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Breast cancer is a common malignant tumor, whose incidence is increasing year by year, and it has become the malignant tumor with the highest incidence rate in women. Purine ligand-gated ion channel 7 receptor (P2X7R) is a cation channel receptor with Adenosine triphosphate ( ATP) as a ligand, which is widely distributed in cells and tissues, and is closely related to tumorigenesis and progression. P2X7R plays an important role in cancer by interacting with ATP. Studies have shown that P2X7R is up-regulated in breast cancer and can promote tumor invasion and metastasis by activating the protein kinase B (AKT) signaling pathway, promoting epithelial-mesenchymal transition (EMT), controlling the generation of extracellular vesicle (EV), and regulating the expression of the inflammatory protein cyclooxygenase 2 (COX-2). Furthermore, P2X7R was proven to play an essential role in the proliferation and apoptosis of breast cancer cells. Recently, inhibitors targeting P2X7R have been found to inhibit the progression of breast cancer. Natural P2X7R antagonists, such as rhodopsin, and the isoquinoline alkaloid berberine, have also been shown to be effective in inhibiting breast cancer progression. In this article, we review the research progress of P2X7R and breast cancer intending to provide new targets and directions for breast cancer treatment.
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Nucleoside natural products show diverse biological activities and serve as leads for various application purposes, including human and veterinary medicine and agriculture. Studies in the past decade revealed that these nucleosides are biosynthesized through divergent mechanisms, in which early steps of the pathways can be classified into two types (C5' oxidation and C5' radical extension), while the structural diversity is created by downstream tailoring enzymes. Based on this biosynthetic logic, we investigated the genome mining discovery potentials of these nucleosides using the two enzymes representing the two types of C5' modifications: LipL-type α-ketoglutarate (α-KG) and Fe-dependent oxygenases and NikJ-type radical S-adenosyl-L-methionine (SAM) enzymes. The results suggest that this approach allows discovery of putative nucleoside biosynthetic gene clusters (BGCs) and the prediction of the core nucleoside structures. The results also revealed the distribution of these pathways in nature and implied the possibility of future genome mining discovery of novel nucleoside natural products.
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Productos Biológicos , Nucleósidos , Humanos , Nucleósidos/química , Productos Biológicos/química , Oxidación-Reducción , Vías Biosintéticas/genéticaRESUMEN
BACKGROUND: Traditionally part of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) are recommended to antiviral therapy referring to liver biopsy. However, liver biopsy is an invasive method with various potential complications. A noninvasive model was established in the study to evaluate liver histology and to identify the need of antiviral therapy. METHODS: A total of 614 liver biopsied CHB patients with ALT less than upper limit of normal from 2 centers were retrospectively analyzed. They were divided into a training cohort and a validation cohort. A noninvasive model to predict the significant liver histological changes was established and validated. RESULTS: The results of analysis showed that ALT, Age, platelet (PLT) and liver stiffness (LS) were independent risk factors for significant liver injury. The model was established based on the 4 indexes, with the area under the curve of 0.85 and 0.87 in training cohort and validation cohort. Meanwhile, 2 cut-off scores were selected. By applying the low cut-off score (- 0.207), patients without significant liver injury could be identified with high accuracy, with negative predictive value of 72.7% and 73.7% in training and validation cohorts. By applying the high cut-off score (0.537), the presence of significant liver injury could be diagnosed with high accuracy, with positive predictive value of 90.3% and 88.8% in the training and validation cohorts. By applying the model, liver biopsy would have been avoided in 87.6% (538/614) patients, with correct prediction in 87.9% (473/538). CONCLUSION: The novel noninvasive model composed of ALT, Age, PLT, LS can correctly assess liver histology in CHB patient with normal ALT, which helps to determine the need of antiviral therapy without liver biopsy.
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Alanina Transaminasa , Hepatitis B Crónica , Humanos , Alanina Transaminasa/sangre , Antivirales/uso terapéutico , Biopsia/efectos adversos , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/patología , Hígado/patología , Cirrosis Hepática/complicaciones , Estudios RetrospectivosRESUMEN
A nucleophilic allylation of acylsilanes in water was developed, generating versatile functionalized tertiary α-silyl alcohols in high yields. With the assistance of hydrogen bonding, a reaction model of less reactive acylsilane was achieved. Unlike the conventional strategy, transition metals and an additional Lewis acid catalyst were not required, and rate acceleration was observed in water.
