This study evaluates the long-term radiometric performance of the USGS new released Landsat Collection 1 archive, including the absolute calibration of each Landsat sensor as well as the relative cross-calibration amo...This study evaluates the long-term radiometric performance of the USGS new released Landsat Collection 1 archive, including the absolute calibration of each Landsat sensor as well as the relative cross-calibration among the four most popular Landsat sensors. A total of 920 Landsat Collection 1 scenes were evaluated against the corresponding Pre-Collection images over a Pseudo-Invariant Site, Railroad Valley Playa Nevada, United States (RVPN). The radiometric performance of the six Landsat solar reflective bands, in terms of both Digital Numbers (DNs) and at-sensor Top of Atmosphere (TOA) reflectance, on the sensor cross-calibration was examined. Results show that absolute radiometric calibration at DNs level was applied to the Landsat-4 and -5 TM (L4 TM and L5 TM) by –1.119% to 0.126%. For L4 TM and L5 TM, the cross-calibration decreased the radiometric measurement level by rescaling at-sensor radiance to DN values. The radiometric changes, –0.77% for L4 TM, 0.95% for L5 TM, –0.26% for L7 ETM+, and –0.01% for L8 OLI, were detected during the cross-calibration stage of converting DNs into TOA reflectance. This study has also indicated that the long-term radiometric performance for the Landsat Collection 1 archive is promising. Supports of these conclusions were demonstrated through the time-series analysis based on the Landsat Collection 1 image stack. Nevertheless, the radiometric changes across the four Landsat sensors raised concerns of the previous Landsat Pre-Collection based results. We suggest that Landsat users should pay attention to differences in results from Pre-Collection and Collection 1 time-series data sets.展开更多
The design of this paper is to present the first installment of a complete and final theory of rational human intelligence. The theory is mathematical in the strictest possible sense. The mathematics involved is stric...The design of this paper is to present the first installment of a complete and final theory of rational human intelligence. The theory is mathematical in the strictest possible sense. The mathematics involved is strictly digital—not quantitative in the manner that what is usually thought of as mathematics is quantitative. It is anticipated at this time that the exclusively digital nature of rational human intelligence exhibits four flavors of digitality, apparently no more, and that each flavor will require a lengthy study in its own right. (For more information,please refer to the PDF.)展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(...Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.展开更多
A redox active medicinal plant and L-leucine mixture (HLM) was investigated in subjects with established osteoarthritis of the knee in a multi-center, rando- m-ized, placebo-controlled, double-blind clinical trial. A ...A redox active medicinal plant and L-leucine mixture (HLM) was investigated in subjects with established osteoarthritis of the knee in a multi-center, rando- m-ized, placebo-controlled, double-blind clinical trial. A total of 96 subjects with osteoarthritis were enrolled and randomized to either placebo (n = 38) or HLM treatment group (n = 38). The HLM group re- ceived a combination of Uncaria tomentosa (300 mg), Boswellia serrata (200 mg), Lepidium meyenii (1000 mg) and L-Leucine (700 mg) given as 3 capsules once a day. The placebo group received matching capsules with carboxymethylcellulose. The treatment period was 8 weeks, with assessments made at days 7, 14, 28 and 56. The primary outcome was reduction in total WOMAC score. VAS pain, tolerability, investigator assessments, use of rescue medication (acetominophen), and safety assessments of vital signs and laboratory assessments were included. Subject randomization was effective for age, gender and disease severity. In the placebo group 32/38 subjects completed the trial and for HLM 35/38. WOMAC scores (pain, stiffness, physical performance and total) steadily declined over the course of the 8 week study in both groups, but the magnitude was significantly greater for HLM (P < 0.05). Total WOMAC was reduced 46.5% for HLM and 25.4 % for placebo. VAS pain was reduced 21.8% in the placebo group (p < 0.002) but the changes were significantly greater (37.8% p < 0.03) with HLM treatment. Investigator’s global assessment rating of good-excellent was 24/35 (69%) for HLM and 14/32 (44%) for placebo (P = 0.05). Rescue medication consumption and tolerability were comparable for HLM and placebo. No safety issues were evident with either group. As expected a placebo effect was observed, nevertheless HLM was clearly more effective in relieving the symptoms of osteoarthritis. This HLM represents a safe and effective new approach to the management of osteoarthritis symptoms.展开更多
AIM: To investigate the effect of adrenalectomy (ADX) on the epididymidis of Sprague-Dawley rats. METHODS: The histological, biochemical (cholesterol protein, zinc, copper, alkaline and acid phosphatase aryl sulphatas...AIM: To investigate the effect of adrenalectomy (ADX) on the epididymidis of Sprague-Dawley rats. METHODS: The histological, biochemical (cholesterol protein, zinc, copper, alkaline and acid phosphatase aryl sulphatase, lactic dehydrogenase and leucine amino peptidase) and hormonal (FSH, LH and testosterone) changes of caput and cauda epididymis in ADX rats were observed. RESULTS: Organ wet weight, histological studies and morphometric measurements indicated a cellular degeneration in caput and cauda epididymis of ADX rats. Serum testosterone level was significantly lower in ADX than in sham-operated rats, while the serum FSH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham-operated rats. Epididymal zinc level increased whereas copper level decreased in ADX rats compared to the sham-operated. CONCLUSION: Adrenalectomy leads to degeneration of caput and cauda epididymidis epithelial cells as a result of decreased supply of testosterone.展开更多
