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1.
Sci Rep ; 14(1): 826, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38191660

ABSTRACT

To analyze the status of binocular visual functions, the relationship between binocular visual function and computer vision-related symptoms in the high-tech industry group. The study sample was comprised of 33 participants aged between 20 and 40 years of age. After completing basic information and the Computer Vision Symptom Scale (CVSS-17) questionnaire, the participants underwent a comprehensive examination of binocular visual function. All data were statistically analyzed with SPSS V26.0 software. The value of the binocular vision function of the Taiwan high-tech industry group was significantly different compared with the Scheiman and Morgan standard value. Study subjects were generally found to exhibit larger exophoric at distance, which in turn might lead to a lower ability to maintain binocular fusion to a single image, or recover from fusional disruption at distance. Subjects also experienced accommodation and convergence problems at near at the same time. Age, gender, and refractive errors had no significant impact on CVSS-17 scores, only the duration of computer usage showed a significant effect, particularly for internal symptom factor (ISF) dimensions. In addition, the interaction between the ISF and external symptom factor resulted in more severe visual symptoms. Long-term use of electronic devices may lead to an imbalance in binocular vision function, thereby increasing or exacerbating visual symptoms. If the use of electronic devices is an unchangeable trend, interventions in prescription, visual training or the visual design of electronic products become worthwhile topics for development.


Subject(s)
Computers , Vision, Binocular , Humans , Young Adult , Adult , Taiwan , Software , Accommodation, Ocular , Intrinsic Factor
2.
Nanotechnology ; 35(20)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38286015

ABSTRACT

A transfer-free graphene with high magnetoresistance (MR) and air stability has been synthesized using nickel-catalyzed atmospheric pressure chemical vapor deposition. The Raman spectrum and Raman mapping reveal the monolayer structure of the transfer-free graphene, which has low defect density, high uniformity, and high coverage (>90%). The temperature-dependent (from 5 to 300 K) current-voltage (I-V) and resistance measurements are performed, showing the semiconductor properties of the transfer-free graphene. Moreover, the MR of the transfer-free graphene has been measured over a wide temperature range (5-300 K) under a magnetic field of 0 to 1 T. As a result of the Lorentz force dominating above 30 K, the transfer-free graphene exhibits positive MR values, reaching ∼8.7% at 300 K under a magnetic field (1 Tesla). On the other hand, MR values are negative below 30 K due to the predominance of the weak localization effect. Furthermore, the temperature-dependent MR values of transfer-free graphene are almost identical with and without a vacuum annealing process, indicating that there are low density of defects and impurities after graphene fabrication processes so as to apply in air-stable sensor applications. This study opens avenues to develop 2D nanomaterial-based sensors for commercial applications in future devices.

3.
Waste Manag ; 176: 128-139, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38281344

ABSTRACT

Municipal solid waste incineration (MSWI) bottom ash, due to its high mineral content, presents great potential as supplementary cementitious material (SCM). Weathering, also known as aging, is a treatment process commonly employed in waste management to minimize the risk of heavy metal leaching from MSWI bottom ash. Using weathered MSWI bottom ash to produce blended cement pastes is considered as a high-value-added and sustainable waste disposal solution. However, a critical challenge arises from the metallic aluminum (Al) in weathered MSWI bottom ash, which is known to induce detrimental effects such as volume expansion and strength loss of blended cement pastes. While most metallic Al in weathered MSWI bottom ash can be removed with eddy current separators in metal recovery plants, the residual metallic Al, owing to its small particle size, cannot be removed with the same technique. This study is dedicated to addressing this issue. An in-depth analysis was conducted on residual metallic Al embedded in weathered MSWI bottom ash particles, aiming to guide the removal of this metal. This analysis revealed that mechanical removal was the most suitable method for extracting metallic Al. The specific processes and mechanisms underlying this method were elucidated. After reducing metallic Al content in weathered MSWI bottom ash by 77 %, a significant improvement in the quality of blended cement pastes was observed. This work contributes to the broader adoption of mechanical treatments for removing residual metallic Al from weathered MSWI bottom ash and facilitates the application of treated ash as SCM.


