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Despite significant advances in phylogenetics over the past decades, the deep relationships within Bivalvia (phylum Mollusca) remain inconclusive. Previous efforts based on morphology or several genes have failed to resolve many key nodes in the phylogeny of Bivalvia. Advances have been made recently using transcriptome data, but the phylogenetic relationships within Bivalvia historically lacked consensus, especially within Pteriomorphia and Imparidentia. Here, we inferred the relationships of key lineages within Bivalvia using matrices generated from specifically designed ultraconserved elements (UCEs) with 16 available genomic resources and 85 newly sequenced specimens from 55 families. Our new probes (Bivalve UCE 2k v.1) for target sequencing captured an average of 849 UCEs with 1085-bp in mean length from in vitro experiments. Our results introduced novel schemes from six major clades (Protobranchina, Pteriomorphia, Palaeoheterodonta, Archiheterodonta, Anomalodesmata and Imparidentia), though some inner nodes were poorly resolved, such as paraphyletic Heterodonta in some topologies potentially due to insufficient taxon sampling. The resolution increased when analyzing specific matrices for Pteriomorphia and Imparidentia. We recovered three Pteriomorphia topologies different from previously published trees, with the strongest support for ((Ostreida + (Arcida + Mytilida)) + (Pectinida + (Limida + Pectinida))). Limida were nested within Pectinida, warranting further studies. For Imparidentia, our results strongly supported the new hypothesis of (Galeommatida + (Adapedonta + Cardiida)), while the possible non-monophyly of Lucinida was inferred but poorly supported. Overall, our results provide important insights into the phylogeny of Bivalvia and show that target enrichment sequencing of UCEs can be broadly applied to study both deep and shallow phylogenetic relationships.

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BACKGROUND: As with many countries worldwide, Singapore is experiencing a rapidly ageing population. Presentation of older persons for urgent but non-emergent conditions to the Emergency Department (ED) represents a growing group of patients utilising public healthcare emergency services and puts a strain on current ED resources. The medical conditions vary, and resources used has been poorly characterized. METHODS: This is a single-center cross-sectional observational study of patients aged 55 to 75 years old who visited the ED with urgent conditions, Patient Acuity Category Scale (PACS) P2 or P3, who were subsequently discharged. The patients visited a public hospital in Singapore on four randomly selected weekdays in April 2023. The utilisation of hospital resources and manpower was studied. A formulated criteria was used to determine the appropriate site of care, such as an Urgent Care Centre (UCC), Primary Care Providers (PCP) clinic or the ED. RESULTS: There were 235 eligible patients during the study period, with a mean age of 65.1 years of which a majority, 183 (77.9%) were allocated to patient acuity category scale P2. Most of the patients were walk-in patients with no referrals (169 (71.9%)). Based on the criteria, the majority of 187 (79.6%) of these patient may be safely managed at an outpatient setting; 71 (30.2%) patients by PCP, 116 (49.4%) patients may be managed by an UCC, with the remaining 48 (20.4%) requiring ED care. CONCLUSION: Our findings indicate that a significant portion of discharged older ED adults with urgent but non-emergent conditions may be adequately managed at outpatient medical services that are appropriately resourced. More research is needed on healthcare initiatives aimed at developing the capabilities of outpatient medical services to manage mild to moderate acute conditions to optimise ED resource allocation.

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Bimetallic atom catalysts exhibit ultra-high oxygen electrocatalytic activity by harnessing mutual promotion and synergistic effects between adjacent metal active centers, surpassing the performance of single metal atomic catalysts. Herein, FeNi atom pairs protected by hierarchical porous annular carbon grids (P-FeNi-NPC) are introduced using a mediator-assisted MOFs-derived strategy. The introduction of the multi-block copolymer P123 ensures the uniform confinement and dispersion of metal ions, followed by thermal decomposition to form a "planetary-ring-like" carbon framework that anchors the bimetallic atomic pairs in the active region. The homogeneous distribution of adjacent Fe-N4 and Ni-N4 active sites significantly enhances catalytic activity and stability. Leveraging unique electronic and geometric structures, the resulting P-FeNi-NPC catalyst demonstrates exceptional ORR and OER activities with an ΔE value of 0.705 (E1/2 = 0.845 V, Ej = 10 = 1.55 V). Theoretical calculations unveil that FeNi bimetallic sites loaded on nitrogen-doped carbon frameworks with specific curvature effectively modulate the energy of d-band centers, thus balancing the free energy of oxygen-containing intermediates. This study presents a novel and versatile approach for synthesizing advanced bifunctional catalysts, poised to drive the future development of Zn-air batteries.

