The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centere...The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.展开更多
BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation...Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.展开更多
F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM...F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM)基础上融入注意力机制(Attention),提出了一种基于BiLSTM-Attention的F_(10.7)预报模型.在加拿大DRAO数据集上其平均绝对误差(MAE)为5.38,平均绝对百分比误差(MAPE)控制在5%以内,相关系数(R)高达0.987,与其他RNN模型相比拥有优越的预测性能.针对中国廊坊L&S望远镜观测的F_(10.7)数据集,提出了一种转换平均校准(Conversion Average Calibration,CAC)方法进行数据预处理,处理后的数据与DRAO数据集具有较高的相关性.基于该数据集对比分析了RNN系列模型的预报效果,实验结果表明,BiLSTM-Attention和BiLSTM两种模型在预测F_(10.7)指数方面具有较好的优势,表现出较好的预测性能和稳定性.展开更多
Mosquitoes are an interesting topic due to their medical importance, as they play an active role in the transmission of many pathogens and parasites, acting as vectors for various pathologies that are deadly to humans...Mosquitoes are an interesting topic due to their medical importance, as they play an active role in the transmission of many pathogens and parasites, acting as vectors for various pathologies that are deadly to humans, such as dengue, yellow fever, chikungunya, West Nile virus, encephalitis and malaria, among many others that are less common. In terms of morbidity and mortality caused by vector-borne diseases, mosquitoes are the most dangerous animals for humanity and, although they also play a role in the ecosystem as a food source for other organisms, their importance for public health cannot be overlooked. As highly efficient vectors, they put more than three billion people at risk, mainly in tropical and subtropical regions as well as in Europe, since heat waves and flooding are becoming more frequent and severe, and summers are getting longer and warmer, accelerating mosquito development, biting rates, and the incubation of the pathogens within their bodies. Female mosquitoes bite to acquire proteins for the development of their ovaries and eggs and, in the process, acquire pathogens and/or parasites from one vertebrate host and transmit them to another, usually after a short period of replication. Three of their four life stages are lived in still freshwater, so it is crucial to understand their range of action when they reach adulthood and leave the water, in order to plan and implement local prevention measures. A set of georeferenced abundance data collected in mainland Portugal over seven years was linked to cartographed water bodies in a geographic information system to estimate the distances at which Culex pipiens s.l. had a significant presence, with criteria based on the size of the catches. The result allows for an estimate of the fly range of those mosquitoes, which can be used to focus countermeasures.展开更多
Understanding the composition and contents of carotenoids in various soybean seed accessions is important for their nutritional assessment.This study investigated the variability in the concentrations of carotenoids a...Understanding the composition and contents of carotenoids in various soybean seed accessions is important for their nutritional assessment.This study investigated the variability in the concentrations of carotenoids and chlorophylls and revealed their associations with other nutritional quality traits in a genetically diverse set of Chinese soybean accessions comprised of cultivars and landraces.Genotype,planting year,accession type,seed cotyledon color,and ecoregion of origin significantly influenced the accumulation of carotenoids and chlorophylls.The mean total carotenoid content was in the range of 8.15–14.72μg g–1 across the ecoregions.The total carotenoid content was 1.2-fold higher in the landraces than in the cultivars.Soybeans with green cotyledons had higher contents of carotenoids and chlorophylls than those with yellow cotyledons.Remarkably,lutein was the most abundant carotenoid in all the germplasms,ranging from 1.35–37.44μg g–1.Carotenoids and chlorophylls showed significant correlations with other quality traits,which will help to set breeding strategies for enhancing soybean carotenoids without affecting the other components.Collectively,our results demonstrate that carotenoids are adequately accumulated in soybean seeds,however,they are strongly influenced by genetic factors,accession type,and germplasm origin.We identified novel germplasms with the highest total carotenoid contents across the various ecoregions of China that could serve as the genetic materials for soybean carotenoid breeding programs,and thereby as the raw materials for food sectors,pharmaceuticals,and the cosmetic industry.展开更多
