RESUMO
BACKGROUND: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15%-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. MATERIALS AND METHODS: The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. RESULTS: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. CONCLUSION: In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.
RESUMO
BACKGROUND: Injuries are a leading cause of death in the United States. Trauma systems aim to ensure all injured patients receive appropriate care. Hospitals that participate in a trauma system, trauma centers (TCs), are designated with different levels according to guidelines that dictate access to medical and research resources but not specific surgical care. This study aimed to identify patterns of injury care that distinguish different TCs and hospitals without trauma designation, non-trauma centers (non-TCs). STUDY DESIGN: We extracted hospital-level features from the state inpatient hospital discharge data in Washington state, including all TCs and non-TCs, in 2016. We provided summary statistics and tested the differences of each feature across the TC/non-TC levels. We then conducted 3 sets of unsupervised clustering analyses using the Partition Around Medoids method to determine which hospitals had similar features. Set 1 and 2 included hospital surgical care (volume or distribution) features and other features (e.g., the average age of patients, payer mix, etc.). Set 3 explored surgical care without additional features. RESULTS: The clusters only partially aligned with the TC designations. Set 1 found the volume and variation of surgical care distinguished the hospitals, while in Set 2 orthopedic procedures and other features such as age, social vulnerability indices, and payer types drove the clusters. Set 3 results showed that procedure volume rather than the relative proportions of procedures aligned more, though not completely, with TC designation. CONCLUSION: Unsupervised machine learning identified surgical care delivery patterns that explained variation beyond level designation. This research provides insights into how systems leaders could optimize the level allocation for TCs/non-TCs in a mature trauma system by better understanding the distribution of care in the system.
Assuntos
Centros de Traumatologia , Humanos , Centros de Traumatologia/estatística & dados numéricos , Análise por Conglomerados , Washington , Hospitais/estatística & dados numéricos , Ferimentos e Lesões/cirurgia , Ferimentos e Lesões/epidemiologia , Feminino , MasculinoRESUMO
Purpose: This study aims to explore the association of inflammatory markers such as the Systemic Immune-Inflammatory Index (SII) and LANR with the comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and lung cancer. Patients and Methods: A cross-sectional analysis was conducted on the clinical data of 309 patients with COPD only and 193 patients with COPD and lung cancer who attended the First Affiliated Hospital of Anhui Medical University. Additionally, we examined autonomous risk factors that contribute to the simultaneous development of COPD and lung cancer through univariate and multivariate logistic regression analyses. This analysis resulted in the development of a nomogram model for visual representation. The effectiveness of the model was assessed using a receiver operating characteristic (ROC) curve, calibration curve, and clinical decision analysis (DCA) curve, with internal validation conducted via repeated sampling methods. Results: Multivariate analysis of clinical characteristics and inflammatory markers showed that smoking history of >60 pack-years, hemoptysis, emphysema, WBC count > 5.53 (×10^9/L), SII > 629.285, and LANR < 11.39 were significantly associated with the comorbidity of COPD and lung cancer. These factors were subsequently integrated into the nomogram model. The AUC of the model stood at 0.849 (95% CI: 0.815-0.882), demonstrating a notable improvement over the COPD-LUCSS scoring system (AUC: 0.716, 95% CI: 0.671-0.761). The DCA curve indicated a notable clinical advantage provided by the model. Additionally, patients with stage IV tumors exhibited elevated SII levels and reduced LANR levels compared to earlier stages, indicating potential prognostic significance for both markers. Conclusion: Increased levels of the inflammatory markers SII and LANR are associated with the risk of comorbidity of COPD and lung cancer.
RESUMO
The Body Talk Scale (BTS) measures both negative body talk (including fat talk and muscle talk) and positive body talk across genders. In this study, we translated it into Chinese and assessed its structure, reliability and validity among mainland Chinese residents. Item analyses indicated that no item deletion was necessary for this study, and both exploratory factor analysis (n = 1853) and exploratory graph analysis (n = 1583) supported the three-factor structure of the original scale. Confirmatory factor analysis showed that the scale had a good model fit with CFI= 0.95, GFI= 0.93, TLI= 0.94, and RMSEA= 0.079(90 %CI [0.075, 0.084]). The results also showed that the Chinese version of the BTS had adequate criterion-related validityï¼internal consistency and six-week test-retest reliability. Meanwhile, the scale has good measurement invariance with respect to gender and can be tested for gender differences. In conclusion, the BTS showed sufficient psychometric properties in a Chinese sample, making it a valid instrument for studying body talk and health status in Chinese populations.
