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AIMS: Despite aggressive treatment, the recurrence of glioma is an inevitable occurrence, leading to unsatisfactory clinical outcomes. A plausible explanation for this phenomenon is the phenotypic alterations that glioma cells undergo aggressive therapies, such as TMZ-therapy. However, the underlying mechanisms behind these changes are not well understood. METHODS: The TMZ chemotherapy resistance model was employed to assess the expression of intercellular adhesion molecule-1 (ICAM1) in both in vitro and in vivo settings. The potential role of ICAM1 in regulating TMZ chemotherapy resistance was investigated through knockout and overexpression techniques. Furthermore, the mechanism underlying ICAM1-mediated TMZ chemotherapy resistance was examined using diverse molecular biological methods, and the lipid raft protein was subsequently isolated to investigate the cellular subcomponents where ICAM1 operates. RESULTS: Acquired TMZ resistant (TMZ-R) glioma models heightened production of intercellular adhesion molecule-1 (ICAM1) in TMZ-R glioma cells. Additionally, we observed a significant suppression of TMZ-R glioma proliferation upon inhibition of ICAM1, which was attributed to the enhanced intracellular accumulation of TMZ. Our findings provide evidence supporting the role of ICAM1, a proinflammatory marker, in promoting the expression of ABCB1 on the cell membrane of TMZ-resistant cells. We have elucidated the mechanistic pathway by which ICAM1 modulates phosphorylated moesin, leading to an increase in ABCB1 expression on the membrane. Furthermore, our research has revealed that the regulation of moesin by ICAM1 was instrumental in facilitating the assembly of ABCB1 exclusively on the lipid raft of the membrane. CONCLUSIONS: Our findings suggest that ICAM1 is an important mediator in TMZ-resistant gliomas and targeting ICAM1 may provide a new strategy for enhancing the efficacy of TMZ therapy against glioma.
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Subfamília B de Transportador de Cassetes de Ligação de ATP , Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos , Glioma , Molécula 1 de Adesão Intercelular , Temozolomida , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/genética , Glioma/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Temozolomida/farmacologia , Linhagem Celular Tumoral , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Camundongos , Microdomínios da Membrana/metabolismo , Microdomínios da Membrana/efeitos dos fármacosRESUMO
Tumor-associated macrophages (TAMs) are key regulators in tumor progression, but the precise role of bone marrow-derived monocytes (Mons) as TAM precursors and their dynamic phenotypes regulated by the tumor microenvironment (TME) remain unclear. Here, we developed an optimized microproteomics workflow to analyze low-cell-number mouse myeloid cells. We sorted TAMs and their corresponding Mons (1 × 105 per sample) from individual melanoma mouse models at both the early and late stages. We established the protein expression profiles for these cells by mass spectrometry. Subsequently, we analyzed the dynamics phenotypes of TAMs and identified a characteristic protein expression profile characterized by upregulated cholesterol metabolism and downregulated immune responses during tumor progression. Moreover, we found the downregulation of both STAT5 and PYCARD expression not only in late-stage TAMs but also in late-stage Mons, indicating a loss of the ability to induce inflammatory responses prior to Mons infiltration into TME. Taken together, our study provides valuable insights into the progression-dependent transitions between TAMs and their precursor cells, as well as the cross-organ communications of tumor and bone marrow.