Subject(s)
Metals, Heavy , Refuse Disposal , Solid Waste/analysis , Coal Ash , Aluminum , Incineration , Refuse Disposal/methods , Metals, Heavy/analysis , Carbon
4.
Neural Netw ; 171: 293-307, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37973499

ABSTRACT

When handling real-world data modeled by a complex network dynamical system, the number of the parameters is often much more than the size of the data. Therefore, in many cases, it is impossible to estimate these parameters and the exact value of each parameter is frequently less interesting than the distribution of the parameters. In this paper, we aim to estimate the distribution of the parameters in the mesoscopic neuronal network model from the macroscopic experimental data, for example, the BOLD (blood oxygen level dependent) signal. Herein, we assume that the parameters of the neurons and synapses are inhomogeneous but independently and identically distributed from certain distributions with unknown hyperparameters. Thus, we estimate these hyperparameters of the distributions of the parameters, instead of estimating the parameters themselves. We formulate this problem under the framework of data assimilation and hierarchical Bayesian method and present an efficient method named Hierarchical Data Assimilation (HDA) to conduct the statistical inference on the neuronal network model with the BOLD signal data simulated by the hemodynamic model. We consider the Leaky Integral-Fire (LIF) neuronal networks with four synapses and show that the proposed algorithm can estimate the BOLD signals and the hyperparameters with high preciseness. In addition, we discuss the influence on the performance of the algorithm configuration and the LIF network model setup.


Subject(s)
Algorithms , Neurons , Bayes Theorem , Neurons/physiology
5.
Biotechnol J ; 19(1): e2200632, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37735964

ABSTRACT

There are few effective treatment options for diffuse pulmonary hemorrhage (DPH). We aimed to elucidate the therapeutic role and underlying mechanisms of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) in DPH. Therapeutic effects of MSCs/MSC-EVs in pristane-induced DPH mice were evaluated via pulmonary function testing and histopathology. Transcriptome sequencing analyzed differentially expressed genes in control, DPH, and MSC groups. The proportion of macrophage polarization was evaluated in vivo and in vitro via fluorescence-activated cell sorting in control, DPH, MSC, MSC-EV inhalation, and MSC-EV intravenous groups. Intraperitoneal injection of pristane induced diffuse alveolar hemorrhage, early fibrosis, and inflammation in C57BL/6 mice. Monocytes were depleted in the peripheral blood in DPH mice and MSCs were recruited to the lungs, resulting in significantly attenuated diffuse alveolar hemorrhage and suppressed immunological response. This was more effective in the hyperacute hemorrhage phase than the early inflammatory phase. An MSC treatment-mediated anti-inflammatory effect was observed in DPH mice. Furthermore, MSC-EVs inhalation or tail-vein injection could effectively reduce DPH injury. MSCs could suppress macrophage M1 polarization in DPH in vivo and in vitro. MSCs displayed significant therapeutic effects in pristane-induced DPH, which may be a promising cell-free therapeutic approach.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Terpenes , Mice , Animals , Mice, Inbred C57BL , Lung/pathology , Hemorrhage/therapy , Hemorrhage/pathology , Anti-Inflammatory Agents , Mesenchymal Stem Cells/physiology , Disease Models, Animal
6.
Int J Biol Macromol ; 257(Pt 1): 128323, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38000599

ABSTRACT

Traditional methods of freezing and thawing may harm the quality of meat products. In order to reduce the negative impact of freezing on surimi products, the magnetic field-assisted freezing method is combined with various curdlan ratios to enhance the gelation characteristics of Penaeus vannamei surimi in this study. The results showed that the magnetic field-assisted freezing technique significantly improved the quality of thawed surimi compared with soaking freezing (SF), whereas the addition of curdlan further improved the gelation properties, and the gel strength, water-holding capacity, textural properties, whiteness, and G' value were significantly improved when its content was increased to 0.6 %. However, excessive amounts of curdlan interfered with protein covalent cross-linking, leading to a decrease in gel quality. Additionally, the addition of magnetic field and curdlan encouraged the shift of the α-helix to the random coil and ß-sheet transition, which stimulated the growth of myofibril molecules, exposed the hydrophobic groups and thiols, improved protein-molecule interactions, and promoted systematic gathering of proteins, leading to the formation of the microstructure of dense and small pores. It also resulted in a drop in water release, an increase in the proton density and a shift in the water condition from free water to more immobile water, which had higher sensory qualities. These effects together resulted in a reduction in thawing and cooking loss to 11.41 % and 13.83 %, respectively. These results also help to clarify the gelation process of shrimp surimi and help to regulate the gelation characteristics of shrimp surimi products.


