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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Jin, Ying-Hui, et al.
(author)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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In: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Journal article (peer-reviewed)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 5. |
- Aisaiti, Adila, et al.
(author)
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Effect of photobiomodulation therapy on painful temporomandibular disorders
- 2021
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- To evaluate the effect of photobiomodulation therapy (PBMT) on painful temporomandibular disorders (TMD) patients in a randomized, double-blinded, placebo-controlled manner. Participants were divided into a masseter myalgia group (n = 88) and a temporomandibular joint (TMJ) arthralgia group (n = 87) according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Both groups randomly received PBMT or placebo treatment once a day for 7 consecutive days, one session. The PBMT was applied with a gallium-aluminum-arsenide (GaAlAs) laser (wavelength = 810 nm) at pre-determined points in the masseter muscle (6 J/cm2, 3 regions, 60 s) or TMJ region (6 J/cm2, 5 points, 30 s) according to their most painful site. Pain intensity was rated on a 0–10 numerical rating scale (NRS) and pressure pain thresholds (PPT) and mechanical sensitivity mapping were recorded before and after the treatment on day 1 and day 7. Jaw function was assessed by pain free jaw opening, maximum unassisted jaw opening, maximum assisted jaw opening, maximum protrusion and right and left excursion. Data were analyzed with a mixed model analysis of variance (ANOVA). Pain intensity in arthralgia patients decreased over time (P < 0.001) for both types of interventions, however, PBMT caused greater reduction in pain scores than placebo (P = 0.014). For myalgia patients, pain intensity decreased over time (P < 0.001) but without difference between interventions (P = 0.074). PPTs increased in both myalgia (P < 0.001) and TMJ arthralgia patients over time (P < 0.001) but without difference between interventions (P ≥ 0.614). Overall, PBMT was associated with marginally better improvements in range of motion compared to placebo in both myalgia and arthralgia patients. Pain intensity, sensory function and jaw movements improve after both PBMT and placebo treatments in myalgia and arthralgia patients indicating a substantial non-specific effect of PBMT.
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| 6. |
- Cheng, Dantong, et al.
(author)
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MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4
- 2016
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In: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 7:29, s. 45199-45213
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Journal article (peer-reviewed)abstract
- Background: Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. Results: miR-20a-5p negatively regulated Smad4 by directly targeting its 3UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Methods: Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. Conclusions: miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.
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| 7. |
- Fan, Baobing, et al.
(author)
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Correlation of Local Isomerization Induced Lateral and Terminal Torsions with Performance and Stability of Organic Photovoltaics
- 2023
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In: Journal of the American Chemical Society. - : AMER CHEMICAL SOC. - 0002-7863 .- 1520-5126. ; 145:10, s. 5909-5919
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Journal article (peer-reviewed)abstract
- Organic photovoltaics (OPVs) have achieved great progress in recent years due to delicately designed non-fullerene acceptors (NFAs). Compared with tailoring of the aromatic heterocycles on the NFA backbone, the incorporation of conjugated side-groups is a cost-effective way to improve the photoelectrical properties of NFAs. However, the modifications of side-groups also need to consider their effects on device stability since the molecular planarity changes induced by side-groups are related to the NFA aggregation and the evolution of the blend morphology under stresses. Herein, a new class of NFAs with localisomerized conjugated side-groups are developed and the impact of local isomerization on their geometries and device performance/stability are systematically investigated. The device based on one of the isomers with balanced side- and terminal-group torsion angles can deliver an impressive power conversion efficiency (PCE) of 18.5%, with a low energy loss (0.528 V) and an excellent photo- and thermal stability. A similar approach can also be applied to another polymer donor to achieve an even higher PCE of 18.8%, which is among the highest efficiencies obtained for binary OPVs. This work demonstrates the effectiveness of applying local isomerization to fine-tune the side-group steric effect and non-covalent interactions between side-group and backbone, therefore improving both photovoltaic performance and stability of fused ring NFA-based OPVs.
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| 8. |
- Garrison, Sean P, et al.
(author)
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Selection against PUMA gene expression in Myc-driven B-cell lymphomagenesis.