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Myokines, which are recently identified cytokines secreted by skeletal muscle in response to stimulation, are crucial for the maintenance of liver function. Fulminant hepatitis (FH) is a life-threatening pathological condition with severe hepatic dysfunction. In this study, we investigated the role of meteorin-like (METRNL), a new myokine, in the pathogenesis of FH. We compared serum samples and liver tissues from FH patients and healthy controls and found that hepatic and serum METRNL levels were significantly increased in FH patients, and serum METRNL levels were related to disease severity in FH patients. We then established a concanavalin A-induced FH model in METRNL-overexpressing and control mice. We found that hepatic METRNL levels in FH mice were significantly increased, and METRNL in the liver was mainly derived from macrophages. In the cultured mouse macrophage line (RAW264.7 cells) and mouse primary peritoneal macrophages (PMs), METRNL overexpression significantly inhibited the release of the proinflammatory cytokines TNF and IL-1ß. In METRNL-overexpressing mice, concanavalin A-induced liver injury was significantly ameliorated. Moreover, METRNL overexpression significantly reduced chemokine-dependent inflammatory cell infiltration into the liver. METRNL overexpression also suppressed liver CD4+ T cell differentiation into Th 1 cells and inhibited the secretion of Th 1 cytokines. Taken together, these data suggest that METRNL overexpression effectively ameliorates FH. Therefore, METRNL may serve as a potential biomarker and therapeutic target for FH.
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Necrosis Hepática Masiva , Ratones , Animales , Concanavalina A , Quimiocinas , Citocinas/metabolismoRESUMEN
The compound 3,5-xylenol is an essential precursor used in pesticides and industrial intermediate in the disinfectants and preservatives industry. Its widespread application makes it an important source of pollution. Microbial bioremediation is more environmentally friendly than the physicochemical treatment process for removing alkylphenols from a polluted environment. However, the 3,5-xylenol-degrading bacteria is unavailable, and its degradation mechanism remains unclear. Here, a 3,5-xylenol-metabolizing bacterial strain, designated Rhodococcus sp. CHJ602, was isolated using 3,5-xylenol as the sole source of carbon and energy from a wastewater treatment factory. Results showed that strain CHJ602 maintained a high 3,5-xylenol-degrading performance under the conditions of 30.15 °C and pH 7.37. The pathway involved in 3,5-xylenol degradation by strain CHJ602 must be induced by 3,5-xylenol. Based on the identification of intermediate metabolites and enzyme activities, this bacterium could oxidize 3,5-xylenol by a novel metabolic pathway. One methyl oxidation converted 3,5-xylenol to 3-hydroxymethyl-5-methylphenol, 3-hydroxy-5-methyl benzaldehyde, and 3-hydroxy-5-methylbenzoate. After that, another methyl oxidation is converted to 5-hydroxyisophthalicate, which is metabolized by the protocatechuate pathway. It is catalyzed by a series of enzymes in strain CHJ602. In addition, toxicity bioassay result indicates that 3,5-xylenol is toxic to zebrafish and Rhodococcus sp. CHJ602 could eliminate 3,5-xylenol in water to protect zebrafish from its toxicity. The results provide insights into the bioremediation of wastewater contaminated 3,5-xylenol.
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Rhodococcus , Pez Cebra , Animales , Pez Cebra/metabolismo , Rhodococcus/metabolismo , Xilenos , Oxidación-Reducción , Biodegradación AmbientalRESUMEN
N'-alkyl benzohydrazides are classic organic compounds that have been widely utilized in organic chemistry. In this study, an efficient method was developed for the synthesis of N'-alkyl benzohydrazides by hydrazine insertion catalyzed by lipase. Under the optimal conditions (Morita-Baylis-Hillman ketone [1 mmol], phenylhydrazine [1.3 mmol], N,N-dimethylformamide [2 ml], lipase [20 mg], room temperature, 12 h), satisfactory yields (71-97%) and substrate tolerance were obtained when porcine pancreatic lipase was used as biocatalyst. These findings imply the great potential for the lipase-catalyzed synthesis of N'-alkyl benzohydrazides and extend the utilization of lipase in organic chemistry.