Subject(s)
Penaeidae , beta-Glucans , Animals , Freezing , Gels/chemistry , Water , Food Handling/methods , Fish Products/analysis , Fish Proteins/chemistry
7.
Wideochir Inne Tech Maloinwazyjne ; 18(3): 494-501, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37868281

ABSTRACT

Introduction: Gallstones are a common digestive system disease. Aim: To assess the effects of laparoscopic and choledochoscopic gallbladder-preserving cholecystolithotomy on the levels of operation indicators, gallbladder function, and cholecystokinin type-A receptor (CCKAR) in patients with gallstones. Material and methods: The medical records of 100 patients with gallstones receiving operation from July 2019 to August 2022 were collected for retrospective analysis. They were divided into a laparoscopic group (n = 48) and a laparoscopic + choledochoscopic group (n = 52). The laparoscopic group received totally laparoscopic cholecystolithotomy, while the laparoscopic + choledochoscopic group underwent laparoscopic and choledochoscopic cholecystolithotomy. Their perioperative indicators, gallbladder function, stress indicators (cortisol (Cor), norepinephrine (NE), and C-reactive protein (CRP)), serum biochemical indicators (liver receptor homologue 1 (LRH-1), CCKAR, and vasoactive intestinal peptide (VIP)), and complications were compared. Results: The fasting gallbladder volume and gallbladder contraction rate increased, and the minimum residual volume and gallbladder wall thickness decreased in the laparoscopic + choledochoscopic group in comparison with those of the laparoscopic group 6 months after operation (p < 0.05). The levels of serum Cor, NE, CRP, and CCKAR were elevated, whereas the levels of serum LRH-1 and VIP were lowered in both groups 3 d after operation compared with those before operation (p < 0.05). The levels of serum Cor, NE, CRP, LRH-1, and VIP were lower, and the level of serum CCKAR was higher in the laparoscopic + choledochoscopic group than those in the laparoscopic group 3 d after operation (p < 0.05). Conclusions: Both laparoscopic gallbladder-preserving cholecystolithotomy and laparoscopic and choledochoscopic cholecystolithotomy are effective for treating gallstones. However, the latter combination method is superior in enhancing postoperative gallbladder function, decreasing the recurrence risk, regulating the expressions of LRH-1, CCKAR, and VIP, and promoting the postoperative recovery of gastrointestinal function.

8.
Oncogene ; 42(48): 3564-3574, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37853162

ABSTRACT

Metastasis remains the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC), in which sustained activation of the Notch signaling plays a critical role. N6-Methyladenosine (m6A)-mediated post-transcriptional regulation is involved in fine-tuning the Notch signaling output; however, the post-transcriptional mechanisms underlying NPC metastasis remain poorly understood. In the present study, we report that insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) serves as a key m6A reader in NPC. IGF2BP3 expression was significantly upregulated in metastatic NPC and correlated with poor prognosis in patients with NPC. IGF2BP3 overexpression promoted, while IGF2BP3 downregulation inhibited tumor metastasis and the stemness phenotype of NPC cells in vitro and in vivo. Mechanistically, IGF2BP3 maintains NOTCH3 mRNA stability via suppression of CCR4-NOT complex-mediated deadenylation in an m6A-dependent manner, which sustains Notch3 signaling activation and increases the transcription of stemness-associated downstream genes, eventually promoting tumor metastasis. Our findings highlight the pro-metastatic function of the IGF2BP3/Notch3 axis and revealed the precise role of IGF2BP3 in post-transcriptional regulation of NOTCH3, suggesting IGF2BP3 as a novel prognostic biomarker and potential therapeutic target in NPC metastasis.