The edible mushroom Agaricus bisporus L.plays a crucial ecological role in nutrient cycling and organic matter decomposition,alongside its increasing importance in the food and nutrition industry.This study explored e...The edible mushroom Agaricus bisporus L.plays a crucial ecological role in nutrient cycling and organic matter decomposition,alongside its increasing importance in the food and nutrition industry.This study explored ecological interventions to enhance the mushroom’s vitamin content by enriching its cultivation substrate with nanomaterials and biostimulatory agents.The experiment was conducted within the mushroom production project at Al-Qadisiyah Governorate,Iraq.The compost-based medium was amended with magnetic iron nanoparticles(N-FeO),carbon nanotube(CNT)suspensions,EM biofertilizer,and Atonik growth stimulant.Their ecological impact on the enrichment of fat-soluble(A,D,E)and water-soluble(B2,B3,B5,B6)vitamins in mushrooms was assessed.The study employed a Completely Randomized Design(CRD)with three replicates.Results revealed that the synergistic application of these eco-friendly treatments significantly enhanced the vitamin profiles of A.bisporus.The highest concentrations of vitamins B2 and B5(5.16 and 17.70 mg kg^(-1),respectively)and vitamin A(6.87 IU ml^(-1))were recorded under the combined quadruple treatment.Additionally,the triple treatment(N-FeO+EM+Atonik)notably increased levels of vitamins B2(4.47 mg kg^(-1)),B6(25.66 mg kg^(-1)),D(34.76 mg kg^(-1)),and vitamin A(6.87 IU ml^(-1)).Dual treatments(EM+Atonik)also significantly improved vitamin B2(4.54 mg kg^(-1))and vitamin E(3.30 mg kg^(-1))contents.These findings demonstrate that integrating nanomaterials and biostimulants can serve as an ecological strategy to improve the nutritional quality of mushrooms while promoting sustainable agricultural practices.展开更多
Industrial activities have caused widespread arsenic(As)contamination in soil and medicinal crops across south-ern Asia.This study constructed interplanting systems combing medicinal crops with Pteris vittata L.,aimin...Industrial activities have caused widespread arsenic(As)contamination in soil and medicinal crops across south-ern Asia.This study constructed interplanting systems combing medicinal crops with Pteris vittata L.,aiming to mitigate the risk of As exposure in medicinal crops,while simultaneously achieving ecological remediation of contaminated soil.The results revealed that interplanting with P.vittata significantly enhanced the yield of Gynos-temma pentaphyllum by 31.90%(P<0.05)compared with monoculture systems.Under monoculture conditions,the As concentration in G.pentaphyllum leaves reached 2.34 mg/kg,exceeding the national food safety standard(GB2762–2017,2 mg/kg).However,interplanting with P.vittata effectively reduced the As concentration in G.pentaphyllum leaves to 1.82 mg/kg.Furthermore,the interplanting of P.vittata with Rhus chinensis significantly inhibited As translocation from belowground to aboveground tissues in R.chinensis.Compared to monoculture,the stem biomass of P.vittata was significantly increased by 57.50%and 70.32%when interplanted with G.pentaphyllum and Cassia obtusifolia L.(P<0.05).So the As enrichment of P.vittata was enhanced in interplanting systems,which is beneficial for the As removal from contaminated soil.The study demonstrated that interplant-ing primarily regulates plant As uptake through modifications of rhizosphere physicochemical properties and As bioavailability,especially for water-soluble As that is easily absorbed by plants.In conclusion,the interplant-ing models integrating medicinal crops and P.vittata can achieve the goal of“remediating while producing”in As-contaminated soil.展开更多
The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the cent...The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.展开更多
This study explores the thin-layer convective solar drying of Marrubium vulgare L.leaves under conditions typical of sun-rich semi-arid climates.Drying experiments were conducted at three inlet-air temperatures(40℃,5...This study explores the thin-layer convective solar drying of Marrubium vulgare L.leaves under conditions typical of sun-rich semi-arid climates.Drying experiments were conducted at three inlet-air temperatures(40℃,50℃,60℃)and two air velocities(1.5 and 2.5 m·s^(-1))using an indirect solar dryer with auxiliary temperature control.Moisture-ratio data were fitted with eight widely used thin-layer models and evaluated using correlation coefficient(r),root-mean-square error(RMSE),and Akaike information criterion(AIC).A complementary heattransfer analysis based on Reynolds and Prandtl numbers with appropriate Nusselt correlations was used to relate flow regime to drying performance,and an energy balance quantified the relative contributions of solar and auxiliary heat.The logarithmic model consistently achieved the lowest RMSE/AIC with r>0.99 across all conditions.Higher temperature and air velocity significantly reduced drying time during the decreasing-rate period,with no constantrate stage observed.On average,solar input supplied the large majority of the thermal demand,while the auxiliary heater compensated short irradiance drops to maintain setpoints.These findings provide a reproducible dataset and a modelling benchmark for M.vulgare leaves,and they support energy-aware design of hybrid solar dryers formedicinal plants in sun-rich regions.展开更多