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Macrófagos , Neoplasias , Camundongos , Animais , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Proteômica , Neoplasias/patologia , Fenótipo , Microambiente Tumoral/genéticaRESUMO
Quantitative glycosylation analysis serves as an effective tool for detecting changes in glycosylation patterns in cancer and various diseases. However, compared with N-glycans, O-glycans present challenges in both qualitative and quantitative mass spectrometry analysis due to their low abundance, ease of peeling, lack of a universal enzyme, and difficult accessibility. To address this challenge, we developed O-GlycoIsoQuant, a novel O-glycome quantitative approach utilizing superbase release and isotopic Girard's P labeling. This method facilitates rapid and efficient nonreducing ß-elimination to dissociate O-glycans from proteins using the organic superbase, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), combined with light and heavy isotopic Girard's reagent P (GP) labeling for relative quantification of O-glycans by mass spectrometry. Employing this method, labeled O-glycans exhibit a double peak with a mass difference of 5 Da, suitable for stable relative quantification. The O-GlycoIsoQuant method is characterized by its high labeling efficiency, excellent reproducibility (CV < 20%), and good linearity (R2 > 0.99), across a dynamic range spanning a 100-fold range. This method was applied to various complex sample types, including human serum, porcine spermatozoa, human saliva, and urinary extracellular vesicles, detecting 33, 39, 49, and 37 O-glycans, respectively, thereby demonstrating its broad applicability.
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Glicômica , Marcação por Isótopo , Polissacarídeos , Polissacarídeos/análise , Polissacarídeos/química , Polissacarídeos/metabolismo , Humanos , Glicômica/métodos , Animais , Glicosilação , Masculino , Espectrometria de MassasRESUMO
BACKGROUND: This study aimed to investigate the relationship between serum testosterone levels and the risk of congestive heart failure (CHF) in adult males. Previous research has suggested a potential link between serum testosterone and cardiovascular health, but the findings have been inconclusive. METHODS: This study was cross-sectional, and the data were obtained from the 2011-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), which included a sample of 6,841 male participants. Serum testosterone levels were measured using a standardized assay, and CHF status was assessed through self-reporting. Covariates such as age, ethnicity, lifestyle factors, and health conditions were considered in the analysis. RESULTS: Among the participants, 242 individuals had a documented history of CHF. We observed a linear correlation between serum testosterone levels and CHF occurrence, with higher serum testosterone levels associated with a decreased risk of CHF (Q4 vs. Q1, OR = 0.29, 95% CI: 0.19-0.47, P < 0.001). After adjusting for confounding variables, multivariate analysis revealed that high serum testosterone levels remained significantly associated with a lower risk of CHF (OR: 0.47, 95% CI: 0.27-0.80, P = 0.01). Subgroup analysis indicated a significant association between high serum testosterone levels and reduced CHF risk in individuals over 50 years old. CONCLUSION: Our findings suggest that the serum testosterone level was positively associated with CHF in adult males. This study highlights the potential role of serum testosterone in cardiovascular health, particularly in older individuals. Further research is needed to elucidate the underlying mechanisms and explore the clinical implications of these findings.
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Insuficiência Cardíaca , Adulto , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de Risco , Estudos Transversais , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , TestosteronaRESUMO
The problems of low polishing efficiency and serious surface damage in the processing of silicon carbide (SiC) ceramics are well-known. In view of the above problems, a new method of photocatalytic vibration composite polishing (PVCP) combined with a compound control strategy was proposed. A vibration-assisted device was developed, and a compound control system was designed for the device to improve the trajectory tracking accuracy. Experiments were carried out to verify the effectiveness of the vibration-assisted device and the compound control system. In addition, methyl orange degradation and fading experiments, redox potential measurement experiments, and SiC ceramic surface hardness characterization experiments were carried out to reveal the effects of vibration and photocatalytic parameters on polishing solution oxidation and SiC ceramic surface mechanical properties. Finally, the effects of photocatalysis, vibration frequency, amplitude, and the compound control system on the polishing effect were analyzed. The results show that when the UV intensity is 100%, the polishing force is 3-4N, the vibration frequency is 400 Hz, the amplitude is 15 µm, and the surface roughness of SiC ceramics is reduced by about 11 nm after the introduction of the compound control system, which verifies the effectiveness of the combination of the compound control system and PVCP.
