is a homolog of OsRZFP34 in rice. Together our findings demonstrate that is positively involved in resistance of wheat to the stripe rust fungus and provides new insights into the roles of AP2 in the host-pathogen interaction.
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http://dx.doi.org/10.3390/ijms22042080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923241PMC
February 2021

Reconstruction of functional uterine tissues through recellularizing the decellularized rat uterine scaffolds by MSCs in vivo and in vitro.

Biomed Mater 2021 Mar 3;16(3):035023. Epub 2021 Mar 3.

Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

Infertile people who suffered from loss of uterine structures and/or functions can be treated through gestational surrogacy or uterus transplantation, which remains challenging due to the ethical and social issues, the lack of donor organs as well as technical and safety risks. One promising solution is to regenerate and reconstruct a bioartificial uterus for transplantation through the engineering of uterine architecture and appropriate cellular constituents. Here, we developed a well-defined system to regenerate a functional rat uterine through recellularization of the decellularized uterine matrix (DUM) patches reseeded with human mesenchymal stem cells (hMSCs). Engraftment of the recellularized DUMs on the partially excised uteri yielded a functional rat uterus with a pregnancy rate and number of fetuses per uterine horn comparable to that of the control group with an intact uterus. Particularly, the recellularized DUMs enhanced the regeneration of traumatic uterine in vivo because of MSC regulation. The established system here will shed light on the treatment of uterine infertility with heterogeneous DUMs/cell resources through tissue engineering in the future.
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http://dx.doi.org/10.1088/1748-605X/abd116DOI Listing
March 2021

[Mechanism of Mahuang Lianqiao Chixiaodou Decoction in treating eczema by network pharmacology and molecular docking technology].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(4):894-901

Henan University of Chinese Medicine Zhengzhou 450046,China.

To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201117.401DOI Listing
February 2021

A deep learning algorithm using CT images to screen for Corona virus disease (COVID-19).

Eur Radiol 2021 Feb 24. Epub 2021 Feb 24.

Department of Biochemistry and Molecular Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.

Objective: The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has caused more than 26 million cases of Corona virus disease (COVID-19) in the world so far. To control the spread of the disease, screening large numbers of suspected cases for appropriate quarantine and treatment are a priority. Pathogenic laboratory testing is typically the gold standard, but it bears the burden of significant false negativity, adding to the urgent need of alternative diagnostic methods to combat the disease. Based on COVID-19 radiographic changes in CT images, this study hypothesized that artificial intelligence methods might be able to extract specific graphical features of COVID-19 and provide a clinical diagnosis ahead of the pathogenic test, thus saving critical time for disease control.

Methods: We collected 1065 CT images of pathogen-confirmed COVID-19 cases along with those previously diagnosed with typical viral pneumonia. We modified the inception transfer-learning model to establish the algorithm, followed by internal and external validation.

Results: The internal validation achieved a total accuracy of 89.5% with a specificity of 0.88 and sensitivity of 0.87. The external testing dataset showed a total accuracy of 79.3% with a specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images, the first two nucleic acid test results were negative, and 46 were predicted as COVID-19 positive by the algorithm, with an accuracy of 85.2%.

Conclusion: These results demonstrate the proof-of-principle for using artificial intelligence to extract radiological features for timely and accurate COVID-19 diagnosis.

Key Points: • The study evaluated the diagnostic performance of a deep learning algorithm using CT images to screen for COVID-19 during the influenza season. • As a screening method, our model achieved a relatively high sensitivity on internal and external CT image datasets. • The model was used to distinguish between COVID-19 and other typical viral pneumonia, both of which have quite similar radiologic characteristics.
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http://dx.doi.org/10.1007/s00330-021-07715-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904034PMC
February 2021

Application of "hand as foot teaching method" in rehabilitation medicine of venous thrombosis after orthopedic surgery.

Asian J Surg 2021 Mar 19;44(3):572-573. Epub 2021 Feb 19.

Inner Mongolia Medical University, Department of Orthopedics, Affiliated Hospital of Inner Mongolia Medical University, Hohhot North Street, Inner Mongolia, 010050, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2020.12.035DOI Listing
March 2021

Similarity-based health risk prediction using Domain Fusion and electronic health records data.