In this essay,our goal is to discover science in Martin Heidegger’s Introduction to Metaphysics,lecture notes for his 1935 summer semester course,because,after all,his subject is metaphysica generalis,or ontology,and...In this essay,our goal is to discover science in Martin Heidegger’s Introduction to Metaphysics,lecture notes for his 1935 summer semester course,because,after all,his subject is metaphysica generalis,or ontology,and this could be construed as a theory of the human brain.Here,by means of verbatim quotes from his text,we attempt to show that indeed these lectures can be viewed as suggestion for an objective scientific theory of human perception,the human capacity for deciphering phenomena,i.e.hermeneutics in its broadest sense.His added notes from the 1953 edition,all of which are comments,not corrections,imply that he never abandoned these thoughts on metaphysics,despite all of his utterances about a need to overcome it,and their popular interpretations to that effect.In his presentation,he further develops the colorful and intuitive style,an hermeneutic language,that he had created in his earlier work Being and Time.The logical functions of Dasein’s anatomical brain are performed by the logos machine,formerly the human soul,using top-down processing based on a global context,the noumenal cosmos which humans maintain internally.Heidegger’s 1942/43 winter semester lectures Parmenides extend in unbroken fashion his 1935 work,proving that he never abandoned,as is widely claimed,his metaphysical avenue of thought.展开更多
Substrate and nutrient supply are essential for vegetable cultivation in greenhouse.The strategies for plant nutrient supply vary depending on the cultivation methods or substrate dosages employed.With the development...Substrate and nutrient supply are essential for vegetable cultivation in greenhouse.The strategies for plant nutrient supply vary depending on the cultivation methods or substrate dosages employed.With the development of mechanization,wide-row spacing substrate cultivation became an optimize mode of the greenhouse cucumber cultivation,aligning with the trend of intelligent agriculture.To determine the optimal nutrient solution supply amount(NS)and supply frequency(SF)for promoting the integrated growth of cucumber under wide-row spacing substrate cultivation,we explored the effects of substrate supply amount(SS),NS,and SF on cucumber yield,quality,and element utilization efficiency.A five-level quadratic orthogonal rotation combination design with three experimental factors(NS,SF,and SS)was implemented for 23 coupling treatments over three growing seasons,including spring(2022S and 2023S)and autumn(2022A).The technique for order preference by similarity to ideal solution(TOPSIS)combining weights based on game theory was applied to construct cucumber comprehensive growth evaluation model.Single and two experimental factors analyses revealed significant effects of single factors and the coupling of NS-SS,NS-SF and SS-SF on the integrated growth of cucumber for all three growing seasons.For the NS-SF-SS combination,the optimal parameters for comprehensive cucumber growth were determined as follows:levels of^(-1).68 for NS,-0.7 for SF,and^(-1).682 for SS in 2022A;-0.43 for NS,-0.06 for SF,and 0.34 for SS in 2022S;0.3 for NS,-0.02 for SF,and 0.04 for SS in 2023S.Furthermore,for SS ranges of 2.00-3.01,3.01-4.50,4.50-5.99,5.99-7.00(L·plant^(-1)),the corresponding NS and SF intervals maximizing cucumber integrated growth in spring were:0.28-0.30(L·plant^(-1))and 6(times·d^(-1)),0.26-0.30(L·plant^(-1))and 6(times·d^(-1)),0.25-0.30(L·plant^(-1))and 6(times·d^(-1)),0.23-0.30(L·plant^(-1))and 6(times·d^(-1)),respectively.With the same SS,the corresponding NS and SF intervals that maximized cucumber integrated growth in autumn were:0.10(L·plant^(-1))and 8(times·d^(-1)),0.18(L·plant^(-1))and 7(times·d^(-1)),0.30(L·plant^(-1))and 6(times·d^(-1)),0.49(L·plant^(-1))and 5(times·d^(-1)),respectively.The results provide a theoretical basis for solution management,and further in-depth research on cucumber cultivation.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic su...Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic surgeries.The unpredictable nature of this condition,combined with limited treatment options,poses a significant burden on patients,their families,and society.Spinal cord ischemia-reperfusion injury leads to reduced neuronal regenerative capacity and complex pathological processes.In contrast,mitophagy is crucial for degrading damaged mitochondria,thereby supporting neuronal metabolism and energy supply.However,while moderate mitophagy can be beneficial in the context of spinal cord ischemia-reperfusion injury,excessive mitophagy may be detrimental.Therefore,this review aims to investigate the potential mechanisms and regulators of mitophagy involved in the pathological processes of spinal cord ischemia-reperfusion injury.The goal is to provide a comprehensive understanding of recent advancements in mitophagy related to spinal cord ischemia-reperfusion injury and clarify its potential clinical applications.展开更多
Background: There are at least 5 very popular methods described for the correction of mild to moderate hallux valgus deformities. Despite of reported and self experienced good results in favorable fitting preoperative...Background: There are at least 5 very popular methods described for the correction of mild to moderate hallux valgus deformities. Despite of reported and self experienced good results in favorable fitting preoperative anatomical conditions of some of these methods;it seems that no one is really satisfying under “difficult” or non favorable preoperative anatomic conditions. How could an optimum operation method for a satisfying correction of a mild to moderate hallux valgus look like? The well known criteria for an optimally satisfying method to achieve full normalization of important forefoot parameters under all conditions should be a lateralization, plantarization and derotation of the Ist metatarsal head and also a normalization of the distal metatarsal articular angle (DMAA) in combination with a soft tissue correction. Methods: In order to achieve this outcome without the disadvantages of shortening or the need for unloading, we developed a new operation technique and new fixation devices. We performed a simple transverse lazy-L subcapital