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Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1, and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation, and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration, and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis, and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC.
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Proteínas Adaptadoras de Transdução de Sinal , Neoplasias da Mama , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Serina-Treonina Quinases , Fatores de Transcrição , Proteínas Supressoras de Tumor , Proteínas de Sinalização YAP , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Animais , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Camundongos , Transdução de Sinais , Metástase Neoplásica , Movimento Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Fosforilação , Camundongos Nus , Carcinogênese/genética , Carcinogênese/metabolismoRESUMO
BACKGROUND: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role and therapeutic value of USP28 (ubiquitin-specific protease 28) on the metabolic vulnerability of diabetic cardiomyopathy. METHODS: The type 2 diabetes mouse model was established using db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced mice. Cardiac-specific knockout of USP28 in the db/db background mice was generated by crossbreeding db/m and Myh6-Cre+/USP28fl/fl mice. Recombinant adeno-associated virus serotype 9 carrying USP28 under cardiac troponin T promoter was injected into db/db mice. High glucose plus palmitic acid-incubated neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes were used to imitate diabetic cardiomyopathy in vitro. The molecular mechanism was explored through RNA sequencing, immunoprecipitation and mass spectrometry analysis, protein pull-down, chromatin immunoprecipitation sequencing, and chromatin immunoprecipitation assay. RESULTS: Microarray profiling of the UPS (ubiquitin-proteasome system) on the basis of db/db mouse hearts and diabetic patients' hearts demonstrated that the diabetic ventricle presented a significant reduction in USP28 expression. Diabetic Myh6-Cre+/USP28fl/fl mice exhibited more severe progressive cardiac dysfunction, lipid accumulation, and mitochondrial disarrangement, compared with their controls. On the other hand, USP28 overexpression improved systolic and diastolic dysfunction and ameliorated cardiac hypertrophy and fibrosis in the diabetic heart. Adeno-associated virus serotype 9-USP28 diabetic mice also exhibited less lipid storage, reduced reactive oxygen species formation, and mitochondrial impairment in heart tissues than adeno-associated virus serotype 9-null diabetic mice. As a result, USP28 overexpression attenuated cardiac remodeling and dysfunction, lipid accumulation, and mitochondrial impairment in high-fat diet/streptozotocin-induced type 2 diabetes mice. These results were also confirmed in neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes. RNA sequencing, immunoprecipitation and mass spectrometry analysis, chromatin immunoprecipitation assays, chromatin immunoprecipitation sequencing, and protein pull-down assay mechanistically revealed that USP28 directly interacted with PPARα (peroxisome proliferator-activated receptor α), deubiquitinating and stabilizing PPARα (Lys152) to promote Mfn2 (mitofusin 2) transcription, thereby impeding mitochondrial morphofunctional defects. However, such cardioprotective benefits of USP28 were largely abrogated in db/db mice with PPARα deletion and conditional loss-of-function of Mfn2. CONCLUSIONS: Our findings provide a USP28-modulated mitochondria homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts, suggesting that USP28 activation or adeno-associated virus therapy targeting USP28 represents a potential therapeutic strategy for diabetic cardiomyopathy.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Células-Tronco Pluripotentes Induzidas , Ubiquitina Tiolesterase , Animais , Humanos , Camundongos , Ratos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Lipídeos , Camundongos Knockout , Miócitos Cardíacos/metabolismo , PPAR alfa/metabolismo , Estreptozocina/metabolismo , Estreptozocina/uso terapêutico , Ubiquitina Tiolesterase/análise , Ubiquitina Tiolesterase/metabolismoRESUMO
Scalable and addressable integrated manipulation of qubits is crucial for practical quantum information applications. Different waveguides have been used to transport the optical and electrical driving pulses, which are usually required for qubit manipulation. However, the separated multifields may limit the compactness and efficiency of manipulation and introduce unwanted perturbation. Here, we develop a tapered fiber-nanowire-electrode hybrid structure to realize integrated optical and microwave manipulation of solid-state spins at nanoscale. Visible light and microwave driving pulses are simultaneously transported and concentrated along an Ag nanowire. Studied with spin defects in diamond, the results show that the different driving fields are aligned with high accuracy. The spatially selective spin manipulation is realized. And the frequency-scanning optically detected magnetic resonance (ODMR) of spin qubits is measured, illustrating the potential for portable quantum sensing. Our work provides a new scheme for developing compact, miniaturized quantum sensors and quantum information processing devices.
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BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.