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Peptidomics was employed to systematically analyze the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants and establish a method for distinguishing Galli Gigerii Endothelium Corneum from its adulterants, including the gizzard membranes from ducks, geese, and pigeons. UPLC-Q-Exactive Orbitrap-MS was combined with multivariate statistical analysis to analyze the peptides in Galli Gigerii Endothelium Corneum and its adulterants. The structures of peptides were identified by pNovo combined with manual recognition of spectra, and synthetic peptide standards were used for validation. LC-MS/MS was used to optimize the sample pre-processing conditions, including the extraction procedure, extraction time, extraction solvents, and solvent volumes, for the characteristic peptide LESY in Galli Gigerii Endothelium Corneum. Multiple reaction monitoring(MRM) in the ESI~+ mode with m/z 511.24→269.11 and 511.24→243.13 as detection ions was employed for qualitative and quantitative analyses. The established UPLC-MS/MS method demonstrated good specificity, stability, and durability. The content of LESY in 16 batches of Galli Gigerii Endothelium Corneum samples ranged from 55.03 to 113.36 µg·g~(-1). Additionally, a qualitative detection method for the common peptide RDPVLVSR in adulterants was established with m/z 471.28→785.45 and 471.28→670.41 as the detection ions. This study established a convenient, rapid, and accurate detection method for the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants. The method possesses good specificity, stability, and durability, providing a valuable reference for the identification and quality control of Galli Gigerii Endothelium Corneum and other traditional Chinese medicines derived from animal sources.

Asunto(s)

Péptidos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Animales , Cromatografía Líquida de Alta Presión/métodos , Péptidos/química , Péptidos/análisis , Endotelio/química , Pollos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Proteómica/métodos , Contaminación de Medicamentos , Cromatografía Líquida con Espectrometría de Masas

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METTL3 and METTL14 are traditionally posited to assemble the m6A methyltransferase complex in a stoichiometric 1:1 ratio, modulating mRNA fate via m6A modifications. Nevertheless, recent investigations reveal inconsistent expression levels and prognostic significance of METTL3 and METTL14 across various tumor types, challenging their consistent functional engagement in neoplastic contexts. A pan-cancer analysis leveraging The Cancer Genome Atlas (TCGA) data has identified pronounced disparities in the expression patterns, functional roles, and correlations with tumor burden between METTL3 and METTL14, particularly in esophageal squamous cell carcinoma (ESCC). Knockdown experiments of METTL3 in EC109 cells markedly suppress cell proliferation both in vitro and in vivo, whereas METTL14 knockdown shows a comparatively muted effect on proliferation and does not significantly alter METTL3 protein levels. mRNA sequencing indicates that METTL3 singularly governs the expression of 1615 genes, with only 776 genes co-regulated with METTL14. Additionally, immunofluorescence co-localization studies suggest discrepancies in cellular localization between METTL3 and METTL14. High-performance liquid chromatography-mass spectrometry (HPLC-MS) analyses demonstrate that METTL3 uniquely associates with the Nop56p-linked pre-rRNA complex and mRNA splicing machinery, independent of METTL14. Preliminary bioinformatics and multi-omics investigations reveal that METTL3's autonomous role in modulating tumor cell proliferation and its involvement in mRNA splicing are potentially pivotal molecular mechanisms. Our study lays both experimental and theoretical groundwork for a deeper understanding of the m6A methyltransferase complex and the development of targeted tumor therapies focusing on METTL3.

Asunto(s)

Proliferación Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Metiltransferasas , Metiltransferasas/metabolismo , Metiltransferasas/genética , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Animales , Adenosina/análogos & derivados , Adenosina/metabolismo , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo

RESUMEN

Five new sesquiterpenoids, (4S, 5S, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (1), (4S, 5 R, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (2), 6-O-propionyl-britannilactone (3), 1ß-hydroxy-3α-acetoxyeudesma-11(13)-en-12,8ß-olide (4) and 1ß,5ß-dihydroxyeudesma-11(13)-en-12,8ß-olide (5), along with twelve known ones were isolated from the flowers of Pentanema britannicum (L.) D.Gut.Larr. Among them, compounds 1 and 2 were stereoisomers which belong to 1,10-seco-eudesmane sesquiterpenoid with rare double bond between C-10 and C-14. The structures of the isolated compounds were elucidated by various spectroscopic methods, including 1D and 2D NMR experiments.

