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Cancer cells undergo metabolic reprogramming that is intricately linked to malignancy. Protein acylations are especially responsive to metabolic changes, influencing signal transduction pathways and fostering cell proliferation. However, as a novel type of acylations, the involvement of malonylation in cancer remains poorly understood. In this study, we observed a significant reduction in malonyl-CoA levels in hepatocellular carcinoma (HCC), which correlated with a global decrease in malonylation. Subsequent nuclear malonylome analysis unveiled nucleolin (NCL) malonylation, which was notably enhanced in HCC biopsies. we demonstrated that NCL undergoes malonylation at lysine residues 124 and 398. This modification triggers the translocation of NCL from the nucleolus to nucleoplasm and cytoplasm, binding to AKT mRNA, and promoting AKT translation in HCC. Silencing AKT expression markedly attenuated HCC cell proliferation driven by NCL malonylation. These findings collectively highlight nuclear signaling in modulating AKT expression, suggesting NCL malonylation as a novel mechanism through which cancer cells drive cell proliferation.
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BACKGROUND: Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae. RESULTS: Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity. CONCLUSIONS: Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems.
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Cyprinidae , Ecosistema , Animales , Filogenia , Cyprinidae/genética , Genómica , Agua de Mar , Adaptación Fisiológica/genéticaRESUMEN
Freeze tolerance, the ability of an organism to survive internal ice formation, is a striking survival strategy employed by some ectotherms living in cold environments. However, the genetic bases of this remarkable adaptation are largely unknown. The Amur sleeper (Perccottus glenii), the only known freeze-tolerant fish species, can overwinter with its entire body frozen in ice. Here, we sequenced the chromosome-level genome of the Amur sleeper and performed comparative genomic, transcriptomic, and metabolomic analyses to investigate its strategies for surviving freezing. Evolutionary analysis suggested that the Amur sleeper diverged from its closest non-cold-hardy relative about 15.07 million years ago and has experienced a high rate of protein evolution. Transcriptomic and metabolomic data identified a coordinated and tissue-specific regulation of genes and metabolites involved in hypometabolism, cellular stress response, and cryoprotectant accumulation involved in freezing and thawing. Several genes show evidence of accelerated protein sequence evolution or family size expansion were found as adaptive responses to freezing-induced stresses. Specifically, genetic changes associated with cytoskeleton stability, cryoprotectant synthesis, transmembrane transport, and neuroprotective adaptations were identified as potentially key innovations that aid in freezing survival. Our work provides valuable resources and opportunities to unveil the molecular adaptations supporting freeze tolerance in ectothermic vertebrates.
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Hielo , Perciformes , Animales , Congelación , Multiómica , Vertebrados , Adaptación Fisiológica/fisiología , Aclimatación/genéticaRESUMEN
Recent genomic analyses of evolutionary radiations suggest that ancient introgression may facilitate rapid diversification and adaptive radiation. The loach genus Triplophysa, a genus with most species endemic to Tibetan Plateau, shows ecological diversity and rapid evolution and represents a potential example of adaptive radiation linked to the uplift of the Tibetan Plateau. Here, we interrogate the complex evolutionary history of Triplophysa fishes through the analysis of whole-genome sequences. By reconstructing the phylogeny of Triplophysa, quantifying introgression across this clade, and simulating speciation and migration processes, we confirm that extensive gene flow events occurred across disparate Triplophysa species. Our results suggest that introgression plays a more substantial role than incomplete lineage sorting in underpinning phylogenetic discordance in Triplophysa. The results also indicate that genomic regions affected by ancient gene flow exhibit characteristics of lower recombination rates and nucleotide diversity and may associate with selection. Simulation analysis of Triplophysa tibetana suggests that the species may have been affected by the Gonghe Movement in the third uplift of the Tibetan Plateau, resulting in founder effects and a subsequent reduction in Ne.
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Altitud , Cipriniformes , Animales , Filogenia , Tibet , Cipriniformes/genética , Adaptación Fisiológica/genéticaRESUMEN
We explore the relationship among the magnetic ordering in real space, the resulting spin texture on the Fermi surface, and the related superconducting gap structure in noncollinear antiferromagnetic metals without spin-orbit coupling. Via a perturbative approach, we show that noncollinear magnetic ordering in a metal can generate momentum-dependent spin texture on its Fermi surface, even in the absence of spin-orbit coupling, if the metal has more than three sublattices in its magnetic unit cell. Thus, our theory naturally extends the idea of altermagnetism to noncollinear spin structures. When superconductivity is developed in a magnetic metal, as the gap-opening condition is strongly constrained by the spin texture, the nodal structure of the superconducting state is also enforced by the magnetism-induced spin texture. Taking the noncollinear antiferromagnet on the kagome lattice as a representative example, we demonstrate how the Fermi surface spin texture induced by noncollinear antiferromagnetism naturally leads to odd-parity spin-triplet superconductivity with nontrivial topological properties.
