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An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1; Verhage and Sørensen, 2020; John et al., 2021). STXBP1 is an essential protein for presynaptic neurotransmitter release. Its haploinsufficiency is the main disease mechanism and impairs both excitatory and inhibitory neurotransmitter release. However, the disease pathogenesis and cellular origins of the broad spectrum of neurological phenotypes are poorly understood. Here we generate cell type-specific Stxbp1 haploinsufficient male and female mice and show that Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons causes developmental delay, epilepsy, and motor, cognitive, and psychiatric deficits, recapitulating majority of the phenotypes observed in the constitutive Stxbp1 haploinsufficient mice and STXBP1 encephalopathy. In contrast, Stxbp1 haploinsufficiency in glutamatergic neurons results in a small subset of cognitive and seizure phenotypes distinct from those caused by Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons. Thus, the contrasting roles of excitatory and inhibitory signaling reveal GABAergic/glycinergic dysfunction as a key disease mechanism of STXBP1 encephalopathy and suggest the possibility to selectively modulate disease phenotypes by targeting specific neurotransmitter systems.
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Encefalopatias , Epilepsia , Transtornos do Neurodesenvolvimento , Animais , Feminino , Masculino , Camundongos , Encefalopatias/genética , Epilepsia/genética , Neurônios GABAérgicos/metabolismo , Proteínas Munc18/genética , Proteínas Munc18/metabolismo , Transtornos do Neurodesenvolvimento/genética , NeurotransmissoresRESUMO
Three key factors determine yield in rice (Oryza sativa): panicle number, grain number, and grain weight. Panicle number is strongly associated with tiller number. Although many genes regulating tillering have been identified, whether Dof proteins are involved in controlling plant architecture remains unknown. The dwarf and less tillers on chromosome 3 (dlt3) rice mutant produces fewer tillers than the wild type. We cloned DLT3, which encodes a Dof protein that interacts with MONOCULM 3 (MOC3) in vivo and in vitro and recruits MOC1, forming a DLT3-MOC3-MOC1 complex. DLT3 binds to the promoter of FLORAL ORGAN NUMBER 1 (FON1) to activate its transcription and positively regulate tiller number. The overexpression of MOC1, MOC3, or FON1 in the dlt3 mutant increased tiller number. Collectively, these results suggest a model in which DLT3 regulates tiller number by maintaining the expression of MOC1, MOC3, and FON1. We discovered that DLT3 underwent directional selection in the Xian/indica and Geng/japonica populations during rice domestication. To provide genetic resources for breeding varieties with optimal panicle numbers, we performed large-scale diversity sequencing of the 1080-bp DLT3 coding region of 531 accessions from different countries and regions. Haplotype analysis showed that the superior haplotype, DLT3H1, produced the most tillers, while haplotype DLT3H6 produced the fewest tillers. Our study provides important germplasm resources for breeding super high-yielding rice varieties with combinations of superior haplotypes in different target genes, which will help overcome the challenge of food and nutritional security in the future.
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OBJECTIVES: To investigate the population structure and antimicrobial resistance (AMR) of avian Pasteurella multocida in China. METHODS: Utilizing WGS analysis, we explored the phylogeny using a dataset of 546 genomes, comprising avian P. multocida isolates from China (n = 121), the USA (n = 165), Australia(n = 153), Bangladesh (n = 3) and isolates of other hosts from China (n = 104). We examined the integrative and conjugative element (ICE) structures and the distribution of their components carrying resistance genes, and reconstructed the evolutionary history of A:L1:ST129 (n = 110). RESULTS: The population structure of avian P. multocida in China was dominated by the A:L1:ST129 clone with limited genetic diversity. A:L1:ST129 isolates possessed a broader spectrum of resistance genes at comparatively higher frequencies than those from other hosts and countries. The novel putative ICEs harboured complex resistant clusters that were prevalent in A:L1:ST129. Bayesian analysis predicted that the A:L1:ST129 clone emerged around 1923, and evolved slowly. CONCLUSIONS: A:L1:ST129 appears to possess a host predilection towards avian species in China, posing a potential health threat to other animals. The complex AMR determinants coupled with high frequencies may strengthen the population dominance of A:L1:ST129. The extensive antimicrobial utilization in poultry farming and the mixed rearing practices could have accelerated AMR accumulation in A:L1:ST129. ICEs, together with their resistant clusters, significantly contribute to resistance gene transfer and facilitate the adaptation of A:L1:ST129 to ecological niches. Despite the genetic stability and slow evolution rate, A:L1:ST129 deserves continued monitoring due to its propensity to retain resistance genes, warranting global attention to preclude substantial economic losses.