RESUMO
In engineered photonic lattices, topological photonic (TP) modes present a promising avenue for designing waveguides with suppressed backscattering. However, the integration of the TP modes in electromagnetic systems has faced longstanding challenges. The primary obstacle is the insufficient development of high-efficiency coupling technologies between the TP modes and the conventional transmission modes. This dilemma leads to significant scattering at waveguide terminals when attempting to connect the TP waveguides with other waveguides. In this study, a topological photonic substrate-integrated waveguide (TPSIW) is proposed that can seamlessly integrate into traditional microstrip line systems. It successfully addresses the matching problem and demonstrates efficient coupling of both even and odd TP modes with the quasi-transverse electromagnetic modes of microstrip lines, resulting in minimal energy losses. In addition, topological leaky states are introduced through designed slots on the TPSIW top surface. These slots enable the creation of TP leaky-wave antennas with beam steering capabilities. A wireless link based on TPSIWs are further established that enables the transmission of distinct signals toward different directions. This work is an important step toward the integration of TP modes in microwave systems, unlocking the possibilities for the development of high-performance wireless devices.
RESUMO
Valosin-containing protein (VCP), an ATPase-associated protein, is emerging as a crucial regulator in cardiac pathologies. However, the pivotal role of VCP in the heart under physiological conditions remains undetermined. In this study, we tested a hypothesis that sufficient VCP expression is required for cardiac development and physiological cardiac function. Thus, we generated a cardiac-specific VCP knockout (KO) mouse model and assessed the consequences of VCP suppression on the heart through physiological and molecular studies at baseline. Our results reveal that homozygous KO mice are embryonically lethal, whereas heterozygous KO mice with a reduction in VCP by ~40% in the heart are viable at birth but progressively develop heart failure and succumb to mortality at the age of 10 to 12 months. The suppression of VCP induced a selective activation of the mammalian target of rapamycin complex 1 (mTORC1) but not mTORC2 at the early age of 12 weeks. The prolonged suppression of VCP increased the expression (by ~2 folds) and nuclear translocation (by >4 folds) of protein phosphatase 1 (PP1), a key mediator of protein dephosphorylation, accompanied by a remarked reduction (~80%) in AKTSer473 phosphorylation in VCP KO mouse hearts at a later age but not the early stage. These temporal molecular alterations were highly associated with the progressive decline in cardiac function. Overall, our findings shed light on the essential role of VCP in the heart under physiological conditions, providing new insights into molecular mechanisms in the development of heart failure.
Assuntos
Insuficiência Cardíaca , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos Knockout , Proteína Fosfatase 1 , Proteína com Valosina , Animais , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Proteína com Valosina/metabolismo , Proteína com Valosina/genética , Camundongos , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 1/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/genética , Miocárdio/metabolismo , Miocárdio/patologia , Masculino , Modelos Animais de DoençasRESUMO
The retention of coal fines in propped fractures impedes the efficient flow of gas and water, leading to a substantial decrease in coal seam permeability and gas production efficiency. In this article, a coal fine plugging removal agent with good dispersion stability and powerful powder-carrying capacity was developed to study the coal fine plugging removal and permeability enhancement in the propped fracture. The results show that 0.8% SDS + 0.4% NaCl + 0.8% BS-12 was the most effective coal fine plugging removal agent compounding system. Increasing the injection rate of the plugging removal agent and performing recycles of intermittent unblocking when it was used as a plugging agent will effectively enhance the gas-liquid two-phase effective permeability of propped fractures and improve the release of retained coal fines. After three recycles of intermittent unblocking, the coal fine discharging rate can be increased to more than 90%, resulting in a 3.88 times increase of the gas-liquid two-phase permeability compared to that with the single unblocking cycle. This method has important practical significance and theoretical value for solving the problem of coal fine plugging in fractures and ensuring the stable and efficient discharge of coalbed gas-water-coal fines.
