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Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons.
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Photonic topological insulators with topologically protected edge states featuring one-way, robustness and backscattering-immunity possess extraordinary abilities to steer and manipulate light. In this work, we construct a topological heterostructure (TH) consisting of a domain of nontrivial pseudospin-type topological photonic crystals (PCs) sandwiched between two domains of trivial PCs based on two-dimensional all-dielectric core-shell PCs in triangle lattice. We consider three THs with different number of layers in the middle nontrivial domain (i.e., one-layer, two-layer, three-layer) and demonstrate that the projected band diagrams of the three THs host interesting topological waveguide states (TWSs) with properties of one-way, large-area, broad-bandwidth and robustness due to coupling effect of the helical edge states associated with the two domain-wall interfaces. Moreover, taking advantage of the tunable bandgap between the TWSs by the layer number of the middle domain due to the coupling effect, a topological Y-splitter with functionality of wavelength division multiplexing is explicitly demonstrated exploiting the unique feature of the dispersion curves of TWSs in the three THs. Our work not only offers a new method to realize pseudospin-polarized large-area TWSs with tunable mode-width, but also could provide new opportunities for practical applications in on-chip multifunctional (i.e., wavelength division multiplexing) photonic devices with topological protection and information processing with pseudospin-dependent transport.
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Acyl radicals have been generated from the decarboxylation of α-oxocarboxylic acids by using a readily accessible organic pyrimidopteridine photoredox catalyst under ultraviolet-A (UV-A) light irradiation. These reactive acyl radicals were smoothly added to olefins such as styrenes and diverse Michael acceptors, with the assistance of H2O/D2O as hydrogen donors, enabling easy access to a diverse range of ketones/ß-deuterio ketones. A wide range of α-oxocarboxylic acids are compatible with this reaction, which shows a reliable, atom-economical, and eco-friendly protocol. Furthermore, postsynthetic diversifications and applications are presented.
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BACKGROUND: Currently, arterial spin labeling (ASL) and amide proton transfer (APT) imaging have shown potential for distinguishing glioblastoma from brain metastases. Thus, a meta-analysis was conducted to investigate this further. METHODS: An extensive and comprehensive search was conducted in 6 English and Chinese databases according to predefined inclusion and exclusion criteria, encompassing data up to July 2023. Data from eligible literature were extracted, and bivariate models were employed to calculate pooled sensitivities, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve. RESULTS: The meta-analysis included 11 articles. For ASL, the pooled sensitivity was 0.77 (95% confidence interval [CI], 0.63-0.87), and the pooled specificity was 0.87 (95% CI, 0.77-0.93). The pooled PLR was 5.89 (95% CI, 2.97-11.69), the pooled NLR was 0.26 (95% CI, 0.15-0.47), the pooled DOR was 22.33 (95% CI, 6.89-72.34), and AUC was 0.90 (95% CI, 0.87-0.92). For APT imaging, the pooled sensitivity was 0.78 (95% CI, 0.70-0.85), and the pooled specificity was 0.86 (95% CI, 0.77-0.92). The pooled PLR was 5.51 (95% CI, 3.24-9.37), the pooled NLR was 0.25 (95% CI, 0.17-0.37), the pooled DOR was 21.99 (95% CI, 10.28-47.03), and the AUC was 0.90 (95% CI, 0.87-0.92). CONCLUSIONS: This meta-analysis suggest that both ASL and APT imaging exhibit high accuracy in distinguishing between glioblastoma and brain metastasis.