Subject(s)
Carcinoma , Nasopharyngeal Neoplasms , Humans , Carcinoma/genetics , Cell Line, Tumor , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Receptor, Notch3/genetics , Signal Transduction/genetics
9.
Biochem Mol Biol Educ ; 51(6): 662-669, 2023.
Article in English | MEDLINE | ID: mdl-37665065

ABSTRACT

With the emergence of innovative technologies, including combinatorial chemistry, high-throughput screening, computer-aided drug design (CADD), artificial intelligence (AI) and big data, the importance of drug design in the field of drug discovery and development is increasing. Additionally, education in drug design plays an important role in the training of pharmaceutical talent. Starting with undergraduates, cultivating pharmaceutical design thinking, developing innovation and creativity, and establishing an interdisciplinary knowledge system will not only provide students with a solid knowledge basis but also promote the development of the pharmaceutical industry in China. This article presents the current status of pharmaceutical education and the distribution of drug design courses in China and summarizes the employment prospects of graduates, thus providing valuable references and evidence for global pharmaceutical design education.


Subject(s)
Curriculum , Education, Pharmacy , Humans , Artificial Intelligence , Drug Industry , Drug Design
10.
Mol Cell ; 83(19): 3502-3519.e11, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37751742

ABSTRACT

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress. We find that mTORC1 regulates MFSD12 by directly phosphorylating residue T254, while mTORC1 inhibition enhances lysosome acidification that activates CTNS. This switch modulates lysosomal cyst(e)ine levels in response to oxidative stress, fine-tuning redox homeostasis to enhance cell fitness. MFSD12-T254A mutant inhibits MFSD12 function and suppresses tumor progression. Moreover, MFSD12 overexpression correlates with poor neoadjuvant chemotherapy response and prognosis in breast cancer patients. Our findings reveal the critical role of lysosomal cyst(e)ine storage in adaptive redox homeostasis and suggest that MFSD12 is a potential therapeutic target.

11.
Int J Biol Macromol ; 253(Pt 7): 126852, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37703970

ABSTRACT

The purpose of this study was to investigate the effect of Kappa (к)-carrageenan on texture and perception of saltiness of low salt surimi. The low-field nuclear magnetic resonance (LF-NMR) and microstructure results showed that к-carrageenan could promote the formation of more immobilized water in low salt surimi gel, change its matrix structure, and lead to the uneven spatial distribution of sodium, thus enhancing saltiness perception. The rheological properties of surimi showed that к-carrageenan could increase the network strength of low salt surimi gel and improve its thermostability. Furthermore, the low salt surimi gel added with к-carrageenan has lower cooking loss, higher water holding capacity (WHC), gel strength and improved texture properties. Therefore, к-carrageenan has the effects of improving the quality and increasing salt perception of surimi gel. This study provides a new method for reducing salt consumption in food industry.


Subject(s)
Fish Proteins , Food Handling , Carrageenan , Fish Proteins/chemistry , Food Handling/methods , Gels/chemistry , Fish Products/analysis , Sodium Chloride , Water , Perception
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(8): 877-883, 2023 Aug 15.
Article in Chinese | MEDLINE | ID: mdl-37668038

ABSTRACT

Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.


Subject(s)
Autism Spectrum Disorder , COVID-19 , Epidemics , Problem Behavior , Humans , Child
13.
J Fluoresc ; 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37615895

ABSTRACT

Cisplatin is an important platinum drug in cancer chemotherapy in clinical practice. It is well established that the main target of cisplatin is nuclear DNA. However, recent studies have demonstrated that platinum drugs may act on some important functional proteins in the human body. E-cadherin is a newly discovered glycoprotein that has been regarded as an important sign of the occurrence and development of some tumors. This study examines the interactions between cisplatin and E-cadherin by fluorescence spectrometry and atomic force microscopy (AFM). The fluorescence spectrometry results indicated that cisplatin can efficiently quench the fluorescence of E-cadherin. The calculated binding constant Kb was 3.20 × 106 (25 ℃), 1.36 × 106(31 ℃), and 8.22 × 105 L mol-1 (37 ℃). These results reveal that the fluorescence quenching effect of cisplatin on E-cadherin is static quenching. The obtained thermodynamic parameters ΔH < 0, ΔS < 0, and ΔG < 0, indicate that the binding of cisplatin on E-cadherin is a spontaneous process dominated by hydrogen bonds and Van der Waals forces. The AFM results revealed that E-cadherins are interlaced with each other to form a spherical-chain structure. The addition of cisplatin can significantly disrupt the interlaced structure of the E-cadherin molecules.