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Infecções por Pasteurella , Pasteurella multocida , Animais , Pasteurella multocida/genética , Infecções por Pasteurella/veterinária , Antibacterianos/farmacologia , Teorema de Bayes , Farmacorresistência Bacteriana , GenômicaRESUMO
With the increased occurrences of wildfires worldwide, there has been an increase in scientific interest surrounding the chemistry of fire-derived "black" carbon (BC). Traditionally, wildfire research has assumed that condensed aromatic carbon (ConAC) is exclusively produced via combustion, and thus, ConAC is equated to BC. However, the lack of correlations between ConAC in soils or rivers and wildfire history suggests that ConAC may be produced non-pyrogenically. Here, we show quantitative evidence that this occurs during the oxidation of biomass with environmentally ubiquitous hydroxyl radicals. Pine wood boards exposed to iron nails and natural weather conditions for 12 years yielded a charcoal-like ConAC-rich material. ConAC was also produced during laboratory oxidations of pine, maple, and brown-rotted oak woods, as well as algae, corn root, and tree bark. Back-of-the-envelope calculations suggest that biomass oxidation could be producing massive non-pyrogenic ConAC fluxes to terrestrial and aquatic environments. These estimates (e.g., 163-182 Tg-ConAC/year to soils) are much higher than the estimated pyrogenic "BC" fluxes (e.g., 128 Tg-ConAC/year to soils) implying that environmental ConAC is primarily non-pyrogenic. This novel perspective suggests that wildfire research trajectories should shift to assessing non-pyrogenic ConAC sources and fluxes, developing new methods for quantifying true BC, and establishing a new view of ConAC as an intermediate species in the biogeochemical processing of biomass during soil humification, aquatic photochemistry, microbial degradation, or mineral-organic matter interactions. We also advise against using BC or pyrogenic carbon (pyC) terminologies for ConAC measured in environmental matrices, unless a pyrogenic source can be confidently assigned.
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Carbono , Incêndios , Biomassa , Carvão Vegetal , Fuligem/análise , SoloRESUMO
BACKGROUND: This study sought to investigate the correlation between serum sex hormone-binding globulin (SHBG) levels and nutrition indicators and the malnutrition exposure risk in men and postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional analysis was conducted, involving patients diagnosed with T2DM at the Guangdong Provincial People's Hospital between May 2018 and December 2019. RESULTS: The study comprised 551 participants (363 men, mean age of 55.55 ± 11.57 years), among whom 167 (30.31%) were classified as with malnutrition exposure risk (GNRI ≤ 98). Multivariable logistic regression analysis revealed that SHBG (OR = 1.04, 95% CI: 1.02-1.05, P < 0.001), glycated hemoglobin (OR = 1.36, 95% CI: 1.22-1.51, P < 0.001), hemoglobin (OR = 0.96, 95% CI: 0.94-0.97, P < 0.001), and non-alcoholic fatty liver disease (OR = 0.41, 95% CI: 0.23-0.73, P < 0.003) were independently associated with the malnutrition exposure risk. SHBG was inversely correlated with body mass index (males: r = -0.34; postmenopausal females: r = -0.22), albumin (males: r = -0.30; postmenopausal females: r = -0.20), transferrin (males: r = -0.28; postmenopausal females: r = -0.19), and prealbumin (males: r = -0.35; postmenopausal females: r = -0.30) (all P < 0.05). CONCLUSIONS: Serum SHBG levels are correlated with nutritional indicators and the risk of malnutrition in men and postmenopausal women with T2DM. A multicenter prospective study is imperative to verify this result in the future.