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Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/diagnostic imaging , Protons , Spin Labels , Brain Neoplasms/diagnostic imaging , ROC Curve , Sensitivity and SpecificityABSTRACT
Zidovudine/lamivudine tablets are nucleoside reverse transcriptase inhibitors that are used to treat human immunodeficiency virus. The objective of this study was to investigate the bioequivalence and pharmacokinetics (PKs) of test and reference preparations of zidovudine/lamivudine tablets in healthy Chinese subjects. We designed a randomized, open, single-center, single-dose, 2-crossover experiment with a 7-day washout period involving 20 healthy subjects. The subjects were given a single dose of the test or reference preparation after fasting overnight for 10 hours. Blood samples were subsequently collected at scheduled time points from 0 hour (preadministration) up to 24 hours postadministration. The plasma concentrations of zidovudine and lamivudine were determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Analysis of variance (ANOVA) was used to compare differences in the mean values of key PK parameters between the 2 preparations. Bioequivalence was evaluated by 2 one-sided t-tests and 90% confidence intervals (CIs) of the geometric mean ratio (GMR). In total, 19 of the 20 subjects completed the trial. Based on the analysis of PK parameters, the relative bioavailability of zidovudine and lamivudine was 101.1% ± 2.0% and 100.3% ± 1.5%, respectively. ANOVA found no significant difference in primary PK parameters when compared between the 2 formulations, and the 90% CIs of the GMR of the 2 formulations were within the bioequivalence margins of 80%-125%. No serious adverse events occurred. Thus, we confirmed that the 2 preparations were bioequivalent in healthy Chinese volunteers. Our analysis demonstrated that both products showed good tolerance in all subjects.
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Lamivudine , Zidovudine , Humans , China , Healthy Volunteers , Lamivudine/pharmacokinetics , Tablets , Therapeutic Equivalency , Zidovudine/pharmacokineticsABSTRACT
Objective To analyze the items and psychometric properties of assessment for development and adaptive behavior. Methods The standardized assessments commonly used in evaluation of children development and adaptive behavior were selected such as Pediatric Evaluation of Disability Inventory-Computer Adaptive Test(PEDI-CAT),Vine-land Adaptive Behavior Scales(VABS-Ⅱ),Adaptive Behavior Assessment System(ABAS-Ⅲ),Bayley Scales of Infant and Toddler Development(Bayley-Ⅲ)and Diagnostic Adaptive Behavior Scale(DABS).Using the ICF's classification framework,linking rules and coding methods,this study conducted a content analysis of the mea-surement dimensions and items of the five assessments,and explored the psychometric properties. Results PEDI-CAT items covered ICF categories such as washing oneself(d510),caring for body parts(d520),toileting(d530),eating(d550),drinking(d560),looking after one's health(d570),basic interpersonal interactions(d710),complex interpersonal interactions(d720),changing basic body position(d410),maintaining body position(d415),and fine hand use(d440),among others.VABS-Ⅱ items covered speaking(d330),conversation(d350),washing oneself(d510),caring for body parts(d520),using transportation(d470),acquisition of goods and ser-vices(d620),basic interpersonal interactions(d710),complex interpersonal interactions(d720),changing body position(d410),and maintaining body position(d415).ABAS-Ⅲ items covered speaking(d330),communicating with-receiving-nonverbal messages(d315),reading(d166),recreation and leisure(d920),community life(d910),handling stress and other psychological demands(d240),looking after one's health(d570),and acquiring,keep-ing and terminating a job(d845).Bayley-Ⅲ items covered memory functions(b144),thought functions(b160),speaking(d330),fine hand use(d440),walking(d450),basic interpersonal interactions(d710),carrying out daily routine(d230),and recreation and leisure(d920).DABS items covered higher-level cognitive functions(b164),reading(d166),basic economic transactions(d860),basic interpersonal interactions(d710),solving problems(d175),handling stress and other psychological demands(d240),carrying out daily routine(d230),and using transportation(d470).All the five assessments were norm-referenced measures.PEDI-CAT had high discrimina-tive validity and reliability,with computer-adaptive testing enabling more precise measurement of children's func-tional levels.VABS-Ⅱ possessed good reliability and validity,with multiple versions for different age and ability levels.ABAS-Ⅲ offered a wide range of adaptive behavior measures with medium to good reliability and validi-ty.Bayley-Ⅲ had excellent internal consistency and test-retest reliability,while DABS showed high validity and reliability indices.The five assessments had high applicability,including norms for different groups and versions for various cultural and language contexts. Conclusion The items of assessments involves multiple ICF categories at the levels of body functions,and activities and participation,mainly focusing on the areas of intellectual functions,high-level cognitive functions,and ability of daily living.All five assessments are norm-referenced and multidimensional,structured assessment tools with strong reliability,validity and applicability.
