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1.
Am J Hum Genet ; 110(8): 1266-1288, 2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37506691

RESUMEN

Most of the single-nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to evaluate the regulatory activities of 5,987 noncoding SNPs associated with IR-relevant phenotypes. We identified 876 SNPs with biased allelic enhancer activity effects (baaSNPs) across 133 loci in three IR-relevant cell lines (HepG2, preadipocyte, and A673), which showed pervasive cell specificity and significant enrichment for cell-specific open chromatin regions or enhancer-indicative markers (H3K4me1, H3K27ac). Further functional characterization suggested several transcription factors (TFs) with preferential allelic binding to baaSNPs. We also incorporated multi-omics data to prioritize 102 candidate regulatory target genes for baaSNPs and revealed prevalent long-range regulatory effects and cell-specific IR-relevant biological functional enrichment on them. Specifically, we experimentally verified the distal regulatory mechanism at IRS1 locus, in which rs952227-A reinforces IRS1 expression by long-range chromatin interaction and preferential binding to the transcription factor HOXC6 to augment the enhancer activity. Finally, based on our STARR-seq screening data, we predicted the enhancer activity of 227,343 noncoding SNPs associated with IR-relevant phenotypes (fasting insulin adjusted for BMI, HDL cholesterol, and triglycerides) from the largest available GWAS summary statistics. We further provided an open resource (http://www.bigc.online/fnSNP-IR) for better understanding genetic regulatory mechanisms of IR-relevant phenotypes.


Asunto(s)
Resistencia a la Insulina , Polimorfismo de Nucleótido Simple , Humanos , Polimorfismo de Nucleótido Simple/genética , Estudio de Asociación del Genoma Completo , Resistencia a la Insulina/genética , Factores de Transcripción/genética , Cromatina/genética , Fenotipo , Elementos de Facilitación Genéticos/genética
2.
J Virol ; 98(3): e0150223, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38315015

RESUMEN

Capsid assembly is critical in the hepatitis B virus (HBV) life cycle, mediated by the viral core protein. Capsid assembly is the target for new anti-viral therapeutics known as capsid assembly modulators (CAMs) of which the CAM-aberrant (CAM-A) class induces aberrant shaped core protein structures and leads to hepatocyte cell death. This study aimed to identify the mechanism of action of CAM-A modulators leading to HBV-infected hepatocyte elimination where CAM-A-mediated hepatitis B surface antigen (HBsAg) reduction was evaluated in a stable HBV replicating cell line and in AAV-HBV-transduced C57BL/6, C57BL/6 SCID, and HBV-infected chimeric mice with humanized livers. Results showed that in vivo treatment with CAM-A modulators induced pronounced reductions in hepatitis B e antigen (HBeAg) and HBsAg, associated with a transient alanine amino transferase (ALT) increase. Both HBsAg and HBeAg reductions and ALT increase were delayed in C57BL/6 SCID and chimeric mice, suggesting that adaptive immune responses may indirectly contribute. However, CD8+ T cell depletion in transduced wild-type mice did not impact antigen reduction, indicating that CD8+ T cell responses are not essential. Transient ALT elevation in AAV-HBV-transduced mice coincided with a transient increase in endoplasmic reticulum stress and apoptosis markers, followed by detection of a proliferation marker. Microarray data revealed antigen presentation pathway (major histocompatibility complex class I molecules) upregulation, overlapping with the apoptosis. Combination treatment with HBV-specific siRNA demonstrated that CAM-A-mediated HBsAg reduction is dependent on de novo core protein translation. To conclude, CAM-A treatment eradicates HBV-infected hepatocytes with high core protein levels through the induction of apoptosis, which can be a promising approach as part of a regimen to achieve functional cure. IMPORTANCE: Treatment with hepatitis B virus (HBV) capsid assembly modulators that induce the formation of aberrant HBV core protein structures (CAM-A) leads to programmed cell death, apoptosis, of HBV-infected hepatocytes and subsequent reduction of HBV antigens, which differentiates CAM-A from other CAMs. The effect is dependent on the de novo synthesis and high levels of core protein.