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OBJECTIVES: We sought to investigate the clinicopathologic features and differential diagnosis of plexiform fibrohistiocytic tumor (PFHT) and its pathogenesis. METHODS: Ten cases of PFHT were collected from Xi Jing Hospital, Fourth Military Medical University, from September 2008 to December 2022 for clinical data as well as microscopic and immunohistochemical observation. CCND1 gene amplification and break were assayed by fluorescence in situ hybridization (FISH). RESULTS: We report 10 cases of PFHT according to histologic classification. Seven cases were of histiocytoid type, and 3 had mucous degeneration in the nodules. One case was of fibroblastic type, which was mainly composed of fibroblast-like cells. Two cases were of mixed type. Immunohistochemically, the osteoclast-like multinucleated giant cells, histiocyte-like cells, and occasional spindle cells in the adjacent fascicles were reactive for CD68 (10/10), CD163 (5/8), CD10 (8/8), cyclin D1 (8/8), CDK4 (5/8), ß-catenin (4/6), MITF (2/6), and PGP9.5 (4/5). Vimentin (9/9) was strongly positive in tumor cells and peripheral fibroblast-like cells. The positive index of Ki-67 was 5% to 40%, with an average of 20%. The FISH analysis showed neither amplification nor break of the CCND1 gene. All cases underwent surgical resection, and patients were followed up for 9 months to 11 years. Only 2 cases recurred. CONCLUSIONS: Plexiform fibrohistiocytic tumor is a low-grade malignant soft tissue neoplasm. The diagnosis mainly depends on histopathologic and immunohistochemical markers. Cyclin D1 and CD10 expression has diagnostic value for the diagnosis and differential diagnosis of PFHT combined with its plexiform morphology. The overexpression of cyclin D1 suggests an involvement of cell cycle regulatory genes in the pathogenesis of PFHT.

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BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Asunto(s)

Artritis Reumatoide , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Análisis de la Aleatorización Mendeliana , Miosinas/genética , Perfilación de la Expresión Génica , Transcriptoma , Sitios de Carácter Cuantitativo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Multiómica

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INTRODUCTION: The expanding geographical range of blacklegged ticks (BLTs), Ixodes scapularis, and its ability to transmit Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi poses an emerging public health risk. Our study determined the geographic distribution and the minimum infection rate (MIR) of B. burgdorferi-, A. phagocytophilum-, Ba. microti-, and B. miyamotoi-infected BLTs in Manitoba submitted to the Public Health Agency of Canada's passive tick surveillance programme from 1995 to 2017. METHODS: Regression models were used to test the association of the MIR by year for each pathogen. Ticks were tested using PCR for B. burgdorferi since 1995, A. phagocytophilum since 2006, and Ba. microti and B. miyamotoi since 2013. The global positioning system coordinates of infected and uninfected ticks submitted during the surveillance period were plotted on a map of Manitoba using ArcGIS Pro version 3.1.2 to detect changes in the geographic distribution of ticks over time. RESULTS: The overall MIR for B. burgdorferi was 139.7 (95% confidence interval [CI]: 129.0-150.5) per 1000 BLTs; however, it varied over time. After remaining stable from 1995 to 2005, the MIR increased by 12.1 per 1000 BLTs per year from 2005 to 2017 (95% CI: 7.0%-17.2%, p-value <0.01). The geographic distribution of B. burgdorferi-infected BLTs was centred around Winnipeg, Manitoba, and spread outward from this locality. The MIRs of A. phagocytophilum, Ba. microti, and B. miyamotoi were 44.8 per 1000 BLTs (95% CI: 38.1-51.6), 10.8 (95% CI: 6.6-15.0), and 5.2 (95% CI: 2.3-8.1) per 1000 BLTs, respectively, and showed no significant change over time. CONCLUSION: Passive surveillance revealed the presence of A. phagocytophilum-, Ba. microti-, and B. miyamotoi-infected BLTs in southern Manitoba and revealed an increased risk of exposure to B. burgdorferi-infected BLTs due to the increasing geographic range and MIR.