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Diabetes Mellitus Tipo 2 , Desnutrição , Pós-Menopausa , Globulina de Ligação a Hormônio Sexual , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Pós-Menopausa/sangue , Desnutrição/sangue , Desnutrição/epidemiologia , Idoso , Biomarcadores/sangue , Estado Nutricional , Fatores de Risco , Índice de Massa Corporal , Adulto , PrognósticoRESUMO
Large-berry coffee (Coffea liberica) is one of the three cultivated coffee species and a precious breeding germplasm in China (Yan et al, 2019). Anthracnose is a damaging epidemic disease on coffee worldwide (Mohammed et al. 2015). Between June and September 2022, anthracnose was observed on coffee plants in Puer area, Yunnan, China and disease incidence (% plants diseased) of 8.5%-28.2% was recorded in the field. The disease symptoms were observed at all growth stages. Lesions on leaves were circular or oval, with a white to gray central zone outlined by a brown margin and surrounded by a chlorotic halo, Φ5.1-18.5 mm; some lesions extended and coalesced later to form large, blighted areas, leading to complete leaf senescence, defoliation and bare blighted branches on heavily infected trees. The spots on coffee berries were oval or fusiform, sunken and brown-black; diseased berries became gray-black and dried-out but remained on the tree. Leaves with typical anthracnose lesions were collected from fields in Simao ( 22.07°E,100.98°N) to isolate the pathogen. Leaf pieces (5×5mm) from the lesion margin were cut, surface-sterilized with 75% ethanol and 2% NaClO, and cultured on PDA at 25°C. Three isolates with the same colony morphology were obtained by hyphal tip purification. Detached and intact leaves of 6-month coffee seedlings were inoculated with Φ5mm mycelial discs of the isolates. Anthracnose lesions developed on the inoculated leaves, with all 3 isolates, 7d after incubation in a growth chamber (25°C, > 90% RH and lighting 8 h/d at 11000 lux). Pathogens with the same colony morphology as those of the original isolates were re-isolated from the infected tissues of inoculated leaves, thus fulfilling Koch's Postulates. The ITS sequence (PP550861) for the isolate was PCR-amplified and Blast-n analyses showed 100 % (554/554bp) identity to Colletotrichum kahawae LWTJ01; so they were the same population and coded as KFTJ02. The actin (ACT), calmodulin(CAL), glyceraldehydes-3-phosphate dehydrogenase (GAPHD) and histone 3 (HIS3) genes (Qiu et al. 2020) were amplified from one of KFTJ02 isolates, sequenced and deposited in NCBI GenBank (OR842543, OR842544, OR842545 & OR842546). A phylogenetic tree was generated based on the concatenated sequences of the four genes and those of related Colletotrichum spp. using MEGA 6.0 and KFTJ02 clustered in the same clade with C. kahawae IMI319418 on the tree (Bootstrap sup.=88%). When cultured at 25°C on PDA for 7 days, its colonies were near round or ovoid, gray-white, contoured, Φ73.2-80.1 (76.2±2.3)mm or growth rate 10.2-11.1(8.1) mm/d (n=10). The hyphae were hyaline, septated, branching at near right angles. Conidial masses formed 14 days after incubation. The conidia were elliptical, hyaline, monocellular, 10.2-15.5 (12.7±1.06)×3.8-5.2 (4.3±0.52) µm (n=50). The appressoria were black-brown, oval or irregular, 7.8-9.3 (8.5±0.81)µm (n= 50). These morphological characteristics were consistent with those of C. kahawae (Bridge et al, 2008). Therefore, KFTJ02 was identified as C. kahawae, which has been found to infect Camellia oleifera, Areca catechu and Ficus microcarpa (Wei et al, 2023; Zhang et al, 2020; Lin 2023). The coffee berry disease pathogen (C. kahawae) is a quarantine species which has not been recorded and so it is first reported on coffee crops in China. Results of the present study provide important references for further studies on this disease.
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In the original publication [...].
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Cooperative perception in the field of connected autonomous vehicles (CAVs) aims to overcome the inherent limitations of single-vehicle perception systems, including long-range occlusion, low resolution, and susceptibility to weather interference. In this regard, we propose a high-precision 3D object detection V2V cooperative perception algorithm. The algorithm utilizes a voxel grid-based statistical filter to effectively denoise point cloud data to obtain clean and reliable data. In addition, we design a feature extraction network based on the fusion of voxels and PointPillars and encode it to generate BEV features, which solves the spatial feature interaction problem lacking in the PointPillars approach and enhances the semantic information of the extracted features. A maximum pooling technique is used to reduce the dimensionality and generate pseudoimages, thereby skipping complex 3D convolutional computation. To facilitate effective feature fusion, we design a feature level-based crossvehicle feature fusion module. Experimental validation is conducted using the OPV2V dataset to assess vehicle coperception performance and compare it with existing mainstream coperception algorithms. Ablation experiments are also carried out to confirm the contributions of this approach. Experimental results show that our architecture achieves lightweighting with a higher average precision (AP) than other existing models.