osteotomy and after an additional soft tissue release the Ist metatarsal head was restored to its preplaned optimum position in terms of narrowing the IM angle, plantarization, correction of the hallux valgus angle, derotation of a pronation l malrotation and improvement of the DMAA. Fixation was achieved with an intramedullary angel-stable transfixed 30 mm titanium plate. The rigidity of the implant rendered interfragmental compression or solid bone contact unnecessary. The goal was only an optimal correction. All patients were allowed to ambulate with full weightbearing immediately after the operation. Results: We retrospectively reviewed 346 patients (433 feet) who underwent subcapital osteotomy between May 2007 and December 2011;308 were women and 38 men;their mean age was 65 years. The follow-up investigation was performed on average after 6.5 years (78 months);range 5.5 to 10 years (66 to 120 months). The AOFAS Score improved from 61.18 to 96.82 (t = 55.13, p ° to 4.21° (t = 89.70, p ° to 7.75° (t = 51.68, p ° to 6.61° (t = 29.34, p < 0.001). Minimal shortening of the first metatarsal (0.33 mm) and no recurrence of the deformity was observed. Conclusion: A new access to hallux valgus surgery is presented. Our results show that interfragmental compression between the osteotomy partners or good interfragmental contact is not necessary when a rigid intramedullary fixation device is used. The goal of this approach to hallux valgus surgery was to achieve excellent correction and a very rigid intramedullary angle-stable locked implant. The procedure yielded excellent results and was associated with no recurrence of hallux valgus.展开更多
We’ll study the FEM for a model for compressible miscible displacement in porous media which includes molecular diffusion and mechanical dispersion in one-dimensional space.A class of vertices-edges-elements interpol...We’ll study the FEM for a model for compressible miscible displacement in porous media which includes molecular diffusion and mechanical dispersion in one-dimensional space.A class of vertices-edges-elements interpolation operator ink is introduced.With the help of ink(not elliptic projection),the optimal error estimate in L∞(J;L2(Ω)) norm of FEM is proved.展开更多
We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies wer...We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.展开更多
AIML To investigate the effect and mechanism of action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on invasion and metastasis of human colorectal cancer cell line SL-174T...AIML To investigate the effect and mechanism of action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on invasion and metastasis of human colorectal cancer cell line SL-174T. METHODS: Human colorectal cancer cel4 line SL-174T was cultured and treated separately with four different dosages of L-NAME for 72 h, Nitric oxide (NO) production was measured with Griess reagent, The effect of L-NAME on invasion and migration of SL-174T cells were evaluated by using Transwell chambers attached with polycarbonate filters and reconstituted basement membrane (Matrigel), RT-PCR was performed to determine the mRNA levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor metalloproteinase-2 (TIMP-2),RESULTS: L-NAME could significantly inhibit NO production of SL-174T in a dose-dependent manner. After being treated for 72 h with 0.2, 0.4, 0.8, and 1.0 mmol/L L- NAME, respectively, the ability of the L-NAME treated SL- 174T cells to invade the reconstituted basement membrane decreased significantly (t = 8.056, P〈0.05; t= 14.467, P〈0.01; t= 27.785, P〈0.01; and t= 29.405, P〈0.01, respectively) and the inhibition rates were 10.29%, 19.62%, 34.08%, and 42.23%, respectively. Moreover, L-NAME could inhibit migration of SL-174T cells, and the inhibition rates were 20.76%, 24.95%, 39.43%, and 46. 85% for L-NAME at 0.2, 0.4, 0.8, and 1.0 mmol/L, respectively (t = 15.116, P〈0.01). In addition, after treatment with L-NAME, expression of MMP-2 mRNA was significantly decreased (t = 71.238, P〈0.01) and that of TIMP-2 mRNA was markedly increased (t = -13.020, P〈0.01). CONCLUSION: L-NAME exerts anti-invasive and anti- metastatic effects on SL-174T cell line via downregulating MNP-2 mRNA expression and upregulating TIMP-2 mRNA expression.展开更多
Amphiphilic block copolymers poly(LysAA-b-DMS) consisting of a hydrophilic poly(N-α-acrylamide-L-lysine) [poly(LysAA)] segment with different molecular weights and a hydrophobic polydimethylsiloxane (PDMS) segment we...Amphiphilic block copolymers poly(LysAA-b-DMS) consisting of a hydrophilic poly(N-α-acrylamide-L-lysine) [poly(LysAA)] segment with different molecular weights and a hydrophobic polydimethylsiloxane (PDMS) segment were prepared as follows. The precursor copolymer poly(Boc-LysAA-OtBu-b-PDMS) was obtained from radical polymerization of N-α-acrylamide-N-ε-tert-butoxycarbonyl-L-lysine-tert-butylester (Boc-LysAA-OtBu) initiated with 4,4’-azobis(polydimethylsiloxane 4-cyanopentanoate) (azo-PDMS) with the molecular weight of PDMS Mw = 4.3 × 103 in the presence of 2-mercaptoethanol (2-ME) as a chain-transfer agent. Removal of the protecting groups of the precursor copolymer was carried out in 80% trifluoroacetic acid aqueous solution to give poly(LysAA-b-DMS)-1-3. The weight average molecular weight of poly(LysAA-b-DMS)-1-3 was Mw = 1.02 × 104 – 2.52 × 104. From the 1H-NMR and fluorescence spectra measurements, poly(LysAA-b-DMS)-1-3 was determined to self-organize and form core-shell micelles in water. The critical micelle concentration (CMC) increased to 1000 - 4000 mg·L–1 with increasing molar ratio of the poly(LysAA) segment from 0.42 to 0.65. From morphological analysis with a scanning probe microscope (SPM), poly(LysAA-b-DMS) has microphase-separated structures made up of hydrophilic and hydrophobic regions with the domain size ranging from several tens to several hundreds of nanometers. Inhibition of thrombin activity of poly(LysAA-b-DMS) was evaluated from the Michaelis constant (KM) and catalytic activity (kcat) for the enzymatic reaction of thrombin and synthetic substrate S-2238 in the presence of poly(LysAA-b-DMS). The KM and kcat were 0.10 - 0.11 mM and 4.04 × 105 – 4.26 × 105 min–1, respectively. Fibrinolytic activity was also verified from the transformation of plasminogen to plasmin by tissue plasminogen activator (t-PA) using synthetic substrate S-2251 in the presence of poly(LysAA-b-DMS). The KM and kcat were 0.07 mM and 5.73 × 106 –5.95 × 106 min–1, respectively.展开更多