14.
J Clin Invest ; 133(14)2023 07 17.
Article in English | MEDLINE | ID: mdl-37463446

ABSTRACT

Human epidermal growth factor receptor 2-targeted (HER2-targeted) therapy is the mainstay of treatment for HER2+ breast cancer. However, the proteolytic cleavage of HER2, or HER2 shedding, induces the release of the target epitope at the ectodomain (ECD) and the generation of a constitutively active intracellular fragment (p95HER2), impeding the effectiveness of anti-HER2 therapy. Therefore, identifying key regulators in HER2 shedding might provide promising targetable vulnerabilities against resistance. In the current study, we found that upregulation of dolichyl-phosphate N-acetylglucosaminyltransferase (DPAGT1) sustained high-level HER2 shedding to confer trastuzumab resistance, which was associated with poor clinical outcomes. Upon trastuzumab treatment, the membrane-bound DPAGT1 protein was endocytosed via the caveolae pathway and retrogradely transported to the ER, where DPAGT1 induced N-glycosylation of the sheddase - ADAM metallopeptidase domain 10 (ADAM10) - to ensure its expression, maturation, and activation. N-glycosylation of ADAM10 at N267 protected itself from ER-associated protein degradation and was essential for DPAGT1-mediated HER2 shedding and trastuzumab resistance. Importantly, inhibition of DPAGT1 with tunicamycin acted synergistically with trastuzumab treatment to block HER2 signaling and reverse resistance. These findings reveal a prominent mechanism for HER2 shedding and suggest that targeting DPAGT1 might be a promising strategy against trastuzumab-resistant breast cancer.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Humans , Female , Trastuzumab/pharmacology , Trastuzumab/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Signal Transduction , Membrane Proteins/metabolism , Drug Resistance, Neoplasm , Cell Line, Tumor , Antineoplastic Agents/pharmacology
15.
PLoS Negl Trop Dis ; 17(6): e0011346, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37289665

ABSTRACT

Dengue fever is a vector-borne disease that has become a serious global public health problem over the past decade. An essential aspect of controlling and preventing mosquito-borne diseases is reduction of mosquito density. Through the process of urbanization, sewers (ditches) have become easy breeding sources of vector mosquitoes. In this study, we, for the first time, used unmanned ground vehicle systems (UGVs) to enter ditches in urban areas to observe vector mosquito ecology. We found traces of vector mosquitoes in ~20.7% of inspected ditches, suggesting that these constitute viable breeding sources of vector mosquitoes in urban areas. We also analyzed the average gravitrap catch of five administrative districts in Kaohsiung city from May to August 2018. The gravitrap indices of Nanzi and Fengshan districts were above the expected average (3.26), indicating that the vector mosquitoes density in these areas is high. Using the UGVs to detect positive ditches within the five districts followed by insecticide application generally yielded good control results. Further improving the high-resolution digital camera and spraying system of the UGVs may be able to effectively and instantly monitor vector mosquitoes and implement spraying controls. This approach may be suitable to solve the complex and difficult task of detecting mosquito breeding sources in urban ditches.