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Higher plants survive terrestrial water deficiency and fluctuation by arresting cellular activities (dehydration) and resuscitating processes (rehydration). However, how plants monitor water availability during rehydration is unknown. Although increases in hypo-osmolarity-induced cytosolic Ca2+ concentration (HOSCA) have long been postulated to be the mechanism for sensing hypo-osmolarity in rehydration1,2, the molecular basis remains unknown. Because osmolarity triggers membrane tension and the osmosensing specificity of osmosensing channels can only be determined in vivo3-5, these channels have been classified as a subtype of mechanosensors. Here we identify bona fide cell surface hypo-osmosensors in Arabidopsis and find that pollen Ca2+ spiking is controlled directly by water through these hypo-osmosensors-that is, Ca2+ spiking is the second messenger for water status. We developed a functional expression screen in Escherichia coli for hypo-osmosensitive channels and identified OSCA2.1, a member of the hyperosmolarity-gated calcium-permeable channel (OSCA) family of proteins6. We screened single and high-order OSCA mutants, and observed that the osca2.1/osca2.2 double-knockout mutant was impaired in pollen germination and HOSCA. OSCA2.1 and OSCA2.2 function as hypo-osmosensitive Ca2+-permeable channels in planta and in HEK293 cells. Decreasing osmolarity of the medium enhanced pollen Ca2+ oscillations, which were mediated by OSCA2.1 and OSCA2.2 and required for germination. OSCA2.1 and OSCA2.2 convert extracellular water status into Ca2+ spiking in pollen and may serve as essential hypo-osmosensors for tracking rehydration in plants.

Asunto(s)

Arabidopsis , Señalización del Calcio , Calcio , Germinación , Concentración Osmolar , Polen , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Calcio/metabolismo , Canales de Calcio/genética , Canales de Calcio/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Germinación/genética , Mutación , Polen/genética , Polen/metabolismo , Agua/metabolismo , Células HEK293 , Humanos , Deshidratación

RESUMEN

In this work, we developed a ratiometric fluorescent probe (NT) based on ICT framework in near-infrared (NIR) which could detect pH and viscosity simultaneously. Long emission wavelength in NIR could protect the probe from interference of background fluorescence and improve the accuracy of the test. Due to the presence of thiazole-salt, the probe possessed good water solubility and could respond immediately to pH in water system. The pH values measured by NT in the actual samples were not much different from that measured by the pH meter, therefore, NT could give excellent accuracy. NT realized the reversible detection of pH by protonation and deprotonation. NT was used successfully to detect the pH of actual water samples, human serum and meat, as well as the viscosity variation caused by thickeners. Additionally, NT could monitor the changes of pH and viscosity in living cells. Therefore, the novel probe exhibited potential application in the fields of the environment, human health and food safety evaluation.

Asunto(s)

Colorantes Fluorescentes , Colorantes Fluorescentes/química , Concentración de Iones de Hidrógeno , Viscosidad , Humanos , Espectrometría de Fluorescencia , Espectroscopía Infrarroja Corta/métodos , Animales , Carne/análisis , Células HeLa , Agua/química

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Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

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Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω(As), ω(Hg), ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Ni), and ω(Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg-1, respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.

Asunto(s)

Metales Pesados , Contaminantes del Suelo , Niño , Adulto , Humanos , Monitoreo del Ambiente , Suelo , Cadmio/análisis , Contaminantes del Suelo/análisis , Metales Pesados/análisis , Medición de Riesgo , China

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BACKGROUND: Deep vein thrombosis (DVT), a frequent complication following percutaneous nephrolithotomy (PCNL), may lead to severe conditions like pulmonary embolism. Current knowledge on postoperative DVT risk factors is, however, limited. The aim of our study was to investigate the risk of DVT after PCNL. METHODS: A retrospective study was conducted on patients who underwent PCNL from March 2020 to March 2023 at our institution. Patient demographics and clinical data, including, DVT-specific information, preoperative labs, and surgical details, was evaluated. RESULTS: One hundred patients were included. Thirty-two (20 males, 12 females, mean age 52.5 ± 7.4 years) developed lower limb DVT post-surgery, while the remaining 68 (48 males, 20 females, mean age 51.1 ± 5.5 years) had no DVT symptoms. Analysis revealed significant correlations between hyperlipidemia, operating time, postoperative bed rest duration, D-dimer level on the first day after surgery, Caprini risk assessment model (RAM) score, and DVT risk. D-dimer on the first day after percutaneous nephrolithotomy, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL. Sex, age, hypertension status, diabetes status and smoking and drinking habits were not significantly associated with DVT risk. CONCLUSIONS: D-dimer on the first day after PCNL, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL.