文摘This study evaluates the long-term radiometric performance of the USGS new released Landsat Collection 1 archive, including the absolute calibration of each Landsat sensor as well as the relative cross-calibration among the four most popular Landsat sensors. A total of 920 Landsat Collection 1 scenes were evaluated against the corresponding Pre-Collection images over a Pseudo-Invariant Site, Railroad Valley Playa Nevada, United States (RVPN). The radiometric performance of the six Landsat solar reflective bands, in terms of both Digital Numbers (DNs) and at-sensor Top of Atmosphere (TOA) reflectance, on the sensor cross-calibration was examined. Results show that absolute radiometric calibration at DNs level was applied to the Landsat-4 and -5 TM (L4 TM and L5 TM) by –1.119% to 0.126%. For L4 TM and L5 TM, the cross-calibration decreased the radiometric measurement level by rescaling at-sensor radiance to DN values. The radiometric changes, –0.77% for L4 TM, 0.95% for L5 TM, –0.26% for L7 ETM+, and –0.01% for L8 OLI, were detected during the cross-calibration stage of converting DNs into TOA reflectance. This study has also indicated that the long-term radiometric performance for the Landsat Collection 1 archive is promising. Supports of these conclusions were demonstrated through the time-series analysis based on the Landsat Collection 1 image stack. Nevertheless, the radiometric changes across the four Landsat sensors raised concerns of the previous Landsat Pre-Collection based results. We suggest that Landsat users should pay attention to differences in results from Pre-Collection and Collection 1 time-series data sets.
文摘The design of this paper is to present the first installment of a complete and final theory of rational human intelligence. The theory is mathematical in the strictest possible sense. The mathematics involved is strictly digital—not quantitative in the manner that what is usually thought of as mathematics is quantitative. It is anticipated at this time that the exclusively digital nature of rational human intelligence exhibits four flavors of digitality, apparently no more, and that each flavor will require a lengthy study in its own right. (For more information,please refer to the PDF.)
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
基金supported by the National Natural Science Foundation of China,No.81471279 and No.81171138(to WJZ)Talent Support Grant from Shantou University Medical College,China,No.2501220118(to WJZ)the Li Kashing Foundation,No.LD030302(to MS)
文摘Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.
文摘A redox active medicinal plant and L-leucine mixture (HLM) was investigated in subjects with established osteoarthritis of the knee in a multi-center, rando- m-ized, placebo-controlled, double-blind clinical trial. A total of 96 subjects with osteoarthritis were enrolled and randomized to either placebo (n = 38) or HLM treatment group (n = 38). The HLM group re- ceived a combination of Uncaria tomentosa (300 mg), Boswellia serrata (200 mg), Lepidium meyenii (1000 mg) and L-Leucine (700 mg) given as 3 capsules once a day. The placebo group received matching capsules with carboxymethylcellulose. The treatment period was 8 weeks, with assessments made at days 7, 14, 28 and 56. The primary outcome was reduction in total WOMAC score. VAS pain, tolerability, investigator assessments, use of rescue medication (acetominophen), and safety assessments of vital signs and laboratory assessments were included. Subject randomization was effective for age, gender and disease severity. In the placebo group 32/38 subjects completed the trial and for HLM 35/38. WOMAC scores (pain, stiffness, physical performance and total) steadily declined over the course of the 8 week study in both groups, but the magnitude was significantly greater for HLM (P < 0.05). Total WOMAC was reduced 46.5% for HLM and 25.4 % for placebo. VAS pain was reduced 21.8% in the placebo group (p < 0.002) but the changes were significantly greater (37.8% p < 0.03) with HLM treatment. Investigator’s global assessment rating of good-excellent was 24/35 (69%) for HLM and 14/32 (44%) for placebo (P = 0.05). Rescue medication consumption and tolerability were comparable for HLM and placebo. No safety issues were evident with either group. As expected a placebo effect was observed, nevertheless HLM was clearly more effective in relieving the symptoms of osteoarthritis. This HLM represents a safe and effective new approach to the management of osteoarthritis symptoms.
文摘AIM: To investigate the effect of adrenalectomy (ADX) on the epididymidis of Sprague-Dawley rats. METHODS: The histological, biochemical (cholesterol protein, zinc, copper, alkaline and acid phosphatase aryl sulphatase, lactic dehydrogenase and leucine amino peptidase) and hormonal (FSH, LH and testosterone) changes of caput and cauda epididymis in ADX rats were observed. RESULTS: Organ wet weight, histological studies and morphometric measurements indicated a cellular degeneration in caput and cauda epididymis of ADX rats. Serum testosterone level was significantly lower in ADX than in sham-operated rats, while the serum FSH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham-operated rats. Epididymal zinc level increased whereas copper level decreased in ADX rats compared to the sham-operated. CONCLUSION: Adrenalectomy leads to degeneration of caput and cauda epididymidis epithelial cells as a result of decreased supply of testosterone.