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Cetonas , Lipasa , Animales , Porcinos , Lipasa/química , Catálisis , Cetonas/química , HidrazinasRESUMEN
While the concept of intercellular mechanical communication has been revealed, the mechanistic insights have been poorly evidenced in the context of myofibroblast-fibroblast interaction during fibrosis expansion. Here we report and systematically investigate the mechanical force-mediated myofibroblast-fibroblast cross talk via the fibrous matrix, which we termed paratensile signaling. Paratensile signaling enables instantaneous and long-range mechanotransduction via collagen fibers (less than 1 s over 70 µm) to activate a single fibroblast, which is intracellularly mediated by DDR2 and integrin signaling pathways in a calcium-dependent manner through the mechanosensitive Piezo1 ion channel. By correlating in vitro fibroblast foci growth models with mathematical modeling, we demonstrate that the single-cell-level spatiotemporal feature of paratensile signaling can be applied to elucidate the tissue-level fibrosis expansion and that blocking paratensile signaling can effectively attenuate the fibroblast to myofibroblast transition at the border of fibrotic and normal tissue. Our comprehensive investigation of paratensile signaling in fibrosis expansion broadens the understanding of cellular dynamics during fibrogenesis and inspires antifibrotic intervention strategies targeting paratensile signaling.
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Fibroblastos/metabolismo , Fibrosis/metabolismo , Miofibroblastos/metabolismo , Transducción de Señal/fisiología , Animales , Receptor con Dominio Discoidina 2/metabolismo , Humanos , Integrinas , Canales Iónicos/metabolismo , Mecanotransducción CelularRESUMEN
Misregulation of spermatogenesis transcription factors (TF) in hybrids can lead to misexpression, which is a mechanism for hybrid male sterility (HMS). We used dzo (male offspring of Bos taurus â × Bos grunniens â) in bovines to investigate the relationship of the key TF with HMS via RNA sequencing and assay for transposase-accessible chromatin with high-throughput sequencing analyses. RNA sequencing showed that the widespread misexpression in dzo was associated with spermatogenesis-related genes and somatic or progenitor genes. The transition from leptotene or zygotene spermatocytes to pachytene spermatocytes may be the key stage for meiosis arrest in dzo. The analysis of TF-binding motif enrichment revealed that the male meiosis-specific master TF MYB proto-oncogene like 1 (MYBL1, known as A-MYB) motif was enriched on the promoters of downregulated pachytene spermatocyte genes in dzo. Assay for transposase-accessible chromatin with high-throughput sequencing revealed that TF-binding sites for MYBL1, nuclear transcription factor Y, and regulatory factor X were enriched in the low-chromatin accessibility region of dzo. The target genes of the MYBL1-binding motif were associated with meiosis-specific genes and significantly downregulated in dzo testis. The transcription factor MYBL1 may be the candidate master regulator for pachytene spermatocyte genes dysregulated in interspecific HMS dzo. This study reported that a few upstream TF regulation changes might exert a cascading effect downstream in a regulatory network as a mechanism for HMS.
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Espermatocitos , Factores de Transcripción , Bovinos , Masculino , Animales , Espermatocitos/fisiología , Factores de Transcripción/genética , Espermatogénesis , Testículo , CromatinaRESUMEN
OBJECTIVE: To explore the clinical features and genetic variants in two children with neonatal severe hyperparathyroidism (NSHPT). METHODS: Two children who were diagnosed with NSHPT at the Children's Hospital Affiliated to Xi'an Jiaotong University respectively in August 2019 and April 2022 were selected as the study subjects. Clinical data were collected, and both children were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. RESULTS: The main clinical features of the two children have included growth delay, hypotonia, hypercalcemia, hypophosphatemia, hyperparathyroid hormonemia, and renal calcium deposition. WES results showed that child 1 has harbored a homozygous c.1378_1G>A splicing variant of the CASR gene, which was unreported previously, whilst child 2 has harbored a homozygous c.2038C>T missense variant of the CASR gene, which was known to be likely pathogenic. Sanger sequencing confirmed that the parents of both children were heterozygous carriers. CONCLUSION: The homozygous c.1378_1G>A and c.2038C>T variants of the CASR gene probably underlay the NSHPT in the two children. Discovery of the c.1378_1G>A variant has enriched the mutational spectrum of the CASR gene.