Asunto(s)
Antivirales , Apoptosis , Regulación Viral de la Expresión Génica , Antígenos del Núcleo de la Hepatitis B , Virus de la Hepatitis B , Hepatocitos , Biosíntesis de Proteínas , Animales , Ratones , Antivirales/farmacología , Antivirales/uso terapéutico , Apoptosis/efectos de los fármacos , Cápside/química , Cápside/clasificación , Cápside/efectos de los fármacos , Cápside/metabolismo , Proteínas de la Cápside/metabolismo , Hepatitis B/tratamiento farmacológico , Hepatitis B/inmunología , Hepatitis B/metabolismo , Hepatitis B/virología , Antígenos del Núcleo de la Hepatitis B/biosíntesis , Antígenos del Núcleo de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/crecimiento & desarrollo , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/metabolismo , Virus de la Hepatitis B/patogenicidad , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Hepatocitos/virología , Ratones Endogámicos C57BL , Ratones SCID , Replicación Viral , Línea Celular , Linfocitos T CD8-positivos/inmunología , Presentación de Antígeno
3.
J Am Chem Soc ; 146(8): 5614-5621, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38354217

RESUMEN

With the emergence of wearable electronics, ferroelectrics are poised to serve as key components for numerous potential applications. Currently, intrinsically elastic ferroelectrics featuring a network structure through a precise "slight cross-linking" approach have been realized. The resulting elastic ferroelectrics demonstrate a combination of stable ferroelectric properties and remarkable resilience under various strains. However, challenges arose as the cross-linking temperature was too high when integrating ferroelectrics with other functional materials, and the Curie temperature of this elastic ferroelectric was comparatively low. Addressing these challenges, we strategically chose a poly(vinylidene fluoride)-based copolymer with high vinylidene fluoride content to obtain a high Curie temperature while synthesizing a cross-linker with carbene intermediate for high reactivity to reduce the cross-linking temperature. At a relatively low temperature, we successfully fabricated elastic ferroelectrics through carbene cross-linking. The resulting elastic polymer ferroelectrics exhibit a higher Curie temperature and show a stable ferroelectric response under strains up to 50%. These materials hold significant potential for integration into wearable electronics.

4.
Diabetes Obes Metab ; 26(1): 135-147, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37779362

RESUMEN

AIM: Genome-wide association studies (GWAS) have identified multiple susceptibility loci associated with insulin resistance (IR)-relevant phenotypes. However, the genes responsible for these associations remain largely unknown. We aim to identify susceptibility genes for IR-relevant phenotypes via a transcriptome-wide association study. MATERIALS AND METHODS: We conducted a large-scale multi-tissue transcriptome-wide association study for IR (Insulin Sensitivity Index, homeostasis model assessment-IR, fasting insulin) and lipid-relevant traits (high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol and total cholesterol) using the largest GWAS summary statistics and precomputed gene expression weights of 49 human tissues. Conditional and joint analyses were implemented to identify significantly independent genes. Furthermore, we estimated the causal effects of independent genes by Mendelian randomization causal inference analysis. RESULTS: We identified 1190 susceptibility genes causally associated with IR-relevant phenotypes, including 58 genes that were not implicated in the original GWAS. Among them, 11 genes were further supported in differential expression analyses or a gene knockout mice database, such as KRIT1 showed both significantly differential expression and IR-related phenotypic effects in knockout mice. Meanwhile, seven proteins encoded by susceptibility genes were targeted by clinically approved drugs, and three of these genes (H6PD, CACNB2 and DRD2) have been served as drug targets for IR-related diseases/traits. Moreover, drug repurposing analysis identified four compounds with profiles opposing the expression of genes associated with IR risk. CONCLUSIONS: Our study provided new insights into IR aetiology and avenues for therapeutic development.