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The interactions between plants and rhizosphere microbes mediated by plant root exudates are increasingly being investigated. The root-derived metabolites of medicinal plants are relatively diverse and have unique characteristics. However, whether medicinal plants influence their rhizosphere microbial community remains unknown. How medicinal plant species drive rhizosphere microbial community changes should be clarified. In this study involving high-throughput sequencing of rhizosphere microbes and an analysis of root exudates using a gas chromatograph coupled with a time-of-flight mass spectrometer, we revealed that the root exudate metabolites and microorganisms differed among the rhizosphere soils of five medicinal plants. Moreover, the results of a correlation analysis indicated that bacterial and fungal profiles in the rhizosphere soils of the five medicinal plants were extremely significantly or significantly affected by 10 root-associated metabolites. Furthermore, among the 10 root exudate metabolites, two (carvone and zymosterol) had opposite effects on rhizosphere bacteria and fungi. Our study findings suggest that plant-derived exudates modulate changes to rhizosphere microbial communities.
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Bactérias , Microbiota , Raízes de Plantas , Plantas Medicinais , Rizosfera , Microbiologia do Solo , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Plantas Medicinais/microbiologia , Plantas Medicinais/metabolismo , Bactérias/metabolismo , Bactérias/classificação , Bactérias/genética , Exsudatos de Plantas/metabolismo , Fungos/metabolismoRESUMO
Soils are important for ecosystem functioning and service provisioning. Soil communities and their functions, in turn, are strongly promoted by plant diversity, and such positive effects strengthen with time. However, plant diversity effects on soil organic matter have mostly been investigated in the topsoil, and there are only very few long-term studies. Thus, it remains unclear if plant diversity effects strengthen with time and to which depth these effects extend. Here, we repeatedly sampled soil to 1 m depth in a long-term grassland biodiversity experiment. We investigated how plant diversity impacted soil organic carbon and nitrogen concentrations and stocks and their stable isotopes 13 C and 15 N, as well as how these effects changed after 5, 10, and 14 years. We found that higher plant diversity increased carbon and nitrogen storage in the topsoil since the establishment of the experiment. Stable isotopes revealed that these increases were associated with new plant-derived inputs, resulting in less processed and less decomposed soil organic matter. In subsoils, mainly the presence of specific plant functional groups drove organic matter dynamics. For example, the presence of deep-rooting tall herbs decreased carbon concentrations, most probably through stimulating soil organic matter decomposition. Moreover, plant diversity effects on soil organic matter became stronger in topsoil over time and reached subsoil layers, while the effects of specific plant functional groups in subsoil progressively diminished over time. Our results indicate that after changing the soil system the pathways of organic matter transfer to the subsoil need time to establish. In our grassland system, organic matter storage in subsoils was driven by the redistribution of already stored soil organic matter from the topsoil to deeper soil layers, for example, via bioturbation or dissolved organic matter. Therefore, managing plant diversity may, thus, have significant implications for subsoil carbon storage and other critical ecosystem services.
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Carbono , Ecossistema , Solo , Biodiversidade , Plantas , NitrogênioRESUMO
BACKGROUND: Ovarian cancer is one of the most lethal cancers in women because it is often diagnosed at an advanced stage. The molecular markers investigated thus far have been unsatisfactory. METHODS: We performed whole-exome sequencing on the human ovarian cancer cell lines 3AO and ES2 and the normal ovarian epithelial cell line IOSE-80. Molecular markers of ovarian cancer were screened from shared mutation genes and copy number variation genes in the 6q21-qter region. RESULTS: We found that missense mutations were the most common mutations in the gene (93%). The MUC12, FLG and MUC16 genes were highly mutated in 3AO and ES2 cells. Copy number amplification occurred mainly in 4p16.1 and 11q14.3, and copy number deletions occurred in 4q34.3 and 18p11.21. A total of 23 hub genes were screened, of which 16 were closely related to the survival of ovarian cancer patients. The three genes CCDC170, THBS2 and COL14A1 are most significantly correlated with the survival and prognosis of ovarian cancer. In particular, the overall survival of ovarian cancer patients with high CCDC170 gene expression was significantly prolonged (P < 0.001). The expression of CCDC170 in normal tissues was significantly higher than that in ovarian cancer tissues (P < 0.05), and its expression was significantly decreased in advanced ovarian cancer. Western blotting and immunofluorescence assays also showed that the expression of CCDC170 in ovarian cancer cells was significantly lower than that in normal cells (P < 0.001, P < 0.01). CONCLUSIONS: CCDC170 is expected to become a new diagnostic molecular target and prognostic indicator for ovarian cancer patients, which can provide new ideas for the design of antitumor drugs.