J Biomed Inform 2021 Feb 19;116:103711. Epub 2021 Feb 19.

Department of Biostatistics, Mailman School of Public Health, Columbia University, United States. Electronic address:

Electronic Health Record (EHR) data represents a valuable resource for individualized prospective prediction of health conditions. Statistical methods have been developed to measure patient similarity using EHR data, mostly using clinical attributes. Only a handful of recent methods have combined clinical analytics with other forms of similarity analytics, and no unified framework exists yet to measure comprehensive patient similarity. Here, we developed a generic framework named Patient similarity based on Domain Fusion (PsDF). PsDF performs patient similarity assessment on each available domain data separately, and then integrate the affinity information over various domains into a comprehensive similarity metric. We used the integrated patient similarity to support outcome prediction by assigning a risk score to each patient. With extensive simulations, we demonstrated that PsDF outperformed existing risk prediction methods including a random forest classifier, a regression-based model, and a naïve similarity method, especially when heterogeneous signals exist across different domains. Using PsDF and EHR data extracted from the data warehouse of Columbia University Irving Medical Center, we developed two different clinical prediction tools for two different clinical outcomes: incident cases of end stage kidney disease (ESKD) and severe aortic stenosis (AS) requiring valve replacement. We demonstrated that our new prediction method is scalable to large datasets, robust to random missingness, and generalizable to diverse clinical outcomes.
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http://dx.doi.org/10.1016/j.jbi.2021.103711DOI Listing
February 2021

Naringin as a plant-derived bitter tastant promotes proliferation of cultured human airway epithelial cells via activation of TAS2R signaling.

Phytomedicine 2021 Apr 5;84:153491. Epub 2021 Feb 5.

Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China. Electronic address:

Background: Bitter tastants can activate bitter taste receptors (TAS2Rs) and thus initiate relaxation of airway smooth muscle cells (ASMCs), which have great potential in the development of novel bronchodilator drugs for asthma therapy. However, the canonical bitter substance, denatonium is known to induce apoptosis of airway epithelial cells (AECs), indicating that other bitter tastants may also impair the epithelial integrity to prevent hazardous particulate matters such as coronaviruses. Therefore, any bitter tastants intended for treating airway disease should be carefully evaluated for potential toxicity to AECs.

Hypothesis/purpose: Considering the vast diversity of bitter tastants in nature and different types of TAS2Rs expressed in airway cells, we hypothesized that there must be some natural bitter tastants to be not only potent in inducing relaxation of ASMCs but also unharmful to AECs.

Study Design And Methods: Here we evaluated a group of bitter flavonoids that are derived from fruits and commonly used in traditional herbal medicine, including apigenin, hesperetin, kaempferol, naringenin, quercetin, and naringin, for their effects on the proliferation of human airway epithelial-like (16HBE14o-, BEAS-2B, and A549) cells cultured in vitro. Cell proliferation and associated signaling pathways were assessed by cell counting, ATP assay, cell cycling assay, quantitative RT-PCR, Fluo-4 labeling, and fluorescence resonance energy transfer, respectively.

Results: The results show that five of the six tested bitter tastants inhibited, but only naringin promoted the proliferation of the 16HBE14o-, BEAS-2B, and A549 cells at the dose of a few hundred micromoles. Furthermore, the naringin-promoted proliferation of the 16HBE14o- cells was associated with enhanced cell cycle progression, mRNA expression of cyclin E, and evoked calcium signaling/ERK signaling, which were all attenuated by inhibition of the TAS2R signaling pathways with specific blockers.

Conclusion: These findings indicate that although the majority of the bitter flavonoids may inhibit the proliferation of AECs, naringin emerged as one to promote the proliferation of AECs via cell cycle progression and TAS2R-activated intracellular signaling. It suggests that naringin and not a few other bitter tastants can be proven with nontoxicity to the airway epithelial structure and function, which provides further confidence in the development of safe and effective TAS2R-based bronchodilators for asthma therapy.
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http://dx.doi.org/10.1016/j.phymed.2021.153491DOI Listing
April 2021

Angiotensin-converting enzyme 2, coronavirus disease 2019, and abdominal aortic aneurysms.