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Mutación , Humanos , Niño , HomocigotoRESUMEN
Target identification is critically important for understanding the mechanism of action of drugs. Here, we reported a new strategy for deconvolution of drug targets (or off-targets) with photoaffinity labeling chemoproteomics in combination with untargeted metabolomics by using doxorubicin (DOX) as a model. The DOX-derived photoaffinity probes were prepared and applied to capture DOX-interacting proteins in living cells. The captured DOX-interacting proteins were then identified by label-free quantitative proteomics. Totally, 151 significant proteins were identified with high confidence (fold change >4, p-value < 0.005). The gene ontology enrichment analysis suggested that the proteins were mainly involved in carbon metabolism, citrate cycle, fatty acid metabolism, and metabolic pathways. Therefore, untargeted metabolomics was applied to quantify the significantly altered metabolites in cells upon drug treatment. The pathway enrichment analysis suggested that DOX mainly interrupted with the processes of pyrimidine and purine metabolism, carbon metabolism, methionine metabolism, and phosphatidylcholine biosynthesis. Integrative analysis of chemoproteomics and metabolomics indicated that adenosylhomocysteinase (AHCY) is a new target (off-target) of DOX leading to the accumulation of S-adenosyl homocysteine. This deduced DOX target was confirmed by the cellular thermal shift assay, affinity competitive pull-down assay, biochemical assay, and siRNA knock down experiments. Our result suggested that AHCY is the uncovered off-target of DOX.
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Doxorrubicina , Metabolómica , Doxorrubicina/farmacología , Doxorrubicina/metabolismo , Redes y Vías Metabólicas , Metabolismo de los Lípidos , CarbonoRESUMEN
Psychiatric disorders are a group of complex psychological syndromes with high prevalence. It has been reported that gut microbiota has a dominant influence on the risks of psychiatric disorders through gut microbiota-brain axis. We extended the classic gene set enrichment analysis (GSEA) approach to detect the association between gut microbiota and complex diseases using published genome-wide association study (GWAS) and GWAS of gut microbiota summary data. We applied our approach to real GWAS data sets of five psychiatric disorders, including attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD). To evaluate the performance of our approach, we also tested the genetic correlations of obesity and type 2 diabetes with gut microbiota. We identified several significant associations between psychiatric disorders and gut microbiota, such as ADHD and genus Desulfovibrio (P = 0.031), order Clostridiales (P = 0.034). For AUT, association signals were observed for genera Bacteroides (P = 0.012) and Desulfovibrio (P = 0.033). Genus Desulfovibrio (P = 0.005) appeared to be associated with BD. For MDD, association signals were observed for genus Desulfovibrio (P = 0.003), order Clostridiales (P = 0.004), family Lachnospiraceae (P = 0.007) and genus Bacteroides (P = 0.007). Genus Desulfovibrio (P = 0.012) and genus Bacteroides (P = 0.038) appeared to be associated with SCZ. Our study results provide novel clues for revealing the roles of gut microbiota in psychiatric disorders. This study also illustrated the good performance of GSEA approach for exploring the relationships between gut microbiota and complex diseases.