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Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/patologia , Exoma/genética , Variações do Número de Cópias de DNA , Mutação , Linhagem Celular Tumoral , BiomarcadoresRESUMO
The occurrence and progression of colorectal cancer (CRC) are closely related to intestinal microecological disorders. Butyrate, the representative of short chain fatty acids, possess anti-inflammatory and antioxidant effects, and its antitumor effect has been gradually paid attention to. In this study, azoxymethane/dextran sodium sulfate induced mouse CRC model was used to explore the role and mechanism of butyrate in regulating colon cancer and its intestinal microecological balance. Outcomes exhibited that butyrate alleviated weight loss, disease activity index, and survival in CRC mice and inhibited tumor number and progression. Further research revealed that butyrate restrained the aggregation of harmful while promoting the colonization of beneficial flora, such as Actinobacteriota, Bifidobacteriales and Muribaculacea through 16S rDNA sequence analysis. This study confirmed that butyrate can ameliorate CRC by repairing intestinal microecology, providing ideas and evidence for chemical prophylactic agents, such as butyrate to remedy tumors and regulate tumor microbiota.
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Neoplasias do Colo , Neoplasias Colorretais , Camundongos , Animais , Butiratos/efeitos adversos , Modelos Animais de Doenças , Azoximetano/efeitos adversos , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: Metagenomic next-generation sequencing (mNGS) is a novel nucleic acid method for the detection of unknown and difficult pathogenic microorganisms, and its application in the etiological diagnosis of fever of unknown origin (FUO) is less reported. We aimed to comprehensively assess the value of mNGS in the etiologic diagnosis of FUO by the pathogen spectrum and diagnostic performance, and to investigate whether it is different in the time to diagnosis, length of hospitalization, antibiotic consumption and cost between FUO patients with and without early application of mNGS. METHODS: A total of 149 FUO inpatients underwent both mNGS and routine pathogen detection was retrospectively analyzed. The diagnostic performance of mNGS, culture and CMTs for the final clinical diagnosis was evaluated by using sensitivity, specificity, positive predictive value, negative predictive value and total conforming rate. Patients were furtherly divided into two groups: the earlier mNGS detection group (sampling time: 0 to 3 days of the admission) and the later mNGS detection group (sampling time: after 3 days of the admission). The length of hospital stay, time spent on diagnosis, cost and consumption of antibiotics were compared between the two groups. RESULTS: Compared with the conventional microbiological methods, mNGS detected much more species and had the higher negative predictive (67.6%) and total conforming rate (65.1%). Patients with mNGS sampled earlier had a significantly shorter time to diagnosis (6.05+/-6.23 vs. 10.5+/-6.4 days, P < 0.001) and days of hospital stay (13.7+/-20.0 vs. 30.3 +/-26.9, P < 0.001), as well as a significantly less consumption (13.3+/-7.8 vs. 19.5+/-8.0, P < 0.001) and cost (4543+/-7326 vs. 9873 +/- 9958 China Yuan [CNY], P = 0.001) of antibiotics compared with the patients sampled later. CONCLUSIONS: mNGS could significantly improve the detected pathogen spectrum, clinical conforming rate of pathogens while having good negative predictive value for ruling out infections. Early mNGS detection may shorten the diagnosis time and hospitalization days and reduce unnecessary consumption of antibiotics.
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Febre de Causa Desconhecida , Humanos , Febre de Causa Desconhecida/diagnóstico , Febre de Causa Desconhecida/tratamento farmacológico , Metagenômica , Estudos Retrospectivos , Pacientes Internados , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/uso terapêutico , Sensibilidade e EspecificidadeRESUMO
Dissolved organic matter (DOM) sustains a substantial part of the organic matter transported seaward, where photochemical reactions significantly affect its transformation and fate. The irradiation experiments can provide valuable information on the photochemical reactivity (photolabile, photoresistant, and photoproduct) of molecules. However, the inconsistency of the fate of irradiated molecules among different experiments curtailed our understanding of the roles the photochemical reactions have played, which cannot be properly addressed by traditional approaches. Here, we conducted irradiation experiments for samples from two large estuaries in China. Molecules that occurred in irradiation experiments were characterized by the Fourier transform ion cyclotron resonance mass spectrometry and assigned probabilistic labels to define their photochemical reactivity. These molecules with probabilistic labels were used to construct a learning database for establishing a suitable machine learning (ML) model. We further applied our well-trained ML model to "un-matched" (i.e., not detected in our irradiation experiments) molecules from five estuaries worldwide, to predict their photochemical reactivity. Results showed that numerous molecules with strong photolability can be captured solely by the ML model. Moreover, comparing DOM photochemical reactivity in five estuaries revealed that the riverine DOM chemistry largely determines their subsequent photochemical transformation. We offer an expandable and renewable approach based on ML to compatibly integrate existing irradiation experiments and shed insight into DOM transformation and degradation processes.