RESUMO
Microplastics generated from fragmentation of leftover plastics and industrial waste has reached in the remotely located Asian water tower (AWT) region, the 3rd pole of earth and origin site of several freshwater rivers. The accumulation of microplastics in AWT ecosystem has potential to alter the climatic condition contributing in global warming and disturbing the biodiversity structural dynamics. The present paper provides a comprehensive critical discussion over quantitative assessment of microplastics in different ecosystems (i.e. river, lakes, sediment and snow or glacier) of AWT. The hydrodynamic fate and transport of microplastics and their ecological impact on hydromorphology and biodiversity of AWT has been exemplified. Furthermore, key challenges, perspectives and research directions are identified to mitigate microplastics associated problems. During survey, the coloured polyethylene and polyurethane fibers are the predominant microplastics found in most areas of AWT. These bio-accumulated MPs alter the rhizospheric community structure and deteriorate nitrogen fixation process in plants. Significance in climate change, MPs pollution is enhancing the emissions of greenhouse gases (NH3 by â¼34% and CH4 by â¼9%), contributing in global warming. Considering the seriousness of MPs pollution, this review study can enlighten the pathways to investigate the effect of MPs and to develop monitoring tools and sustainable remediation technologies with feasible regulatory strategies maintaining the natural significance of AWT region.
Assuntos
Monitoramento Ambiental , Microplásticos , Poluentes Químicos da Água , Microplásticos/análise , Poluentes Químicos da Água/análise , Ásia , Rios/química , Ecossistema , Mudança Climática , Recuperação e Remediação Ambiental/métodos , Plásticos/análiseRESUMO
A functionalization process has been developed and the experimental conditions optimized allowing the immobilization of first-row transition metal (Mn+) containing polyoxometalates (POMs) with the formula [M(H2O)P2W17O61](10-n)- on transparent indium-tin oxide (ITO) electrodes for electrochromic applications. Both flat ITO grafted with 4-sulfophenyl moieties and sulfonate-functionalized vertically oriented silica films on ITO have been used as electrode supports to evaluate possible confinement effects provided by the mesoporous matrix on the stability of the modified surfaces and their electrochromic properties. Functionalization involved a two-step sequential process: (i) the immobilization of hexaaqua metallic ions, such as Fe(H2O)63+, onto the sulfonate-functionalized materials achieved through hydrogen bonding interactions between the sulfonate functions and aqua ligands (water molecules) coordinated to the metallic ions facilitating and stabilizing the attachment of the metallic ions to the sulfonated surfaces; (ii) their coordination to [P2W17O61]10- species to generate "in situ" the target [Fe(H2O)P2W17O61]7- moieties. Comparison of the characterized surfaces clearly evidenced a significant improvement in the long-term stability of the nanostructured [Fe(H2O)P2W17O61]7--functionalized silica films compared to the less constrained flat [Fe(H2O)P2W17O61]7--modified ITO electrodes for which a rapid loss of [P2W17O61]10- species was observed. Concordantly, the [Fe(H2O)P2W17O61]7- POM confined in the mesoporous films coated on ITO gave rise to much better and stable electrochromic properties, with a transmittance modulation of 40% at 515 nm.
RESUMO
Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.
RESUMO
The capacity of microplastics to harbor and propagate bacteria has been the focus of attention over the last decade. Such microplastic-supported bacterial colonization behavior in the municipal sewer system could be a critical ecological link influencing the biogeochemical activities and risks in receiving waters in urban areas, given the alarming microplastic loads discharged there. This study conducted a large-scale survey covering a wide range of residential and industrial catchments in Shanghai, China. We aimed to assess the microplastic prevalence and bacterial colonization patterns in different sewer habitats and to explore the role of land use, stratified wastewater and sediment, and microplastic attributes in shaping the patterns. We found that the sewer system formed a temporal but pronounced microplastic pool, with land use playing a significant role in the variability of microplastic prevalence. Industrial sewers contained a high abundance of microplastics with large particle sizes, diverse polymer compositions, and shapes. However, while there was a spatial discrepancy between urban and suburban areas in the abundance of microplastics in residential sewers, their predominant polymer and shape types were simple, i.e., polyethylene terephthalate (PET) and fibers. Sewer habitat characteristics, particularly the stratified wastewater and sediment determined microbial colonization patterns. The latter acted as a long-term sink for microplastics and supported the high growth of colonizers. In contrast, the wastewater plastisphere presented novel niches, hosting communities with a marked proportion of unique bacterial genera after colonization. Besides, statistics showed a highly positive and dense co-occurrence network of the plastisphere communities, especially those from the industrial sewer sediment, with enhanced metabolic activity, cellular processes and systems, and increased human pathogenic potential. Findings indicated a coarse and uncertain effect of the selective pressure of microplastic attributes on plastisphere community structure differentiation.
Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Plásticos , Águas Residuárias , Prevalência , Poluentes Químicos da Água/análise , China , Ecossistema , Bactérias , Monitoramento AmbientalRESUMO
Deep Brain Stimulation (DBS) is an experimental treatment for medication-refractory neuropathic pain. The ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei of the thalamus are popular targets for the treatment of facial and limb pain, respectively. While intraoperative testing is used to adjust targeting of patient-specific pain locations, a better understanding of thalamic somatotopy may improve targeting of specific body regions including the individual trigeminal territories, face, arm, and leg. To elucidate the somatotopic organization of the ventral nuclear group of the dorsal thalamus using in vivo macrostimulation data from patients undergoing DBS for refractory neuropathic pain. In vivo macrostimulation data was retrospectively collected for 14 patients who underwent DBS implantation for neuropathic pain syndromes at our institution. 56 contacts from 14 electrodes reconstructed with LeadDBS were assigned to macrostimulation-related body regions: tongue, face, arm, or leg. 33 contacts from 9 electrodes were similarly assigned to one of three trigeminal territories: V1, V2, or V3. MNI coordinates in the x, y, and z axes were compared by using MANOVA. Across the horizontal plane of the ventral nuclear group of the dorsal thalamus, the tongue was represented significantly medially, followed by the face, arm, and leg most laterally (p < 0.001). The trigeminal territories displayed significant mediolateral distribution, proceeding from V1 and V2 most medial to V3 most lateral (p < 0.001). Along the y-axis, V2 was also significantly anterior to V3 (p = 0.014). While our results showed that the ventral nuclear group of the dorsal thalamus displayed mediolateral somatotopy of the tongue, face, arm, and leg mirroring the cortical homunculus, the mediolateral distribution of trigeminal territories did not mirror the established cortical homunculus. This finding suggests that the facial homunculus may be inverted in the ventral nuclear group of the dorsal thalamus.
Assuntos
Estimulação Encefálica Profunda , Neuralgia , Humanos , Núcleos Ventrais do Tálamo , Estimulação Encefálica Profunda/métodos , Estudos Retrospectivos , Tálamo/fisiologia , Neuralgia/terapiaRESUMO
Uridine-disphosphate glucuronosyltransferase 1A9 (UGT1A9), an important detoxification and inactivation enzyme for toxicants, regulates the exposure level of environmental pollutants in the human body and induces various toxicological consequences. However, an effective tool for high-throughput monitoring of UGT1A9 function under exposure to environmental pollutants is still lacking. In this study, 1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one (DDAO) was found to exhibit excellent specificity and high affinity towards human UGT1A9. Remarkable changes in absorption and fluorescence signals after reacting with UGT1A9 were observed, due to the intramolecular charge transfer (ICT) mechanism. Importantly, DDAO was successfully applied to monitor the biological functions of UGT1A9 in response to environmental pollutant exposure not only in microsome samples, but also in living cells by using a high-throughput screening method. Meanwhile, the identified pollutants that disturb UGT1A9 functions were found to significantly influence the exposure level and retention time of bisphenol S/bisphenol A in living cells. Furthermore, the molecular mechanism underlying the inhibition of UGT1A9 by these pollutant-derived disruptors was elucidated by molecular docking and molecular dynamics simulations. Collectively, a fluorescent probe to characterize the responses of UGT1A9 towards environmental pollutants was developed, which was beneficial for elucidating the health hazards of environmental pollutants from a new perspective.