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Microbioma Gastrointestinal/genética , Trastornos Mentales/genética , Trastornos Mentales/microbiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , HumanosRESUMEN
Keloids are fibrotic lesions that grow unceasingly and invasively and are driven by local mechanical stimuli. Unlike other fibrotic diseases and normal wound healing, keloids exhibit little transformation of dermal fibroblasts into α-SMA+ myofibroblasts. This study showed that asporin is the most strongly expressed gene in keloids and its gene-ontology terms relate strongly to ECM metabolism/organization. Experiments with human dermal cells (HDFs) showed that asporin overexpression/treatment abrogated the HDF ability to adopt a perpendicular orientation when subjected to stretching tension. It also induced calcification of the surrounding 3D collagen matrix. Asporin overexpression/treatment also prevented the HDFs from remodeling the surrounding 3D collagen matrix, leading to a disorganized network of thick, wavy collagen fibers that resembled keloid collagen architecture. This in turn impaired the ability of the HDFs to contract the collagen matrix. Asporin treatment also made the fibroblasts impervious to the fibrous collagen contraction of α-SMA+ myofibroblasts, which normally activates fibroblasts. Thus, by calcifying collagen, asporin prevents fibroblasts from linearly rearranging the surrounding collagen; this reduces both their mechanosensitivity and mechanosignaling to each other through the collagen network. This blocks fibroblast activation and differentiation into the mature myofibroblasts that efficiently remodel the extracellular matrix. Consequently, the fibroblasts remain immature, highly proliferative, and continue laying down abundant extracellular matrix, causing keloid growth and invasion. Notably, dermal injection of asporin-overexpressing HDFs into murine wounds recapitulated keloid collagen histopathological characteristics. Thus, disrupted interfibroblast mechanocommunication may promote keloid progression. Asporin may be a new diagnostic biomarker and therapeutic target for keloids.
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Colágeno/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Queloide/prevención & control , Mecanotransducción Celular , Animales , Células Cultivadas , Progresión de la Enfermedad , Proteínas de la Matriz Extracelular/genética , Fibroblastos/patología , Regulación de la Expresión Génica , Humanos , Queloide/genética , Queloide/metabolismo , Queloide/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Piel/metabolismoRESUMEN
In the past 10-15 years, the government of China has made various efforts in tackling excessive antibiotics use. Yet, little is known about their effects at rural primary care settings. This study aimed to determine the impact of government policies and the COVID-19 pandemic on antibiotic prescribing practices at such settings utilizing data from separate studies carried out pre- and during the pandemic, in 2016 and 2021 in Anhui province, China, using identical sampling and survey approaches. Data on antibiotics prescribed, diagnosis, socio-demographic, etc., were obtained through non-participative observation and a structured exit survey. Data analysis comprised mainly descriptive comparisons of 1153 and 762 patients with respiratory infections recruited in 2016 and 2021, respectively. The overall antibiotics prescription rate decreased from 89.6% in 2016 to 69.1% in 2021, and the proportion of prescriptions for two or more classes of antibiotics was estimated as 35.9% in 2016 and 11.0% in 2021. There was a statistically significant decrease in the number of days from symptom onset to clinic visits between the year groups. In conclusion, measures to constrain excessive prescription of antibiotics have led to some improvements at the rural primary care level, and the COVID-19 pandemic has had varying effects on antibiotic use.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Infecciones del Sistema Respiratorio , Antibacterianos/uso terapéutico , COVID-19/epidemiología , China/epidemiología , Humanos , Pandemias , Pautas de la Práctica en Medicina , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
Paris polyphylla var. yunnanensis is a perennial herb in the family Trilliacea. The plants have immense medicinal and economic importance (Chen et al., 2021). Large-scale artificial planting has led to the emergence of various viral diseases in Paris polyphylla var. yunnanensis, including paris virus 1 (ParV1), paris mosaic necrosis virus (PMNV), paris polyphylla virus X, and pepper mild mottle virus (PMMoV) (Chen et al., 2021; Chen et al., 2022). However, tobacco mosaic virus (TMV) had not been reported as a pathogen on this host. In September 2021, symptoms of leaf shrinking, withering and mottling, and the plants demonstrating dwarfing first observed on Paris polyphylla var. yunnanensis in Qujing Province, Yunnan, China (Suppl Figure 1A). Leaves with these characteristic symptoms were collected from 20 plants. Virus particles in the samples were observed by transmission electron microscopy (TEM) using