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BACKGROUND: Medical groups, health systems, and professional associations are concerned about potential increases in physician turnover, which may affect patient access and quality of care. OBJECTIVE: To examine whether turnover has changed over time and whether it is higher for certain types of physicians or practice settings. DESIGN: The authors developed a novel method using 100% of traditional Medicare billing to create national estimates of turnover. Standardized turnover rates were compared by physician, practice, and patient characteristics. SETTING: Traditional Medicare, 2010 to 2020. PARTICIPANTS: Physicians billing traditional Medicare. MEASUREMENTS: Indicators of physician turnover-physicians who stopped practicing and those who moved from one practice to another-and their sum. RESULTS: The annual rate of turnover increased from 5.3% to 7.2% between 2010 and 2014, was stable through 2017, and increased modestly in 2018 to 7.6%. Most of the increase from 2010 to 2014 came from physicians who stopped practicing increasing from 1.6% to 3.1%; physicians moving increased modestly from 3.7% to 4.2%. Modest but statistically significant (P < 0.001) differences existed across rurality, physician sex, specialty, and patient characteristics. In the second and third quarters of 2020, quarterly turnover was slightly lower than in the corresponding quarters of 2019. LIMITATION: Measurement was based on traditional Medicare claims. CONCLUSION: Over the past decade, physician turnover rates have had periods of increase and stability. These early data, covering the first 3 quarters of 2020, give no indication yet of the COVID-19 pandemic increasing turnover, although continued tracking of turnover is warranted. This novel method will enable future monitoring and further investigations into turnover. PRIMARY FUNDING SOURCE: The Physicians Foundation Center for the Study of Physician Practice and Leadership.
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COVID-19 , Médicos , Anciano , Humanos , Estados Unidos , Medicare , Pandemias , COVID-19/epidemiología , Cuidados PaliativosRESUMEN
BACKGROUND: Lysine glutarylation (Kglu) is one of the most important Post-translational modifications (PTMs), which plays significant roles in various cellular functions, including metabolism, mitochondrial processes, and translation. Therefore, accurate identification of the Kglu site is important for elucidating protein molecular function. Due to the time-consuming and expensive limitations of traditional biological experiments, computational-based Kglu site prediction research is gaining more and more attention. RESULTS: In this paper, we proposed GBDT_KgluSite, a novel Kglu site prediction model based on GBDT and appropriate feature combinations, which achieved satisfactory performance. Specifically, seven features including sequence-based features, physicochemical property-based features, structural-based features, and evolutionary-derived features were used to characterize proteins. NearMiss-3 and Elastic Net were applied to address data imbalance and feature redundancy issues, respectively. The experimental results show that GBDT_KgluSite has good robustness and generalization ability, with accuracy and AUC values of 93.73%, and 98.14% on five-fold cross-validation as well as 90.11%, and 96.75% on the independent test dataset, respectively. CONCLUSION: GBDT_KgluSite is an effective computational method for identifying Kglu sites in protein sequences. It has good stability and generalization ability and could be useful for the identification of new Kglu sites in the future. The relevant code and dataset are available at https://github.com/flyinsky6/GBDT_KgluSite .