BACKGROUND The coaxial radiography-guided puncture technique(CR-PT)is a novel technique for endoscopic lumbar discectomy.As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction,t...BACKGROUND The coaxial radiography-guided puncture technique(CR-PT)is a novel technique for endoscopic lumbar discectomy.As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction,the X-ray beam can be used to guide the trajectory angle,facilitating the choice of the puncture site and providing real-time guidance.This puncture technique offers numerous advantages over the conventional anterior-posterior and lateral radiography-guided puncture technique(AP-PT),especially in cases of herniated lumbar discs with a hypertrophied transverse process or articular process,high iliac crest,and narrowed intervertebral foramen.AIM To confirm whether CR-PT is a superior approach to percutaneous transforaminal endoscopic lumbar discectomy compared to AP-PT.METHODS In this parallel,controlled,randomized clinical trial,herniated lumbar disc patients appointed to receive percutaneous endoscopic lumbar discectomy treatment were recruited from the Pain Management Department of the Affiliated Hospital of Xuzhou Medical University and Nantong Hospital of Traditional Chinese Medicine.Sixty-five participants were enrolled and divided into either a CR-PT group or an AP-PT group.The CR-PT group underwent CR-PT,and the AP-PT group underwent AP-PT.The number of fluoroscopies during puncturing,puncture duration(min),surgery duration(min),VAS score during puncturing,and puncture success rate were recorded.RESULTS Sixty-five participants were included,with 31 participants in the CR-PT group and 34 in the AP-PT group.One participant in the AP-PT group dropped out due to unsuccessful puncturing.The number of fluoroscopies[median(P25,P75)]was 12(11,14)in the CR-PT group vs 16(12,23)in the AP-PT group,while the puncture duration(mean±SD)was 20.42±5.78 vs 25.06±5.46,respectively.The VAS score was 3(2,4)in the CR-PT group vs 3(3,4)in the AP-PT group.Further subgroup analysis was performed,considering only the participants with L5/S1 segment herniation:9 patients underwent CR-PT,and 9 underwent AP-PT.The number of fluoroscopies was 11.56±0.88 vs 25.22±5.33;the puncture duration was 13.89±1.45 vs 28.89±3.76;the surgery duration was 105(99.5,120)vs 149(125,157.5);and the VAS score was 2.11±0.93 vs 3.89±0.6,respectively.All the above outcomes demonstrated statistical significance(P<0.05),favoring the CR-PT treatment.CONCLUSION CR-PT is a novel and effective technique.As opposed to conventional AP-PT,this technique significantly improves puncture accuracy,shortens puncture time and operation time,and reduces pain intensity during puncturing.展开更多
Breeding for salinity tolerance using Bangladeshi rice landraces and understand genetic diversity has been limited by the complex and polygenic nature of salt tolerance in rice genotypes. A genetic diversity and assoc...Breeding for salinity tolerance using Bangladeshi rice landraces and understand genetic diversity has been limited by the complex and polygenic nature of salt tolerance in rice genotypes. A genetic diversity and association mapping analysis was conducted using 96 germplasm accessions with variable response to salt stress at the seedling stage. These included86 landraces and 10 indica varieties and lines including Nona Bokra, from southern Bangladesh. A total of 220 alleles were detected at 58 Simple Sequence Repeat(SSR) marker loci randomly distributed on all 12 rice chromosomes and 8 Sequence Tagged Site(STS) markers developed for genes SKC1, DST, and SalT. The average gene diversity was 0.5075 and polymorphism information content value was 0.4426, respectively. Cluster analysis revealed that 68 and 21 accessions were clustered into 2 distinct groups, possibly corresponding to indica and japonica groups, respectively and the remaining 7 landraces were classified as an admixed group. In addition to Wn11463, the STS marker for SKC1, RM22418 on Chr. 8 was significantly associated with salinity tolerance, at the location of a QTL detected in previous studies. Our findings of favorable alleles associated with salinity tolerance in Bangladeshi rice landraces, as well as the development of STS markers for salt tolerance genes, will be helpful in future efforts to breed salinity tolerance in rice.展开更多
AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications ad...AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn's disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE data-bases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when necessary to generate a standardized set of data from these studies. From these data, odds ratio (OR) with 95% confidence interval (CI) were calculated.RESULTS: Twenty-five studies of CD were analyzed, 14 of which involved cases of UC. The variant G allele of ATG16L1 was positively associated with CD (OR=1.32, 95% CI: 1.26-1.39, P<0.00001) and UC (OR =1.06, 95% CI:1.01-1.10, P=0.02). For child-onset IBD, a higher G allele frequency was found for cases of CD (OR=1.35, 95% CI: 1.16-1.57, P=0.0001) than for cases of UC (OR = 0.98, 95% CI: 0.81-1.19, P = 0.84) relative to controls.CONCLUSION: The ATG16L1 T300A polymorphism contributes to susceptibility to CD and UC in adults, but different in children, which implicates a role for autophagy in the pathogenesis of IBD.展开更多
Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective vi...Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.展开更多
The aim of this work was to evaluate the photokilling efficiency of synthesized titanium dioxide nanoparticles in suspension. Two strains of Escherichia coli, Lactobacillus casei rhamnosus and Staphylococcus aureus we...The aim of this work was to evaluate the photokilling efficiency of synthesized titanium dioxide nanoparticles in suspension. Two strains of Escherichia coli, Lactobacillus casei rhamnosus and Staphylococcus aureus were used as probes to test the photokilling activities of the nanoparticles. The toxicity effects of TiO2 nanoparticles on the environment were determined by a standard test using gram-negative bioluminescent bacteria Vibrio fischeri. The antimicrobial activity of these nanoparticles (NPs) was then investigated versus NPs concentration, UV irradiation time and micro- organism strains. We evaluated the LC50 values of the nanoparticles suspension by counting the Colony-Forming Units. Results highlighted the differences in bacteria sensitivity facing photokilling treatment induced by the irradiation of anatase TiO2 nanoparticles suspension. At the concentration of 1 g·L-1 TiO2, tested bacteria were killed after 30 minutes of photo-treatment. Using different TiO2 concentrations, the Staphylococcus aureus gram-positive/catalase-positive bacteria were more resistant than gram-negative/catalase-positive ones or gram-positive/catalase-negative bacteria. An effect of UV irradiation was evaluated by the quantification of hydrogen peroxide generated by the photolysis of water molecules in presence of the nanoparticles with or without the most resistant bacterium (S. aureus). After 30 minutes with UV irradiation in these two conditions, the concentration of hydrogen peroxide was 35 μM in presence of 1.2 g·L-1 TiO2 suspension. This result suggested that the resistance mechanism of S. aureus was not due to an extracelullar H2O2 enzymatic degradation.展开更多
Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute tre...Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Eg5 (kinesin spindle protein), which is crucial for bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy. The aim of this study was to investigate the anticancer efficacy of $-(methoxytrityl)-L-cysteine (S(MeO)TLC), a novel Eg5 inhibitor in prostate cancer. Eg5 expression was examined in human prostate cancer cell lines and tissue microarrays were constructed from clinical specimens. Antiproliferative activity of S(MeO)TLC in prostate cancer cells was assessed by a cell viability assay. The anticancer effect and inhibitory mechanism of S(MeO)TLC in prostate cancer cells was further explored by Hoechst staining, flow cytometry and immunofluorescence. In addition, the antitumor effect of S(MeO)TLC on subcutaneous xenograft models was assessed. Eg5 expression was identified in PC3, DU145 and LNCaP cells. More than half of prostate cancer clinical specimens displayed Eg5 expression. S(Me0)TLC exhibited more powerful anticancer activity in prostate cancer cells compared with the other four Eg5 inhibitors tested. S(MeO)TLC induced cell death after arresting dividing cells at mitosis with distinct monopolar spindle formation. S(MeO)TLC exhibited its significant inhibitory activity (P〈0.05) on subcutaneous xenograft models also through induction of mitotic arrest. We conclude that Eg5 is a good target for prostate cancer chemotherapy, and S(MeO)TLC is a potent promising anticancer agent in prostate cancer.展开更多
Objective:To determine fauna and some ecological aspects of Anopheles mosquitoes in northeast of Iran.Methods:In this descriptive study,3 villages in Kalaleh County were selected in different geographical zones.Anophe...Objective:To determine fauna and some ecological aspects of Anopheles mosquitoes in northeast of Iran.Methods:In this descriptive study,3 villages in Kalaleh County were selected in different geographical zones.Anopheles mosquitoes were collected biweekly from May to October using standard dipping method for larvae,and hand catch,total catch,artificial pit shelter as well as night-biting collections on human and animal baits for adults.Results:Totally 399 larvae and 2 602 adults of Anopheles mosquitoes were collected and identified as 2 species:Anopheles superpictus s.l.(An.superpictus s.l.) and Anopheles maculipennis s.l.The dominant species was An.superpictus s.l.(92.1%).Activity of these mosquitoes found to be started from middle of May and extended till September with two peaks of activity in July and August.Conclusions:An.superpictus s.l.as one of the main malaria vectors in Iran as well as some other parts of the world is the dominant species in the study area.This species has high potential for transmission and possibility of establishing a transmission cycle with low abundance.Other species,Anopheles maculipennis s.l.also has introduced as a malaria vector in northern parts of Iran.As this Anopheles is a complex species,genetic studies are recommended to determine the members of this complex in the study area.展开更多