negative staining (Zhang et al., 2016). These samples revealed the presence of rod-shaped virions, which were approximately 300 nm long with a diameter of approximately 18nm (Suppl Figure 1B). Based on particle morphology these were identified as a putative Tobamovirus. To further identify the exact virus, total RNA was obtained using an RNA-easy Isolation Reagent (TaKaRaBiotech, Dalian, China), cDNA synthesis was performed and RT-PCR assays allowed to amplify a fragment of the CP gene of TMV using specific primers (Suppl table 1). A 480 bp fragment (Suppl Figure 1C) was obtained and cloned into the pMD-18T vector (TaKaRa Biotech, Dalian, China) and sequenced. BLASTn- analysis revealed that the 20 amplicons were identical and shared coat sequence (100%) identity with the TMV isolates Mile-1 (acc. no. MK584554.1) and the diseased P. polyphylla was infected with TMV. The sequence was deposited in the GenBank database with the accession number OM366238 (CP). The sap from infected plants was used as inoculum for transmission of TMV to 10 healthy Nicotiana glutinosa and N. tabacum K326, respectively. 15 days post-inoculation, obvious symptoms of necrosis and chlortisis for viral infection were observed on inoculated and systemic leaves. The systemic leaves of 20 from two species plants were collected, and tested positive for TMV by RT-PCR with the specific primers (Suppl table 1). The sequences of the movement protein (MP) gene (807 bp, OM3662406) and RNA-dependent RNA polymerase (RdRp) gene (3351 bp, OM366242) of TMV were obtained by RT-PCR assays using MP-and RdRp-specific primers (Suppl Table 1). A disease incidence survey was conducted by our team in three Paris polyphylla var. yunnanensis fields in Qujing province and we observed a symptom incidence of 60% across all three fields. To confirm that the symptoms corresponded to TMV infection, leaf samples from 20 plants were collected from per field and all plants tested positive for TMV using RT-PCR assays. To the best of our knowledge, this is the first report of TMV infection in P. polyphylla var. yunnanensis in China. This report, in combination with another recent report of new viruses (Paris mitovirus 1, Paris virus 2) that infects the plants (Chen et al., 2022), points toward a need to intensively monitor the viruses in fields to protect the P. polyphylla var. yunnanensis industry.
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Focusing on the undergraduate specialty construction of big data management and application in medical colleges and universities in the context of New Medical Education, we first analyzed, in this paper, the demand for trained personnel of this specialization and the status of program construction at the national and regional levels. Then, taking Anhui Medical University as an example, a key medical university in Anhui Province, we introduced the preparations made by medical colleges and universities to set up big data management and application specialty. Finally, from the perspectives of the objectives of personnel training, curriculum system, and practical teaching system, we presented in detail the exploratory efforts made by Anhui Medical University to construct a training system for personnel specializing in big data management and application. In this paper, we reported mainly the work done on the exploration of the personnel training curriculum system, covering general education, professional education, and extracurricular activities, highlighting the interdisciplinary characteristics of a personnel training curricular system that integrates medicine, engineering, and management. We also reported on a practice teaching system that combined in-class practical teaching and extracurricular activities, and that incorporated tiered contents of increasing challenge--basic practice level, cognitive practice level, comprehensive practice level, and innovative practice level. This study is expected to provide useful references for the training of personnel specializing in medical big data in the context of New Medical Education.
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Manejo de Datos , Facultades de Medicina , Macrodatos , Curriculum , Humanos , UniversidadesRESUMEN
Tumour radioresistance is a major problem for cancer radiation therapy. To identify the underlying mechanisms of this resistance, we used human non-small cell lung cancer (NSCLC) cell lines and focused on the Inhibitor of Apoptosis Protein (IAP) family, which contributes to tumourigenesis and chemoresistance. We investigated the possible correlation between radioresistance in six NSCLC cell lines and IAP protein levels and tested the radiosensitizing effect of birinapant in vitro, a molecule that mimics the second mitochondria-derived activator of caspase. We found that birinapant-induced apoptosis and inhibited the proliferation of NSCLC cells after exposure to radiation. These effects were induced by birinapant downregulation of cIAP protein levels and changes of cIAP gene expression. Overall, birinapant can inhibit tumour growth of NSCLC cell lines to ironizing radiation and act as a promising strategy to overcome radioresistance in NSCLC.