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Lisina , Proteínas , Lisina/metabolismo , Proteínas/metabolismo , Secuencia de Aminoácidos , Procesamiento Proteico-Postraduccional , Mitocondrias/metabolismo , Biología Computacional/métodosRESUMEN
BACKGROUND: Primary care "teamlets" in which a staff member and physician consistently work together might provide a simple, cost-effective way to improve care, with or without insertion within a team. OBJECTIVE: To determine the prevalence and performance of teamlets and teams. DESIGN: Cross-sectional observational study linking survey responses to Medicare claims. PARTICIPANTS: Six hundred eighty-eight general internists and family physicians. INTERVENTIONS: Based on survey responses, physicians were assigned to one of four teamlet/team categories (e.g., teamlet/no team) and, in secondary analyses, to one of eight teamlet/team categories that classified teamlets into high, medium, and low collaboration as perceived by the physician (e.g., teamlet perceived-high collaboration/no team). MAIN MEASURES: Descriptive: percentage of physicians in teamlet/team categories. OUTCOME MEASURES: physician burnout; ambulatory care sensitive emergency department and hospital admissions; Medicare spending. KEY RESULTS: 77.4% of physicians practiced in teamlets; 36.7% in teams. Of the four categories, 49.1% practiced in the teamlet/no team category; 28.3% in the teamlet/team category; 8.4% in no teamlet/team; 14.1% in no teamlet/no team. 15.7%, 47.4%, and 14.4% of physicians practiced in perceived high-, medium-, and low-collaboration teamlets. Physicians who practiced neither in a teamlet nor in a team had significantly lower rates of burnout compared to the three teamlet/team categories. There were no consistent, significant differences in outcomes or Medicare spending by teamlet/team or teamlet perceived-collaboration/team categories compared to no teamlet/no team, for Medicare beneficiaries in general or for dual-eligible beneficiaries. CONCLUSIONS: Most general internists and family physicians practice in teamlets, and some practice in teams, but neither practicing in a teamlet, in a team, or in the two together was associated with lower physician burnout, better outcomes for patients, or lower Medicare spending. Further study is indicated to investigate whether certain types of teamlet, teams, or teamlets within teams can achieve higher performance.
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Médicos , Atención Primaria de Salud , Anciano , Humanos , Estados Unidos/epidemiología , Estudios Transversales , Medicare , Agotamiento PsicológicoRESUMEN
INTRODUCTION: Apolipoprotein E (APOE) is considered the major susceptibility gene for developing Alzheimer's disease. However, the strength of this risk factor is not well established across diverse Hispanic populations. METHODS: We investigated the associations among APOE genotype, dementia prevalence, and memory performance (immediate and delayed recall scores) in Caribbean Hispanics (CH), African Americans (AA), Hispanic Americans (HA) and non-Hispanic White Americans (NHW). Multivariable logistic regressions and negative binomial regressions were used to examine these associations by subsample. RESULTS: Our final dataset included 13,516 participants (5198 men, 8318 women) across all subsamples, with a mean age of 74.8 years. Prevalence of APOE ε4 allele was similar in CHs, HAs, and NHWs (21.8%-25.4%), but was substantially higher in AAs (33.6%; P < 0.001). APOE ε4 carriers had higher dementia prevalence across all groups. DISCUSSION: APOE ε4 was similarly associated with increased relative risk of dementia and lower memory performance in all subsamples.
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Enfermedad de Alzheimer , Apolipoproteína E4 , Masculino , Humanos , Femenino , Anciano , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Genotipo , Hispánicos o Latinos/genética , Región del Caribe , AlelosRESUMEN
BACKGROUND: Some generalist physicians whose training prepared them for primary care practice increasingly practice in a facility (eg, hospitals, nursing homes); however, whether this trend was accompanied by a complimentary rise in generalist physicians who focused their practice on office-based care is unknown. OBJECTIVES: Our objective in this study was to examine trends in the prevalence of generalist physicians and physician groups that practice in a single setting. RESEARCH DESIGN: This was a retrospective cross-sectional study of generalist physicians trained in family medicine, internal medicine, or geriatrics. We used 2014-2017 billing data for Medicare fee-for-service beneficiaries to measure the proportion of all patient visits made by physicians in the following care settings: office, outpatient hospital department, inpatient hospital, and other sites. RESULTS: From 2014 to 2017, the proportion of generalist physicians who narrowed their practice to a single setting increased by 6.69% (from 62.80% to 67.00%, p for trend <0.001). In 2017, 4.63% of physician groups included more than 1 type of setting-based physicians. CONCLUSIONS: Generalist physicians treating older adults increasingly narrowed their practice focus to a single type of health care setting. This trend was not accompanied by growth among physician groups that included different types of setting-based physicians. Further evaluation of the consequences of these trends on the fragmentation of primary care delivery across different health care settings and primary care outcomes is needed.