Asunto(s)
Resistencia a la Insulina , Transcriptoma , Animales , Humanos , Ratones , LDL-Colesterol , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Resistencia a la Insulina/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Análisis de la Aleatorización Mendeliana
5.
Mycopathologia ; 189(3): 35, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637433

RESUMEN

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.


Asunto(s)
Antifúngicos , Candidiasis , Humanos , Antifúngicos/farmacología , Candidiasis/microbiología , Candida auris , Candida , Anfotericina B/farmacología , Farmacorresistencia Fúngica/genética , Pruebas de Sensibilidad Microbiana
6.
J Fish Biol ; 104(2): 497-504, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37278092

RESUMEN

A total of 40 specimens of the genus Schizothorax (Cyprinidae: Schizothoracinae), including 10 matured males, 19 matured females and 11 juveniles, were captured from the Kirong Tsangpo River in China, which is located in the southern slope of the Central Himalayas. These specimens are identified as Schizothorax richardsonii (Grey, 1832) based on morphological characters and molecular analyses using mitochondrial Cyt b gene sequences. The Kirong population of S. richardsonii is relatively isolated from other populations in the Himalayas and has low genetic diversity. This is the first record of the genus Schizothorax fish in rivers of the Central Himalayas in China. As S. richardsonii is a vulnerable species on the IUCN Red List, a protection plan should be conducted to reduce the impact of anthropogenic disturbance by monitoring the natural population dynamics and assessing the ecological determinants of its distribution.


Asunto(s)
Cyprinidae , Ríos , Animales , Himalayas , Filogenia , China , Cyprinidae/genética
7.
Angew Chem Int Ed Engl ; 63(19): e202400511, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38488202

RESUMEN

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

8.
Mol Ecol ; 32(8): 1955-1971, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36704928

RESUMEN

Anthropogenic biological invasions represent major concerns but enable us to investigate rapid evolutionary changes and adaptation to novel environments. The goldfish Carassius auratus with sexual diploids and unisexual triploids coexisting in natural waters is one of the most widespread invasive fishes in Tibet, providing an ideal model to study evolutionary processes during invasion in different reproductive forms from the same vertebrate. Here, using whole-genome resequencing data of 151 C. auratus individuals from invasive and native ranges, we found different patterns of genomic responses between diploid and triploid populations during their invasion of Tibet. For diploids, although invasive individuals derived from two different genetically distinct sources had a relative higher diversity (π) at the population level, their individual genetic diversity (genome-wide observed heterozygosity) was significantly lower (21.4%) than that of source individuals. Population structure analysis revealed that the invasive individuals formed a specific genetic cluster distinct from the source populations. Runs of homozygosity analysis showed low inbreeding only in invasive individuals, and only the invasive population experienced a recent decline in effective population size reflecting founder events. For triploids, however, invasive populations showed no loss of individual genetic diversity and no genetic differentiation relative to source populations. Regions of putative selective sweeps between invasive and source populations of diploids mainly involved genes associated with mannosidase activity and embryo development. Our results suggest that invasive diploids deriving from distinct sources still lost individual genetic diversity resulting from recent inbreeding and founder events and selective sweeps, and invasive triploids experienced no change in genetic diversity owing to their reproduction mode of gynogenesis that precludes inbreeding and founder effects and may make them more powerful invaders.


Asunto(s)
Diploidia , Carpa Dorada , Animales , Carpa Dorada/genética , Triploidía , Altitud , Evolución Biológica , Variación Genética/genética
9.
Paediatr Perinat Epidemiol ; 36(3): 390-398, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34431114

RESUMEN

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.


