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Grasslands are integral to maintaining biodiversity and key ecosystem services and are under threat from climate change. Plant and soil microbial diversity, and their interactions, support the provision of multiple ecosystem functions (multifunctionality). However, it remains virtually unknown whether plant and soil microbial diversity explain a unique portion of total variation or shared contributions to supporting multifunctionality across global grasslands. Here, we combine results from a global survey of 101 grasslands with a novel microcosm study, controlling for both plant and soil microbial diversity to identify their individual and interactive contribution to support multifunctionality under aridity and experimental drought. We found that plant and soil microbial diversity independently predict a unique portion of total variation in above- and belowground functioning, suggesting that both types of biodiversity complement each other. Interactions between plant and soil microbial diversity positively impacted multifunctionality including primary production and nutrient storage. Our findings were also climate context dependent, since soil fungal diversity was positively associated with multifunctionality in less arid regions, while plant diversity was strongly and positively linked to multifunctionality in more arid regions. Our results highlight the need to conserve both above- and belowground diversity to sustain grassland multifunctionality in a drier world and indicate climate change may shift the relative contribution of plant and soil biodiversity to multifunctionality across global grasslands.
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Biodiversidad , Cambio Climático , Pradera , Microbiología del Suelo , Ecosistema , Suelo/química , Sequías , Plantas , Hongos/fisiologíaRESUMEN
Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1ß, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation.
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The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H2) in their synthesis. Using CVD growth of MoSe2 as an example, this study illustrates the role of a H2-free environment during temperature ramping in suppressing the reduction of MoO3, which promotes effective vaporization and selenization of the Mo precursor to form MoSe2 monolayers with excellent crystal quality. As-synthesized MoSe2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm2/(V·s) with an on-off ratio of 7 × 107. This approach can be extended to other TMDs, such as WSe2, MoTe2, and MoSe2/WSe2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.
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OBJECTIVE: Colonic diverticulosis is a prevalent condition among older adults, marked by the presence of thin-walled pockets in the colon wall that can become inflamed, infected, haemorrhage or rupture. We present a case-control genetic and transcriptomic study aimed at identifying the genetic and cellular determinants underlying this condition and the relationship with other gastrointestinal disorders. DESIGN: We conducted DNA and RNA sequencing on colonic tissue from 404 patients with (N=172) and without (N=232) diverticulosis. We investigated variation in the transcriptome associated with diverticulosis and further integrated this variation with single-cell RNA-seq data from the human intestine. We also integrated our expression quantitative trait loci with genome-wide association study using Mendelian randomisation (MR). Furthermore, a Polygenic Risk Score analysis gauged associations between diverticulosis severity and other gastrointestinal disorders. RESULTS: We discerned 38 genes with differential expression and 17 with varied transcript usage linked to diverticulosis, indicating tissue remodelling as a primary diverticula formation mechanism. Diverticula formation was primarily linked to stromal and epithelial cells in the colon including endothelial cells, myofibroblasts, fibroblasts, goblet, tuft, enterocytes, neurons and glia. MR highlighted five genes including CCN3, CRISPLD2, ENTPD7, PHGR1 and TNFSF13, with potential causal effects on diverticulosis. Notably, ENTPD7 upregulation was confirmed in diverticulosis cases. Additionally, diverticulosis severity was positively correlated with genetic predisposition to diverticulitis. CONCLUSION: Our results suggest that tissue remodelling is a primary mechanism for diverticula formation. Individuals with an increased genetic proclivity to diverticulitis exhibit a larger numbers of diverticula on colonoscopy.
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Diverticulosis del Colon , Estudio de Asociación del Genoma Completo , Transcriptoma , Humanos , Diverticulosis del Colon/genética , Masculino , Femenino , Anciano , Estudios de Casos y Controles , Persona de Mediana Edad , Sitios de Carácter Cuantitativo , Análisis de la Aleatorización Mendeliana , Predisposición Genética a la EnfermedadRESUMEN
Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.
