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BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).
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Doenças Cardiovasculares/prevenção & controle , Dieta Hipossódica , Hipertensão/dietoterapia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Doenças Cardiovasculares/epidemiologia , China , Dieta Hipossódica/efeitos adversos , Feminino , Humanos , Hiperpotassemia/complicações , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Potássio na Dieta/efeitos adversos , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologiaRESUMO
The advent of wearable sensors heralds a transformation in the continuous, noninvasive analysis of biomarkers critical for disease diagnosis and fitness management. Yet, their advancement is hindered by the functional challenges affiliated with their active sensing analysis layer. Predominantly due to suboptimal intrinsic material properties and inconsistent dispersion leading to aggregation, thus compromising sensor repeatability and performance. Herein, an innovative approach to the functionalization of wearable electrochemical sensors was introduced, specifically addressing these limitations. The method involves a proton-induced self-assembly technique at the organic-water (O/W) interface, facilitating the generation of biomarker-responsive films. This research offers flexible, breathable sensor capable of real-time precision tracking l-cysteine (l-Cys) precision tracking. Utilizing an activation mechanism for Prussian blue nanoparticles by hydrogen peroxide, the catalytic core exhibits a specific response to l-Cys. The implications of this study refine the fabrication of film-based analysis electrodes for wearable sensing applications and the broader utilization of two-dimensional materials in functional-specific response films. Findings illuminate the feasibility of this novel strategy for precise biomarker tracking and extend to pave the way for constructing high-performance electrocatalytic analytical interfaces.
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Cisteína , Técnicas Eletroquímicas , Ferrocianetos , Dispositivos Eletrônicos Vestíveis , Cisteína/análise , Cisteína/química , Humanos , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Ferrocianetos/química , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Eletrodos , Técnicas Biossensoriais , Biomarcadores/análise , Nanopartículas/químicaRESUMO
Rechargeable aluminum batteries (RABs) are an emerging energy storage device owing to the vast Al resources, low cost, and high safety. However, the poor cyclability and inferior reversible capacity of cathode materials have limited the enhancement of RABs performance. Herein, a high configurational entropy strategy is presented to improve the electrochemical properties of RABs for the first time. The high-entropy (Fe, Mn, Ni, Zn, Mg)3 O4 cathode exhibits an ultra-stable cycling ability (109 mAh g-1 after 3000 cycles), high specific capacity (268 mAh g-1 at 0.5 A g-1 ), and rapid ion diffusion. Ex situ characterizations indicate that the operational mechanism of (Fe, Mn, Ni, Zn, Mg)3 O4 cathode is mainly based on the redox process of Fe, Mn, and Ni. Theoretical calculations demonstrate that the oxygen vacancies make a positive contribution to adjusting the distribution of electronic states, which is crucial for enhancing the reaction kinetics at the electrolyte and cathode interface. These findings not only propose a promising cathode material for RABs, but also provide the first elucidation of the operational mechanism and intrinsic information of high-entropy electrodes in multivalent ion batteries.
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Diode lasers with high beam quality and high power have many promising applications. However, high beam quality is always in conflict with high power. In this Letter, we theoretically and experimentally confirm the mode instability property of supersymmetric structures at higher operating currents. Meanwhile, we propose a loss-tailoring diode laser based on a supersymmetric structure, which enables the higher-order lateral modes to obtain higher losses, raises the excitation threshold of the higher-order lateral modes, and achieves a stable fundamental-lateral-mode output at higher current operation. The device obtained a quasi-single-lobe lateral far-field distribution with the full width at half maximum (FWHM) of 7.58° at 350â mA under room temperature, which is a 65% reduction compared to the traditional Fabry-Perot (FP) diode lasers. Moreover, the M2 of 2.181@350â mA has an improvement of about 37% over traditional FP and supersymmetric structure lasers.