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BACKGROUND:Satisfactory clinical results have been achieved in the treatment of Sanders Ⅲ calcaneal fractures by percutaneous compression fixation with three-dimensional frame screws.However,whether the stability of minimally invasive plate internal fixation can be achieved in terms of biomechanics,and the advantages and disadvantages after comparison are still unknown. OBJECTIVE:To investigate the fixation effect of different internal fixation devices on Sanders Ⅲ calcaneal fractures by finite element analysis. METHODS:A finite element model of Sanders Ⅲ calcaneal fracture was made based on CT data of a 26-year-old healthy male volunteer.The calcaneal fracture models were fixed by minimally invasive three-dimensional frame screws and minimally invasive Y-plate.The longitudinal loads of 350 and 700 N were applied respectively.The displacement and stress distribution of the two models were analyzed,and the stability of each model was compared. RESULTS AND CONCLUSION:(1)The peak stress of bone block and implant in the minimally invasive three-dimensional frame screw model was significantly lower than that in the minimally invasive minimally invasive plate model.The average stress of bone block and implant in the three-dimensional frame screw model was also significantly lower than that in the minimally invasive plate model.(2)The maximum displacement of the two models was located at the medial side of the articular surface of the posterior talus,and the maximum displacement of the three-dimensional frame screw model was smaller than that of the minimally invasive plate model.(3)The longitudinal displacement between the anterior fragment and the medial fragment of the minimally invasive plate model was smaller,and the transverse and vertical displacement between the medial fragment and the middle fragment of the three-dimensional group screw model was smaller.(4)It is concluded that both of the two internal fixation models can provide satisfactory fixation effect.The three-dimensional frame screw model can provide better transverse and vertical stability with more uniform stress distribution and smaller comprehensive displacement of bone fragments,while the minimally invasive plate has more advantages in maintaining longitudinal stability.
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ObjectiveTo systematically review the evidences of impact of exercise rehabilitation and adapted physical activity on psychomotor skills, motor abilities, and motor development in children with spastic cerebral palsy (CP). MethodsRelevant literature was retrieved from PubMed, Embase, Web of Science and CNKI, from January, 2010 to June, 2023. The contents were coded using International Classification of Diseases, Eleventh Revision, and International Classification of Functioning, Disability and Health; and evidences were analyzed with theoretical framework and code of ICD-11 and ICF. ResultsA total of nine articles were included, from Denmark, South Korea, Australia, Saudi Arabia, Ghana, India and Japan, published from 2015 to 2022. The intervention programs primarily involved exercise rehabilitation (including physical therapy) and adapted physical activity. Exercise rehabilitation included upper limb strength training, lower limb strength training, balance and coordination training, gait training, functional aerobic exercise, stretching and flexibility exercises, flexibility training, muscle relaxation techniques; ten to 50 minutes a time, two to six times a week,with the intensity of low to high, for six to 20 weeks. Adapted physical activities mainly involved adapted running training, virtual games; 60 minutes a time, two to four times a week, with the intensity of medium to high, for six to twelve weeks. Interventions primarily took place in medical and rehabilitation institutions, schools, and home-based communities, with professionals including occupational physical therapists, university researchers, community health personnel and teachers. The outcomes were mainly reflected in four aspects: psychomotor skills, motor abilities, motor development, and quality of life and well-being. In terms of psychomotor skills, adolescents with CP mastered running techniques and knowledge, and enhanced their response to balance threats. In terms of motor abilities, adolescents with CP showed an increase in muscle strength, enhanced muscle endurance, and an expansion of muscle tone; improvements in gait functionality, walking ability, and gait symmetry; increases in walking endurance; improvements in standing function; and improvements in dynamic balance; as well as enhanced control over balance posture. In terms of