Assuntos
Dimetilaminas , Poluentes Ambientais , Glucuronosiltransferase , Humanos , Corantes Fluorescentes , Uridina , Simulação de Acoplamento MolecularRESUMO
The aim of this study was to identify Artemis as a predictive biomarker for guiding preoperative chemoradiotherapy in locally advanced rectal cancer. The resection specimens were collected from 50 patients with rectal cancer who underwent preoperative chemoradiotherapy. Artemis expression in biopsy tissues was evaluated using immunohistochemical staining according to the percentage of positively stained cells combined with staining intensity. Among the 50 patients, 36 (72%) had a weakly positive Artemis protein expression, 10 (20%) had a moderately positive expression, and 4 (8%) showed a strongly positive expression. The criteria of magnetic resonance imaging tumor regression grade (mrTRG) and pathological rectal cancer regression grade (RCRG) were used to assess the tumor response to chemoradiotherapy. Correlation analysis shows that there is a significant negative correlation between high Artemis immunoscore and treatment response (r = -0.532, p < 0.001). The results imply that high Artemis expression was associated with poor treatment response. Our study suggested a potential role of Artemis as a predictive biomarker of the tumor response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.
Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Biópsia , Biomarcadores , QuimiorradioterapiaRESUMO
BACKGROUND: Computed tomography angiography (CTA) is a reliable, non-invasive screening method for diagnosing panvascular disease. By using low contrast agent volume, CTA imaging enables one-stop multi-organ scanning, thereby minimizing the potential risk of contrast-induced nephropathy in patients with impaired renal function. PURPOSE: To evaluate the feasibility of one-stop CTA following a heart rate (HR)-based protocol using a low volume of contrast medium (CM) for examination of the coronary, carotid and cerebrovascular arteries. MATERIAL AND METHODS: Sixty patients undergoing coronary carotid, and cerebrovascular CTA after a single injection of CM were recruited and randomly divided into two groups. Group A (n = 30) underwent CTA following a traditional protocol. The timing of the scans in Group B (n = 30) was determined according to the patient's HR. RESULTS: The CT values for the thoracic aorta (432.2 ± 104.28â HU), anterior cerebral artery (303.96 ± 99.29â HU), and right coronary artery (366.70 ± 85.10â HU) in Group A did not differ significantly from those in Group B (445.80 ± 106.13, 293.73 ± 75.25 and 344.13 ± 111.04â HU, respectively). The qualities of most of the scanned images for both groups were scored as 3 or 4 (on a five-point scale). The radiation dose and the volume of CM were significantly higher in Group A (303.05 ± 110.95â mGy) (100â mL) than in Group B (239.46 ± 101.12â mGy) (50â mL). CONCLUSION: The radiation dose and volume of CM were significantly reduced in CTA following the HR-based protocol. The personalized administration of CM also simplified the scanning process.
Assuntos
Angiografia por Tomografia Computadorizada , Meios de Contraste , Humanos , Angiografia por Tomografia Computadorizada/métodos , Frequência Cardíaca , Tomografia Computadorizada por Raios X/métodos , Artérias Carótidas , Doses de Radiação , Angiografia Coronária/métodosRESUMO
PURPOSE: To investigate the effect of inflammation-based indexes in predicting radiation pneumonitis (RP) and prognosis in lung tumor patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: The data of one hundred and seventy-two patients with 272 lung lesions from November 2015 to December 2020 were retrospectively analyzed. Pretreatment hematological indexes including platelet count, neutrophil count, and lymphocyte count were collected before treatment. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated. The receiver operating characteristic (ROC) curve was established to predict the RP and overall survival of patients, and the Youden index was calculated to determine the cutoff values of SII, NLR, and PLR before radiotherapy. RESULTS: Pretreatment SII, NLR, and PLR could predict RP in lung tumor patients treated with SBRT, the optimal cutoff values of SII, NLR, and PLR were 355.38, 2.04, and 141.09, respectively. Pretreatment PLR could predict survival and the optimal cutoff value of PLR was 166.83, patients with a PLR > 166.83 predict worse overall survival (OS) (P < 0.001). The 1-year and 2-year OS for patients with a PLR ≤ 166.83 were 96.3% and 82.4%, while for those with a PLR > 166.83 were 82.0% and 58.5%, respectively. CONCLUSION: In lung tumor patients treated with SBRT, pretreatment SII, NLR, and PLR can effectively predict RP and a higher PLR predicts poor OS. These inflammation-based indexes could serve as reliable and convenient predictors to guide treatment for physicians in clinical practice.