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OBJECTIVES: To develop radiomics models based on multi-sequence MRI from two centers for the preoperative prediction of the WHO/ISUP grade of Clear Cell Renal Cell Carcinoma (ccRCC). METHODS: This retrospective study included 334 ccRCC patients from two centers. Significant clinical factors were identified through univariate and multivariate analyses. MRI sequences included Dynamic contrast-enhanced MRI, axial fat-suppressed T2-weighted imaging, diffusion-weighted imaging, and in-phase/out-of-phase images. Feature selection methods and logistic regression (LR) were used to construct clinical and radiomics models, and a combined model was developed using the Rad-score and significant clinical factors. Additionally, seven classifiers were used to construct the combined model and different folds LR was used to construct the combined model to evaluate its performance. Models were evaluated using receiver operating characteristic (ROC) curves, area under the curve (AUC), and decision curve analysis (DCA). The Delong test compared ROC performance, with p < 0.050 considered significant. RESULTS: Multivariate analysis identified intra-tumoral vessels as an independent predictor of high-grade ccRCC. In the external validation set, the radiomics model (AUC = 0.834) outperformed the clinical model (AUC = 0.762), with the combined model achieving the highest AUC (0.855) and significantly outperforming the clinical model (p = 0.003). DCA showed that the combined model had a higher net benefit within the 0.04-0.54 risk threshold range than clinical model. Additionally, the combined model constructed using logistic regression has a higher priority compared to other classifiers. Additionally, 10-fold cross-validation with LR for the combined model showed consistent AUC values (0.849-0.856) across different folds. CONCLUSION: The radiomics models based on multi-sequence MRI might be a noninvasive and effective tool, demonstrating good efficacy in preoperatively predicting the WHO/ISUP grade of ccRCC.
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Carcinoma de Células Renais , Neoplasias Renais , Imageamento por Ressonância Magnética , Gradação de Tumores , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Idoso , Adulto , Curva ROC , Idoso de 80 Anos ou mais , Período Pré-Operatório , RadiômicaRESUMO
Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.
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Carcinoma Hepatocelular , Proliferação de Células , Progressão da Doença , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Fator de Transcrição STAT1 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/imunologia , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/imunologia , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Fator de Transcrição STAT1/metabolismo , Animais , Camundongos , Humanos , Proliferação de Células/efeitos dos fármacos , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologiaRESUMO
The theory of heat conduction paths has been widely recognized and widely studied in the research about the thermal conductivity of thermal conductive polymer composites at present. Encapsulating polymer pellets with thermally conductive fillers and processing them into thermally conductive polymer composites is a simple and effective method for constructing heat conduction paths. It is meaningful to investigate the related heat conduction mechanism of this method. Otherwise, this approach can significantly preserve the performance of the polymer substrate, making it highly valuable for practical material applications. In this work, polyethylene-octene elastomer (POE) pellets were encapsulated with thermal conductive fillers by physical absorption. Subsequently, the composite films containing heat conduction paths were fabricated using the encapsulated POE pellets through a heating press. Alumina (Al2O3), boron nitride (BN), and alumina/boron nitride hybrid (Al2O3/BN) fillers were used to prepare Al2O3@POE, BN@POE, and BN/Al2O3@POE composite films to investigate the influence of filler shapes on heat conduction path construction. The influence of the constitute and density of heat conduction paths on the thermal conductivity of composite films was analyzed by infrared thermal imaging, finite element analysis, and thermal resistance theory in detail. Owing to the reserved good adhesion and flexibility of the POE substrate, the composite films could be directly used as thermal interface materials for chip cooling, which presented a good heat dissipation effect. Furthermore, a series of integrated composite materials were prepared by the combination of encapsulated pellets with various functional films (copper foil, aluminum foil, and graphite sheet) through a one-pot heating press, exhibiting a good electromagnetic shielding effect. The performance of the composites and the corresponding preparation method demonstrate the strong significance of this research for practical applications.
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Methods for regioselective N-trideuteromethylation of tautomeric polyaza heterocycles are highly sought-after. Disclosed herein is an N-trideuterated methylation reaction of imidazoles and pyrazoles with high regioselectivity and deuterium purity using easily available CF3SO3CD3 as the -CD3 source. This method enables the easy synthesis of important deuterium-labeled azoles, including dimetridazole-d3, ipronidazole-d3, hydroxy dimetridazole-d3, and ronidazole-d3.