- 2008
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In: Molecular and cellular biology. - 1098-5549. ; 28:17, s. 5391-402
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Journal article (peer-reviewed)abstract
- The p53 tumor suppressor pathway limits oncogenesis by inducing cell cycle arrest or apoptosis. A key p53 target gene is PUMA, which encodes a BH3-only proapoptotic protein. Here we demonstrate that Puma deletion in the Emu-Myc mouse model of Burkitt lymphoma accelerates lymphomagenesis and that approximately 75% of Emu-Myc lymphomas naturally select against Puma protein expression. Furthermore, approximately 40% of primary human Burkitt lymphomas fail to express detectable levels of PUMA and in some tumors this is associated with DNA methylation. Burkitt lymphoma cell lines phenocopy the primary tumors with respect to DNA methylation and diminished PUMA expression, which can be reactivated following inhibition of DNA methyltransferases. These findings establish that PUMA is silenced in human malignancies, and they suggest PUMA as a target for the development of novel chemotherapeutics.
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| 9. |
- Ge, Qi, et al.
(author)
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Structure-Based Low-Rank Model With Graph Nuclear Norm Regularization for Noise Removal
- 2017
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In: IEEE Transactions on Image Processing. - : Institute of Electrical and Electronics Engineers (IEEE). - 1057-7149 .- 1941-0042. ; 26:7, s. 3098-3112
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Journal article (peer-reviewed)abstract
- Nonlocal image representation methods, including group-based sparse coding and block-matching 3-D filtering, have shown their great performance in application to low-level tasks. The nonlocal prior is extracted from each group consisting of patches with similar intensities. Grouping patches based on intensity similarity, however, gives rise to disturbance and inaccuracy in estimation of the true images. To address this problem, we propose a structure-based low-rank model with graph nuclear norm regularization. We exploit the local manifold structure inside a patch and group the patches by the distance metric of manifold structure. With the manifold structure information, a graph nuclear norm regularization is established and incorporated into a low-rank approximation model. We then prove that the graph-based regularization is equivalent to a weighted nuclear norm and the proposed model can be solved by a weighted singular-value thresholding algorithm. Extensive experiments on additive white Gaussian noise removal and mixed noise removal demonstrate that the proposed method achieves a better performance than several state-of-the-art algorithms.
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| 10. |
- Guo, Jian Jun, et al.
(author)
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Intranasal administration of α-synuclein preformed fibrils triggers microglial iron deposition in the substantia nigra of Macaca fascicularis
- 2021
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In: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:1
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Journal article (peer-reviewed)abstract
- Iron deposition is present in main lesion areas in the brains of patients with Parkinson’s disease (PD) and an abnormal iron content may be associated with dopaminergic neuronal cytotoxicity and degeneration in the substantia nigra of the midbrain. However, the cause of iron deposition and its role in the pathological process of PD are unclear. In the present study, we investigated the effects of the nasal mucosal delivery of synthetic human α-synuclein (α-syn) preformed fibrils (PFFs) on the pathogenesis of PD in Macaca fascicularis. We detected that iron deposition was clearly increased in a time-dependent manner from 1 to 17 months in the substantia nigra and globus pallidus, highly contrasting to other brain regions after treatments with α-syn PFFs. At the cellular level, the iron deposits were specifically localized in microglia but not in dopaminergic neurons, nor in other types of glial cells in the substantia nigra, whereas the expression of transferrin (TF), TF receptor 1 (TFR1), TF receptor 2 (TFR2), and ferroportin (FPn) was increased in dopaminergic neurons. Furthermore, no clear dopaminergic neuron loss was observed in the substantia nigra, but with decreased immunoreactivity of tyrosine hydroxylase (TH) and appearance of axonal swelling in the putamen. The brain region-enriched and cell-type-dependent iron localizations indicate that the intranasal α-syn PFFs treatment-induced iron depositions in microglia in the substantia nigra may appear as an early cellular response that may initiate neuroinflammation in the dopaminergic system before cell death occurs. Our data suggest that the inhibition of iron deposition may be a potential approach for the early prevention and treatment of PD.
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