motor development, there was a significant improvement in activities of daily living, participation levels in school and leisure activities during free time, and an expanded range of motion. In terms of quality of life and well-being, adolescents with CP showed significant enhancements in self-confidence and self-esteem, significant relief from (spastic) pain, and improvements in social well-being and acceptance. ConclusionThis systematic review has synthesized the evidences of benefits of exercise rehabilitation and adapted physical activity on the psychomotor skills, motor abilities and motor development of children and adolescents with spastic CP. In terms of psychomotor skills, exercise rehabilitation and adapted physical activity help to improve the cognitive and motor skills of adolescents with spastic CP. In terms of motor abilities, exercise rehabilitation and adapted physical activity can improve muscle-related functions, gait and walking abilities, as well as balance and coordination. In terms of motor development, exercise rehabilitation and adapted physical activity significantly enhance activities of daily living and the level of participation in leisure physical activities. Finally, exercise rehabilitation and adapted physical activity can increase energy and motivation, alleviate pain, and enhance social well-being and acceptance.
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Acupuncture is increasingly used to manage high blood pressure (BP) as a complementary therapy. However, the mechanisms underlying its hypotensive effects remain unclear. Our previous studies have shown that electroacupuncture (EA) at the ST36-37 acupoints, overlying the deep peroneal nerve, attenuates pressor responses through adenosine A2A receptors (A2AR) in the rostral ventrolateral medulla (rVLM). However, it is uncertain whether rVLM A2AR contributes to EA's BP-lowering effect in sustained hypertension. We hypothesized that a course of EA treatment lowers BP, in part, through the activation of adenosine A2AR in the rVLM in hypertensive rats. To mimic essential hypertension in the clinic, we performed EA in conscious Dahl salt-sensitive hypertensive rats (DSHRs). EA (0.1-0.4â mA, 2â Hz) was applied at ST36-37 for 30â min twice weekly for four weeks, while sham-EA was conducted in a similar manner but without electrical input. In hypertensive rats, BP was reduced by EA (n = 14) but neither by sham-EA (n = 14) nor in the absence of needling (n = 8). Following four weeks of eight treatments and then under anesthesia, EA's modulatory effect on elevated BP was reversed by unilateral rVLM microinjection of SCH 58261 (1â mM in 50â nl; an A2AR antagonist; n = 7; P < 0.05) but not the vehicle (n = 5) in EA-treated DSHRs. Activation of rVLM A2AR in DSHRs treated with sham-EA by an A2AR agonist, CGS-21680 (0.4â mM in 50â nl; n = 8), decreased BP. Unilateral administration of SCH 58261 or CGS-21680 into the rVLM did not alter basal BP in Dahl salt-sensitive rats fed a regular diet with normal BP. The A2AR level in the rVLM after EA was increased compared to the sham-EA and untreated DSHRs (n = 5 in each group; all P < 0.05). These data suggest that a 4-week twice weekly EA treatment reduced BP in salt-sensitive hypertensive rats likely through adenosine-mediated A2AR in the rVLM.
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As a major load-bearing component of trains, the weld quality of the bogie beam is critical to the safety of railway operations. This study specifically investigates the inertia friction welding process of S355 bogie crosshead tubes, with the aim of improving the weld quality and achieving one-time formation of the crosshead tube and tube seat. The microstructural features and mechanical properties of S355 inertia-welded joints were also compared with the base metal. Research indicates that inertia friction welds have no visible defects, and that the microstructure of the welding seam (WS) consists of granular bainite, acicular ferrite and little pearlite. The thermo-mechanically affected zone (TMAZ) consists of granular bainite bands and ferrite + pearlite bands. The hot work strengthening mechanism of inertia friction welding results in a higher level of hardness for both WS and TMAZ. The tensile property of the welded joints can be compared to the base metal. The yield strength, tensile strength and elongation of the welded joints, respectively, reach 87.5%, 100% and 79.5% of S355. However, the impact toughness of the welds at room temperature is lower than that of the base material, particularly in the TMAZ zone. Conversely, in an environment with a temperature of -40 °C, WS's impact toughness surpasses that of the parent material.