Asunto(s)
Neumotórax , Síndrome de Dificultad Respiratoria del Recién Nacido , Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Neumotórax/etiología , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Estudios Retrospectivos
10.
J Enzyme Inhib Med Chem ; 37(1): 817-831, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35220836

RESUMEN

T-LAK-cell-originated protein kinase (TOPK), a novel member of the mitogen-activated protein kinase family, is considered an effective therapeutic target for skin inflammation. In this study, a series (A - D) of paeonol derivatives was designed and synthesised using a fragment growing approach, and their anti-inflammatory activities against lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 cells were tested. Among them, compound B12 yielded the best results (IC50 = 2.14 µM) with low toxicity (IC50 > 50 µM). Preliminary mechanistic studies indicated that this compound could inhibit the TOPK-p38/JNK signalling pathway and phosphorylate downstream related proteins. A murine psoriasis-like skin inflammation model was used to determine its therapeutic effect.


Asunto(s)
Acetofenonas/farmacología , Antiinflamatorios no Esteroideos/farmacología , Descubrimiento de Drogas , Inflamación/tratamiento farmacológico , Piel/efectos de los fármacos , Acetofenonas/síntesis química , Acetofenonas/química , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inflamación/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos BALB C , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Transducción de Señal/efectos de los fármacos , Piel/metabolismo , Relación Estructura-Actividad , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
11.
J Fish Biol ; 2022 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-36571395

RESUMEN

Phylogeographic congruence among co-distributed taxa is regarded as an inherent inference to vicariance events. Nonetheless, incongruent patterns of contemporary lineage divergence among taxa indicated that species differ in their response to common past events. To investigate the role of past events, ecological traits and lineage diversification time in shaping the contemporary phylogeographic patterns, comparative analyses were conducted for Tibetan stone loaches in the Himalayas using three gene markers and two ecological traits (depth of caudal peduncle in their length and presence/absence of posterior chamber of the air bladder). By a thorough sampling in two flanks of the Himalayas, the authors detected that phylogenetic breaks were spatially discordant and divergences of populations were also temporally asynchronous in co-distributed loaches. Estimated divergence time using fossil-calibrated node dating indicated that the Tibetan stone loaches colonised into the south flank of the Himalayas until the Pleistocene. The demographic expansions were also disconcerted between populations in north and south flanks, or east and west Himalayas. Ongoing gene flows between populations in north and south sides implied that the Himalayas do not strictly impede dispersal of cold-adapted species. The results highlight that the quaternary climatic oscillation, in conjunction with ecological traits and lineage diversification time, shaped contemporary phylogenetic patterns of stone loaches in the Himalayas and provide new insights into the biodiversity and composition of species in the Himalayas and surrounding region.

12.
Appl Opt ; 60(28): 8930-8938, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34613122

RESUMEN

With the development of laser communication networking, laser-ranging technology is becoming more and more applicable. In this paper, high-accuracy ranging is implemented based on intradyne coherent detection at a communication rate of 1048.576 Mbps. The ranging accuracy is affected by clock phase calculation error and code loop track error. Parallel clock phase difference calculation, frame head correlation, and ranging ambiguity region handle are combined with the ranging calibration method, realizing millimeter-level corrected distance measurement. Dynamic range measurement above 1 m is proven to be continuous through the ranging ambiguity region handle. In addition, high-precision clock frequency deviation between two asynchronous terminals can be obtained through derivation of one-way distance at static ranging or by derivative of distance difference at bidirectional ranging. The methods proposed in this paper are verified by inter-satellite laser-ranging on orbit, and the results are analyzed.

13.
Acta Biochim Biophys Sin (Shanghai) ; 53(3): 304-316, 2021 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-33355622