J Vasc Surg 2021 Feb 15. Epub 2021 Feb 15.

Department of Surgery, Stanford University School of Medicine, Stanford, Calif.

Objective: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiologic agent of the current, world-wide coronavirus disease 2019 (COVID-19) pandemic. Angiotensin-converting enzyme 2 (ACE2) is the SARS-CoV-2 host entry receptor for cellular inoculation and target organ injury. We reviewed ACE2 expression and the role of ACE2-angiotensin 1-7-Mas receptor axis activity in abdominal aortic aneurysm (AAA) pathogenesis to identify potential COVID-19 influences on AAA disease pathogenesis.

Methods: A comprehensive literature search was performed on PubMed, National Library of Medicine. Key words included COVID-19, SARS-CoV-2, AAA, ACE2, ACE or angiotensin II type 1 (AT1) receptor inhibitor, angiotensin 1-7, Mas receptor, age, gender, respiratory diseases, diabetes, and autoimmune diseases. Key publications on the epidemiology and pathogenesis of COVID-19 and AAAs were identified and reviewed.

Results: All vascular structural cells, including endothelial and smooth muscle cells, fibroblasts, and pericytes express ACE2. Cigarette smoking, diabetes, chronic obstructive pulmonary disease, lupus, certain types of malignancies, and viral infection promote ACE2 expression and activity, with the magnitude of response varying by sex and age. Genetic deficiency of AT1 receptor, or pharmacologic ACE or AT1 inhibition also increases ACE2 and its catalytic product angiotensin 1-7. Genetic ablation or pharmacologic inhibition of ACE2 or Mas receptor augments, whereas ACE2 activation or angiotensin 1-7 treatment attenuates, progression of experimental AAAs. The potential influences of SARS-CoV-2 on AAA pathogenesis include augmented ACE-angiotensin II-AT1 receptor activity resulting from decreased reciprocal ACE2-angiotensin 1-7-Mas activation; increased production of proaneurysmal mediators stimulated by viral spike proteins in ACE2-negative myeloid cells or by ACE2-expressing vascular structural cells; augmented local or systemic cross-talk between viral targeted nonvascular, nonleukocytic ACE2-expressing cells via ligand recognition of their cognate leukocyte receptors; and hypoxemia and increased systemic inflammatory tone experienced during severe COVID-19 illness.

Conclusions: COVID-19 may theoretically influence AAA disease through multiple SARS-CoV-2-induced mechanisms. Further investigation and clinical follow-up will be necessary to determine whether and to what extent the COVID-19 pandemic will influence the prevalence, progression, and lethality of AAA disease in the coming decade.
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http://dx.doi.org/10.1016/j.jvs.2021.01.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944865PMC
February 2021

Clinical Trial Outcomes and Thoracic Aorta Morphometry after One Year with the Valiant Navion Stent Graft System.

J Vasc Surg 2021 Feb 13. Epub 2021 Feb 13.

Cedars-Sinai Medical Center, Los Angeles, CA.

Authors' Note: On February 17, 2021, Medtronic Inc issued a global voluntary recall of the Valiant Navion Thoracic Stent Graft System (the device being studied in the Valiant Evo Global Clinical Program that is the subject of this publication), and instructed physicians to immediately cease use of the Valiant Navion system and return any unused product. Medtronic initiated the recall in response to three clinical trial subjects being recently observed with stent fractures, two of which have confirmed type IIIb endoleaks. The data collection, analysis, and manuscript submission occurred prior to the notice of this recall and specifically, the 100 procedures reviewed for this series were free of events at 1 year related to the reason for this device recall. The authors of this article and the manufacturer were unaware of the recently detected adverse events at the time of the preparation of the manuscript and 1-year trial results, and imaging-based analyses described herein are unchanged. Management of thoracic aortic aneurysms remains to be a challenging problem and outcomes are dependent on patient anatomy. The publication focuses on the importance of achieving proximal and distal seal as well as consideration of the temporal changes of the aortic morphology as part of the TEVAR planning process. The authors feel there is still scientific merit in disclosing this information, despite the current non-availability of the Valiant Navion system OBJECTIVES: The Valiant Navion stent graft system (Medtronic Inc, Santa Rosa, CA) is a third-generation device with improved conformability. One-year clinical trial outcomes are reported along with a focus on an imaging-based analysis of aortic morphology. Specifically, the authors assess the effect of graft implantation on the native anatomy and vice versa how one-year changes in thoracic aorta morphology can affect the original seal zones of the stent graft.