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BACKGROUND: Severe COVID-19 disease is typically associated with an urgent need for supplemental oxygen therapy that may be successfully delivered through conventional methods or require invasive mechanical ventilation. Early prediction of the need for invasive mechanical ventilation could significantly improve outcomes of COVID-19 patients. Plasma levels of D-dimer and a number of inflammatory markers as well as values of complete blood counts, all measured in the first two days of hospital admission of COVID-19 patients, were evaluated for their significance as predictors of the eventual need for invasive mechanical ventilation support as well as their values as predictors of post-ventilation morbidly and mortality. METHODS: This retrospective cohort study was conducted at a single center and included data pertaining to 200 patients with previously confirmed moderate to severe COVID-19 disease in the period between May 2021 and the end of December 2022. Data were retrieved from medical records for further analysis. RESULTS: The mean (SD) age of patients stood at 59 (14) years of age, and with a majority of patients being male (77%). About 18% of cases, all of significantly older age, had been connected to invasive mechanical ventilation (IMV). Total leucocytic count (TLC), as well as levels of urea, creatinine, D-dimer, ferritin, and CRP in IMV patients were significantly higher than non-ventilated patients (p < 0.01 for all). In contrast, lymphocytic count, hemoglobin level, and platelet count were significantly lower in IMV patients (p < 0.001, 0.04, and 0.002, respectively). The mortality rate was significantly higher in IMV patients (p < 0.001). D-dimer independently predicted IMV demand (OR = 1, p = 0.001 in adjusted and unadjusted models). The utility of D-dimer was excellent; and the cutoff level of above 1415 µ/L showed sensitivity and specificity of about 92% and 76%, respectively. Also, the D-dimer level was very effective in predicting post-IMV survival; the AUC = 0.86, p = 0.02, and a cutoff value below 4558 µ/L was associated with 100% and 66% sensitivity and specificity, respectively. CONCLUSIONS: High D-dimer levels independently correlated with the need for invasive mechanical ventilation. Low levels of this marker could evidently predict post-IMV survival of mechanically ventilated COVID-19 patients. Measuring D-dimer levels during routine follow up of those patients would thus be useful in predicting patient outcomes.
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COVID-19 , Humans , Male , Middle Aged , Female , COVID-19/therapy , Respiration, Artificial , SARS-CoV-2 , Retrospective StudiesSubject(s)
Glioma , Programmed Cell Death 1 Receptor , Humans , B7-H1 Antigen , Prognosis , Biomarkers, Tumor/metabolismABSTRACT
Elevated sympathetic activity and chronic inflammation are known contributory factors observed in hypertension. We have observed that sympathoinhibitory electroacupuncture (SI-EA) at acupoints ST36-37 alleviates sympathetic activity and hypertension. Additionally, EA at acupoints SP6-7 exerts anti-inflammatory (AI-EA) effects. However, it is not known whether simultaneous stimulation of this combination of acupoints attenuates or enhances individual effects. A 2 × 2 factorial design was used to test the hypothesis that combining SI-EA and AI-EA (cEA) leads to greater reduction of hypertension by decreasing sympathetic activity and inflammation in hypertensive rats than either set of acupoints alone. Dahl salt-sensitive hypertensive (DSSH) rats were treated with four EA regimens including cEA, SI-EA, AI-EA, and sham-EA twice weekly for five weeks. A group of normotensive (NTN) rats served as control. Systolic and diastolic BP (SBP and DBP) and heart rate (HR) were measured non-invasively by tail-cuff. Plasma norepinephrine (NE), high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) concentrations were determined with ELISA at the completion of treatments. DSSH rats on high salt diet progressively developed moderate hypertension within five weeks. DSSH rats treated with sham-EA showed continuous increase in SBP and DBP and elevations in plasma NE, hs-CRP, and IL-6 levels relative to NTN control. Both SI-EA and cEA decreased SBP and DBP, and had corresponding changes in biomarkers (NE, hs-CRP, and IL-6) compared with sham-EA. AI-EA prevented SBP and DBP elevation and decreased IL-6 and hs-CRP relative to sham-EA. Importantly in DSSH rats that received repetitive cEA treatment, SI-EA interacted positively with AI-EA leading to greater reduction of SBP, DBP, NE, hs-CRP, and IL-6 than SI-EA or AI-EA alone. These data suggest that by targeting both elevated sympathetic activity and chronic inflammation, cEA regimen results in a greater reduction of BP effects in treating hypertension compared to using individual SI-EA or AI-EA alone.