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OBJECTIVES: Gout is a common inflammatory arthritis, which is caused by hyperuricemia. Limited efforts have been paid to systematically explore the relationships between gout and common psychiatric disorders. METHODS: Genome-wide association study summary data of gout were obtained from the GeneATLAS, which contained 452,264 participants including 3,528 gout cases. Linkage disequilibrium score regression (LDSC) was first conducted to evaluate the genetic relationships between gout and 5 common psychiatric disorders. Transcriptome-wide association studies (TWAS) was then conducted to explore the potential biological mechanism underlying the observed genetic correlation between gout and attention-deficit hyperactivity disorder (ADHD). The Database for Annotation, Visualization and Integrated Discovery online functional annotation system was applied for pathway enrichment analysis and gene ontology enrichment analysis. RESULTS: LDSC analysis observed significant genetic correlation between gout and ADHD (genetic correlation coefficients = 0.29, standard error = 0.09 and P value = 0.0015). Further TWAS of gout identified 105 genes with P value < 0.05 in muscle skeleton and 228 genes with P value < 0.05 in blood. TWAS of ADHD also detected 300 genes with P value < 0.05 in blood. Further comparing the TWAS results identified 9 common candidate genes shared by gout and ADHD, such as CD300C (Pgout = 0.0040; PADHD = 0.0226), KDM6B (Pgout = 0.0074; PADHD = 0.0460), and BST1 (Pgout = 0.0349; PADHD = 0.03560). CONCLUSION: We observed genetic correlation between gout and ADHD and identified multiple candidate genes for gout and ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Gota , ADP-Ribosil Ciclasa , Antígenos CD , Antígenos de Superficie , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Proteínas Ligadas a GPI , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Gota/epidemiología , Gota/genética , Humanos , Histona Demetilasas con Dominio de Jumonji , Glicoproteínas de Membrana , TranscriptomaRESUMEN
Underlying topography plays an important role in the national economic construction, military security, resource exploration and investigation. Since synthetic aperture radar tomography (TomoSAR) can achieve the three-dimensional imaging of forests, it has been widely used in underlying topography estimation. At present, there are two kinds of TomoSAR based on the applied datasets: single polarimetric TomoSAR (SP-TomoSAR) and fully polarimetric TomoSAR (FP-TomoSAR). However, SP-TomoSAR cannot obtain the underlying topography accurately due to the lack of enough observations. FP-TomoSAR can improve the estimation accuracy of underlying topography. However, it requires high-cost data acquisition for the large-scale application. Thus, this paper proposes the dual polarimetric TomoSAR (DP-TomoSAR) as another suitable candidate to estimate the underlying topography because of its wide swath and multiple polarimetric observations. Moreover, three frequently used spectral estimation algorithms, namely, Beamforming, Capon and MUSIC, are used in DP-TomoSAR. For validation, a series of simulated experiments was carried out, and the airborne P-band multiple polarimetric SAR data over the Lope, Gabon was also acquired to estimate the underlying topography. The results suggest that DP-TomoSAR in HH & HV combination is more suitable to estimate underlying topography over forest areas than other DP combinations. Moreover, the estimation accuracy of DP-TomoSAR is slightly lower than that of FP-TomoSAR but is higher than that of SP-TomoSAR.
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Monitoreo del Ambiente , Radar , Bosques , Menogaril , TomografíaRESUMEN
AIMS: To develop a model illustrating the factors that can influence care needs in daily living (CNDL) of older adults and the pathways between these. BACKGROUND: The care needs in community-dwelling older adults have increased sharply. A better understanding of the elderly's CNDL would thus help policymakers define which types of support and services should be given. METHODS: A multicentre study with structural equation modelling was conducted in this study. We recruited 3,448 community-dwelling older adults in China by using a stratified random cluster sampling technique. RESULTS: Physical and mental health was the strongest predictor of CNDL. Both age and living situation had positive effects on CNDL, while economic factors, social support and family support were the major risk factors for CNDL. CONCLUSION: The presented model provides a better understanding of how to address CNDL in the targeted population. The older adults who are the oldest, low-income, non-empty nesters, and with poor self-rated health or the signs of loneliness should be firstly targeted for daily assistance. IMPLICATIONS FOR NURSING MANAGEMENT: Using this model could provide health authorities and managers with the information of distinguishing between the priority group and the strategies for easing the caregiving burden in older adults care, and thus improving resource utilization.