The effects of rotation and gravity on an electro-magneto-thermoelastic medium with diffusion and voids in a generalized thermoplastic half-space are studied by using the Lord-Shulman (L-S) model and the dual-phase-la...The effects of rotation and gravity on an electro-magneto-thermoelastic medium with diffusion and voids in a generalized thermoplastic half-space are studied by using the Lord-Shulman (L-S) model and the dual-phase-lag (DPL) model. The analytical solutions for the displacements, stresses, temperature, diffusion concentration, and volume fraction field with different values of the magnetic field, the rotation, the gravity, and the initial stress are obtained and portrayed graphically. The results indicate that the effects of gravity, rotation, voids, diffusion, initial stress, and electromagnetic field are very pronounced on the physical properties of the material.展开更多
cDNA libraries were constructed from the leaves of a rice (Oryza sativa L.) salt tolerancevariety Tesan抋i 2 growing in solutions with 150 mmol/L NaCl for 3 h or without salt stress. Three salt-responsive cDNA clones,...cDNA libraries were constructed from the leaves of a rice (Oryza sativa L.) salt tolerancevariety Tesan抋i 2 growing in solutions with 150 mmol/L NaCl for 3 h or without salt stress. Three salt-responsive cDNA clones, Ts1, Ts2 and Ts3 were isolated by differential screening. Northern blottinganalysis showed that the transcription levels of Ts1 and Ts2 increased within 3 h salt stress and kept onincreasing within 24 h, while the transcription level of Ts3 reached its peak within 3 h. Sequence analysisindicated that there were no homologies between the three cDNA clones and any known gene. The threecDNA clones were mapped using a doubled haploid (DH) population derived from an indica variety ZYQ8,which was a salt tolerance parent of Tesan抋i 2, with a japonica variety JX17. Ts1, Ts2 and Ts3 werelocated on chromosomes 1, 3 and 7, respectively. It was noted that Ts1, Ts2, and Ts3 were in or near theregions of major or minor salt tolerance quantitative trait loci (QTLs), which were mapped in the same DHpopulation in a parallel study.展开更多
Relations between helicity coupling amplitude and L-S coupling amplitude are discussed. The equivalence condition for these two kinematic analysis methods and the limitations of the L-S coupling amplitude are also stu...Relations between helicity coupling amplitude and L-S coupling amplitude are discussed. The equivalence condition for these two kinematic analysis methods and the limitations of the L-S coupling amplitude are also studied in this paper.展开更多
文摘The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
文摘Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.
文摘F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM)基础上融入注意力机制(Attention),提出了一种基于BiLSTM-Attention的F_(10.7)预报模型.在加拿大DRAO数据集上其平均绝对误差(MAE)为5.38,平均绝对百分比误差(MAPE)控制在5%以内,相关系数(R)高达0.987,与其他RNN模型相比拥有优越的预测性能.针对中国廊坊L&S望远镜观测的F_(10.7)数据集,提出了一种转换平均校准(Conversion Average Calibration,CAC)方法进行数据预处理,处理后的数据与DRAO数据集具有较高的相关性.基于该数据集对比分析了RNN系列模型的预报效果,实验结果表明,BiLSTM-Attention和BiLSTM两种模型在预测F_(10.7)指数方面具有较好的优势,表现出较好的预测性能和稳定性.
文摘Mosquitoes are an interesting topic due to their medical importance, as they play an active role in the transmission of many pathogens and parasites, acting as vectors for various pathologies that are deadly to humans, such as dengue, yellow fever, chikungunya, West Nile virus, encephalitis and malaria, among many others that are less common. In terms of morbidity and mortality caused by vector-borne diseases, mosquitoes are the most dangerous animals for humanity and, although they also play a role in the ecosystem as a food source for other organisms, their importance for public health cannot be overlooked. As highly efficient vectors, they put more than three billion people at risk, mainly in tropical and subtropical regions as well as in Europe, since heat waves and flooding are becoming more frequent and severe, and summers are getting longer and warmer, accelerating mosquito development, biting rates, and the incubation of the pathogens within their bodies. Female mosquitoes bite to acquire proteins for the development of their ovaries and eggs and, in the process, acquire pathogens and/or parasites from one vertebrate host and transmit them to another, usually after a short period of replication. Three of their four life stages are lived in still freshwater, so it is crucial to understand their range of action when they reach adulthood and leave the water, in order to plan and implement local prevention measures. A set of georeferenced abundance data collected in mainland Portugal over seven years was linked to cartographed water bodies in a geographic information system to estimate the distances at which Culex pipiens s.l. had a significant presence, with criteria based on the size of the catches. The result allows for an estimate of the fly range of those mosquitoes, which can be used to focus countermeasures.