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In additive manufacturing (AM), the mechanical properties of manufactured parts are often insufficient due to complex defects and residual stresses, limiting their use in high-value or mission-critical applications. Therefore, the research and application of nondestructive testing (NDT) technologies to identify defects in AM are becoming increasingly urgent. This article reviews the recent progress in online detection technologies in AM, a special introduction to the high-speed synchrotron X-ray technology for real-time in situ observation, and analysis of defect formation processes in the past 5 years, and also discusses the latest research efforts involving process monitoring and feedback control algorithms. The formation mechanism of different defects and the influence of process parameters on defect formation, important parameters such as defect spatial resolution, detection speed, and scope of application of common NDT methods, and the defect types, advantages, and disadvantages associated with current online detection methods for monitoring three-dimensional printing processes are summarized. In response to the development requirements of AM technology, the most promising trends in online detection are also prospected. This review aims to serve as a reference and guidance for the work to identify/select the most suitable measurement methods and corresponding control strategy for online detection.
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OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disease that is associated with oxidative stress. Due to the anti-inflammatory and antioxidant functions of Selenium (Se), this molecule may have neuroprotective functions in PD; however, the involvement of Se in such a protective function is unclear. METHODS: 1-methyl-4-phenylpyridinium (MPP+), which inhibits mitochondrial respiration, is generally used to produce a reliable cellular model of PD. In this study, a MPP+-induced PD model was used to test if Se could modulate cytotoxicity, and we further capture gene expression profiles following PC12 cell treatment with MPP+ with or without Se by genome wide high-throughput sequencing. RESULTS: We identified 351 differentially expressed genes (DEGs) and 14 differentially expressed long non-coding RNAs (DELs) in MPP+-treated cells when compared to controls. We further document 244 DEGs and 27 DELs in cells treated with MPP+ and Se vs. cells treated with MPP+ only. Functional annotation analysis of DEGs and DELs revealed that these groups were enriched in genes that respond to reactive oxygen species (ROS), metabolic processes, and mitochondrial control of apoptosis. Thioredoxin reductase 1 (Txnrd1) was also identified as a biomarker of Se treatment. CONCLUSIONS: Our data suggests that the DEGs Txnrd1, Siglec1 and Klf2, and the DEL AABR07044454.1 which we hypothesize to function in cis on the target gene Cdkn1a, may modulate the underlying neurodegenerative process, and act a protective function in the PC12 cell PD model. This study further systematically demonstrated that mRNAs and lncRNAs induced by Se are involved in neuroprotection in PD, and provides novel insight into how Se modulates cytotoxicity in the MPP+-induced PD model.