Assuntos
Lesão Pulmonar , Neoplasias Pulmonares , Radiocirurgia , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Prognóstico , Inflamação , Pulmão/patologiaRESUMO
BACKGROUND: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT. PURPOSE: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (seven female; mean age, 60.9 years). FIELD STRENGTH/SEQUENCE: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence. ASSESSMENT: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated. STATISTICAL TESTS: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05. RESULTS: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT. DATA CONCLUSION: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
Assuntos
Neoplasias Encefálicas , Disfunção Cognitiva , Humanos , Feminino , Pessoa de Meia-Idade , Neuritos/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Estudos Prospectivos , Irradiação Craniana , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologiaRESUMO
Dissolved organic matter (DOM) is an essential component of river pollutants. Under the new situation of black water treatment in urban areas of China, in view of the widespread problem of unclear sources of multiple pollutants, further analysis of DOM components in urban rivers from the molecular level is a key link to deeply explore the sources, causes, and mechanism of river pollution so as to achieve efficient management. In this study, the urban rivers in the central city were selected as the research object, and a total of five rivers were selected that were seriously affected by the discharge sewage of four combined and separated sewer systems, respectively. Using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), this study identified the molecular formulae and analyzed the elemental composition and compound groups of DOM in water and sediment samples at each site in dry and wet weather. The results showed that:â although CHO molecules and lignins were the main compounds in the urban river DOM, the high proportion of lipids, proteins, and heteroatomic compounds (especially CHOS molecules) revealed the anthropogenic pollution in rivers, which also led to the increase in DOC, TN, and NH+4-N. â¡Surfactants such as C17H28O3S and C18H30O3S were ubiquitous in all urban rivers, which could be used as markers of domestic wastewater pollution. â¢In wet weather, the rainfall inputs, storm runoffs, and hydraulic disturbance jointly led to the increase in the proportion of CHO molecules and lignin compounds; the decrease in proteins and lipids; the rise of DOC, TN, and NH+4-N concentrations in river water; and the decrease in DOC, TN, and NH+4-N concentrations and proteins and lipids in river sediments. â£The abundance of multi-heteroatomic compounds and condensed aromatics in the combined sewer system was higher than that in the separated sewer system, which may have been more severely polluted by domestic wastewater and storm runoff, especially kitchen wastewater. This study provides new insight for clarifying the critical causes of pollution in the new stage and provides an essential basis for further precision prevention and control of water pollution.
RESUMO
Barbituric acid derivative (TDPT) is an achiral molecule, and its adsorption on a surface results in two opposite enantiomerically oriented motifs, namely TDPT-Sp and Rp. Two types of building blocks can be formed; block I is enantiomer-pure and is built up of the same motifs (format SpSp or RpRp) whereas block II is enantiomer-mixed and composes both motifs (format SpRp), respectively. The organization of the building blocks determines the formation of different nanoarchitectures which are investigated using scanning tunneling microscopy at a liquid/HOPG interface. Sophisticated, highly symmetric "nanowaves" are first formed from both building blocks I and II and are heterochiral. The "nanowaves" are metastable and evolve stepwisely into more close-packed "nanowires" which are formed from enantiomer-pure building block I and are homochiral. A dynamic hetero- to homochiral transformation and simultaneous multi-scale phase transitions are demonstrated at the single-molecule level. Our work provides novel insights into the control and the origin of chiral assemblies and chiral transitions, revealing the various roles of enantiomeric selection and chiral competition, driving forces, stability and molecular coverage.
RESUMO
The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using an SMC-specific SMYD2 knockout mouse model, we found that SMYD2 ablation in VSMCs exacerbated neointima formation after vascular injury in vivo. Conversely, SMYD2 overexpression inhibited VSMC proliferation and migration in vitro and attenuated arterial narrowing in injured vessels in mice. SMYD2 downregulation promoted VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulated VSMC contractile gene expression and suppressed VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacted with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism.