MicroRNA miR-31 is implicated in the neoplastic process of various malignancies including oral squamous cell carcinoma (OSCC). Silent information regulator 3 (Sirtuin3 or SIRT3) is a NAD-dependent ...deacetylase that regulates metabolic process. Suppressor role of SIRT3 has been found in neoplasms. This study investigates the disruptions of miR-31-SIRT3 cascade to explore their potential association with metabolic change in OSCC. We identified that miR-31 directly targeted SIRT3 in OSCC cells, and a reverse correlation between miR-31 expression and SIRT3 expression was noted in OSCC tumors. SIRT3 expression attenuated the miR-31 enhanced tumor cell migration and invasion. It also reduced the tumorigenic potential of FaDu cell line. miR-31-SIRT3 impaired the mitochondrial membrane potential and structural integrity. The dis-regulation of this axis also contributed to the genesis of oxidative stress. In addition, miR-31 switched tumor cells from aerobic metabolism to glycolytic metabolism. This study provides novel evidences demonstrating the presence of miR-31-mediated post-transcriptional regulation of SIRT3 in OSCC. The disruption of miR-31-SIRT3 cascade and the consequential metabolic aberrances are involved in OSCC progression.
•miR-31 targets SIRT3 to drive OSCC invasion.•OSCC tumors exhibit miR-31 upregulation and SIRT3 downregulation.•miR-31-SIRT3 disruption underlies the mitochondrial disturbance.•miR-31-SIRT3 cascade induces ROS, glycolytic metabolism and lactate production.
Purpose
To investigate the role of computed tomography (CT) radiomics for the preoperative prediction of lymph node (LN) metastasis in gastric cancer.
Materials and methods
This retrospective study ...included 247 consecutive patients (training cohort, 197 patients; test cohort, 50 patients) with surgically proven gastric cancer. Dedicated radiomics prototype software was used to segment lesions on preoperative arterial phase (AP) CT images and extract features. A radiomics model was constructed to predict the LN metastasis by using a random forest (RF) algorithm. Finally, a nomogram was built incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were used to validate the capability of the radiomics model and nomogram on both the training and test cohorts.
Results
The radiomics model showed a favorable discriminatory ability in the training cohort with an area under the curve (AUC) of 0.844 (95% CI, 0.759 to 0.909), which was confirmed in the test cohort with an AUC of 0.837 (95% CI, 0.705 to 0.926). The nomogram consisted of radiomics scores and the CT-reported LN status showed excellent discrimination in the training and test cohorts with AUCs of 0.886 (95% CI, 0.808 to 0.941) and 0.881 (95% CI, 0.759 to 0.956), respectively.
Conclusions
The CT-based radiomics nomogram holds promise for use as a noninvasive tool in the individual prediction of LN metastasis in gastric cancer.
Key Points
• CT radiomics showed a favorable performance for the prediction of LN metastasis in gastric cancer.
• Radiomics model outperformed the routine CT in predicting LN metastasis in gastric cancer.
• The radiomics nomogram holds potential in the individualized prediction of LN metastasis in gastric cancer.
Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra ...snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mitochondrial dysfunction and impaired Ca
handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its ...level of phosphorylation, and the Orai1 (Ca
release-activated calcium channel protein 1) calcium channel is important for the increase in Ca
entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca
influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca
entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1-Drp1 axis is a novel target for treating DCM.
Anhedonia is the inability to experience pleasure from rewarding or enjoyable activities and is a core symptom of depression in humans. Here, we describe a protocol for the measurement of anhedonia ...in mice, in which anhedonia is measured by a sucrose preference test (SPT) based on a two-bottle choice paradigm. A reduction in the sucrose preference ratio in experimental relative to control mice is indicative of anhedonia. To date, inconsistent and variable results have been reported following the use of the SPT by different groups, probably due to the use of different protocols and equipment. In this protocol, we describe how to set up a clearly defined apparatus for SPT and provide a detailed protocol to ensure greater consistency when carrying out SPT. This optimized protocol is highly sensitive, reliable, and adaptable for evaluation of chronic stress-related anhedonia, as well as morphine-induced dependence. The whole SPT, including adaptation, baseline measurement, and testing, takes 8 d.
All‐inorganic CsPbX3 (X=I, Br, Cl) perovskite quantum dots (PQDs) have been investigated because of their optical properties, such as tunable wavelength, narrow band, and high quantum efficiency. ...These features have been used in light emitting diode (LED) devices. LED on‐chip fabrication uses mixed green and red quantum dots with silicone gel. However, the ion‐exchange effect widens the narrow emission spectrum. Quantum dots cannot be mixed because of anion exchange. We address this issue with a mesoporous PQD nanocomposite that can prevent ion exchange and increase stability. We mixed green quantum‐dot‐containing mesoporous silica nanocomposites with red PQDs, which can prevent the anion‐exchange effect and increase thermal and photo stability. We applied the new PQD‐based LEDs for backlight displays. We also used PQDs in an on‐chip LED device. Our white LED device for backlight display passed through a color filter with an NTSC value of 113 % and Rec. 2020 of 85 %.
Points of light: Green CsPbBr3 perovskite quantum dots (PQDs), embedded in mesoporous silica (MP), were mixed with red CsPb(Br0.4I0.6)3 quantum dots in a silicone resin and placed on an InGaN blue chip. The green and red QDs were excited by blue light with λ=450 nm. The resulting PQD white light emitting diode (LED) exhibits a wide color gamut because of its narrow emission wavelength.
CsPbX
3
(X = Cl, Br, and I), as a potential luminescent material with excellent optical characteristics, has attracted researchers for several years but it is difficult to use it commercially due to ...its low stability. Herein, a simple green process was successfully optimized without using any solvents for synthesizing an ultra-stable CsPbBr
3
@SiO
2
composite. The phase transformation process in obtaining the CsPbBr
3
@SiO
2
composite was resolved according to
in situ
X-ray diffraction measurements. Based on the results, the best sintering condition for the CsPbBr
3
@SiO
2
composite was obtained, realizing the highest photoluminescence quantum yield of 15.5%. The obtained CsPbBr
3
@SiO
2
exhibited a narrowband green emission and achieved ultra-high stability with an intensity of 100% being maintained after the 196 h test under double-85 conditions. Moreover, it maintained the emission intensity and color coordinate during the 1000 h irradiation test in the light-emitting diode package. This excellent performance revealed the great potential of the CsPbBr
3
@SiO
2
composite for commercialization in backlight applications.
We successfully optimized a simple process without using any solvents for synthesizing an ultra-stable CsPbBr
3
@SiO
2
luminescent material. The achieved CsPbBr
3
@SiO
2
showed ultra-high stability for LED application.
Constructing efficient artificial solid electrolyte interface (SEI) film is extremely vital for the practical application of lithium metal batteries. Herein, a dense artificial SEI film, in which ...lithiophilic Zn/LixZny are uniformly but nonconsecutively dispersed in the consecutive Li+‐conductors of LixSiOy, Li2O and LiOH, is constructed via the in situ reaction of layered zinc silicate nanosheets and Li. The consecutive Li+‐conductors can promote the desolvation process of solvated‐Li+ and regulate the transfer of lithium ions. The nonconsecutive lithiophilic metals are polarized by the internal electric field to boost the transfer of lithium ions, and lower the nucleation barrier. Therefore, a low polarization of ≈50 mV for 750 h at 2.0 mA cm−2 in symmetric cells, and a high capacity retention of 99.2 % in full cells with a high lithium iron phosphate areal loading of ≈13 mg cm−2 are achieved. This work offers new sights to develop advanced alkali metal anodes for efficient energy storage.
A dense and heterogeneous artificial SEI film is constructed via in situ reaction of layered zinc silicate nanosheets with Li. The consecutive Li+‐conductors promote the desolvation process of solvated‐Li+ and regulate the transfer of lithium ions. The nonconsecutive lithiophilic metals are polarized by the internal electric field to boost the transfer of Li+, and lower the nucleation barrier.
Plant laccase (LAC) enzymes belong to the blue copper oxidase family and polymerize monolignols into lignin. Recent studies have established the involvement of microRNAs in this process; however, ...physiological functions and regulation of plant laccases remain poorly understood. Here, we show that a laccase gene, LAC4, regulated by a microRNA, miR397b, controls both lignin biosynthesis and seed yield in Arabidopsis. In transgenic plants, overexpression of miR397b (OXmiR397b) reduced lignin deposition. The secondary wall thickness of vessels and the fibres was reduced in the OXmiR397b line, and both syringyl and guaiacyl subunits are decreased, leading to weakening of vascular tissues. In contrast, overexpression of miR397b‐resistant laccase mRNA results in an opposite phenotype. Plants overexpressing miR397b develop more than two inflorescence shoots and have an increased silique number and silique length, resulting in higher seed numbers. In addition, enlarged seeds and more seeds are formed in these miR397b overexpression plants. The study suggests that miR397‐mediated development via regulating laccase genes might be a common mechanism in flowering plants and that the modulation of laccase by miR397 may be potential for engineering plant biomass production with less lignin.
Adaptive O-CNN Wang, Peng-Shuai; Sun, Chun-Yu; Liu, Yang ...
ACM transactions on graphics,
12/2018, Letnik:
37, Številka:
6
Journal Article
Recenzirano
We present an Adaptive Octree-based Convolutional Neural Network (Adaptive O-CNN) for efficient 3D shape encoding and decoding. Different from volumetric-based or octree-based CNN methods that ...represent a 3D shape with voxels in the same resolution, our method represents a 3D shape adaptively with octants at different levels and models the 3D shape within each octant with a planar patch. Based on this adaptive patch-based representation, we propose an Adaptive O-CNN encoder and decoder for encoding and decoding 3D shapes. The Adaptive O-CNN encoder takes the planar patch normal and displacement as input and performs 3D convolutions only at the octants at each level, while the Adaptive O-CNN decoder infers the shape occupancy and subdivision status of octants at each level and estimates the best plane normal and displacement for each leaf octant. As a general framework for 3D shape analysis and generation, the Adaptive O-CNN not only reduces the memory and computational cost, but also offers better shape generation capability than the existing 3D-CNN approaches. We validate Adaptive O-CNN in terms of efficiency and effectiveness on different shape analysis and generation tasks, including shape classification, 3D autoencoding, shape prediction from a single image, and shape completion for noisy and incomplete point clouds.