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Neoplasias Encefálicas , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glioma , Cotransportadores de K Cl , Simportadores , Humanos , Glioma/genética , Glioma/patología , Glioma/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Simportadores/genética , Simportadores/metabolismo , Movimiento Celular/genética , Pronóstico , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genéticaRESUMEN
The immune response to Mycoplasma pneumoniae infection plays a key role in clinical symptoms. Previous investigations focused on the pro-inflammatory effects of leukocytes and the pivotal role of epithelial cell metabolic status in finely modulating the inflammatory response have been neglected. Herein, we examined how glycolysis in airway epithelial cells is affected by M. pneumoniae infection in an in vitro model. Additionally, we investigated the contribution of ATP to pulmonary inflammation. Metabolic analysis revealed a marked metabolic shift in bronchial epithelial cells during M. pneumoniae infection, characterized by increased glucose uptake, enhanced aerobic glycolysis, and augmented ATP synthesis. Notably, these metabolic alterations are orchestrated by adaptor proteins, MyD88 and TRAM. The resulting synthesized ATP is released into the extracellular milieu via vesicular exocytosis and pannexin protein channels, leading to a substantial increase in extracellular ATP levels. The conditioned medium supernatant from M. pneumoniae-infected epithelial cells enhances the secretion of both interleukin (IL)-1ß and IL-18 by peripheral blood mononuclear cells, partially mediated by the P2X7 purine receptor (P2X7R). In vivo experiments confirm that addition of a conditioned medium exacerbates pulmonary inflammation, which can be attenuated by pre-treatment with a P2X7R inhibitor. Collectively, these findings highlight the significance of airway epithelial aerobic glycolysis in enhancing the pulmonary inflammatory response and aiding pathogen clearance.
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Neumonía por Mycoplasma , Humanos , Mycoplasma pneumoniae , Leucocitos Mononucleares/metabolismo , Medios de Cultivo Condicionados , Células Epiteliales/microbiología , Pulmón/metabolismo , Interleucina-1beta/metabolismo , Adenosina TrifosfatoRESUMEN
Glycosides make up a biomedically important class of secondary metabolites. Most naturally occurring glycosides were isolated from plants and bacteria; however, the chemical diversity of glycosylated natural products in fungi remains largely unexplored. Herein, we present a paradigm to specifically discover diverse and bioactive glycosylated natural products from fungi by combining tailoring enzyme-guided genome mining with mass spectrometry (MS)-based metabolome analysis. Through in vivo genes deletion and heterologous expression, the first fungal C-glycosyltransferase AuCGT involved in the biosynthesis of stromemycin was identified from Aspergillus ustus. Subsequent homology-based genome mining for fungal glycosyltransferases by using AuCGT as a probe revealed a variety of biosynthetic gene clusters (BGCs) containing its homologues in diverse fungi, of which the glycoside-producing capability was corroborated by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. Consequently, 28 fungal aromatic polyketide C/O-glycosides, including 20 new compounds, were efficiently discovered and isolated from the three selected fungi. Moreover, several novel fungal C/O-glycosyltransferases, especially three novel α-pyrone C-glycosyltransferases, were functionally characterized and verified in the biosynthesis of these glycosides. In addition, a proof of principle for combinatorial biosynthesis was applied to design the production of unnatural glycosides in Aspergillus nidulans. Notably, the newly discovered glycosides exhibited significant antiviral, antibacterial, and antidiabetic activities. Our work demonstrates the promise of tailoring enzyme-guided genome-mining approach for the targeted discovery of fungal glycosides and promotes the exploration of a broader chemical space for natural products with a target structural motif in microbial genomes.
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Aspergillus nidulans , Productos Biológicos , Glicosiltransferasas/metabolismo , Metaboloma , Espectrometría de Masas , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Glicósidos , Familia de MultigenesRESUMEN
While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibodyâdrug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)âapproved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.
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Antineoplásicos , Inmunoconjugados , Neoplasias , Estados Unidos , Humanos , Inmunoconjugados/uso terapéutico , United States Food and Drug Administration , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Resultado del TratamientoRESUMEN
Pleiotropy is frequently detected in agronomic traits of wheat (Triticum aestivum). A locus on chromosome 4B, QTn/Ptn/Sl/Sns/Al/Tgw/Gl/Gw.caas-4B, proved to show pleiotropic effects on tiller, spike, and grain traits using a recombinant inbred line (RIL) population of Qingxinmai × 041133. The allele from Qingxinmai increased tiller numbers, and the allele from line 041133 produced better performances of spike traits and grain traits. Another 52 QTL for the eight traits investigated were detected on 18 chromosomes, except for chromosomes 5D, 6D, and 7B. Several genes in the genomic interval of the locus on chromosome 4B were differentially expressed in crown and inflorescence samples between Qingxinmai and line 041133. The development of the KASP marker specific for the locus on chromosome 4B is useful for molecular marker-assisted selection in wheat breeding.