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Matéria Orgânica Dissolvida , Compostos Orgânicos , Compostos Orgânicos/análise , Fotoquímica , Espectrometria de Massas , EstuáriosRESUMO
BACKGROUND: There is mounting evidence that Circular RNAs (circRNAs) are essential for the initiation and development of gastric cancer (GC). In this study, we further investigated the clinical importance and applicability of serum hsa_circ_0000702 in the diagnosis and treatment of GC. METHODS: Sanger sequencing, agarose gel electrophoresis, and RNase R assay were used to confirm the origin, alterations, and stability of hsa_circ_0000702 in GC patients. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression level of hsa_circ_0000702 in GC cell lines, serum, and tissues. Additionally, receiver operating characteristic (ROC) curves were built to evaluate their prognostic value and how well they would work in conjunction with popular biochemical markers for GC. Finally, real-time dynamic monitoring was used to assess its prognostic usefulness. RESULTS: Hsa_circ_0000702 exhibited the fundamental traits of circRNA. Hsa_circ_0000702 had good sensitivity, specificity, and stability. It was discovered that hsa_circ_0000702 was down-regulated in GC cell lines, serum, and tissues, and that the level of tumor differentiation and tumor node metastasis (TNM) staging were connected with serum hsa_circ_0000702. The area under the ROC curve of serum hsa_circ_0000702 was calculated to be 0.745 (95% CI: 0.669-0.821), indicating high diagnostic efficacy. The diagnostic value was greatly increased by combining serum CEA and CA19-9. Finally, preoperative and postoperative dynamic monitoring revealed serum hsa_circ_0000702 to be of clinical application. CONCLUSION: Serum hsa_circ_0000702 was variably expressed in GC patients, indicating that serum hsa_circ_0000702 may be a novel biomarker for GC diagnosis and dynamic monitoring.
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RNA Circular , Neoplasias Gástricas , Humanos , RNA Circular/genética , Neoplasias Gástricas/genética , Biomarcadores Tumorais/genética , Prognóstico , Estadiamento de Neoplasias , RNA/genéticaRESUMO
BACKGROUND: Numerous studies have identified risk factors for physical restraint (PR) use in older adults in long-term care facilities. Nevertheless, there is a lack of predictive tools to identify high-risk individuals. OBJECTIVE: We aimed to develop machine learning (ML)-based models to predict the risk of PR in older adults. METHODS: This study conducted a cross-sectional secondary data analysis based on 1026 older adults from 6 long-term care facilities in Chongqing, China, from July 2019 to November 2019. The primary outcome was the use of PR (yes or no), identified by 2 collectors' direct observation. A total of 15 candidate predictors (older adults' demographic and clinical factors) that could be commonly and easily collected from clinical practice were used to build 9 independent ML models: Gaussian Naïve Bayesian (GNB), k-nearest neighbor (KNN), decision tree (DT), logistic regression (LR), support vector machine (SVM), random forest (RF), multilayer perceptron (MLP), extreme gradient boosting (XGBoost), and light gradient boosting machine (Lightgbm), as well as stacking ensemble ML. Performance was evaluated using accuracy, precision, recall, an F score, a comprehensive evaluation indicator (CEI) weighed by the above indicators, and the area under the receiver operating characteristic curve (AUC). A net benefit approach using the decision curve analysis (DCA) was performed to evaluate the clinical utility of the best model. Models were tested via 10-fold cross-validation. Feature importance was interpreted using Shapley Additive Explanations (SHAP). RESULTS: A total of 1026 older adults (mean 83.5, SD 7.6 years; n=586, 57.1% male older adults) and 265 restrained older adults were included in the study. All ML models performed well, with an AUC above 0.905 and an F score above 0.900. The 2 best independent models are RF (AUC 0.938, 95% CI 0.914-0.947) and SVM (AUC 0.949, 95% CI 0.911-0.953). The DCA demonstrated that the RF model displayed better clinical utility than other models. The stacking model combined with SVM, RF, and MLP performed best with AUC (0.950) and CEI (0.943) values, as well as the DCA curve indicated the best clinical utility. The SHAP plots demonstrated that the significant contributors to model performance were related to cognitive impairment, care dependency, mobility decline, physical agitation, and an indwelling tube. CONCLUSIONS: The RF and stacking models had high performance and clinical utility. ML prediction models for predicting the probability of PR in older adults could offer clinical screening and decision support, which could help medical staff in the early identification and PR management of older adults.