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Medicare , Médicos , Anciano , Estudios Transversales , Humanos , Medicina Interna , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND: Medicare's Merit-based Incentive Payment System (MIPS) is a major value-based purchasing program. Little is known about how physician practice leaders view the program and its benefits and challenges. OBJECTIVE: To understand practice leaders' perceptions of MIPS. DESIGN AND PARTICIPANTS: Interviews were conducted from December 12, 2019, to June 23, 2020, with leaders of 30 physician practices of various sizes and specialties across the USA. Practices were randomly selected using the Medical Group Management Association's membership database. Practices included small primary care and general surgery practices (1-9 physicians); medium primary care and general surgery practices (10-25 physicians); and large multispecialty practices (50 or more physicians). Participants were asked about their perceptions of MIPS measures; the program's effect on patient care; administrative burden; and rationale for participation. MAIN MEASURES: Major themes related to practice participation in MIPS. KEY RESULTS: Interviews were conducted with 30 practices representing all US census regions. Six major themes emerged: (1) MIPS is understood as a continuation of previous value-based payment programs and a precursor to future programs; (2) measures are more relevant to primary care practices than other specialties; (3) leaders are conflicted on whether the program improves patient care; (4) MIPS creates a substantial administrative burden, exacerbated by annual programmatic changes; (5) incentives are small relative to the effort needed to participate; and (6) external support for participation can be helpful. Many participants indicated that their practice only participated in MIPS to avoid financial penalties; some reported that physicians cared for fewer patients due to the program's administrative burden. CONCLUSIONS: Practice leaders reported several challenges related to MIPS, including irrelevant measures, administrative burden, frequent programmatic changes, and small incentives. They held mixed views on whether the program improves patient care. These findings may be useful to policymakers hoping to improve MIPS.
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Motivación , Médicos , Anciano , Humanos , Medicare , Atención Primaria de Salud , Reembolso de Incentivo , Estados UnidosRESUMEN
Engineered nanomaterials (ENMs) and nanotechnology have shown great potential in addressing complex problems and creating innovative approaches in soil remediation due to their unique features of high reactivity, selectivity and versatility. Meanwhile, valid concerns exist with regard to their implications towards the terrestrial environment and the ecosystem. This review summarizes: (i) the applications and the corresponding mechanisms of various types of ENMs for soil remediation; (ii) the environmental behavior of ENMs in soils and their interactions with the soil content; (iii) the environmental implications of ENMs during remedial applications. The overall objective is to promote responsible innovations so as to take optimal advantage of ENMs and nanotechnology while minimizing their adverse effects to the ecological system. It is critical to establish sustainable remediation methods that ensure a healthy and safe environment without bringing additional risk.
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Restauración y Remediación Ambiental/métodos , Nanoestructuras , Nanotecnología/métodos , Contaminantes del Suelo , Suelo/química , Ecosistema , Nanoestructuras/química , Nanoestructuras/toxicidad , Contaminantes del Suelo/química , Contaminantes del Suelo/toxicidadRESUMEN
Importance: The US Merit-based Incentive Payment System (MIPS) is a major Medicare value-based payment program aimed at improving quality and reducing costs. Little is known about how physicians' performance varies by social risk of their patients. Objective: To determine the relationship between patient social risk and physicians' scores in the first year of MIPS. Design, Setting, and Participants: Cross-sectional study of physicians participating in MIPS in 2017. Exposures: Physicians in the highest quintile of proportion of dually eligible patients served; physicians in the 3 middle quintiles; and physicians in the lowest quintile. Main Outcomes and Measures: The primary outcome was the 2017 composite MIPS score (range, 0-100; higher scores indicate better performance). Payment rates were adjusted -4% to 4% based on scores. Results: The final sample included 284â¯544 physicians (76.1% men, 60.1% with ≥20 years in practice, 11.9% in rural location, 26.8% hospital-based, and 24.6% in primary care). The mean composite MIPS score was 73.3. Physicians in the highest risk quintile cared for 52.0% of dually eligible patients; those in the 3 middle risk quintiles, 21.8%; and those in the lowest risk quintile, 6.6%. After adjusting for medical complexity, the mean MIPS score for physicians in the highest risk quintile (64.7) was lower relative to scores for physicians in the middle 3 (75.4) and lowest (75.9) risk quintiles (difference for highest vs middle 3, -10.7 [95% CI, -11.0 to -10.4]; highest vs lowest, -11.2 [95% CI, -11.6 to -10.8]; P < .001). This relationship was found across specialties except psychiatry. Compared with physicians in the lowest risk quintile, physicians in the highest risk quintile were more likely to work in rural areas (12.7% vs 6.4%; difference, 6.3 percentage points [95% CI, 6.0 to 6.7]; P < .001) but less likely to care for more than 1000 Medicare beneficiaries (9.4% vs 17.8%; difference, -8.3 percentage points [95% CI, -8.7 to -8.0]; P < .001) or to have more than 20 years in practice (56.7% vs 70.6%; difference, -13.9 percentage points [95% CI, -14.4 to -13.3]; P < .001). For physicians in the highest risk quintile, several characteristics were associated with higher MIPS scores, including practicing in a larger group (mean score, 82.4 for more than 50 physicians vs 46.1 for 1-5 physicians; difference, 36.2 [95% CI, 35.3 to 37.2]; P < .001) and reporting through an alternative payment model (mean score, 79.5 for alternative payment model vs 59.9 for reporting as individual; difference, 19.7 [95% CI, 18.9 to 20.4]; P < .001). Conclusions and Relevance: In this cross-sectional analysis of physicians who participated in the first year of the Medicare MIPS program, physicians with the highest proportion of patients dually eligible for Medicare and Medicaid had significantly lower MIPS scores compared with other physicians. Further research is needed to understand the reasons underlying the differences in physician MIPS scores by levels of patient social risk.