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Alelos , Cromosomas de las Plantas , Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Triticum/crecimiento & desarrollo , Cromosomas de las Plantas/genética , Fenotipo , Pleiotropía Genética , FitomejoramientoRESUMEN
BACKGROUND: Lipid-lowering drugs and antihypertensive drugs are commonly combined for cardiovascular disease (CVD). However, the relationship of combined medications with CVD remains controversial. We aimed to explore the associations of genetically proxied medications of lipid-lowering and antihypertensive drugs, either alone or both, with risk of CVD, other clinical and safety outcomes. METHODS: We divided 423,821 individuals in the UK Biobank into 4 groups via median genetic scores for targets of lipid-lowering drugs and antihypertensive drugs: lower low-density lipoprotein cholesterol (LDL-C) mediated by targets of statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lower systolic blood pressure (SBP) mediated by targets of ß-blockers (BBs) or calcium channel blockers (CCBs), combined genetically lower LDL-C and SBP, and reference (genetically both higher LDL-C and SBP). Associations with risk of CVD and other clinical outcomes were explored among each group in factorial Mendelian randomization. RESULTS: Independent and additive effects were observed between genetically proxied medications of lipid-lowering and antihypertensive drugs with CVD (including coronary artery disease, stroke, and peripheral artery diseases) and other clinical outcomes (ischemic stroke, hemorrhagic stroke, heart failure, diabetes mellitus, chronic kidney disease, and dementia) (P > 0.05 for interaction in all outcomes). Take the effect of PCSK9 inhibitors and BBs on CVD for instance: compared with the reference, PCSK9 group had a 4% lower risk of CVD (odds ratio [OR], 0.96; 95%CI, 0.94-0.99), and a 3% lower risk was observed in BBs group (OR, 0.97; 95%CI, 0.94-0.99), while combined both were associated with a 6% additively lower risk (OR, 0.94; 95%CI, 0.92-0.97; P = 0.87 for interaction). CONCLUSIONS: Genetically proxied medications of combined lipid-lowering and antihypertensive drugs have an independent and additive effects on CVD, other clinical and safety outcomes, with implications for CVD clinical practice, subsequent trials as well as drug development of polypills.
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Antihipertensivos , Enfermedades Cardiovasculares , Análisis de la Aleatorización Mendeliana , Humanos , Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/tratamiento farmacológico , Masculino , Femenino , Hipolipemiantes/uso terapéutico , Persona de Mediana Edad , Anciano , Variación Genética , Reino Unido/epidemiología , Quimioterapia Combinada , Presión Sanguínea/efectos de los fármacosRESUMEN
BACKGROUND: Annual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit-harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals. METHODS: We conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for < 15 years. A total of 34 risk-based screening strategies, varying by different risk groups for screening eligibility and screening intervals (1-year, 2-year, 3-year, one-off, non-screening), were evaluated and were compared with annual screening for all heavy smokers (the status quo strategy). The analysis was undertaken from the health service perspective with a 30-year time horizon. The willingness-to-pay (WTP) threshold was adopted as three times the gross domestic product (GDP) of China in 2021 (CNY 242,928) per quality-adjusted life year (QALY) gained. RESULTS: Compared with the status quo strategy, nine risk-based screening strategies were found to be cost-effective, with two of them even resulting in cost-saving. The most cost-effective strategy was the risk-based approach of annual screening for individuals with a 5-year risk threshold of ≥ 1.70%, biennial screening for individuals with a 5-year risk threshold of 1.03 ~ 1.69%, and triennial screening for individuals with a 5-year risk threshold of < 1.03%. This strategy had the highest incremental net monetary benefit (iNMB) of CNY 1032. All risk-based screening strategies were more efficient than the status quo strategy, requiring 129 ~ 656 fewer screenings per lung cancer death avoided, and 0.5 ~ 28 fewer screenings per life-year gained. The cost-effectiveness of risk-based screening was further improved when individual adherence to screening improved and individuals quit smoking after being screened. CONCLUSIONS: Risk-based screening strategies are more efficient in reducing lung cancer deaths and gaining life years compared to the status quo strategy. Risk-stratified screening intervals can potentially balance long-term benefit-harm trade-offs and improve the cost-effectiveness of lung cancer screenings.