基金financially supported by the National Natural Science Foundation of China(32161143033 and 32001574)the Agricultural Science and Technology Innovation Program of CAAS(2060203-2).
文摘Understanding the composition and contents of carotenoids in various soybean seed accessions is important for their nutritional assessment.This study investigated the variability in the concentrations of carotenoids and chlorophylls and revealed their associations with other nutritional quality traits in a genetically diverse set of Chinese soybean accessions comprised of cultivars and landraces.Genotype,planting year,accession type,seed cotyledon color,and ecoregion of origin significantly influenced the accumulation of carotenoids and chlorophylls.The mean total carotenoid content was in the range of 8.15–14.72μg g–1 across the ecoregions.The total carotenoid content was 1.2-fold higher in the landraces than in the cultivars.Soybeans with green cotyledons had higher contents of carotenoids and chlorophylls than those with yellow cotyledons.Remarkably,lutein was the most abundant carotenoid in all the germplasms,ranging from 1.35–37.44μg g–1.Carotenoids and chlorophylls showed significant correlations with other quality traits,which will help to set breeding strategies for enhancing soybean carotenoids without affecting the other components.Collectively,our results demonstrate that carotenoids are adequately accumulated in soybean seeds,however,they are strongly influenced by genetic factors,accession type,and germplasm origin.We identified novel germplasms with the highest total carotenoid contents across the various ecoregions of China that could serve as the genetic materials for soybean carotenoid breeding programs,and thereby as the raw materials for food sectors,pharmaceuticals,and the cosmetic industry.
文摘BACKGROUND The coaxial radiography-guided puncture technique(CR-PT)is a novel technique for endoscopic lumbar discectomy.As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction,the X-ray beam can be used to guide the trajectory angle,facilitating the choice of the puncture site and providing real-time guidance.This puncture technique offers numerous advantages over the conventional anterior-posterior and lateral radiography-guided puncture technique(AP-PT),especially in cases of herniated lumbar discs with a hypertrophied transverse process or articular process,high iliac crest,and narrowed intervertebral foramen.AIM To confirm whether CR-PT is a superior approach to percutaneous transforaminal endoscopic lumbar discectomy compared to AP-PT.METHODS In this parallel,controlled,randomized clinical trial,herniated lumbar disc patients appointed to receive percutaneous endoscopic lumbar discectomy treatment were recruited from the Pain Management Department of the Affiliated Hospital of Xuzhou Medical University and Nantong Hospital of Traditional Chinese Medicine.Sixty-five participants were enrolled and divided into either a CR-PT group or an AP-PT group.The CR-PT group underwent CR-PT,and the AP-PT group underwent AP-PT.The number of fluoroscopies during puncturing,puncture duration(min),surgery duration(min),VAS score during puncturing,and puncture success rate were recorded.RESULTS Sixty-five participants were included,with 31 participants in the CR-PT group and 34 in the AP-PT group.One participant in the AP-PT group dropped out due to unsuccessful puncturing.The number of fluoroscopies[median(P25,P75)]was 12(11,14)in the CR-PT group vs 16(12,23)in the AP-PT group,while the puncture duration(mean±SD)was 20.42±5.78 vs 25.06±5.46,respectively.The VAS score was 3(2,4)in the CR-PT group vs 3(3,4)in the AP-PT group.Further subgroup analysis was performed,considering only the participants with L5/S1 segment herniation:9 patients underwent CR-PT,and 9 underwent AP-PT.The number of fluoroscopies was 11.56±0.88 vs 25.22±5.33;the puncture duration was 13.89±1.45 vs 28.89±3.76;the surgery duration was 105(99.5,120)vs 149(125,157.5);and the VAS score was 2.11±0.93 vs 3.89±0.6,respectively.All the above outcomes demonstrated statistical significance(P<0.05),favoring the CR-PT treatment.CONCLUSION CR-PT is a novel and effective technique.As opposed to conventional AP-PT,this technique significantly improves puncture accuracy,shortens puncture time and operation time,and reduces pain intensity during puncturing.