Asunto(s)

Nefrolitotomía Percutánea , Complicaciones Posoperatorias , Trombosis de la Vena , Humanos , Femenino , Masculino , Persona de Mediana Edad , Factores de Riesgo , Trombosis de la Vena/etiología , Trombosis de la Vena/epidemiología , Estudios Retrospectivos , Nefrolitotomía Percutánea/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Adulto , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Tempo Operativo , Reposo en Cama , Medición de Riesgo

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In this editorial, we review the article published in World J Gastrointest Oncol 2019, 11: 1031-1042. We specifically focus on the occurrence, clinical characteristics, and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors. Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors, the incidence and mortality rates of treatment-related cardiotoxicity have been increasing, severely impacting the survival and prognosis of cancer patients. Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors, including gastrointestinal tumors, and they represent the second largest class of drugs associated with cardiotoxicity. However, there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.

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Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Asunto(s)

Quimiocina CXCL13 , Inmunoterapia , Cáncer Papilar Tiroideo , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Microambiente Tumoral , Microambiente Tumoral/inmunología , Humanos , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/terapia , Carcinoma Anaplásico de Tiroides/inmunología , Animales , Ratones , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/inmunología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/terapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/genética , Inmunoterapia/métodos , Quimiocina CXCL13/metabolismo , Quimiocina CXCL13/genética , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Análisis de la Célula Individual , Pronóstico , Linfocitos T/inmunología , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino

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In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons （PAHs） in soils of Guangzhou， 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method （ERL/ERM） and the （BaP） toxicity equivalent method， and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that： the content of surface soil （∑16PAHs） in Guangzhou was 38-11 115 µg·kg-1， with an average of 526 µg·kg-1， and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou， and there was already a significant ecological risk of PAHs pollution in individual sampling points， which were generally in a state of mild pollution. Based on the results of the health risk assessment， the contribution rates of total cancer risk in both adults and children were presented as follows： skin contact > ingestion of soil > respiratory intake. The health risk of children was greater than that of adults， and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal （37.1%）； diesel （32%）； coking （17.3%）； and mixed sources of traffic emissions， biomass combustion， and petrochemical product volatilization （13.6%）. The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.

Asunto(s)

Neoplasias , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Niño , Adulto , Humanos , Suelo/química , Monitoreo del Ambiente/métodos , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes del Suelo/análisis , Contaminación Ambiental/análisis , Medición de Riesgo , China

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The calcium-activated TMEM16 proteins and the mechanosensitive/osmolarity-activated OSCA/TMEM63 proteins belong to the Transmembrane Channel/Scramblase (TCS) superfamily. Within the superfamily, OSCA/TMEM63 proteins, as well as TMEM16A and TMEM16B, likely function solely as ion channels. However, the remaining TMEM16 members, including TMEM16F, maintain an additional function as scramblases, rapidly exchanging phospholipids between leaflets of the membrane. Although recent studies have advanced our understanding of TCS structure-function relationships, the molecular determinants of TCS ion and lipid permeation remain unclear. Here we show that single lysine mutations in transmembrane helix (TM) 4 allow non-scrambling TCS members to permeate phospholipids. This study highlights the key role of TM 4 in controlling TCS ion and lipid permeation and offers novel insights into the evolution of the TCS superfamily, suggesting that, like TMEM16s, the OSCA/TMEM63 family maintains a conserved potential to permeate ions and phospholipids.

RESUMEN

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.

Asunto(s)

Trastorno Depresivo Mayor , Reflujo Gastroesofágico , Trastornos Mentales , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Trastornos Mentales/epidemiología , Trastornos Mentales/genética , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/genética , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/genética , Estudio de Asociación del Genoma Completo

RESUMEN

Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.