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BACKGROUND: Suicide was an important cause of death in prostate cancer. This study intended to investigate trends in suicide mortality among prostate cancer (PCa) survivors from 1975 to 2019 in the United States. METHOD: We identified PCa survivors from the Surveillance, Epidemiology, and End Results (SEER) program from January 1975 to December 2019. Standardized mortality rate (SMR) was calculated d to assess the relative risk of suicide in PCa survivors compared with the general men population. Poisson regression model was performed to test for trend of SMRs. The cumulative mortality rate of suicide was calculated to assess the clinical burden of suicide mortality. RESULTS: 7108 (0.2%) cases were death from suicide cause, and 2,308,923(65.04%%) cases recorded as dying from non-suicidal causes. Overall, a slightly higher suicide mortality rate among PCa survivors was observed compared with general male population (SMR: 1.15, 95%CI: 1.09-1.2). The suicide mortality rate declined significantly relative to the general population by the calendar year of diagnosis, from an SMR of 1.74(95%CI: 1.17-2.51) in 1975-1979 to 0.99(0.89-1.1) in 2015-2019 (Ptrend < 0.001). PCa survivors with aged over 84 years, black and other races, registered in registrations (including Utah, New Mexico, and Hawaii) failed to observe a decrease in suicide mortality (Ptrend > 0.05). The cumulative suicide mortality during 1975-1994 was distinctly higher than in 1995-2019(P < 0.001). CONCLUSION: The trend in suicide mortality declined significantly from 1975 to 2019 among PCa survivors compared with the general male population in the United States. Notably, part of PCa survivors had no improvement in suicide mortality, and additional studies in the future were needed to explore it.
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Sobreviventes de Câncer , Neoplasias da Próstata , Suicídio , Humanos , Masculino , Idoso , Próstata , Sobreviventes , HavaíRESUMO
The continuous excessive application of phosphorus (P) fertilizers in intensive agricultural production leads to a large accumulation of P in surface soils, increasing the risk of soil P loss by runoff and leaching. However, there are few studies on the accumulation and loss of P from surface soil to deep soil profiles driven by shallow groundwater table (SGT) fluctuations. This study used the intensive cropland around 7 plateau lakes in Yunnan Province as an example and conducted in situ monitoring of P storage in the soil profile and SGT during the rainy season (RS) and dry season (DS) as well as simulation experiments on soil P loss. The aim was to study the spatiotemporal variation in P accumulation in the soil profile of cropland driven by SGT fluctuations in the RS and DS and estimate the P loss in the soil profile driven by SGT fluctuations. The results showed that fluctuations in the SGT promoted P accumulation from the surface soil to deeper soil. The proportions of P stored in various forms in the 30-60 cm and 60-100 cm soil layers in the RS were greater than those in the DS, while the average proportion in the 0-30 cm soil layer in the DS was as high as 48%. Compared with those in the DS, the maximum decreases in the proportion of P stored as TP and Olsen-P in the 0-100 cm soil layer in the RS were 16% and 58%, respectively, due to the rise in the SGT (SGT <30 cm), while the soil TP storage decreased by only 1% when the SGT was maintained at 60-100 cm. The critical thresholds for soil Olsen-P and TP gradually decreased with increasing soil depth, and the risk of P loss in deeper soil increased. The loss of soil P was increased by fluctuations in the SGT. Based on the cropland area around the 7 plateau lakes, P storage, and SGT fluctuations, the average loss intensity and loss amount of TP in the 0-100 cm soil layer around the 7 plateau lakes were estimated to be 25 kg/ha and 56 t, respectively. Therefore, reducing exogenous P inputs, improving soil endogenous P utilization efficiency and maintaining deep soil P retention are the basic strategies for preventing and controlling P accumulation and loss in deep soil caused by SGT fluctuations.