Methods: A total of 100 subjects were enrolled in the prospective single-arm clinical trial investigating the Valiant Navion stent graft system. An independent Core Lab (Syntactx, New York, NY) assessed anatomical characteristics and performance outcomes.

Results: Through one year, the freedom from all-cause mortality, aneurysm related mortality, and secondary procedures was 89.8%, 97.0%, and 94.8% respectively. There were five subjects that received a total of six secondary procedures and there were nine subjects with endoleaks (Type IA and Ib (1), Type IA (1), Type IB (3), Type II (4)) within the first year. After one year, 2.6% (2/76) of the patients had an increase in their maximum aneurysm diameter of 5mm or more, 81.6% (62/76) had stable sacs, and 15.8% (12/76) had sac shrinkage. While there were no deployment failures, 36% (36/100) of the proximal and 31% (31/100) of the distal attachment zones were considered short based on author definitions. The stent graft conformed to the native anatomy at implant as the pre-procedural thoracic aorta tortuosity (1.45±.02) was not significantly changed one-month post-implant (1.46±.02). Despite a natural increase in thoracic tortuosity after one year (1.49±.02), wall apposition was maintained over time as evidenced by the low endoleak rates. Aortic elongation and dilation occurred at the proximal end of the graft on average by 1.2mm and 1.6mm, respectively. The aortic remodeling was more pronounced at the distal end with an average increase of 4.2mm in length and 2.8mm in diameter.

Conclusions: Subjects had positive one-year outcomes with high freedom from mortality, endoleaks, and secondary procedures. Aortic elongation and dilation were more prevalent at the distal end which emphasizes the importance of distal attachment zone consideration as part of pre-case planning. As aortic remodeling is expected to continue over time, additional follow up and imaging analysis in the trial is necessary to assess aortic morphology and its effects on stent graft performance.
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http://dx.doi.org/10.1016/j.jvs.2021.01.047DOI Listing
February 2021

Highly Sensitive and Multiplexed Protein Imaging With Cleavable Fluorescent Tyramide Reveals Human Neuronal Heterogeneity.

Front Cell Dev Biol 2020 8;8:614624. Epub 2021 Jan 8.

Biodesign Institute & School of Molecular Sciences, Arizona State University, Tempe, AZ, United States.

The ability to comprehensively profile proteins in intact tissues is crucial for our understanding of health and disease. However, the existing methods suffer from low sensitivity and limited sample throughput. To address these issues, here we present a highly sensitive and multiplexed protein analysis approach using cleavable fluorescent tyramide and off-the-shelf antibodies. Compared with the current methods, this approach enhances the detection sensitivity and reduces the imaging time by 1-2 orders of magnitude, and can potentially detect hundreds of proteins in intact tissues at the optical resolution. Applying this approach, we studied protein expression heterogeneity in a population of genetically identical cells, and performed protein expression correlation analysis to identify co-regulated proteins. We also profiled >6,000 neurons in a human formalin-fixed paraffin-embedded (FFPE) hippocampus tissue. By partitioning these neurons into varied cell clusters based on their multiplexed protein expression profiles, we observed different sub-regions of the hippocampus consist of neurons from distinct clusters.
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http://dx.doi.org/10.3389/fcell.2020.614624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874177PMC
January 2021

Comparative Transcriptomic Analysis of Gene Expression Inheritance Patterns Associated with Cabbage Head Heterosis.

Plants (Basel) 2021 Jan 31;10(2). Epub 2021 Jan 31.

College of Horticulture, Northwest A&F University, Yangling 712100, China.