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The aberrant accumulation of the transactive response deoxyribonucleic acid (DNA)-binding protein of 43 kDa (TDP-43) aggregates in the cytoplasm of motor neurons is the main pathological hallmark of amyotrophic lateral sclerosis (ALS). Previous experiments reported that adenosine triphosphate (ATP), the universal energy currency for all living cells, could induce aggregation and enhance the folding of TDP-43 fibrillar aggregates. However, the significance of ATP on TDP-43 fibrillation and the mechanism behind it remain elusive. In this work, we conducted multiple atomistic molecular dynamics (MD) simulations totaling 20 µs to search the critical nucleus size of TDP-43282-360 and investigate the impact of ATP molecules on preformed protofibrils. The results reveal that the trimer is the critical nucleus for TDP-43282-360 fibril formation and the tetramer is the minimal stable nucleus. When ATP molecules bind to the TDP-43282-360 trimer and tetramer, they can consolidate the TDP-43282-360 protofibrils by increasing the content of the ß-sheet structure and promoting the formation of hydrogen bonds (H-bonds). Binding site analyses show that the N-terminus of TDP-43282-360 protofibrils is the main binding site of ATP, and R293 dominates the direct binding of ATP. Further analyses reveal that the π-π, cation-π, salt bridge, and H-bonding interactions together contribute to the binding of ATP to TDP-43282-360 protofibrils. This study decoded the detailed stabilization mechanism of protofibrillar TDP-43282-360 oligomers by ATP, and may provide new avenues for the development of drug design against ALS.
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Trifosfato de Adenosina , Proteínas de Ligação a DNA , Simulação de Dinâmica Molecular , Trifosfato de Adenosina/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Humanos , Estabilidade Proteica , Ligação de HidrogênioRESUMO
AIM: The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. METHODS: A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. RESULTS: A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. CONCLUSIONS: With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. TRIAL REGISTRATION: This was a retrospective study and it did not interfere with treatment decisions.
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Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Recidiva Local de Neoplasia , Intervalo Livre de Doença , Resultado do Tratamento , Quimioembolização Terapêutica/métodosRESUMO
The approval of Trodelvy® validates TROP2 as a druggable but challenging target for antibody-drug conjugates (ADCs) to treat metastatic triple-negative breast cancer (mTNBC). Here, based on the TROP2-targeted antibody sacituzumab, we designed and developed several site-specific ADC candidates, which employ MMAE (monomethyl auristatin E) as the toxin, via IgG glycoengineering or affinity-directed traceless conjugation. Systematic evaluation of these site-specific ADCs in homogeneity, hydrophilicity, stability, and antitumor efficiency was conducted. The results indicate that the site-specific ADCs gsADC 3b made from one-step glycoengineering exhibit good aggregation stability and in vivo efficacy, providing a new format of ADCs that target TROP2.
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Antígenos de Neoplasias , Antineoplásicos , Moléculas de Adesão Celular , Desenho de Fármacos , Imunoconjugados , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/imunologia , Animais , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Camundongos , Feminino , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/farmacologia , OligopeptídeosRESUMO
Poststroke aphasia is an acquired language disorder and has been proven to have adverse effects on patients' social skills and quality of life. However, there are some inconsistencies in the neuroimaging studies investigating poststroke aphasia from the perspective of regional alterations. A meta-analysis has been employed to examine the common pattern of abnormal regional spontaneous brain activity in poststroke aphasia in the current study. Specifically, the Anisotropic effect-size version of seed-based d mapping was utilized, and 237 poststroke aphasia patients and 242 healthy controls (HCs) from 12 resting-state functional magnetic resonance imaging studies using amplitude of low-frequency fluctuations (ALFF), fractional ALFF, or regional homogeneity were included. The results showed that compared with HCs, patients with poststroke aphasia demonstrated increased regional spontaneous brain activity in the right insula, right postcentral gyrus, left cerebellar lobule IX, left angular gyrus, right caudate nucleus, left parahippocampal gyrus, and right supplementary motor area, and decreased regional spontaneous brain activity in the left cerebellar lobule VI, left median cingulate and paracingulate gyri, right cerebellar crus I, and left supplementary motor area. The study could provide further evidence for pathophysiological mechanism of poststroke aphasia and help find targets for treatment.