RESUMEN

Lung cancer is a common type of cancer that causes a very large public health burden worldwide. Achieving a better understanding of the molecular mechanism underlying the progression of lung cancer is of benefit for the diagnosis, prognosis, and treatment of lung cancer. Here, we first identified dramatically decreased expression of miR-338-5p in lung cancer tissues and cells using quantitative polymerase chain reaction (qPCR) analysis. We then revealed that miR-338-5p inhibited the cell growth and migration of lung cancer cells using cell counting kit 8 (CCK8), EdU, and Transwell analysis. Furthermore, we demonstrated that miR-338-5p inhibited METTL3 expression by qPCR, western blot analysis, and luciferase reporter assay, while upregulation of METTL3 alleviated the role of miR-338-5p in lung cancer cells. We also showed that METTL3 promoted c-Myc expression by increasing the m6A modification of c-Myc, and overexpression of c-Myc restored the inhibition of cell growth and migration of lung cancer cells induced by METTL3 silencing. Ultimately, this research illustrated that modification of the miR-338-5p/METTL3/c-Myc pathway affected cellular progression in lung cancer cells. Collectively, our study revealed the underlying mechanism of miR-338-5p in lung cancer, providing a novel regulatory pathway in lung cancer. There is potential for this pathway to serve as a diagnostic, prognostic, and therapeutic biomarker for lung cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/metabolismo , Metiltransferasas/biosíntesis , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-myc/biosíntesis , ARN Neoplásico/metabolismo , Transducción de Señal , Células A549 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Metiltransferasas/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas c-myc/genética , ARN Neoplásico/genética
14.
Angew Chem Int Ed Engl ; 60(15): 8488-8493, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33369828

RESUMEN

The first highly enantioselective CuI -catalyzed azide-alkyne cycloaddition (CuAAC) of tertiary alcohols and their kinetic resolution is reported. This approach allows facile access to multifunctional tertiary alcohols featuring an α-ethynyl or α-triazole moiety, and represents the first successful kinetic resolution of racemates with a tetrasubstituted carbon stereocenter via CuAAC. Newly developed pyridinebisoxazoline (PYBOX) ligands with a C4 phosphonate group play a key role.

15.
BMC Genomics ; 21(1): 835, 2020 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-33246415

RESUMEN

BACKGROUND: The scale degeneration is thought to be related to the adaptation to the extreme environment with cold climate and high-altitude in schizothoracine fishes. Gymnocypris eckloni, a schizothoracine fish living in plateau waters with the elevation above 2500 m, is nearly esquamate and only covered with shoulder scales and anal scales, making it a good model species to study the molecular mechanism of scale degeneration. RESULTS: The transcriptomes of shoulder scaled skins (SSS), anal scaled skins (ASS) and scaleless skins (NSS) were sequenced and analyzed in G. eckloni at the age of 1 year. Histological examination showed that shoulder scale had completed its differentiation and anal scale just initiated the differentiation. A total of 578,046 unigenes were obtained from the transcriptomes, with 407,799 unigenes annotated in public databases. A total of 428 and 142 differentially expressed unigenes (DEUs) were identified between SSS and NSS, and between ASS and NSS, respectively, with 45 DEUs that were overlapped. Annotation analysis indicated that these DEUs were mainly enriched in Gene Ontology (GO) terms and KEGG pathways associated with bone and muscle formation, such as myofibril, contractile fiber, cytoskeletal protein binding, muscle structure development, cardiac muscle contraction, hypertrophic cardiomyopathy (HCM) and calcium signaling pathway. CONCLUSIONS: Our results would provide insights into the molecular mechanisms of scale degeneration in G. eckloni and other congeneric fishes. In addition, the transcriptome data provides candidate genes and markers for future studies.


Asunto(s)
Cyprinidae , Transcriptoma , Animales , Cyprinidae/genética , Perfilación de la Expresión Génica , Ontología de Genes , Anotación de Secuencia Molecular , Filogenia
16.
J Vasc Interv Radiol ; 31(10): 1661-1667, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32921564