The molecular mechanism of heterosis or hybrid vigor, where F1 hybrids of genetically diverse parents show superior traits compared to their parents, is not well understood. Here, we studied the molecular regulation of heterosis in four F1 cabbage hybrids that showed heterosis for several horticultural traits, including head size and weight. To examine the molecular mechanisms, we performed a global transcriptome profiling in the hybrids and their parents by RNA sequencing. The proportion of genetic variations detected as single nucleotide polymorphisms and small insertion-deletions as well as the numbers of differentially expressed genes indicated a larger role of the female parent than the male parent in the genetic divergence of the hybrids. More than 86% of hybrid gene expressions were non-additive. More than 81% of the genes showing divergent expressions showed dominant inheritance, and more than 56% of these exhibited maternal expression dominance. Gene expression regulation by cis-regulatory mechanisms appears to mediate most of the gene expression divergence in the hybrids; however, trans-regulatory factors appear to have a higher effect compared to cis-regulatory factors on parental expression divergence. These observations bring new insights into the molecular mechanisms of heterosis during the cabbage head development.
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http://dx.doi.org/10.3390/plants10020275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912167PMC
January 2021

Structural insights into the human D1 and D2 dopamine receptor signaling complexes.

Cell 2021 Feb 10;184(4):931-942.e18. Epub 2021 Feb 10.

The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address:

The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G and D2R-G signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system.
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http://dx.doi.org/10.1016/j.cell.2021.01.027DOI Listing
February 2021

The Efficacy of an Intensive Lifestyle Modification Program on Psychosocial Outcomes among Rural Women with Prior Gestational Diabetes Mellitus: Six Months Follow-Up of a Randomized Controlled Trial.

Int J Environ Res Public Health 2021 Feb 5;18(4). Epub 2021 Feb 5.

School of Nursing, University of California, San Francisco, CA 94143, USA.

Women with prior gestational diabetes mellitus (GDM) are at a higher risk of type 2 diabetes and other health issues after delivery. They may have a lower quality of life (QoL), experience more medical-related stress, and need more support than those without it. This study aimed to examine the six-month efficacy of an intensive lifestyle modification program on perceived stress, social support, and QoL among women with prior GDM in rural China. A total of 320 women with prior GDM were randomly assigned to an intervention group ( = 160) and a control group ( = 160). Participants in the intervention group received an intensive lifestyle modification (ILSM) program, including a series of six biweekly face-to-face sessions and five biweekly phone sessions delivered by trained local health workers. The control group received the usual care. Data about perceived stress, social support, QoL, and HbA1c were collected at baseline, at three months, and at six-month follow-ups. Generalized estimating equation analysis was used to assess the efficacy of the intervention. There were significant improvements in the psychological domain (β = 0.479 ± 0.153, = 0.002) and environmental domain (β = 0.462 ± 0.145, = 0.001) of QoL over six months; there were significant group effects (β = -0.718 ± 0.280, = 0.010) and time effects (β = 0.453 ± 0.211, = 0.032) in physiological domain, and there were significant group effects in the social relations domain (β = -0.669 ± 0.321, = 0.037). The ILSM group had a more pronounced downward trend in HbA1c than the control group (β = -0.050 ± 0.026, = 0.059). The ILSM program can help women with GDM improve their psychological and environmental domain of QoL. It can be recommended as a form of health promotion for improving QoL among women with prior GDM in rural primary care settings in developing countries.
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http://dx.doi.org/10.3390/ijerph18041519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915428PMC
February 2021

A CT-based radiomics nomogram for distinguishing between benign and malignant bone tumours.

Cancer Imaging 2021 Feb 6;21(1):20. Epub 2021 Feb 6.

Department of Radiology, The Affiliated Hospital of Qingdao University Qingdao, 16 Jiangsu Road, Qingdao, Shandong, China.

Background: We sought to evaluate the performance of a computed tomography (CT)-based radiomics nomogram we devised in distinguishing benign from malignant bone tumours.