基金supported by the National High Technology Research and Development Program of China(2012AA101102)the Technology Research Program of Zhejiang province(2011C24001)
文摘Breeding for salinity tolerance using Bangladeshi rice landraces and understand genetic diversity has been limited by the complex and polygenic nature of salt tolerance in rice genotypes. A genetic diversity and association mapping analysis was conducted using 96 germplasm accessions with variable response to salt stress at the seedling stage. These included86 landraces and 10 indica varieties and lines including Nona Bokra, from southern Bangladesh. A total of 220 alleles were detected at 58 Simple Sequence Repeat(SSR) marker loci randomly distributed on all 12 rice chromosomes and 8 Sequence Tagged Site(STS) markers developed for genes SKC1, DST, and SalT. The average gene diversity was 0.5075 and polymorphism information content value was 0.4426, respectively. Cluster analysis revealed that 68 and 21 accessions were clustered into 2 distinct groups, possibly corresponding to indica and japonica groups, respectively and the remaining 7 landraces were classified as an admixed group. In addition to Wn11463, the STS marker for SKC1, RM22418 on Chr. 8 was significantly associated with salinity tolerance, at the location of a QTL detected in previous studies. Our findings of favorable alleles associated with salinity tolerance in Bangladeshi rice landraces, as well as the development of STS markers for salt tolerance genes, will be helpful in future efforts to breed salinity tolerance in rice.
文摘AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn's disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE data-bases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when necessary to generate a standardized set of data from these studies. From these data, odds ratio (OR) with 95% confidence interval (CI) were calculated.RESULTS: Twenty-five studies of CD were analyzed, 14 of which involved cases of UC. The variant G allele of ATG16L1 was positively associated with CD (OR=1.32, 95% CI: 1.26-1.39, P<0.00001) and UC (OR =1.06, 95% CI:1.01-1.10, P=0.02). For child-onset IBD, a higher G allele frequency was found for cases of CD (OR=1.35, 95% CI: 1.16-1.57, P=0.0001) than for cases of UC (OR = 0.98, 95% CI: 0.81-1.19, P = 0.84) relative to controls.CONCLUSION: The ATG16L1 T300A polymorphism contributes to susceptibility to CD and UC in adults, but different in children, which implicates a role for autophagy in the pathogenesis of IBD.
基金National Natural Science Foundation of China (30830088 and 30800938)The National Key and Special Projects on Major Infectious Disease Grant (2008 ZX10001-004)
文摘Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.
文摘The aim of this work was to evaluate the photokilling efficiency of synthesized titanium dioxide nanoparticles in suspension. Two strains of Escherichia coli, Lactobacillus casei rhamnosus and Staphylococcus aureus were used as probes to test the photokilling activities of the nanoparticles. The toxicity effects of TiO2 nanoparticles on the environment were determined by a standard test using gram-negative bioluminescent bacteria Vibrio fischeri. The antimicrobial activity of these nanoparticles (NPs) was then investigated versus NPs concentration, UV irradiation time and micro- organism strains. We evaluated the LC50 values of the nanoparticles suspension by counting the Colony-Forming Units. Results highlighted the differences in bacteria sensitivity facing photokilling treatment induced by the irradiation of anatase TiO2 nanoparticles suspension. At the concentration of 1 g·L-1 TiO2, tested bacteria were killed after 30 minutes of photo-treatment. Using different TiO2 concentrations, the Staphylococcus aureus gram-positive/catalase-positive bacteria were more resistant than gram-negative/catalase-positive ones or gram-positive/catalase-negative bacteria. An effect of UV irradiation was evaluated by the quantification of hydrogen peroxide generated by the photolysis of water molecules in presence of the nanoparticles with or without the most resistant bacterium (S. aureus). After 30 minutes with UV irradiation in these two conditions, the concentration of hydrogen peroxide was 35 μM in presence of 1.2 g·L-1 TiO2 suspension. This result suggested that the resistance mechanism of S. aureus was not due to an extracelullar H2O2 enzymatic degradation.