RESUMEN

PURPOSE: To evaluate safety and efficacy of percutaneous mechanical thrombectomy using the Rotarex catheter combined with drug-coated balloon (DCB) in treatment of femoropopliteal artery occlusive disease. MATERIALS AND METHODS: Between January 2016 and February 2018, 81 patients with acute or subacute femoropopliteal artery occlusions were treated with the Rotarex catheter combined with DCB. Lesions were classified according to the onset of symptoms as acutely (< 14 d) or subacutely (14 d to 3 mo) occluded. The mean lesion length was 12.1 cm ± 6.7. The primary endpoint was target lesion patency at 1 year as evaluated by duplex ultrasound (peak systolic velocity ratio < 2.4) and freedom from clinically indicated target lesion revascularization. Amputation rate, major adverse events, and ankle-brachial index at 12 months were evaluated. RESULTS: Technical success rate was 100% (n = 81). Bailout stents were necessary in 14 patients owing to residual stenosis or flow-limiting dissection. Additional thrombolysis was applied in 10 interventions. No major adverse events occurred during hospital stay. There were 9 restenosis cases during the 12-month follow-up period. Primary patency rate was 87.3% (62/71), and freedom from target lesion revascularization rate was 90.1% (64/71). Ankle-brachial index significantly increased from 0.46 ± 0.15 to 0.77 ± 0.14 during follow-up. The amputation rate was 1.4% at 12 months. CONCLUSIONS: These initial data from 2 centers suggest that the combination of the Rotarex catheter and DCB may be safe and effective for treatment of acute or subacute thrombotic femoropopliteal occlusion with superior immediate and midterm results achieved.


Asunto(s)
Angioplastia de Balón/instrumentación , Fármacos Cardiovasculares/administración & dosificación , Arteria Femoral , Paclitaxel/administración & dosificación , Enfermedad Arterial Periférica/terapia , Arteria Poplítea , Trombectomía , Dispositivos de Acceso Vascular , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica , Angioplastia de Balón/efectos adversos , Beijing , Fármacos Cardiovasculares/efectos adversos , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/fisiopatología , Humanos , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/fisiopatología , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Trombectomía/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular
17.
BMC Pediatr ; 20(1): 321, 2020 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-32600275

RESUMEN

BACKGROUND: The objective of this prospective, multicentre, observational cohort study was to evaluate the association between admission hypothermia and neonatal outcomes in very low-birth weight (VLBW) infants in multiple neonatal intensive care units (NICUs) in China. METHODS: Since January 1, 2018, a neonatal homogeneous cooperative research platform-Shandong Neonatal Network (SNN) has been established. The platform collects clinical data in a prospective manner on preterm infants with birth weights (BWs) < 1500 g and gestational ages (GAs) < 34 weeks born in 28 NICUs in Shandong Province. These infants were divided into normothermia, mild or moderate/severe hypothermia groups according to the World Health Organization (WHO) classifications of hypothermia. Associations between outcomes and hypothermia were tested in a bivariate analysis, followed by a logistic regression analysis. RESULTS: A total of 1247 VLBW infants were included in this analysis, of which 1100 infants (88.2%) were included in the hypothermia group, 554 infants (44.4%) in the mild hypothermia group and 546 infants (43.8%) in the moderate/severe hypothermia group. Small for gestational age (SGA), caesarean section, a low Apgar score at 5 min and intubation in the delivery room (DR) were related to admission hypothermia (AH). Mortality was the lowest when their admission temperature was 36.5 ~ 37.5 °C, and after adjustment for maternal and infant characteristics, mortality was significantly associated with AH. Compared with infants with normothermia (36.5 ~ 37.5 °C), the adjusted ORs of all deaths increased to 4.148 (95% CI 1.505-11.437) and 1.806 (95% CI 0.651-5.009) for infants with moderate/severe hypothermia and mild hypothermia, respectively. AH was also associated with a high likelihood of respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), and late-onset neonatal sepsis (LOS). CONCLUSIONS: AH is still very high in VLBW infants in NICUs in China. SGA, caesarean section, a low Apgar score at 5 min and intubation in the DR were associated with increased odds of hypothermia. Moderate/severe hypothermia was associated with mortality and poor outcomes, such as RDS, IVH, LOS.