Methods: Two hundred and six patients with bone tumours were spilt into two groups: a training set (n = 155) and a validation set (n = 51). A feature extraction process based on 3D Slicer software was used to extract the radiomics features from unenhanced CT images, and least absolute shrinkage and selection operator logistic regression was used to calculate the radiomic score to generate a radiomics signature. A clinical model comprised demographics and CT features. A radiomics nomogram combined with the clinical model and the radiomics signature was constructed. The performance of the three models was comprehensively evaluated from three aspects: identification ability, accuracy, and clinical value, allowing for generation of an optimal prediction model.

Results: The radiomics nomogram comprised clinical and radiomics signature features. The nomogram model displayed good performance in training and validation sets with areas under the curve of 0.917 and 0.823, respectively. The areas under the curve, decision curve analysis, and net reclassification improvement showed that the radiomics nomogram model could obtain better diagnostic performance than the clinical model and achieve greater clinical net benefits than the clinical and radiomics signature models alone.

Conclusions: We constructed a combined nomogram comprising a clinical model and radiomics signature as a noninvasive preoperative prediction method to distinguish between benign and malignant bone tumours and assist treatment planning.
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http://dx.doi.org/10.1186/s40644-021-00387-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866630PMC
February 2021

Are the factors associated with overweight/general obesity and abdominal obesity different depending on menopausal status?

PLoS One 2021 4;16(2):e0245150. Epub 2021 Feb 4.

Department of Family Health Care Nursing, University of California, San Francisco, California, United States of America.

Rapid modernization in China has impacted the daily lives and health of women, including a rise in obesity. However, little is known about the impact of menopausal status, behavior, and psychosocial factors on the risk of obesity for rural women in China. The aim of this study is to identify risk factors, including demographic information (education, family history of T2DM, menopausal status), obesity-related behavior, and psychosocial factors associated with overweight/general obesity and abdominal obesity. In a cross-sectional study design, participants had their weight, height, and waist circumference measured and completed questionnaires regarding family demographics, obesity-related health behaviors (physical activity, diet, sleep), and psychosocial information (stress, social support, and self-efficacy related to physical activity and healthy diet). A total of 646 women were included in this study; 46.6% were overweight/generally obese, and 48% had abdominal obesity. Postmenopausal women had a higher prevalence of general and central obesity. Regular physical activity decreased the risk for overweight/general obesity and abdominal obesity (OR = .41 and .31, respectively, p = .04) in premenopausal women. Postmenopausal women who had not breastfed their infants and reported moderate/high-stress had a higher risk for overweight/general obesity (OR = 3.93, and 2, respectively) and those who reported less than 6 hours of sleep per day increased their risk for abdominal obesity (OR = 2.08). Different factors associated with obesity were found in Chinese women, depending on menopausal status. Future studies should examine the impact of menopause on a woman's risk for obesity, as well as develop tailored interventions to improve health, well-being and reduce the risk of obesity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245150PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861369PMC
February 2021

Diffusion kurtosis imaging assessment of the response to radiotherapy in a VX2 bone tumor model: an animal study.

Acta Radiol 2021 Feb 3:284185121989519. Epub 2021 Feb 3.

Department of Radiology; The Affiliated Hospital of Qingdao University Qingdao, Shandong, PR China.

Background: Neoadjuvant radiotherapy plays a vital role in the treatment of malignant bone tumors, and non-invasive imaging methods are needed to evaluate the response to treatment.

Purpose: To assess the value of diffusion kurtosis imaging (DKI) for monitoring early response to radiotherapy in malignant bone tumors.

Material And Methods: Treatment response was evaluated in a rabbit VX2 bone tumor model (n = 35) using magnetic resonance imaging (MRI), DKI, and histopathologic examinations. Subjects were divided into three groups: pre-treatment, post-treatment, and control groups. The post-treatment group was subclassified into good response and poor response groups according to the results of histopathologic examination. Apparent diffusion coefficient (ADC) and DKI parameters (mean diffusion coefficient [MD] and mean kurtosis [MK]) were recorded. The relationship between ADC, DKI parameters, and histopathologic changes after radiotherapy was determined using Pearson's correlation coefficient. The diagnostic performance of these parameters was assessed using receiver operating characteristic analysis.