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População do Leste Asiático , Assistência de Longa Duração , Aprendizado de Máquina , Restrição Física , Idoso , Humanos , Estudos Transversais , População do Leste Asiático/estatística & dados numéricos , Assistência de Longa Duração/estatística & dados numéricos , Restrição Física/estatística & dados numéricos , Fatores de Risco , Masculino , Feminino , Idoso de 80 Anos ou mais , Algoritmos , Modelos Teóricos , Instituições de Cuidados Especializados de Enfermagem/estatística & dados numéricos , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , China/epidemiologiaRESUMO
Wax apple (Syzygium samarangense) is an important fruit tree widely cultivated in China. Yield losses are usually serious due to different diseases among which anthracnose (Colletotrichum spp.) is one of the most damaging (He et al, 2019). This disease was found in Yunnan, China and an average incidence of 56.7% diseased leaves was recorded in21 orchards surveyed in July2021. The disease lesions on leaves were circular, angular or oval (7.2-15.6 mm), with whitish center and brown outer area surrounded by a yellow halo; irregular spots or blight areas formed later. It can also infect fruits forming pale-brown, circular and sunken spots before harvest and rot of stored fruits. Diseased leaves were sampled from orchards in Ximeng (N117.78oE39.89o) and Ninger (E101.04oN23.05o) counties of Yunnan for fungal isolation; three and five pure isolates were recovered from Ximeng (LWTJ1-LWTJ3) and Ninger (LB4-LB8) samples, respectively, by plating disinfested tissue (surface-sterilized with 2% NaClO3) on potato dextrose agar (PDA) followed by hyphal tip purification and incubation at 25oC. Two repeated tests following Koch's postulates were conducted to verify pathogenicity of the eight isolates. In each test, three healthy seedlings per isolate were sprayed with conidia suspenson (2.26×105cfu/mL) until runoff from leaves while control plants were sprayed with sterile water. The plants were kept in the dark at RH100 for 24 h in a black box and then in a growth chamber (28oC, RH>90% and lighting 12h/d). Detached fruits were inoculated with mycelial discs on the puncture-wound surface. Anthracnose symptoms developed on all seedlings and fruits inoculated with LWTJ2 or LB4 isolates, which were re-isolated from lesions of inoculated leaf/fruit, completing Koch's postulates. Control plants were healthy and symptomless. LWTJ2 and LB4 isolates were morphologically the same: the colonies on PDA were circular, pale-white, with cottony surface and readily forming orange conidium masses. The hyphae were hyaline, septate, branched mostly in near right angles. The conidia were hyaline, one-celled, smooth-walled, cylindrical with round ends, 9.8-17.5 (av.13.8) µm×4.4-6.5 (5.6) µm. The teleomorph was not observed in culture or on orchard trees. The morphological characters were consistent with those of C. siamense described by Weir et al (2012). The internal transcribed spacer region (ITS) was amplified from the two isolates by PCR and sequenced (1990) and were 545 bp in length (OL963924 & OL413460). BLAST analysis showed that both were 100% identical and they shared 99.08% identity with C. siamense WZ-365 from the ITS region (MN856443).The Tub2 (788 bp, ON637119) and Cal (768 bp, ON622249) genes (Weir et al, 2012) of LB4 were also obtained and they shared closest identity (99.45% & 100%) with those of C. siamense WZ-365 as well. Phylogenetic tree (neighbor-joining) analysis of the concatenated sequence of ITS, Tub2 and Cal genes of LB4 and those of related Colletotrichum spp. showed that LB4 clustered IN the same end-branch with C. siamense ICMP18578 (Bootstrap sup. = 98%). Thus, C. siamense was identified as the pathogen of wax apple anthracnose in Yunnan. It caused anthracnose on other crops as oranges and cacao (Azad et al, 2020). Also, C. fructicola and C. syzygicola were identified as pathogens of wax apple anthracnose in Thailand (Al-Obaidi et al, 2017). To our knowledge, this is the first report of C. siamense causing wax apple anthracnose in China.