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Neoplasias Pulmonares , Fumadores , Humanos , Anciano , Análisis Costo-Beneficio , Análisis de Costo-Efectividad , Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Tamizaje Masivo , Años de Vida Ajustados por Calidad de VidaRESUMEN
Transition metal-based catalysts possess high catalytic activity for oxygen evolution reaction (OER). However, the preparation of high-performance OER electrocatalysts using simple strategies with a low cost still faces a major challenge. Herein, this work presents an innovative, in situ-induced preparation of the Fe2O3, FeS, and NiS nanoparticles, supported on carbon blacks (CBs) (denoted as Fe2O3-Fe(Ni)S/C) as a high-efficiency oxygen evolution electrocatalyst by employing biomineralization. Biomineralization, a simple synthesis strategy, demonstrates a huge advantage in controlling the size of the Fe2O3 and Fe(Ni)S nanoparticles, as well as achieving uniform nanoparticle distribution on carbon blacks. It is found that the electrocatalyst Fe2O3-Fe(Ni)S/C-200 shows a good OER electrocatalytic activity with a small loading capacity, and it has a small overpotential and Tafel slope in 1 m KOH solution with values of 264 mV and 42 mV dec-1, respectively, at a current density of 10 mA cm-2. Additionally, it presents good electrochemical stability for over 24 h. The remarkable and robust electrocatalytic performance of Fe2O3-Fe(Ni)S/C-200 is attributed to the synergistic effect of Fe2O3, FeS, and doped-Ni species as well as its distinct 3D spherical structure. This approach indicates the promising applications of biomineralization for the bio-preparation of functional materials and energy conversion.
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BACKGROUND: Natural products are important sources for the discovery of new biopesticides to control the worldwide destructive pests Acyrthosiphon pisum Harris. Here, insecticidal substances were discovered and characterized from the secondary metabolites of the bio-control microorganism Bacillus velezensis strain ZLP-101, as informed by whole-genome sequencing and analysis. RESULTS: The genome was annotated, revealing the presence of four potentially novel gene clusters and eight known secondary metabolite synthetic gene clusters. Crude extracts, prepared through ammonium sulfate precipitation, were used to evaluate the effects of strain ZLP-101 on Acyrthosiphon pisum Harris aphid pests via exposure experiments. The half lethal concentration (LC50) of the crude extract from strain ZLP-101 against aphids was 411.535 mg/L. Preliminary exploration of the insecticidal mechanism revealed that the crude extract affected aphids to a greater extent through gastric poisoning than through contact. Further, the extracts affected enzymatic activities, causing holes to form in internal organs along with deformation, such that normal physiological activities could not be maintained, eventually leading to death. Isolation and purification of extracellular secondary metabolites were conducted in combination with mass spectrometry analysis to further identify the insecticidal components of the crude extracts. A total of 15 insecticidal active compounds were identified including iturins, fengycins, surfactins, and spergualins. Further insecticidal experimentation revealed that surfactin, iturin, and fengycin all exhibited certain aphidicidal activities, and the three exerted synergistic lethal effects. CONCLUSIONS: This study improved the available genomic resources for B. velezensis and serves as a foundation for comprehensive studies of the insecticidal mechanism by Bacillus velezensis ZLP-101 in addition to the active components within biological control strains.
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Áfidos , Bacillus , Insecticidas , Lipopéptidos , Animales , Áfidos/efectos de los fármacos , Bacillus/genética , Bacillus/metabolismo , Lipopéptidos/farmacología , Lipopéptidos/química , Lipopéptidos/metabolismo , Lipopéptidos/aislamiento & purificación , Insecticidas/farmacología , Insecticidas/metabolismo , Insecticidas/química , Familia de Multigenes , Metabolismo Secundario , Control Biológico de Vectores , Secuenciación Completa del Genoma , Genoma Bacteriano/genéticaRESUMEN
Synthetic aperture Ladar (SAL) is an extension of synthetic aperture technology in the optical frequency band. Owing to the short wavelength of lasers, the system has high-resolution, high-data-rate, and refined imaging capabilities, which has potential in high-resolution observation fields such as ground observation and space target observation. However, the short wavelength of lasers also makes SAL severely sensitive to vibrations even on the micron order which cause azimuth defocusing and range cell migration. To address this problem, we establish a de-chirp signal model under vibration environment, and propose a vibration error estimation and compensation method using triangular interferometric signals. According to the symmetrical characteristics of triangular frequency modulated continuous wave (T-FMCW) and the time-frequency information introduced by the azimuthal vibration phase, we use a two-stage interferometry method to estimate instantaneous frequency introduced by the vibration errors that cause range cell migration. For the scenarios without obvious range cell migration, we use a one-stage interferometry method to estimate the instantaneous frequency. Subsequently, we establish a vibration compensation filter using the estimated instantaneous frequency to compensate for the vibration errors. We use two experiments to verify the effectiveness and superiority of the proposed method. The results show that the proposed method effectively eliminates range cell migration and azimuthal phase errors introduced by vibration errors, producing SAL imaging results with higher resolution than the conventional spectral correlation method.