Results: MD in the good response group was higher after treatment than before treatment ( < 0.001) and higher than that in the poor response group ( = 0.009). MD was highly correlated with tumor cell density and apoptosis rate (r = -0.771,  < 0.001 and r = 0.625,  < 0.001, respectively). MD was superior to other parameters for determining the curative effect of radiotherapy, with a sensitivity of 75.0%, specificity of 100.0%, and area under the curve of 0.917 ( < 0.001).

Conclusion: The correlations between MD, tumor cell density, and apoptosis suggest that MD could be useful for assessing the early response to radiotherapy in rabbit VX2 malignant bone tumors.
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http://dx.doi.org/10.1177/0284185121989519DOI Listing
February 2021

Computer-assisted tooth preparation template and predesigned restoration: a digital workflow.

Int J Comput Dent 2020 ;23(4):351-362

This article introduces a new, fully digital workflow for the preparation of a guiding template and the procedure of the clinical operation in which it is put to use. A step-by-step technique is described including the virtual CAD of the preparation, the design of the template, the restoration based on the contours of the virtual preparation, the tooth preparation guided by the template, and the bonding of the predesigned restoration. The design and manufacture of all the templates and restorations are completed before the clinical operation.
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January 2021

Hydrogen Sulfide Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Apoptosis and Affects Autophagy.

Oxid Med Cell Longev 2020 30;2020:8868564. Epub 2020 Dec 30.

School of Life Sciences, Lanzhou University, Lanzhou, China.

Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness among the elderly. AMD is characterized by retinal pigment epithelial (RPE) cell dysfunction. However, the pathogenesis of AMD is still unclear, and there is currently no effective treatment. Accumulated evidence indicates that oxidative stress and autophagy play a crucial role in the development of AMD. HS is an antioxidant that can directly remove intracellular superoxide anions and hydrogen peroxide. The purpose of this study is to investigate the antioxidative effect of HS in RPE cells and its role in autophagy. The results show that exogenous HS (NaHS) pretreatment effectively reduces HO-induced oxidative stress, oxidative damage, apoptosis, and inflammation in ARPE-19 cells. NaHS pretreatment also decreased autophagy levels raised by HO, increased cell viability, and ameliorated cell morphological damage. Interestingly, the suppression of autophagy by its inhibitor 3-MA showed an increase of cell viability, amelioration of morphology, and a decrease of apoptosis. In summary, oxidative stress causes ARPE-19 cell injury by inducing cell autophagy. However exogenous HS is shown to attenuate ARPE-19 cell injury, decrease apoptosis, and reduce the occurrence of autophagy-mediated by oxidative stress. These findings suggest that autophagy might play a crucial role in the development of AMD, and exogenous HS has a potential value in the treatment of AMD.
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http://dx.doi.org/10.1155/2020/8868564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790554PMC
December 2020

RNAi-mediated stable silencing of TaCSN5 confers broad-spectrum resistance to Puccinia striiformis f. sp. tritici.

Mol Plant Pathol 2021 Apr 24;22(4):410-421. Epub 2021 Jan 24.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, China.

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a versatile regulator of plant growth, development, and response to diverse pathogens. However, little research has been done to understand the function of those CSN genes in broad-spectrum resistance to pathogens. In this study, we found that the transcript levels of wheat TaCSN5 were induced in response to inoculation with Puccinia striiformis f. sp. tritici (Pst) and treatment with salicylic acid (SA). Overexpression of TaCSN5 in Arabidopsis resulted in increased susceptibility to Pseudomonas syringae pv. tomato DC3000 infection accompanied by down-regulation of AtPR1 expression. Overexpression of TaCSN5 in wheat lines significantly increased susceptibility to Pst accompanied by decreased SA accumulation, whereas TaCSN5-RNAi wheat lines exhibited opposite trends. Moreover, we found that TaCSN5 negatively regulated TaG3NPR1 genes involved in the SA signalling pathway. In addition, TaCSN5-RNAi lines showed increased resistance to multiple races of Pst. Taken together, we demonstrate that TaCSN5 contributes to negative regulation of wheat resistance to Pst in an SA-dependent manner.
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http://dx.doi.org/10.1111/mpp.13034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938628PMC
April 2021