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Neurodegenerative Diseases , Parkinson Disease , Selenium , Humans , Parkinson Disease/genetics , Parkinson Disease/metabolism , 1-Methyl-4-phenylpyridinium/toxicity , Selenium/pharmacology , Oxidative Stress/genetics , Reactive Oxygen Species/metabolism , Apoptosis/geneticsABSTRACT
Background: Tumor necrosis factor (TNF) is an inflammatory cytokine that can coordinate tissue homeostasis by co-regulating the production of cytokines, cell survival, or death. It widely expresses in various tumor tissues and correlates with the malignant clinical features of patients. As an important inflammatory factor, the role of TNFα is involved in all steps of tumorigenesis and development, including cell transformation, survival, proliferation, invasion and metastasis. Recent research has showed that long non-coding RNAs (lncRNAs), defined as RNA transcripts >200 nucleotides that do not encode a protein, influence numerous cellular processes. However, little is known about the genomic profile of TNF pathway related-lncRNAs in GBM. This study investigated the molecular mechanism of TNF related-lncRNAs and their immune characteristics in glioblastoma multiforme (GBM) patients. Methods: To identify TNF associations in GBM patients, we performed bioinformatics analysis of public databases - The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). The ConsensusClusterPlus, CIBERSORT, Estimate, GSVA and TIDE and first-order bias correlation and so on approaches were conducted to comprehensively characterize and compare differences among TNF-related subtypes. Results: Based on the comprehensive analysis of TNF-related lncRNAs expression profiles, we constructed six TNF-related lncRNAs (C1RL-AS1, LINC00968, MIR155HG, CPB2-AS1, LINC00906, and WDR11-AS1) risk signature to determine the role of TNF-related lncRNAs in GBM. This signature could divide GBM patients into subtypes with distinct clinical and immune characteristics and prognoses. We identified three molecular subtypes (C1, C2, and C3), with C2 showing the best prognosis; otherwise, C3 showing the worst prognosis. Moreover, we assessed the prognostic value, immune infiltration, immune checkpoints, chemokines cytokines and enrichment analysis of this signature in GBM. The TNF-related lncRNA signature was tightly associated with the regulation of tumor immune therapy and could serve as an independent prognostic biomarker in GBM. Conclusion: This analysis provides a comprehensive understanding of the role of TNF-related characters, which may improve the clinical outcome of GBM patients.
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A new cascade alkoxycarbonylation/cyclization reaction of heterocycle-bearing unactivated alkenes is disclosed. The transformation is mediated by silver carbonate under photoirradiation. This method provides efficient access to pharmaceutically valuable molecules and natural product analogues containing quinazolinone-fused esters. Furthermore, this protocol is compatible with a variety of quinazolinone-bearing unactivated alkenes and alkyloxalyl chlorides that are readily prepared from abundant alcohols and oxalyl chlorides.
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Artificial neural networks (ANNs) have been an important approach for predicting the value of flow stress, which is dependent on temperature, strain, and strain rate. However, there is still a lack of sufficient knowledge regarding what structure of ANN should be used for predicting metal flow stress. In this paper, we train an ANN for predicting flow stress of In718 alloys at high temperatures using our experimental data, and the structure of the ANN is optimized by comparing the performance of four ANNs in predicting the flow stress of In718 alloy. It is found that, as the size of the ANN increases, the ability of the ANN to retrieve the flow stress results from a training dataset is significantly enhanced; however, the ability to predict the flow stress results absent from the training does not monotonically increase with the size of the ANN. It is concluded that the ANN with one hidden layer and four nodes possesses optimized performance for predicting the flow stress of In718 alloys in this study. The reason why there exists an optimized ANN size is discussed. When the ANN size is less than the optimized size, the prediction, especially the strain dependency, falls into underfitting and fails to predict the curve. When the ANN size is less than the optimized size, the predicted flow stress curves with the temperature, strain, and strain rate will contain non-physical fluctuations, thus reducing their prediction accuracy of extrapolation. For metals similar to the In718 alloy, ANNs with very few nodes in the hidden layer are preferred rather than the large ANNs with tens or hundreds of nodes in the hidden layers.
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OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.