文摘Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Eg5 (kinesin spindle protein), which is crucial for bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy. The aim of this study was to investigate the anticancer efficacy of $-(methoxytrityl)-L-cysteine (S(MeO)TLC), a novel Eg5 inhibitor in prostate cancer. Eg5 expression was examined in human prostate cancer cell lines and tissue microarrays were constructed from clinical specimens. Antiproliferative activity of S(MeO)TLC in prostate cancer cells was assessed by a cell viability assay. The anticancer effect and inhibitory mechanism of S(MeO)TLC in prostate cancer cells was further explored by Hoechst staining, flow cytometry and immunofluorescence. In addition, the antitumor effect of S(MeO)TLC on subcutaneous xenograft models was assessed. Eg5 expression was identified in PC3, DU145 and LNCaP cells. More than half of prostate cancer clinical specimens displayed Eg5 expression. S(Me0)TLC exhibited more powerful anticancer activity in prostate cancer cells compared with the other four Eg5 inhibitors tested. S(MeO)TLC induced cell death after arresting dividing cells at mitosis with distinct monopolar spindle formation. S(MeO)TLC exhibited its significant inhibitory activity (P〈0.05) on subcutaneous xenograft models also through induction of mitotic arrest. We conclude that Eg5 is a good target for prostate cancer chemotherapy, and S(MeO)TLC is a potent promising anticancer agent in prostate cancer.
基金Supported by the Research deputy of Golestan University of Medical Sciences(No.:35/678)
文摘Objective:To determine fauna and some ecological aspects of Anopheles mosquitoes in northeast of Iran.Methods:In this descriptive study,3 villages in Kalaleh County were selected in different geographical zones.Anopheles mosquitoes were collected biweekly from May to October using standard dipping method for larvae,and hand catch,total catch,artificial pit shelter as well as night-biting collections on human and animal baits for adults.Results:Totally 399 larvae and 2 602 adults of Anopheles mosquitoes were collected and identified as 2 species:Anopheles superpictus s.l.(An.superpictus s.l.) and Anopheles maculipennis s.l.The dominant species was An.superpictus s.l.(92.1%).Activity of these mosquitoes found to be started from middle of May and extended till September with two peaks of activity in July and August.Conclusions:An.superpictus s.l.as one of the main malaria vectors in Iran as well as some other parts of the world is the dominant species in the study area.This species has high potential for transmission and possibility of establishing a transmission cycle with low abundance.Other species,Anopheles maculipennis s.l.also has introduced as a malaria vector in northern parts of Iran.As this Anopheles is a complex species,genetic studies are recommended to determine the members of this complex in the study area.
文摘The effects of rotation and gravity on an electro-magneto-thermoelastic medium with diffusion and voids in a generalized thermoplastic half-space are studied by using the Lord-Shulman (L-S) model and the dual-phase-lag (DPL) model. The analytical solutions for the displacements, stresses, temperature, diffusion concentration, and volume fraction field with different values of the magnetic field, the rotation, the gravity, and the initial stress are obtained and portrayed graphically. The results indicate that the effects of gravity, rotation, voids, diffusion, initial stress, and electromagnetic field are very pronounced on the physical properties of the material.
文摘cDNA libraries were constructed from the leaves of a rice (Oryza sativa L.) salt tolerancevariety Tesan抋i 2 growing in solutions with 150 mmol/L NaCl for 3 h or without salt stress. Three salt-responsive cDNA clones, Ts1, Ts2 and Ts3 were isolated by differential screening. Northern blottinganalysis showed that the transcription levels of Ts1 and Ts2 increased within 3 h salt stress and kept onincreasing within 24 h, while the transcription level of Ts3 reached its peak within 3 h. Sequence analysisindicated that there were no homologies between the three cDNA clones and any known gene. The threecDNA clones were mapped using a doubled haploid (DH) population derived from an indica variety ZYQ8,which was a salt tolerance parent of Tesan抋i 2, with a japonica variety JX17. Ts1, Ts2 and Ts3 werelocated on chromosomes 1, 3 and 7, respectively. It was noted that Ts1, Ts2, and Ts3 were in or near theregions of major or minor salt tolerance quantitative trait loci (QTLs), which were mapped in the same DHpopulation in a parallel study.
基金国家自然科学基金,DURF of SEC,国家重点实验室基金,CTNP of LHIA National Lab of China,中国博士后科学基金
文摘Relations between helicity coupling amplitude and L-S coupling amplitude are discussed. The equivalence condition for these two kinematic analysis methods and the limitations of the L-S coupling amplitude are also studied in this paper.