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Evaluación del Rendimiento de Empleados , Medicare/economía , Médicos , Reembolso de Incentivo , Factores Socioeconómicos , Estudios Transversales , Femenino , Disparidades en el Estado de Salud , Humanos , Masculino , Medicaid , Planes de Incentivos para los Médicos , Indicadores de Calidad de la Atención de Salud , Estados UnidosRESUMEN
Nitrogen doping can provide a large number of active sites for lithium-ion storage, thus can yield a higher capacity for lithium-ion batteries. However, most of the reported N-doped graphene-based materials have low nitrogen content (<10 wt%) as the introduction of nitrogen atoms prefer to be produced at edges and defects in the graphene lattices. Owing to the formation of edges and defects, the doped states or active sites can easily be located and nitrogen contents can be determined precisely. Here we present the preparation of N-doped graphene nanoribbons with high nitrogen contents (11.8 wt%) and a facile tunable configuration of doped states. The material can be used as an anode for lithium-ion batteries and shows a higher capacity (the electrode has a reversible capacity of 1100.34 mA h g-1 at a charge/discharge rate of 100 mA g-1, corresponds to a discharge time of about 9 h), better rate performance (the electrode has a reversible capacity of 471 mA h g-1 at the current density of 2 A g-1, corresponds to a discharge time of about 11.6 min) and improved cycling stability (87.37% of the initial capacity after 200 cycles). The experimental results and first-principle calculations suggest that the residual oxygen-containing functional groups of N-doped graphene nanoribbons promote the formation of pyrrolic nitrogen at edges and substantially increase the room for nitrogen doping. This work opens new strategies for designing and developing N-doped graphene anodes for high performance lithium-ion batteries.
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BACKGROUND AND AIM: To appraise the current reporting methodological quality of meta-analyses in five leading gastroenterology and hepatology journals, and to identify the variables associated with the reporting quality. METHODS: We systematically searched the literature of meta-analyses in Gastroenterology, Gut, Hepatology, Journal of Hepatology (J HEPATOL) and American Journal of Gastroenterology (AM J GASTROENTEROL) from 2006 to 2008 and from 2012 to 2014. Characteristics were extracted based on the PRISMA statement and the AMSTAR tool. Country, number of patients, funding source were also revealed and descriptively reported. RESULTS: A total of 127 meta-analyses were enrolled in this study and were compared among journals, study years, and other characters. Compliances with the PRISMA statement and the AMSTAR checklist were 20.8 ± 4.2 out of a maximum of 27 and 7.6 ± 2.4 out of a maximum of 11, respectively. Some domains were poorly reported including describing a protocol and/or registration (item 5, 0.0%), describing methods, and giving results of additional analyses (item 16, 45.7% and item 23, 48.0%) for PRISMA and duplicating study selection and data extraction (item 2, 53.5%), and providing a list of included and excluded studies (item 5, 14.2%) for AMSTAR. Publication in recent years showed a significantly better methodological quality than those published in previous years. CONCLUSIONS: This study shows that methodological reporting quality of MAs in the major gastroenterology and hepatology journals has improved in recent years after the publication of the developed PRISMA statement, and it can be further improved.