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The implementation of microstructured optical fibers (MOFs) with novel micro-structures and perfect performance is challenging due to the complex fabrication processes. Physics-informed neural networks (PINNs) offer what we believe to be a new approach to solving complex partial differential equations within the virtual fabrication model of MOFs. This study, for what appears to be the first time, integrates the complex partial differential equations and boundary conditions describing the fiber drawing process into the loss function of a neural network. To more accurately solve the free boundary of the fiber's inner and outer diameters, we additionally construct a neural network to describe the free boundary conditions. This model not only captures the evolution of the fiber's inner and outer diameters but also provides the velocity distribution and pressure distribution within the molten glass, thus laying the foundation for a quantitative analysis of capillary collapse. Furthermore, results indicate that the trends in the effects of temperature, feed speed, and draw speed on the fiber drawing process align with actual fabrication conditions, validating the feasibility of the model. The methodology proposed in this study offers what we believe to be a novel approach to simulating the fiber drawing process and holds promise for advancing the practical applications of MOFs.
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Radioresistance is an inevitable obstacle in the clinical treatment of inoperable patients with non-small cell lung cancer (NSCLC). Combining treatment with radiosensitizers may improve the efficacy of radiotherapy. Previously, the quinoline derivative 10E as new exporter of Nur77 has shown superior antitumor activity in hepatocellular carcinoma. Here, we aimed to investigate the radiosensitizing activity and acting mechanisms of 10E. In vitro, A549 and H460 cells were treated with control, ionizing radiation (IR), 10E, and 10E + IR. Cell viability, apoptosis, and cycle were examined using CCK-8 and flow cytometry assays. Protein expression and localization were examined using western blotting and immunofluorescence. Tumor xenograft models were established to evaluate the radiosensitizing effect of 10E in vivo. 10E significantly inhibited cell proliferation and increased their radiosensitivity while reducing level of p-BCRA1, p-DNA-PKs, and 53BP1 involved in the DNA damage repair pathway, indicating that its radiosensitizing activity is closely associated with repressing DNA damage repair. A549 cells showed low level of Nur77 and a low response to IR but 10E-treated A549 cells showed high level of Nur77 indicating that Nur77 is a core radiosensitivity factor and 10E restores the expression of Nur77. Nur77 and Ku80 extranuclear co-localization in the 10E-treated A549 cells suggested that 10E-modulated Nur77 nuclear exportation inhibits DNA damage repair pathways and increases IR-triggered apoptosis. The combination of 10E and IR significantly inhibits tumor growth in a tumor xenograft model. Our findings suggest that 10E acts as a radiosensitizer and that combining 10E with radiotherapy may be a potential strategy for NSCLC treatment.
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Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Neoplasias Pulmonares , Ratones Desnudos , Quinolinas , Fármacos Sensibilizantes a Radiaciones , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Quinolinas/farmacología , Quinolinas/uso terapéutico , Apoptosis/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Bases de Schiff/farmacología , Bases de Schiff/uso terapéutico , Indoles/farmacología , Indoles/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Tolerancia a Radiación/efectos de los fármacosRESUMEN
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC. METHODS: From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients' demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression. FINDINGS: In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307). INTERPRETATION: In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.