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Água Subterrânea , Lagos , Fósforo , Solo , Fósforo/análise , Solo/química , China , Água Subterrânea/química , Agricultura , Fertilizantes/análiseRESUMO
Despite impressive advances in the construction of enantioenriched silacarbocycles featuring silicon-stereogenic centers via a selection of well-defined sila-synthons, the development of a more convenient and economic method with readily available starting materials is significantly less explored and remains a considerable challenge. Herein, we report the first example of copper-catalyzed sequential hydrosilylation of readily accessible methylenecyclopropanes (MCPs) and primary silanes, affording an efficient and convenient route to a wide range of chiral silacyclopentanes bearing consecutive silicon- and carbon-stereogenic centers with excellent enantio- and diastereoselectivities (generally ≥98% ee, > 25:1 dr). Mechanistic studies reveal that these reactions combine copper-catalyzed intermolecular ring-opening hydrosilylation of aryl MCPs and intramolecular asymmetric hydrosilylation of the resultant Z/E mixture of homoallylic silanes.
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Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Anemia Aplástica/diagnóstico , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , China/epidemiologia , População do Leste AsiáticoRESUMO
The microstructure, corrosion resistance, and phase-transition process of micro-arc oxidation (MAO) coatings prepared on LaFe11.6Si1.4 alloy surfaces in different electrolyte systems were systematically investigated. Research has demonstrated that various electrolyte systems do not alter the main components of the coatings. However, the synergistic action of Na2CO3 and Na2B4O7 more effectively modulated the ionization and chemical reactions of the MAO process and accelerated the formation of α-Al2O3. Moreover, the addition of Na2CO3 and Na2B4O7 improved the micromorphology of the coating, resulting in a uniform coating thickness and good bonding with the LaFe11.6Si1.4 substrate. The dynamic potential polarization analysis was performed in a three-electrode system consisting of a LaFe11.6Si1.4 working electrode, a saturated calomel reference electrode, and a platinum auxiliary electrode. The results showed that the self-corrosion potential of the LaFe11.6Si1.4 alloy without surface treatment was -0.68 V, with a current density of 8.96 × 10-6 A/cm2. In contrast, the presence of a micro-arc electrolytic oxidation coating significantly improved the corrosion resistance of the LaFe11.6Si1.4 substrate, where the minimum corrosion current density was 1.32 × 10-7 A/cm2 and the corrosion potential was -0.50 V. Similarly, after optimizing the MAO electrolyte with Na2CO3 and Na2B4O7, the corrosion resistance of the material further improved. Simultaneously, the effect of the coatings on the order of the phase transition, latent heat, and temperature is negligible. Therefore, micro-arc oxidation technology based on the in situ growth coating of the material surface effectively improves the working life and stability of La(Fe, Si)13 materials in the refrigeration cycle, which is an excellent alternative as a protection technology to promote the practical process of magnetic refrigeration technology.
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Background: Studies have shown that glucocorticoid receptor (GR) has inconsistent effects on the proliferation of prostate cancer cells, we found dexamethasone inhibited the proliferation of androgen receptor-negative prostate cancer cells, but the underlying mechanisms remain to be illustrated. Methods: GR expression and its prognosis role were analyzed based on the TCGA dataset. Bioinformatic analysis was performed to identify the candidate of GR downstream, which includes FOXO3a. After overexpressing FOXO3a in PC-3 cells, cell counting kit-8 (CCK-8) and migration assays were performed to evaluate cell proliferation and migration ability. Regulation of FOXO3a on GAS5 was also analyzed by JASPAR and PCR. Results: GR had low expression in prostate cancer and predicted poor prognosis. FOXO3a was identified as the downstream of GR to inhibit the proliferation of prostate cancer cells. Moreover, FOXO3a directly induces GAS5 expression, forming the GR-FOXO3a-GAS5 signaling pathway. Conclusion: Our study showed that GR played a role as a tumor suppressor gene in androgen receptor-negative prostate cancer cells via the GR-FOXO3a-GAS5 axis. Our results suggested patients with prostate cancer should be classified and develop a treatment plan according to the expression of AR and GR.
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Background: COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated. Methods: We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases. Results: We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan. Conclusion: This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.