Asunto(s)
Hipotermia , Cesárea , China/epidemiología , Femenino , Humanos , Hipotermia/epidemiología , Hipotermia/etiología , Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Embarazo , Estudios Prospectivos
18.
Opt Express ; 27(17): 23996-24006, 2019 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-31510295

RESUMEN

We report a coherent tracking system based on fiber nutation for inter-satellite beaconless laser communication, which uses a piezo-electric ceramic tube (PCT) to drive the end face of single mode fiber (SMF) for nutation, and uses coherent demodulation method to directly calculate the boresight error from the intensity envelope fluctuation of signal light. The method is given theoretically and verified experimentally. Under the condition of fiber nutation frequency is 2000Hz and nutation radius is 1.1um, the experimental verification results in our interested range of signal light power (1nW-10nW) meet our design requirements. The receiving field of view (FOV) of tracking system is more than 300urad, and the closed-loop tracking bandwidth (-3dB) is about 115 Hz. When the boresight error is fixed at 80urad, the real calculation error is less than 10%. The closed-loop performance of tracking system is insensitive to the change of signal light power. Our coherent tracking system is of great significance to the inter-satellite beaconless laser communication.

19.
Appl Opt ; 58(27): 7517-7522, 2019 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-31674403

RESUMEN

We designed an intensity modulation direct detection free-space laser communication terminal. In this system, the output power of the signal-modulated semiconductor laser amplified by two-stage fiber amplifier is 2 W, and the modulation contrast is 15 dB. Tracking of the incident beam and demodulation of the communication signal are realized by using a quadrant avalanche photodiode (APD). By means of rotating double Risley prisms, the ranges of the pitching angle and azimuth angle are ±35 and ±180 deg, respectively. The focal length of the transceiver lens is 125 mm, and the final communication field of view is 4 mrad. Without error correction coding, the sensitivity of -44.5 dBm was achieved, while the bit-error rate was below 10-3 at 70 Mbps. We also established a laser communication experiment at the laboratory; the platform jitter below 5 Hz can be effectively suppressed. The laser communication system has a compact structure, low power consumption, and effective suppression of low-frequency and high-amplitude angle jitter of the platform. The experiments demonstrate that the laser communication terminal can be used in an inter-satellite laser communication with a distance of thousands of kilometers. The theoretical analysis and experimental results are presented in the paper.

20.
Int J Mol Sci ; 20(15)2019 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-31382526

RESUMEN

Many Salicaceae s.l. plants are recognized for their important role in the production of products such as wood, oils, and medicines, and as a model organism in life studies. However, the difference in plastid sequence, phylogenetic relationships, and lineage diversification of the family Salicaceae s.l. remain poorly understood. In this study, we compare 24 species representing 18 genera of the family. Simple sequence repeats (SSRs) are considered effective molecular markers for plant species identification and population genetics. Among them, a total of 1798 SSRs were identified, among which mononucleotide repeat was the most common with 1455 accounts representing 80.92% of the total. Most of the SSRs are located in the non-coding region. We also identified five other types of repeats, including 1750 tandems, 434 forward, 407 palindromic, 86 reverse, and 30 complementary repeats. The species in Salicaceae s.l. have a conserved plastid genome. Each plastome presented a typical quadripartite structure and varied in size due to the expansion and contraction of the inverted repeat (IR) boundary, lacking major structural variations, but we identified six divergence hotspot regions. We obtained phylogenetic relationships of 18 genera in Salicaceae s.l. and the 24 species formed a highly supported lineage. Casearia was identified as the basal clade. The divergence time between Salicaceae s.l. and the outgroup was estimated as ~93 Mya; Salix, and Populus diverged around 34 Mya, consistent with the previously reported time. Our research will contribute to a better understanding of the phylogenetic relationships among the members of the Salicaceae s.l.


Asunto(s)
Genoma de Plastidios , Filogenia , Plastidios/genética , Salicaceae/genética , Evolución Molecular , Secuencias Invertidas Repetidas , Repeticiones de Microsatélite
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