Subject(s)
Aedes , Culicidae , Dengue , Animals , Mosquito Vectors , Ecology , Cities , Urbanization , Mosquito Control/methods , Dengue/epidemiology
16.
Food Chem ; 426: 136587, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37364422

ABSTRACT

In the present study, D-α-Tocopherol polyethylene glycol 1000 succinate-based self-microemulsifying drug delivery systems (TPGS-SMEDDS) were introduced to enhance the solubility and stability of luteolin. The ternary phase diagrams were constructed to obtain the maximum area of microemulsion and suitable formulations of TPGS-SMEDDS. The particle size distribution and polydispersity index of selected TPGS-SMEDDS were analyzed to be less than 100 nm and 0.4, respectively. The thermodynamic stability results suggested that the TPGS-SMEDDS was stable during the heat-cool and freeze-thaw cycle. Moreover, the TPGS-SMEDDS exhibited excellent encapsulation capacity (51.21 ± 4.39 to 85.71 ± 2.40%) and loading efficiency (61.46 ± 5.27 to 102.86 ± 2.88 mg/g) to luteolin. In addition, the TPGS-SMEDDS showed an admirable vitro release ability with a ratio of more than 88.40 ± 1.14% for luteolin in 24 h. Therefore, TPGS-based SMEDDS might provide an effective role for the oral administration of luteolin and holds promise as a potential delivery for poorly soluble bioactive compounds.


Subject(s)
Luteolin , alpha-Tocopherol , Emulsions/chemistry , Polyethylene Glycols/chemistry , Drug Delivery Systems/methods , Vitamin E/chemistry , Solubility , Succinates , Particle Size , Biological Availability , Administration, Oral
17.
J Transl Med ; 21(1): 310, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37158918

ABSTRACT

BACKGROUND: Cognitive dysfunction is the most common non-motor symptom in Parkinson's disease (PD), and timely detection of a slight cognitive decline is crucial for early treatment and prevention of dementia. This study aimed to build a machine learning model based on intra- and/or intervoxel metrics extracted from diffusion tensor imaging (DTI) to automatically classify PD patients without dementia into mild cognitive impairment (PD-MCI) and normal cognition (PD-NC) groups. METHODS: We enrolled PD patients without dementia (52 PD-NC and 68 PD-MCI subtypes) who were assigned to the training and test datasets in an 8:2 ratio. Four intravoxel metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and two novel intervoxel metrics, local diffusion homogeneity (LDH) using Spearman's rank correlation coefficient (LDHs) and Kendall's coefficient concordance (LDHk), were extracted from the DTI data. Decision tree, random forest, and eXtreme gradient boosting (XGBoost) models based on individual and combined indices were built for classification, and model performance was assessed and compared via the area under the receiver operating characteristic curve (AUC). Finally, feature importance was evaluated using SHapley Additive exPlanation (SHAP) values. RESULTS: The XGBoost model based on a combination of the intra- and intervoxel indices achieved the best classification performance, with an accuracy of 91.67%, sensitivity of 92.86%, and AUC of 0.94 in the test dataset. SHAP analysis showed that the LDH of the brainstem and MD of the right cingulum (hippocampus) were important features. CONCLUSIONS: More comprehensive information on white matter changes can be obtained by combining intra- and intervoxel DTI indices, improving classification accuracy. Furthermore, machine learning methods based on DTI indices can be used as alternatives for the automatic identification of PD-MCI at the individual level.


Subject(s)
Cognitive Dysfunction , Dementia , Parkinson Disease , Humans , Diffusion Tensor Imaging , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnostic imaging , Decision Trees
18.
Cancer Gene Ther ; 30(9): 1249-1259, 2023 09.
Article in English | MEDLINE | ID: mdl-37258811

ABSTRACT

Radiotherapy is the backbone of nasopharyngeal carcinoma (NPC), nearly 11-17% NPC patients suffered local relapse and 18-37% suffered distant metastasis mainly due to radioresistance. Therefore, the key of improving patients' survivals is to investigate the mechanism of radioresistance. In this study, we revealed that the expression level of long intergenic nonprotein coding RNA 173 (LINC00173) was significantly increased in the radioresistant NPC patients' tumour tissues compared with the radiosensitive patients by RNA-sequencing, which also predict poor prognosis in NPC. Overexpression of LINC00173 induced radioresistance of NPC cells in vitro and in vivo. Mechanistically, LINC00173 bound with checkpoint kinase 2 (CHK2) in nucleus, and impaired the irradiation-induced CHK2 phosphorylation, then suppressed the activation of P53 signalling pathway, which eventually inhibiting apoptosis and leading to radioresistance in NPC cells. In summary, LINC00173 decreases the occurrence of apoptosis through inhibiting the CHK2/P53 pathway, leads to NPC radioresistance and could be considered as a novel predictor and therapeutic target in NPC.