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COVID-19 , Carcinoma de Células Renais , Neoplasias Renais , Humanos , COVID-19/genética , SARS-CoV-2/genética , Carcinoma de Células Renais/genética , Reprodutibilidade dos Testes , Neoplasias Renais/genética , RimRESUMO
Although cobalt nitride (CoN)-based nanomaterials have been widely designed as advanced oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and oxygen reduction reaction (ORR) catalysts, the continuous consumption of lithium-ion batteries (LIBs) has led to a high price of cobalt metal. Therefore, in the future, recycling valuable Co elements from spent devices and boosting their service efficiency will inevitably promote the utilization of Co-based materials in water splitting and zinc-air batteries (ZABs). Herein, we realize the Co recycling from spent LIBs by a simple hydrometallurgy method. Under the assistance of hexamethylenetetramine and polystyrene spheres, after the hydrothermal and pyrolysis treatment in the NH3 atmosphere, the as-reclaimed cobalt oxalates were successfully transformed into novel three-dimensional (3D) CoN nanoflowers (denoted as CoN NFs). Benefiting from the unique 3D flower-like architectures, intrinsic high conductivity, large surface area, uniformly dispersed CoN nanoparticles, and the synergistic effect between Co3N and CoO phases, the 3D flower-like CoN NFs exhibited excellent OER catalytic activity. The performance was much better than commercial RuO2 in the 1.0 M KOH solution. Furthermore, the CoN NFs-based water splitting cell needed a voltage of 1.608 V to achieve the current density of 10 mA cm-2, which is even 16 mV smaller than that of Pt/C||RuO2 benchmark (1.624 V). Meanwhile, the CoN NFs-derived ZAB exhibited a high peak power density of 107.3 mW cm-2 (vs. 103.2 mW cm-2 of Pt/C-RuO2-based ZAB) and a low charge-discharge voltage gap (0.93 V vs. 1.43 V of Pt/C-RuO2-based ZAB). Due to the excellent structural and elemental stabilities, the corresponding water splitting cell and ZAB had outstanding durability. This work successfully explored an advanced industrial chain from recycling Co metal in spent devices to designing the high-efficiency HER/OER/ORR electrocatalysts for advanced water splitting devices and ZABs. This will further promote the value-added utilization of valuable Co metal in various energy storage or conversion devices.
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Background: CSMD2 has been reported as a potential prognostic factor in several cancers. However, whether CSMD2 affects bladder cancer (BC) remains unclear. Methods: Public data were obtained from the TCGA (https://cancergenome.nih.gov) databases. CSMD2expression and its prognostic value were analyzed using bioinformatics methods. CSMD2 mRNA level in patients with BC and BC cell lines was evaluated via quantitative reverse transcriptase polymerase chain reaction. CSMD2 protein level in patients with BC was evaluated via immunohistochemistry. BC cell lines T24 and UMUC-3 were selected for loss-of-function assays targeting CSMD2. Cell viability was determined by CCK8 and clone formation experiments. Cell migration and invasion were evaluated using Transwell assays. Furthermore, the transcriptome of UMUC-3 with CSMD2 knockdown was sequenced to analyze potential signaling network pathways. Finally, the TIMER2.0 database was employed to identify the correlation between CSMD2 and immune cells in the tumor microenvironment. Results: CSMD2 expression was up-regulated in BC tissues compared to adjacent tissues. High CSMD2 expression was associated with poor survival and could serve as an independent predictor for survival in patients with BC. Furthermore, down-regulation of CSMD2 notably restrained the viability, migration, and invasion abilities of T24 and UMUC-3 cells. Moreover, transcriptomic sequencing after CSMD2 knockdown in UMUC-3 cells revealed its involvement in the regulation of the malignant phenotype in BC. Finally, public databases suggest a connection between CSMD2 and immune cell infiltration in BC. Conclusions: These findings suggest that CSMD2 may promote proliferation and tumorigenicity, and could represent a potential target for improving the prognosis of BC.