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Bibliografía de Medicina , Exactitud de los Datos , Gastroenterología , Metaanálisis como Asunto , Publicaciones Periódicas como Asunto , Proyectos de InvestigaciónAsunto(s)
Planificación Anticipada de Atención , Médicos , Anciano , Humanos , Medicare , Mecanismo de Reembolso , Estados UnidosRESUMEN
PURPOSE: Study the contribution of long non-coding RNAs (lncRNAs) to progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC). METHODS: We explored lncRNAs profilings in PanIN cell line (SH-PAN) isolated from Pdx-1-Cre; LSL-Kras (G12D/+) mice and PDAC cell line (DT-PCa) isolated from Pdx-1-Cre; LSL- Kras (G12D/+) ; LSL- Tp53 (R172H/+) mice by lncRNAs microarray, and detected expression of lncRNAs and genes in PDAC by Real-time PCR, Western blot, ChIP and immunohistochemistry. RESULTS: Eight lncRNAs and five protein-coding genes, associated with Wnt pathway, were identified with more than five-fold changes between DT-PCa cells and SH-PAN cells. Of them, lincRNA1611 and Ppp3ca were validated significantly high expression in DT-PCa cells and in 22 of 26 fresh resected human PDAC tissues, compared to SH-PAN cells and normal pancreatic tissues, respectively. Moreover, Tp53 mutation status displayed a positive correlation with lincRNA1611 or Ppp3ca level. Immunohistochemical staining for Ppp3ca was weak or lack in 91 of 107 normal pancreatic tissues, 24 of 29 PanIN-I and 13 of 16 PanIN-II tissues, however, was strong in 10 of 27 PanIN-III and 62 of 107 PDAC tissues post operation. CONCLUSIONS: LincRNA1611 and Ppp3ca were high expression in PDAC and may serve as new potential targets for intervention of the disease.
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Carcinoma in Situ/genética , Carcinoma Ductal Pancreático/genética , Mutación , Neoplasias Pancreáticas/genética , ARN Largo no Codificante/genética , Proteína p53 Supresora de Tumor/genética , Vía de Señalización Wnt/genética , Animales , Western Blotting , Calcineurina/genética , Calcineurina/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Progresión de la Enfermedad , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Ratones Mutantes , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Leuciscus merzbacheri is a native fish species found exclusively in the Junggar Basin in Xinjiang. It exhibits remarkable adaptability, thriving in varying water conditions such as the saline waters, the semi-saline water, and the freshwater. Despite its significant economic and ecological value, the underlying mechanisms of its remarkable salinity tolerance remain elusive. Our study marks the first time the full-length transcriptome of L. merzbacheri has been reported, utilizing RNA-Seq and PacBio Iso-Seq technologies. We found that the average length of the full-length transcriptome is 1,780 bp, with an N50 length of 2,358 bp. We collected RNA-Seq data from gill, liver, and kidney tissues of L. merzbacheri from both saline water and freshwater environments and conducted comparative analyses across these tissues. Further analysis revealed significant enrichment in several key functional gene categories and signalling pathways related to stress response and environmental adaptation. The findings provide a valuable genetic resource for further investigation into saline-responsive candidate genes, which will deepen our understanding of teleost adaptation to extreme environmental stress. This knowledge is crucial for the future breeding and conservation of native fish species.
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RNA-Seq , Transcriptoma , Animales , Cyprinidae/genética , Adaptación Fisiológica/genética , Estrés Salino , Salinidad , Perfilación de la Expresión Génica , Branquias/metabolismoRESUMEN
Topmouth culter (Culter alburnus) is an ecologically and economically important species belonging to the subfamily Culterinae that is native to and widespread in East Asia. Intraspecific variation of semi-buoyant and adhesive eggs in topmouth culter provides an ideal opportunity to investigate the genetic mechanisms of spawning habits underlying the adaptive radiation of cyprinids in East Asia. In this study, we present a chromosome-level genome assembly of topmouth culter and re-sequenced 158 individuals from six locations in China covering three geographical groups and two egg type variations. The topmouth culter genome size was 1.05 Gb, with a contig N50 length of 17.8 Mb and anchored onto 24 chromosomes. Phylogenetic analysis showed that the divergence time of the Culterinae was coinciding with the time of initiation of the Asian monsoon intensification. Gene family evolutionary analysis indicated that the expanded gene families in topmouth culter were associated with dietary adaptation. Population-level genetic analysis indicated clear differentiation among the six populations, which were clustered into three distinct clusters, consistent with their geographical divergence. The historical effective population size of topmouth culter correlated with the Tibetan Plateau uplifting according to the demographic history reconstruction. A selective sweep analysis between adhesive and semi-buoyant egg populations revealed the genes associated with the hydration and adhesiveness of eggs, indicating divergent selection towards different hydrological environments. This study offers a high-resolution genetic resource for further studies on evolutionary adaptation, genetic breeding and conservation of topmouth culter, providing insights into the molecular mechanisms for egg type variation of East Asian cyprinids.