文摘The edible mushroom Agaricus bisporus L.plays a crucial ecological role in nutrient cycling and organic matter decomposition,alongside its increasing importance in the food and nutrition industry.This study explored ecological interventions to enhance the mushroom’s vitamin content by enriching its cultivation substrate with nanomaterials and biostimulatory agents.The experiment was conducted within the mushroom production project at Al-Qadisiyah Governorate,Iraq.The compost-based medium was amended with magnetic iron nanoparticles(N-FeO),carbon nanotube(CNT)suspensions,EM biofertilizer,and Atonik growth stimulant.Their ecological impact on the enrichment of fat-soluble(A,D,E)and water-soluble(B2,B3,B5,B6)vitamins in mushrooms was assessed.The study employed a Completely Randomized Design(CRD)with three replicates.Results revealed that the synergistic application of these eco-friendly treatments significantly enhanced the vitamin profiles of A.bisporus.The highest concentrations of vitamins B2 and B5(5.16 and 17.70 mg kg^(-1),respectively)and vitamin A(6.87 IU ml^(-1))were recorded under the combined quadruple treatment.Additionally,the triple treatment(N-FeO+EM+Atonik)notably increased levels of vitamins B2(4.47 mg kg^(-1)),B6(25.66 mg kg^(-1)),D(34.76 mg kg^(-1)),and vitamin A(6.87 IU ml^(-1)).Dual treatments(EM+Atonik)also significantly improved vitamin B2(4.54 mg kg^(-1))and vitamin E(3.30 mg kg^(-1))contents.These findings demonstrate that integrating nanomaterials and biostimulants can serve as an ecological strategy to improve the nutritional quality of mushrooms while promoting sustainable agricultural practices.
基金supported by the National Key Research and Development Program of China(No.2020YFC1807805)the Science and Technology Planning Project of Guangzhou,Guangdong Province,China(No.202206010176).
文摘Industrial activities have caused widespread arsenic(As)contamination in soil and medicinal crops across south-ern Asia.This study constructed interplanting systems combing medicinal crops with Pteris vittata L.,aiming to mitigate the risk of As exposure in medicinal crops,while simultaneously achieving ecological remediation of contaminated soil.The results revealed that interplanting with P.vittata significantly enhanced the yield of Gynos-temma pentaphyllum by 31.90%(P<0.05)compared with monoculture systems.Under monoculture conditions,the As concentration in G.pentaphyllum leaves reached 2.34 mg/kg,exceeding the national food safety standard(GB2762–2017,2 mg/kg).However,interplanting with P.vittata effectively reduced the As concentration in G.pentaphyllum leaves to 1.82 mg/kg.Furthermore,the interplanting of P.vittata with Rhus chinensis significantly inhibited As translocation from belowground to aboveground tissues in R.chinensis.Compared to monoculture,the stem biomass of P.vittata was significantly increased by 57.50%and 70.32%when interplanted with G.pentaphyllum and Cassia obtusifolia L.(P<0.05).So the As enrichment of P.vittata was enhanced in interplanting systems,which is beneficial for the As removal from contaminated soil.The study demonstrated that interplant-ing primarily regulates plant As uptake through modifications of rhizosphere physicochemical properties and As bioavailability,especially for water-soluble As that is easily absorbed by plants.In conclusion,the interplant-ing models integrating medicinal crops and P.vittata can achieve the goal of“remediating while producing”in As-contaminated soil.
基金supported by the Wellcome Trust(grant No.103852).
文摘The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.
文摘This study explores the thin-layer convective solar drying of Marrubium vulgare L.leaves under conditions typical of sun-rich semi-arid climates.Drying experiments were conducted at three inlet-air temperatures(40℃,50℃,60℃)and two air velocities(1.5 and 2.5 m·s^(-1))using an indirect solar dryer with auxiliary temperature control.Moisture-ratio data were fitted with eight widely used thin-layer models and evaluated using correlation coefficient(r),root-mean-square error(RMSE),and Akaike information criterion(AIC).A complementary heattransfer analysis based on Reynolds and Prandtl numbers with appropriate Nusselt correlations was used to relate flow regime to drying performance,and an energy balance quantified the relative contributions of solar and auxiliary heat.The logarithmic model consistently achieved the lowest RMSE/AIC with r>0.99 across all conditions.Higher temperature and air velocity significantly reduced drying time during the decreasing-rate period,with no constantrate stage observed.On average,solar input supplied the large majority of the thermal demand,while the auxiliary heater compensated short irradiance drops to maintain setpoints.These findings provide a reproducible dataset and a modelling benchmark for M.vulgare leaves,and they support energy-aware design of hybrid solar dryers formedicinal plants in sun-rich regions.
文摘In this essay,our goal is to discover science in Martin Heidegger’s Introduction to Metaphysics,lecture notes for his 1935 summer semester course,because,after all,his subject is metaphysica generalis,or ontology,and this could be construed as a theory of the human brain.Here,by means of verbatim quotes from his text,we attempt to show that indeed these lectures can be viewed as suggestion for an objective scientific theory of human perception,the human capacity for deciphering phenomena,i.e.hermeneutics in its broadest sense.His added notes from the 1953 edition,all of which are comments,not corrections,imply that he never abandoned these thoughts on metaphysics,despite all of his utterances about a need to overcome it,and their popular interpretations to that effect.In his presentation,he further develops the colorful and intuitive style,an hermeneutic language,that he had created in his earlier work Being and Time.The logical functions of Dasein’s anatomical brain are performed by the logos machine,formerly the human soul,using top-down processing based on a global context,the noumenal cosmos which humans maintain internally.Heidegger’s 1942/43 winter semester lectures Parmenides extend in unbroken fashion his 1935 work,proving that he never abandoned,as is widely claimed,his metaphysical avenue of thought.