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Background: Studies have shown that the stimulator of interferon genes (STING) is critical in tumorigenesis, and development. This study aimed to investigate the immune profile and prognostic significance of STING-mediated immune senescence in bladder cancer (BLCA). Methods: We identified differential genes between tumor and normal tissue based on the Cancer Genome Atlas database, and used consensus clustering to identify BLCA subtypes. The genes most associated with overall survival were screened by further analysis and used to construct risk models. Then, comparing the immune microenvironment, tumor mutational load (TMB), and microsatellite instability (MSI) scores between different risk groups. Eventually, a nomogram was constructed based on clinical information and risk scores. The model was validated using receiver operating curves (ROC) and calibration plots. Results: We identified 160 differential genes, including 13 genes most associated with prognosis. Three subtypes of bladder cancer with different clinical and immunological features were identified. Immunotherapy was more likely to benefit the low-risk group, which had higher TMB and MSI scores. The nomogram was found to be highly predictive based on ROC analysis and calibration plots. Conclusion: The risk model and nomogram not only predict the prognosis of BLCA patients but also can guide the treatment.
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BACKGROUND: Mucopolysaccharidosis type I (MPS-I) is a rare autosomal recessive genetic lysosomal storage disorder that is caused by pathogenic variants of the α-L-iduronidase (IDUA) gene. This study aimed to identify the genetic causes of MPS-I in a Chinese patient and construct a minigene of IDUA to analyze its variants upon splicing. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the potential causative variants. Single-nucleotide polymorphism (SNP) array was subsequently performed to confirm uniparental disomy (UPD). Minigene assay was performed to analyze the effect on splicing of mRNA. We meanwhile explored the conservative analysis and protein homology simulation. RESULTS: A novel homozygous splicing mutation of IDUA, c.159-9T>A, was identified in an individual presenting with overlapping features of MPS-I. Interestingly, only the father and sisters, but not the mother, carried the variant in a heterozygous state. WES and SNP array analyses validated paternal UPD on chromosome 4. Minigene splicing revealed two aberrant splicing events: exon 2 skipping and intron 1 retention. Moreover, the specific structure of the mutant protein obviously changed according to the results of the homologous model. CONCLUSIONS: This study describes a rare autosomal recessive disorder with paternal UPD of chromosome 4 leading to the homozygosity of the IDUA splicing variant in patients with MPS-I for the first time. This study expands the variant spectrum of IDUA and provides insights into the splicing system, facilitating its enhanced diagnosis and treatment.
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Cromossomos Humanos Par 4 , Homozigoto , Iduronidase , Mucopolissacaridose I , Splicing de RNA , Dissomia Uniparental , Humanos , Dissomia Uniparental/genética , Dissomia Uniparental/patologia , Iduronidase/genética , Mucopolissacaridose I/genética , Mucopolissacaridose I/patologia , Masculino , Cromossomos Humanos Par 4/genética , Feminino , Polimorfismo de Nucleotídeo Único , Mutação , População do Leste AsiáticoRESUMO
Increasing dissolved organic carbon (DOC) in groundwater as a carbon source for microorganisms that stimulate nitrate attenuation is considered a sustainable strategy to mitigate nitrate pollution in groundwater. However, little is known on the stoichiometric ratio of DOC and nitrate required in groundwater nitrate reduction processes, which has become an obstacle for evaluating the current status of DOC limitations on nitrate reduction. Here, the NO3--N and DOC concentrations in groundwater around 8 plateau lakes were investigated, and a microcosm experiment was performed to elucidate the effects of different DOC:NO3--N levels in groundwater on NO3--N reduction, and the current status of DOC limitations on groundwater NO3--N reduction around 8 lakes was further evaluated. The results indicated that nearly 41 % of the groundwater NO3--N concentrations exceeded the WHO threshold for drinking water (11.3 mg L-1) and 79 % of the groundwater DOC concentrations exceeded 5 mg L-1. The differences in groundwater NO3--N and DOC concentrations among the 8 lakes were controlled by the intensity of agricultural and human activities and hydrogeological background. The stoichiometric ratio of DOC:NO3--N regulated the NO3--N reduction process, and groundwater NO3--N accumulation rate appeared to become limited and sharply decreased when the DOC concentration was approximately 10 mg L-1 or when the DOC:NO3--N ratio was close to 1:1, and the DOC:NO3--N ratio threshold for limiting the NO3--N reduction process was approximately 2.25. Based on this threshold, >33 %-86 % of the groundwater samples around the 8 plateau lakes were strongly limited in the reduction of groundwater NO3--N due to a lack of sufficient DOC provides energy for heterotrophic microorganisms. Additionally, we highlight that the sustainable strategy of increasing DOC to stimulate groundwater NO3- attenuation should be combined with short-term strategies to jointly coordinate and control groundwater NO3- pollution.