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Afasia , Qualidade de Vida , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Afasia/diagnóstico por imagem , Afasia/etiologia , Mapeamento Encefálico/métodosRESUMO
In hyperspectral images, every pixel encompasses continuous spectral information. Compared with traditional colorimeters, using hyperspectral imaging systems (HIS) for fabric color measurement can result in obtaining richer color information. However, measuring fabric colors with liquid crystal tunable filter HIS can lead to challenges related to light consistency. In this paper, we adopted an innovative approach, integrating gradient boosted decision trees with a sliding window algorithm to develop a uniformity calibration model addressing the illumination uniformity issue. To address the consistency issues across various light sources, we further adopted a deep neural network (DNN) model to correct the reflectance measurements under different light sources. Subsequently, this model was merged with the uniformity calibration model to form a light-consistency correction model. Through calibration, we successfully reduced the color difference of the corrected samples from 3.636 to 0.854, an enhancement of 76.51%. This means that after calibration we can achieve consistency in fabric color measurements under nonuniform lighting and different light sources.
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BACKGROUND: Males have accounted for a significant share of new HIV infections among young people in the recent years. This study aimed to identify the factors associated with risky sexual behaviors, including early sexual debut, multiple sexual partnership and condomless sex, among sexually active male college students and provide implications for tailored health interventions. METHODS: The cross-sectional study was conducted from December 2020 to December 2021 in 16 colleges that were located in Sichuan Province, one of the high-risk areas in China. Overall 1640 male college students who reported sexually experienced were analyzed in this study. Multivariable logistic regression analysis was applied to determine factors associated with early sexual debut, multiple sexual partnership and condomless sex. RESULTS: The average age of included male students was 19.95 ± 1.56. Of them, 27.74% initiated sexual behavior early, 48.60% reported multiple sexual partnership, and 16.52% did not use condoms at the latest sexual intercourse. Students who were younger (age ≤ 19, AOR = 7.60, 95%CI: 4.84-11.93; age20-21, AOR = 3.26, 95%CI: 2.04-5.21) and self-identified as sexual minorities (AOR = 2.38, 95%CI: 1.69-3.36) were more likely to have early sexual debut. The odds of having multiple sexual partners were higher among those who were ethnic minorities (AOR = 1.79, 95%CI: 1.33-2.41) and accepted extramarital sex (AOR = 1.33, 95%CI: 1.03-1.71). The likelihood of engaging in condomless sex at the latest sexual intercourse was lower among those who had sufficient knowledgeable about HIV (AOR = 0.63, 95%CI: 0.44-0.89), were very confident in condom use efficacy (AOR = 0.26, 95%CI: 0.16-0.43) and confident (AOR = 0.48, 95%CI: 0.34-0.69). Early sexual debut was positively associated with multiple sexual partnership (AOR = 3.64, 95%CI: 2.82-4.71) and condomless sex at the latest intercourse (AOR = 1.53, 95%CI: 1.07-2.20), respectively. CONCLUSION: Early sexual debut, multiple sexual partnership and condomless sex were of considerable concern among male college students. Comprehensive sex education curricula were advised by developing customized information on HIV prevention, sexuality and empowering students with assertiveness and negotiation skills with regard to condom use during and before college.