基金supported by the China Agriculture Research System(Grant No.CARS-23-D06)the Key Research and Development Program of Shaanxi Province(Grant Nos.2024NC2-GJHX-29 and 2024NC-ZDCYL-05-08)Shaanxi Agricultural Collaborative Innovation and Extension Alliance Project(Grant No.LMZD202202).
文摘Substrate and nutrient supply are essential for vegetable cultivation in greenhouse.The strategies for plant nutrient supply vary depending on the cultivation methods or substrate dosages employed.With the development of mechanization,wide-row spacing substrate cultivation became an optimize mode of the greenhouse cucumber cultivation,aligning with the trend of intelligent agriculture.To determine the optimal nutrient solution supply amount(NS)and supply frequency(SF)for promoting the integrated growth of cucumber under wide-row spacing substrate cultivation,we explored the effects of substrate supply amount(SS),NS,and SF on cucumber yield,quality,and element utilization efficiency.A five-level quadratic orthogonal rotation combination design with three experimental factors(NS,SF,and SS)was implemented for 23 coupling treatments over three growing seasons,including spring(2022S and 2023S)and autumn(2022A).The technique for order preference by similarity to ideal solution(TOPSIS)combining weights based on game theory was applied to construct cucumber comprehensive growth evaluation model.Single and two experimental factors analyses revealed significant effects of single factors and the coupling of NS-SS,NS-SF and SS-SF on the integrated growth of cucumber for all three growing seasons.For the NS-SF-SS combination,the optimal parameters for comprehensive cucumber growth were determined as follows:levels of^(-1).68 for NS,-0.7 for SF,and^(-1).682 for SS in 2022A;-0.43 for NS,-0.06 for SF,and 0.34 for SS in 2022S;0.3 for NS,-0.02 for SF,and 0.04 for SS in 2023S.Furthermore,for SS ranges of 2.00-3.01,3.01-4.50,4.50-5.99,5.99-7.00(L·plant^(-1)),the corresponding NS and SF intervals maximizing cucumber integrated growth in spring were:0.28-0.30(L·plant^(-1))and 6(times·d^(-1)),0.26-0.30(L·plant^(-1))and 6(times·d^(-1)),0.25-0.30(L·plant^(-1))and 6(times·d^(-1)),0.23-0.30(L·plant^(-1))and 6(times·d^(-1)),respectively.With the same SS,the corresponding NS and SF intervals that maximized cucumber integrated growth in autumn were:0.10(L·plant^(-1))and 8(times·d^(-1)),0.18(L·plant^(-1))and 7(times·d^(-1)),0.30(L·plant^(-1))and 6(times·d^(-1)),0.49(L·plant^(-1))and 5(times·d^(-1)),respectively.The results provide a theoretical basis for solution management,and further in-depth research on cucumber cultivation.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
基金supported by Cuiying Scientific and Technological Innovation Program of Second Hospital of Lanzhou University,Nos.CY2023-QN-B18(to YD),2020QN-16(to YZ)the Natural Science Foundation of Gansu Province,No.22JR11RA082(to YZ)Key R&D Plan of Gansu Provincial Department of Science and Technology-Social Development Projects,No.23YFFA0043(to XK).
文摘Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic surgeries.The unpredictable nature of this condition,combined with limited treatment options,poses a significant burden on patients,their families,and society.Spinal cord ischemia-reperfusion injury leads to reduced neuronal regenerative capacity and complex pathological processes.In contrast,mitophagy is crucial for degrading damaged mitochondria,thereby supporting neuronal metabolism and energy supply.However,while moderate mitophagy can be beneficial in the context of spinal cord ischemia-reperfusion injury,excessive mitophagy may be detrimental.Therefore,this review aims to investigate the potential mechanisms and regulators of mitophagy involved in the pathological processes of spinal cord ischemia-reperfusion injury.The goal is to provide a comprehensive understanding of recent advancements in mitophagy related to spinal cord ischemia-reperfusion injury and clarify its potential clinical applications.
文摘Background: There are at least 5 very popular methods described for the correction of mild to moderate hallux valgus deformities. Despite of reported and self experienced good results in favorable fitting preoperative anatomical conditions of some of these methods;it seems that no one is really satisfying under “difficult” or non favorable preoperative anatomic conditions. How could an optimum operation method for a satisfying correction of a mild to moderate hallux valgus look like? The well known criteria for an optimally satisfying method to achieve full normalization of important forefoot parameters under all conditions should be a lateralization, plantarization and derotation of the Ist metatarsal head and also a normalization of the distal metatarsal articular angle (DMAA) in combination with a soft tissue correction. Methods: In order to achieve this outcome without the disadvantages of shortening or the need for unloading, we developed a new operation technique and new fixation devices. We performed a simple transverse lazy-L subcapital osteotomy and after an additional soft tissue release the Ist metatarsal head was restored to its preplaned optimum position in terms of narrowing the IM angle, plantarization, correction of the hallux valgus angle, derotation of a pronation l malrotation and improvement of the DMAA. Fixation was achieved with an intramedullary angel-stable transfixed 30 mm titanium plate. The rigidity of the implant rendered interfragmental compression or solid bone contact unnecessary. The goal was only an optimal correction. All patients were allowed to ambulate with full weightbearing immediately after the operation. Results: We retrospectively reviewed 346 patients (433 feet) who underwent subcapital osteotomy between May 2007 and December 2011;308 were women and 38 men;their mean age was 65 years. The follow-up investigation was performed on average after 6.5 years (78 months);range 5.5 to 10 years (66 to 120 months). The AOFAS Score improved from 61.18 to 96.82 (t = 55.13, p ° to 4.21° (t = 89.70, p ° to 7.75° (t = 51.68, p ° to 6.61° (t = 29.34, p < 0.001). Minimal shortening of the first metatarsal (0.33 mm) and no recurrence of the deformity was observed. Conclusion: A new access to hallux valgus surgery is presented. Our results show that interfragmental compression between the osteotomy partners or good interfragmental contact is not necessary when a rigid intramedullary fixation device is used. The goal of this approach to hallux valgus surgery was to achieve excellent correction and a very rigid intramedullary angle-stable locked implant. The procedure yielded excellent results and was associated with no recurrence of hallux valgus.