Subject(s)
Carcinoma , Nasopharyngeal Neoplasms , RNA, Long Noncoding , Humans , Carcinoma/genetics , Cell Line, Tumor , Checkpoint Kinase 2/genetics , Checkpoint Kinase 2/metabolism , Gene Expression Regulation, Neoplastic , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/genetics , Radiation Tolerance/genetics , RNA, Long Noncoding/genetics , Signal Transduction/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
19.
Int J Med Sci ; 20(6): 810-817, 2023.
Article in English | MEDLINE | ID: mdl-37213666

ABSTRACT

Interferon gamma (IFNγ) is a cytokine implicated in the pathogenesis of autoimmune diseases. SAM and HD domain-containing protein 1 (SAMHD1) is an IFNγ-inducible protein that modulates cellular dNTP levels. Mutations in the human SAMHD1 gene cause Aicardi-Goutières (AG) syndrome, an autoimmune disease sharing similar clinical features with systemic lupus erythematosus (SLE). Klotho is an anti-inflammatory protein which suppresses aging through multiple mechanisms. Implication of Klotho in autoimmune response is identified in rheumatologic diseases such as SLE. Little information exists regarding the effect of Klotho in lupus nephritis, one of the prevalent symptoms of SLE. The present study verified the effect of IFNγ on SAMHD1 and Klotho expression in MES-13 glomerular mesangial cells, a special cell type in glomerulus that is critically involved in lupus nephritis. IFNγ upregulated SAMHD1 expression in MES-13 cells through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT1) and the nuclear factor kappa B (NFκB) signaling pathways. IFNγ decreased Klotho protein expression in MES-13 cells. Treatment of MES-13 cells with recombinant Klotho protein inhibited SAMHD1 expression by blocking IFNγ-induced NFκB nuclear translocation, but showed no effect on JAK-STAT1 signaling. Collectively, our findings support the protective role of Klotho in attenuating lupus nephritis through the inhibition of IFNγ-induced SAMHD1 expression and IFNγ downstream signaling in MES-13 cells.


Subject(s)
Lupus Nephritis , NF-kappa B , Humans , Cells, Cultured , Interferon-gamma/metabolism , Lupus Nephritis/genetics , Mesangial Cells/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , SAM Domain and HD Domain-Containing Protein 1/genetics , SAM Domain and HD Domain-Containing Protein 1/metabolism , SAM Domain and HD Domain-Containing Protein 1/pharmacology , Interferon gamma Receptor
20.
Cell Rep ; 42(6): 112542, 2023 06 27.
Article in English | MEDLINE | ID: mdl-37210725

ABSTRACT

Alternative splicing (AS) is a critical mechanism for the aberrant biogenesis of long non-coding RNA (lncRNA). Although the role of Wnt signaling in AS has been implicated, it remains unclear how it mediates lncRNA splicing during cancer progression. Herein, we identify that Wnt3a induces a splicing switch of lncRNA-DGCR5 to generate a short variant (DGCR5-S) that correlates with poor prognosis in esophageal squamous cell carcinoma (ESCC). Upon Wnt3a stimulation, active nuclear ß-catenin acts as a co-factor of FUS to facilitate the spliceosome assembly and the generation of DGCR5-S. DGCR5-S inhibits TTP's anti-inflammatory activity by protecting it from PP2A-mediated dephosphorylation, thus fostering tumor-promoting inflammation. Importantly, synthetic splice-switching oligonucleotides (SSOs) disrupt the splicing switch of DGCR5 and potently suppress ESCC tumor growth. These findings uncover the mechanism for Wnt signaling in lncRNA splicing and suggest that the DGCR5 splicing switch may be a targetable vulnerability in ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , RNA, Long Noncoding , Humans , Esophageal Squamous Cell Carcinoma/genetics , RNA, Long Noncoding/genetics , Esophageal Neoplasms/genetics , Inflammation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics , Cell Movement/genetics
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