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Neoplasias Colorrectales , Calidad de Vida , Humanos , Persona de Mediana Edad , Pueblo Asiatico , China/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/terapia , EscolaridadRESUMEN
Upwelling plays a pivotal role in supplying methylmercury (MeHg) to the upper oceans, contributing to the bioaccumulation of MeHg in the marine food web. However, the influence of the upwelling of Circumpolar Deep Water (CDW), the most voluminous water mass in the Southern Ocean, on the MeHg cycle in the surrounding oceans and marine biota of Antarctica remains unclear. Here, we study the mercury (Hg) isotopes in an ornithogenic sedimentary profile strongly influenced by penguin activity on Ross Island, Antarctica. Results indicate that penguin guano is the primary source of Hg in the sediments, and the mass-independent isotope fractionation of Hg (represented by Δ199Hg) can provide insights on the source of marine MeHg accumulated by penguin. The Δ199Hg in the sediments shows a significant decrease at â¼1550 CE, which is primarily attributed to the enhanced upwelling of CDW that brought more MeHg with lower Δ199Hg from the deeper seawater to the upper ocean. We estimate that the contribution of MeHg from the deeper seawater may reach more than 38% in order to explain the decline in Δ199Hg at â¼1550 CE. Moreover, we found that the intensified upwelling may have increased the MeHg exposure for marine organisms, highlighting the importance of CDW upwelling on the MeHg cycle in Antarctic coastal ecosystems.
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Mercurio , Compuestos de Metilmercurio , Contaminantes Químicos del Agua , Compuestos de Metilmercurio/análisis , Isótopos de Mercurio/análisis , Regiones Antárticas , Ecosistema , Agua , Monitoreo del Ambiente/métodos , Mercurio/análisis , Océanos y Mares , Cadena Alimentaria , Contaminantes Químicos del Agua/análisisRESUMEN
STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the risk factors of tracheostomy and decannulation after cervical spinal cord injury (CSCI) and their epidemiological changes over the past 8 years in Beijing Bo'ai Hospital, China Rehabilitation Research Center (CRRC), China. SETTING: Beijing Bo'ai Hospital, CRRC. METHODS: We reviewed 8 years of patient data (2013.1.1 to 2020.12.31) at CRRC, focusing on those hospitalized and diagnosed with CSCI. We analyzed changes in demographic and clinical data's trends. Logistic regression analysis was used to determine factors impacting tracheostomy and decannulation. RESULTS: Finally, 1641 CSCI patients met the inclusion criteria. Over the past 8 years, the proportion of tracheostomized patients with CSCI was 16.3%, and the proportion of successfully decannulated of tracheostomized patients with TCSCI was 77.9%. We found that Traumatic (OR = 1.8, 95% CI = 1.06, 3.22; p = 0.046), Motor level of injury (C5-C8) (OR = 0.32, 95% CI = -1.91,-0.34; p = 0.005), AIS = A/B/C (OR = 22.7/11.1/4.2, 95% CI = 12.16,42.26/5.74,21.56/2.23,7.89; p < 0.001/p < 0.001/p < 0.001), age > 56 (OR = 1.6, 95% CI = 1.04, 2.32; p = 0.031) were the risk factors for tracheostomy. By analyzing the risk factors of decannulation failure in tracheostomized patients with TCSCI through multivariable logistic regression, statistically significant differences were found in age > 45 (OR = 4.1, 95% CI = 1.44, 11.81; p = 0.008), complete injury (OR = 2.7, 95% CI = 1.26, 5.95; p = 0.011), facet dislocation (OR = 2.8, 95% CI = 1.13,7.07; p = 0.027). CONCLUSIONS: Recent years have witnessed shifts in the epidemiological characteristics of CSCI. Identifying the factors influencing tracheostomy and decannulation in CSCI can aid in improving patient prognosis.
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Médula Cervical , Traumatismos de la Médula Espinal , Traqueostomía , Humanos , Traqueostomía/tendencias , Traqueostomía/estadística & datos numéricos , Traqueostomía/métodos , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/cirugía , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Adulto , Médula Cervical/lesiones , Vértebras Cervicales/lesiones , Vértebras Cervicales/cirugía , Remoción de Dispositivos/tendencias , Anciano , China/epidemiología , Adulto JovenRESUMEN
The present study was carried out to evaluate the effects of dietary vitamin E (VE) or grape seed extract (GSE) on the growth performance and antioxidant function of broilers. Two hundred sixteen broiler chicks were randomly assigned to 3 diets: diet supplemented with oxidized rice bran oil (CN group), CN group with 25 mg/kg VE or 100 mg/kg GSE. Dietary VE or GSE improved the growth performance, reverted the disturbed levels of liver antioxidant enzymes, and reduced liver damage of broilers fed oxidized rice bran oil. The mRNA data showed that supplementation of VE or GSE enhanced the antioxidant capacity of the broiler liver through activation of the Keap1-Nrf2/ARE signaling pathway. The results suggested that VE and GSE can increase weight gain, improve the oxidative status, and alleviate liver injury in broiler chicken fed oxidized rice bran oil.