RESUMO
BACKGROUND: The current treatment spontaneous intracerebral hemorrhage (sICH) is limited. AIM: To determine the optimal time window for minimally invasive surgery in patients with sICH. MATERIALS AND METHODS: sICH patients with a hematoma volume of 30-80 mL in the basal ganglia region were included in our study. A total of 357 patients were divided into groups according to different operative times from ICH onset (group 1: 0-6 h, group 2: 6-12 h, group 3: >12 h) and hematoma volumes (30-50 mL and >50 mL). All patients were followed-up for three months' post-operation, and their clinical outcomes were compared. RESULTS: In the three groups of patients with hematoma volumes of 30-50 mL, the rebleeding and mortality rate were higher in group 1 than groups 2 and 3 (p < .05). The activities of daily living evaluated by Barthel Index (BI) three months' post-operation was significantly lower in group 3 than other groups (p < .05) and group 2 had the highest proportion of good outcomes. Among the patients with the hematoma volumes of 50-80 mL, the rebleeding risk was higher in group 1 than groups 2 and 3 (p < .05). However, there were no significant differences in mortality rates among these three groups. Moreover, group 1 had significantly higher BI than groups 2 and 3 (p < .05). CONCLUSIONS: Minimally invasive surgery is safe and effective in patients with sICH. 6-12 h after sICH onset is the optimal surgical window for patients with hematoma volumes of 30-50 mL, while ultra-early (≤6 h) may achieve better results in patients with hematoma volumes of >50 mL.
Assuntos
Atividades Cotidianas , Hemorragia dos Gânglios da Base , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia Cerebral/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Hematoma/cirurgia , Gânglios da Base/cirurgia , Hemorragia dos Gânglios da Base/cirurgiaRESUMO
Polybrominated diphenyl ethers (PBDEs) are classic and emerging pollutants that are potentially harmful to the human immune system. Research on their immunotoxicity and mechanisms suggests that they play an important role in the resulting pernicious effects of PBDEs. 2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is the most biotoxic PBDE congener, and, in this study, we evaluated its toxicity toward RAW264.7 cells of mouse macrophages. The results show that exposure to BDE-47 led to a significant decrease in cell viability and a prominent increase in apoptosis. A decrease in mitochondrial membrane potential (MMP) and an increase in cytochrome C release and caspase cascade activation thus demonstrate that cell apoptosis induced by BDE-47 occurs via the mitochondrial pathway. In addition, BDE-47 inhibits phagocytosis in RAW264.7 cells, changes the related immune factor index, and causes immune function damage. Furthermore, we discovered a significant increase in the level of cellular reactive oxygen species (ROS), and the regulation of genes linked to oxidative stress was also demonstrated using transcriptome sequencing. The degree of apoptosis and immune function impairment caused by BDE-47 could be reversed after treatment with the antioxidant NAC and, conversely, exacerbated by treatment with the ROS-inducer BSO. These findings indicate that oxidative damage caused by BDE-47 is a critical event that leads to mitochondrial apoptosis in RAW264.7 macrophages, ultimately resulting in the suppression of immune function.
Assuntos
Éteres Difenil Halogenados , Mitocôndrias , Camundongos , Animais , Humanos , Espécies Reativas de Oxigênio/metabolismo , Éteres Difenil Halogenados/farmacologia , Mitocôndrias/metabolismo , Macrófagos/metabolismoRESUMO
Various products made from biodegradable polymers have been increasing rapidly in the market since the use of non-biodegradable materials has been banned, particularly for the disabled packaging materials. Burning remains the most popular method that is increasingly used in treating city wastes. The impact of these polymers on environmental during thermal degradation and combustion is an important issue for city waste management. In this work, the thermal degradation and combustion behaviours of the most popular synthetic biodegradable polymers in the market, poly(lactide acid) (PLA), poly(e-caprolactone) (PCL), poly(butylene succinate) (PBS), poly(butylene adipate-co-terephthalate) (PBAT) and polyhydroxyalkenoates (PHA), are investigated. Both isothermal and non-isothermal thermal decomposition in oxygen and nitrogen environment were studied using thermogravimetric analysis combining with differential scanning calorimeter and coupled with Fourier transform infrared spectroscopy and gas chromatograph/mass spectroscopy. The combustion behaviour was investigated by a combustion colorimeter. The study results show that thermal degradation temperatures are PCL > PBS > PLA > PBAT > PHA. The thermal decomposition of all the polyesters started from scission reaction (cis-elimination), and then a stereoselective cis-elimination, which resulted in the formation of trans-crotonic acid and its oligomers. They all decomposed into CO2 and water in excess oxygen environment above 800°C. Various chemical products with smaller molecules were detected under oxygen-free conditions, including oligomers and unsaturated carboxylic acid. The order of the total heat release of the materials from high to low is as follows: PHA > PCL > PBAT > PBS > PLA. The combustion values of these polyesters are lower than those of polyolefins; thus, they will not damage furnace used currently. The results provide some important and useful data for managing these new city waste.