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Preservativos , Infecções por HIV , Assunção de Riscos , Comportamento Sexual , Estudantes , Sexo sem Proteção , Humanos , Masculino , Estudos Transversais , China/epidemiologia , Estudantes/estatística & dados numéricos , Estudantes/psicologia , Adulto Jovem , Adolescente , Comportamento Sexual/estatística & dados numéricos , Universidades , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Preservativos/estatística & dados numéricos , Sexo sem Proteção/estatística & dados numéricos , Parceiros Sexuais , Inquéritos e Questionários , AdultoRESUMO
BACKGROUND: Psychopathy is closely related to many negative interpersonal outcomes in daily life, including violence. Therefore, psychopathy intervention in subclinical individuals has significant application value. OBJECTIVE: Guided by the personality-relationship transaction model and social investment theory, this study examined how marital quality affects self- and partner-rated psychopathy. We also used the actor-partner interdependence mediation model to explore the mediating effect of communication. METHODS: We examined self-reports and partner reports of psychopathy, marital quality, and communication among 260 married Chinese couples. RESULTS: The results indicated that marital quality directly influenced couples' self-rated psychopathy, with both actor and partner effects on husbands' psychopathy and actor effects on wives' psychopathy. Moreover, verbal communication had mediating effects at time 2 between marital quality at time 1 and partner-reported psychopathy at time 3. Meanwhile, the mediating effect of nonverbal communication was not significant. CONCLUSION: Our investigation of relationship effects on psychopathy revealed that the underlying mechanisms differed between self- and partner-rated psychopathy. The findings can highlight directions for exploring potential intervention strategies for subclinical psychopathy.
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Relações Interpessoais , Satisfação Pessoal , Humanos , Estudos Longitudinais , Casamento , Cônjuges , ChinaRESUMO
BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.
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Países em Desenvolvimento , Pandemias , Humanos , Brasil , República da Macedônia do Norte , República da GeórgiaRESUMO
High-latitude and high-altitude regions contain vast stores of permafrost carbon. Climate warming may result in the release of CO2 from both the thawing of permafrost and accelerated autotrophic respiration, but it may also increase the fixation of CO2 by plants, which could relieve or even offset the CO2 losses. The Tibetan Plateau contains the largest area of alpine permafrost on Earth. However, the current status of the net CO2 balance and feedbacks to warming remain unclear, given that the region has recently experienced an atmospheric warming rate of over 0.3 °C decade-1 We examined 32 eddy covariance sites and found an unexpected net CO2 sink during 2002 to 2020 (26 of the sites yielded a net CO2 sink) that was four times the amount previously estimated. The CO2 sink peaked at an altitude of roughly 4,000 m, with the sink at lower and higher altitudes limited by a low carbon use efficiency and a cold, dry climate, respectively. The fixation of CO2 in summer is more dependent on temperature than the loss of CO2 than it is in the winter months, especially at higher altitudes. Consistently, 16 manipulative experiments and 18 model simulations showed that the fixation of CO2 by plants will outpace the loss of CO2 under a wetting-warming climate until the 2090s (178 to 318 Tg C y-1). We therefore suggest that there is a plant-dominated negative feedback to climate warming on the Tibetan Plateau.
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Altitude , Dióxido de Carbono/metabolismo , Simulação por Computador , Modelos Biológicos , Pergelissolo , Plantas/metabolismo , Ciclo do Carbono , Mudança Climática , Ecossistema , Estações do Ano , TibetRESUMO
Objective: To analyze the effect of Linc00511 on thyroid cancer through the miR-4739/RNF38 pathway. Methods: A total of 78 patients in our hospital from July 2020 to July 2021 were collected, which were diagnosed with thyroid cancer after clinicopathological examination. Their cancer tissue samples were included in the thyroid cancer tissue group, and the fat 2 cm tissue samples were included in the para-cancer tissue group. Real-time quantitative PCR was used to detect the expression of Linc00511, miR-4739 and RNF38 in tissue samples from the two groups. Statistical analysis of data was performed using SPSS26.0. The correlation between Linc00511, miR-4739 and RNF38 were analyzed by Pearson's correlation coefficient. The expression of Linc00511 in thyroid cancer tissues with different clinicopathological characteristics were compared. Results: The expression levels of Linc00511 and RNF38 in thyroid cancer group were significantly higher than paracancer group, while miR-4739 levels were significantly lower (P < .05). Pearson correlation coefficient analysis showed that there was significant negative correlation between Linc00511 and miR-4739 expression and significant positive correlation between Linc00511 and RNF38 expression (P < .05). There was no significant difference in the expression of Linc00511 among different ages, sexes, and cancer types (P > .05). The expression of Linc00511 in patients with TNM stages I, II, and III were increased with the increase of TNM stage (P < .05). The expression of Linc00511 in patients with tumor diameter ≥1 cm was higher than that in patients with tumor diameter <1 cm and the difference was statistically significant (P < .05). Conclusion: Linc00511 and RNF38 were significantly overexpressed in thyroid cancer tissues, while miR-4739 was significantly underexpressed. In thyroid cancer, Linc00511 can promote the invasion and metastasis of thyroid cancer cells by targeting miR-4739 and RNF38, and its expression level may reflect the progression of thyroid cancer, which can provide target reference for the clinical treatment of thyroid cancer.