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The key role of RNA-binding proteins (RBPs) in posttranscriptional regulation of gene expression is intimately tied to their subcellular localization. Here, we show a subcellular-specific RNA labeling method for efficient enrichment and deep profiling of nuclear and cytoplasmic RBPs. A total of 1221 nuclear RBPs and 1333 cytoplasmic RBPs were enriched and identified using nuclear/cytoplasm targeting enrichment probes, representing an increase of 54.4% and 85.7% compared with previous reports. The probes were further applied in the omics-level investigation of subcellular-specific RBP-RNA interactions upon ferroptosis induction. Interestingly, large-scale RBPs display enhanced interaction with RNAs in nucleus but reduced association with RNAs in cytoplasm during ferroptosis process. Furthermore, we discovered dozens of nucleoplasmic translocation candidate RBPs upon ferroptosis induction and validated representative ones by immunofluorescence imaging. The enrichment of Tricarboxylic acid cycle in the translocation candidate RBPs may provide insights for investigating their possible roles in ferroptosis induced metabolism dysregulation.
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Ferroptose , Proteoma , Proteoma/metabolismo , Ferroptose/genética , RNA/genética , RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Citoplasma/metabolismoRESUMO
The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients. We conducted a cross-sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high-density lipoprotein cholesterol (HDL-C) levels increased with age. In the CKD and non-CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non-CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = -0.002, p < 0.001). HDL-C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle-aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL-C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression.
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HDL-Colesterol , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Insuficiência Renal Crônica/sangue , Estudos Transversais , HDL-Colesterol/sangue , Lipídeos/sangue , Triglicerídeos/sangue , Taxa de Filtração Glomerular , Dislipidemias/sangue , Colesterol/sangueRESUMO
PURPOSE: To investigate the computed tomography (CT) characteristics of air-containing space and its specific patterns in neoplastic and non-neoplastic ground glass nodules (GGNs) for clarifying their significance in differential diagnosis. MATERIALS AND METHODS: From January 2015 to October 2022, 1328 patients with 1,350 neoplastic GGNs and 462 patients with 465 non-neoplastic GGNs were retrospectively enrolled. Their clinical and CT data were analyzed and compared with emphasis on revealing the differences of air-containing space and its specific patterns (air bronchogram and bubble-like lucency [BLL]) between neoplastic and non-neoplastic GGNs and their significance in differentiating them. RESULTS: Compared with patients with non-neoplastic GGNs, female was more common (P < 0.001) and lesions were larger (P < 0.001) in those with neoplastic ones. Air bronchogram (30.1% vs. 17.2%), and BLL (13.0% vs. 2.6%) were all more frequent in neoplastic GGNs than in non-neoplastic ones (each P < 0.001), and the BLL had the highest specificity (93.6%) in differentiation. Among neoplastic GGNs, the BLL was more frequently detected in the larger (14.9 ± 6.0 mm vs. 11.4 ± 4.9 mm, P < 0.001) and part-solid (15.3% vs. 10.7%, P = 0.011) ones, and its incidence significantly increased along with the invasiveness (9.5-18.0%, P = 0.001), whereas no significant correlation was observed between the occurrence of BLL and lesion size, attenuation, or invasiveness. CONCLUSION: The air containing space and its specific patterns are of great value in differentiating GGNs, while BLL is a more specific and independent sign of neoplasms.