基金This research is supported by the Foundation for Talents for Next Century of Shandong University
文摘We’ll study the FEM for a model for compressible miscible displacement in porous media which includes molecular diffusion and mechanical dispersion in one-dimensional space.A class of vertices-edges-elements interpolation operator ink is introduced.With the help of ink(not elliptic projection),the optimal error estimate in L∞(J;L2(Ω)) norm of FEM is proved.
文摘We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.
文摘AIML To investigate the effect and mechanism of action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on invasion and metastasis of human colorectal cancer cell line SL-174T. METHODS: Human colorectal cancer cel4 line SL-174T was cultured and treated separately with four different dosages of L-NAME for 72 h, Nitric oxide (NO) production was measured with Griess reagent, The effect of L-NAME on invasion and migration of SL-174T cells were evaluated by using Transwell chambers attached with polycarbonate filters and reconstituted basement membrane (Matrigel), RT-PCR was performed to determine the mRNA levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor metalloproteinase-2 (TIMP-2),RESULTS: L-NAME could significantly inhibit NO production of SL-174T in a dose-dependent manner. After being treated for 72 h with 0.2, 0.4, 0.8, and 1.0 mmol/L L- NAME, respectively, the ability of the L-NAME treated SL- 174T cells to invade the reconstituted basement membrane decreased significantly (t = 8.056, P〈0.05; t= 14.467, P〈0.01; t= 27.785, P〈0.01; and t= 29.405, P〈0.01, respectively) and the inhibition rates were 10.29%, 19.62%, 34.08%, and 42.23%, respectively. Moreover, L-NAME could inhibit migration of SL-174T cells, and the inhibition rates were 20.76%, 24.95%, 39.43%, and 46. 85% for L-NAME at 0.2, 0.4, 0.8, and 1.0 mmol/L, respectively (t = 15.116, P〈0.01). In addition, after treatment with L-NAME, expression of MMP-2 mRNA was significantly decreased (t = 71.238, P〈0.01) and that of TIMP-2 mRNA was markedly increased (t = -13.020, P〈0.01). CONCLUSION: L-NAME exerts anti-invasive and anti- metastatic effects on SL-174T cell line via downregulating MNP-2 mRNA expression and upregulating TIMP-2 mRNA expression.
文摘Amphiphilic block copolymers poly(LysAA-b-DMS) consisting of a hydrophilic poly(N-α-acrylamide-L-lysine) [poly(LysAA)] segment with different molecular weights and a hydrophobic polydimethylsiloxane (PDMS) segment were prepared as follows. The precursor copolymer poly(Boc-LysAA-OtBu-b-PDMS) was obtained from radical polymerization of N-α-acrylamide-N-ε-tert-butoxycarbonyl-L-lysine-tert-butylester (Boc-LysAA-OtBu) initiated with 4,4’-azobis(polydimethylsiloxane 4-cyanopentanoate) (azo-PDMS) with the molecular weight of PDMS Mw = 4.3 × 103 in the presence of 2-mercaptoethanol (2-ME) as a chain-transfer agent. Removal of the protecting groups of the precursor copolymer was carried out in 80% trifluoroacetic acid aqueous solution to give poly(LysAA-b-DMS)-1-3. The weight average molecular weight of poly(LysAA-b-DMS)-1-3 was Mw = 1.02 × 104 – 2.52 × 104. From the 1H-NMR and fluorescence spectra measurements, poly(LysAA-b-DMS)-1-3 was determined to self-organize and form core-shell micelles in water. The critical micelle concentration (CMC) increased to 1000 - 4000 mg·L–1 with increasing molar ratio of the poly(LysAA) segment from 0.42 to 0.65. From morphological analysis with a scanning probe microscope (SPM), poly(LysAA-b-DMS) has microphase-separated structures made up of hydrophilic and hydrophobic regions with the domain size ranging from several tens to several hundreds of nanometers. Inhibition of thrombin activity of poly(LysAA-b-DMS) was evaluated from the Michaelis constant (KM) and catalytic activity (kcat) for the enzymatic reaction of thrombin and synthetic substrate S-2238 in the presence of poly(LysAA-b-DMS). The KM and kcat were 0.10 - 0.11 mM and 4.04 × 105 – 4.26 × 105 min–1, respectively. Fibrinolytic activity was also verified from the transformation of plasminogen to plasmin by tissue plasminogen activator (t-PA) using synthetic substrate S-2251 in the presence of poly(LysAA-b-DMS). The KM and kcat were 0.07 mM and 5.73 × 106 –5.95 × 106 min–1, respectively.