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Cadmium (Cd) pollution is considered a pressing challenge to eco-environment and public health worldwide. Although it has been well-documented that Cd exhibits various adverse effects on aquatic animals, it is still largely unknown whether and how Cd at environmentally relevant concentrations affects iron metabolism. Here, we studied the effects of environmental Cd exposure (5 and 50⯵g/L) on iron homeostasis and possible mechanisms in common carp. The data revealed that Cd elevated serum iron, transferrin saturation and iron deposition in livers and spleens, leading to the disruption of systemic iron homeostasis. Mechanistic investigations substantiated that Cd drove hemolysis by compromising the osmotic fragility and inducing defective morphology of erythrocytes. Cd concurrently exacerbated hepatic inflammatory responses, resulting in the activation of IL6-Stat3 signaling and subsequent hepcidin transcription. Notably, Cd elicited ferroptosis through increased iron burden and oxidative stress in livers. Taken together, our findings provide evidence and mechanistic insight that environmental Cd exposure could undermine iron homeostasis via erythrotoxicity and hepatotoxicity. Further investigation and ecological risk assessment of Cd and other pollutants on metabolism-related effects is warranted, especially under the realistic exposure scenarios.
Assuntos
Carpas , Ferroptose , Animais , Cádmio/metabolismo , Carpas/metabolismo , Hemólise , Fígado , Inflamação/induzido quimicamente , Inflamação/metabolismo , Homeostase , Ferro/metabolismoRESUMO
To fully comprehend the patterns of land and ecological damage caused by coal mining subsidence, and to scientifically carry out ecological mine restoration and management, it is urgent to accurately grasp the information of coal mining, particularly in complex coaling areas, such as North Anhui, China. In this paper, a space-air-ground collaborative monitoring system was constructed for coal mining areas based on multi-source remote sensing data and subsidence characteristics of coaling areas were investigated in North Anhui. It was found that from 2019 to 2022, 16 new coal mining subsidence areas were found in northern Anhui, with the total area increasing by 8.1%. In terms of land use, water areas were increased by 101.9 km2 from 2012 to 2022, cultivated land was decreased by 99.3 km2, and residence land was decreased by 11.8 km2. The depth of land subsidence in the subsidence areas is divided into 307.9 km2 of light subsidence areas with a subsidence depth of less than 500 mm; 161.8 km2 of medium subsidence areas with a subsidence depth between 500 mm and 1500 mm; and 281.2 km2 of heavy subsidence areas with a subsidence depth greater than 1500 mm. The total subsidence governance area is 191.2 km2, accounting for 26.5% of the total subsidence area. From the perspective of prefecture-level cities, the governance rate reaches 51.3% in Huaibei, 10.1% in Huainan, and 13.6% in Fuyang. The total reclamation area is 68.8 km2, accounting for 34.5% of the subsidence governance area. At present, 276.1 km2 within the subsidence area has reached stable subsidence conditions, mainly distributed in the Huaibei mining area, which accounts for about 60% of the total stable subsidence area.