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Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Receptor IGF Tipo 1 , Transdução de Sinais , Humanos , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Acrilamidas/farmacologia , RNA Circular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Compostos de Anilina/farmacologia , Linhagem Celular Tumoral , Animais , Camundongos , Apoptose , Movimento Celular/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Feminino , Indóis , PirimidinasRESUMO
Background Diagnosing osteoporosis is challenging due to its often asymptomatic presentation, which highlights the importance of providing screening for high-risk populations. Purpose To evaluate the effectiveness of dual-energy x-ray absorptiometry (DXA) screening in high-risk patients with osteoporosis identified by an artificial intelligence (AI) model using chest radiographs. Materials and Methods This randomized controlled trial conducted at an academic medical center included participants 40 years of age or older who had undergone chest radiography between January and December 2022 without a history of DXA examination. High-risk participants identified with the AI-enabled chest radiographs were randomly allocated to either a screening group, which was offered fully reimbursed DXA examinations between January and June 2023, or a control group, which received usual care, defined as DXA examination by a physician or patient on their own initiative without AI intervention. A logistic regression was used to test the difference in the primary outcome, new-onset osteoporosis, between the screening and control groups. Results Of the 40 658 enrolled participants, 4912 (12.1%) were identified by the AI model as high risk, with 2456 assigned to the screening group (mean age, 71.8 years ± 11.5 [SD]; 1909 female) and 2456 assigned to the control group (mean age, 72.1 years ± 11.8; 1872 female). A total of 315 of 2456 (12.8%) participants in the screening group underwent fully reimbursed DXA, and 237 of 315 (75.2%) were identified with new-onset osteoporosis. After including DXA results by means of usual care in both screening and control groups, the screening group exhibited higher rates of osteoporosis detection (272 of 2456 [11.1%] vs 27 of 2456 [1.1%]; odds ratio [OR], 11.2 [95% CI: 7.5, 16.7]; P < .001) compared with the control group. The ORs of osteoporosis diagnosis were increased in screening group participants who did not meet formalized criteria for DXA compared with those who did (OR, 23.2 [95% CI: 10.2, 53.1] vs OR, 8.0 [95% CI: 5.0, 12.6]; interactive P = .03). Conclusion Providing DXA screening to a high-risk group identified with AI-enabled chest radiographs can effectively diagnose more patients with osteoporosis. Clinical trial registration no. NCT05721157 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Smith and Rothenberg in this issue.
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Absorciometria de Fóton , Redes Neurais de Computação , Osteoporose , Radiografia Torácica , Humanos , Feminino , Osteoporose/diagnóstico por imagem , Masculino , Radiografia Torácica/métodos , Absorciometria de Fóton/métodos , Idoso , Programas de Rastreamento/métodos , Pessoa de Meia-IdadeRESUMO
Phonon-based frequency combs that can be generated in the optical and microwave frequency domains have attracted much attention due to the small repetition rates and the simple setup. Here, we experimentally demonstrate a new type of phonon-based frequency comb in a silicon optomechanical crystal cavity including both a breathing mechanical mode (â¼GHz) and flexural mechanical modes (tens of MHz). We observe strong mode competition between two approximate flexural mechanical modes, i.e., 77.19 and 90.17 MHz, resulting in only one preponderant lasing, while maintaining the lasing of the breathing mechanical mode. These simultaneous observations of two-mode phonon lasing state and significant mode competition are counterintuitive. We have formulated comprehensive theories to elucidate this phenomenon in response to this intriguing outcome. In particular, the self-pulse induced by the free carrier dispersion and thermo-optic effects interacts with two approximate flexural mechanical modes, resulting in the repetition rate of the comb frequency-locked to exact fractions of one of the flexural mechanical modes and the mode hopping between them. This phonon-based frequency comb has at least 260 comblines and a repetition rate as low as a simple fraction of the flexural mechanical frequency. Our demonstration offers an alternative optomechanical frequency comb for sensing, timing, and metrology applications.
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Free radicals are increasingly recognized as active intermediate reactive species that can participate in various redox processes, significantly influencing the mechanistic pathways of reactions. Numerous researchers have investigated the generation of one or more distinct photogenerated radicals, proposing various hypotheses to explain the reaction mechanisms. Notably, recent research has demonstrated the emergence of photogenerated radicals in innovative processes, including organic chemical reactions and the photocatalytic dissolution of precious metals. To harness the potential of these free radicals more effectively, it is imperative to consolidate and analyze the processes and action modes of these photogenerated radicals. This conceptual paper delves into the latest advancements in understanding the mechanics of photogenerated radicals.
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BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. METHODS: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'É' determinant variants were evaluated if indicated. RESULTS: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. CONCLUSION: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.
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Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B , Vírus da Hepatite B , Hepatite B , Humanos , Taiwan/epidemiologia , Feminino , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Masculino , Antígenos de Superfície da Hepatite B/sangue , Adulto , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Anticorpos Anti-Hepatite B/sangue , Pessoa de Meia-Idade , Criança , Lactente , Adolescente , Adulto Jovem , Pré-Escolar , Carga Viral , Genótipo , Prevalência , Vacinação/estatística & dados numéricos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Programas de Imunização , Estudos SoroepidemiológicosRESUMO
PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.
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Carbapenêmicos , Transplante de Pulmão , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Transplantados , Pulmão , Programas de Rastreamento , Transplante de Pulmão/efeitos adversosRESUMO
Hydropower plays a pivotal role in low-carbon electricity generation, yet many projects are situated in regions facing heightened water scarcity risks. This research devised a plant-level Hydropower Water Scarcity Index (HWSI), derived from the ratio of water demand for electricity generation to basin-scale available runoff water. We assessed the water scarcity of 1736 hydropower plants in China for the baseline year 2018 and projected into the future from 2025 to 2060. The results indicate a notable increase in hydropower generation facing moderate to severe water scarcity (HWSI >0.05), rising from 10% in 2018 to 24-34% of the national total (430-630 TWh), with a projected peak in the 2030s-2040s under the most pessimistic scenarios. Hotspots of risk are situated in the southwest and northern regions, primarily driven by decreased river basin runoff and intensified sectoral water use, rather than by hydropower demand expansion. Comparative analysis of four adaptation strategies revealed that sectoral water savings and enhancing power generation efficiency are the most effective, potentially mitigating a high of 16% of hydropower risks in China. This study provides insights for formulating region-specific adaptation strategies and assessing energy-water security in the face of evolving environmental and societal challenges.
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Mudança Climática , Centrais Elétricas , China , Abastecimento de ÁguaRESUMO
Understanding the impact of heavy precipitation on human mobility is critical for finer-scale urban flood risk assessment and achieving sustainable development goals #11 to build resilient and safe cities. Using â¼2.6 million mobile phone signal data collected during the summer of 2018 in Jiangsu, China, this study proposes a novel framework to assess human mobility changes during rainfall events at a high spatial granularity (500 m grid cell). The fine-scale mobility map identifies spatial hotspots with abnormal clustering or reduced human activities. When aggregating to the prefecture-city level, results show that human mobility changes range between -3.6 and 8.9%, revealing varied intracity movement across cities. Piecewise structural equation modeling analysis further suggests that city size, transport system, and crowding level directly affect mobility responses, whereas economic conditions influence mobility through multiple indirect pathways. When overlaying a historical urban flood map, we find such human mobility changes help 23 cities reduce 2.6% flood risks covering 0.45 million people but increase a mean of 1.64% flood risks in 12 cities covering 0.21 million people. The findings help deepen our understanding of the mobility pattern of urban dwellers after heavy precipitation events and foster urban adaptation by supporting more efficient small-scale hazard management.
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Big Data , Inundações , Humanos , Cidades , ChinaRESUMO
BACKGROUND: There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions. METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study. RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p < 0.001) and UMIC (p < 0.001) and not HIC (p = 0.220) countries/regions. Similarly, higher 90-day mortality was associated with increased qSOFA in LLMIC (p < 0.001) and UMIC (p < 0.001) only. In contrast, higher 3-day mortality with increasing qSOFA score was observed across all income countries/regions (p < 0.001). Multivariate analysis showed that qSOFA remained associated with 28-day mortality (adjusted RR 1.09 (1.00-1.18), p = 0.038) even after adjustments for covariates including APACHE II, SOFA, income country/region and administration of antibiotics within 3 h. CONCLUSIONS: qSOFA was independently associated with 28-day mortality in ICU patients admitted for sepsis. In LLMIC and UMIC countries/regions, qSOFA was associated with early to late mortality but only early mortality in HIC countries/regions.
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Escores de Disfunção Orgânica , Sepse , Humanos , APACHE , Unidades de Terapia Intensiva , Prognóstico , Estudos ProspectivosRESUMO
INTRODUCTION: The relationship among physiologic reserve, intrinsic capacity, and physical resilience has not been examined, and a conceptual model that includes these key determinants of healthy ageing is needed. This study aimed to test a conceptual model using real-world data to determine the relationships among physiologic reserve, intrinsic capacity, physical resilience, and clinical outcomes. METHODS: This longitudinal study was conducted at a 1,343-bed tertiary-care medical centre. Patients were eligible for inclusion if they were 65 years of age or older and able to communicate independently. Demographic factors, cumulative illness rating scale for geriatrics [CIRS-G] (assessing physiologic reserve), intrinsic capacity, physical resilience instrument for older adults [PRIFOR] (assessing physical resilience), and clinical frailty scale [CFS] were collected at admission. The CFS and EuroQoL 5-dimension 3-level questionnaire [EQ5D] were administered at discharge. RESULTS: The mean age of the 413 patients was 76.34 ± 6.72 (52.5% female). Two conceptual models were identified and supported. Specifically, the path coefficients in the two models showed that the CIRS-G had diverse associations with each intrinsic capacity domain, and that all intrinsic capacity domains (except vitality) were significantly associated with PRIFOR. Moreover, PRIFOR was significantly associated with follow-up CFS, baseline control, and EQ5D scores. CONCLUSION: Physiologic reserve positively correlated with the cognitive and locomotive domains of intrinsic capacity. Moreover, older patients with better intrinsic capacity may have improved physical resilience, which may lead to better clinical outcomes. Efforts to improve the intrinsic capacity and physical resilience of older patients are necessary to promote healthy ageing.
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Resiliência Psicológica , Humanos , Feminino , Idoso , Masculino , Estudos Longitudinais , Análise de Classes LatentesRESUMO
INTRODUCTION: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS. METHODS: The participants comprised first-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) who were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC). RESULTS: The mean age of the 114 outpatients was 78.3 ± 7.6 years, and 79 (69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r = 0.494; p < 0.001), and the binary score showed excellent correlation (r = 0.944; p < 0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90). DISCUSSION/CONCLUSION: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards.
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To be aware of and to move one's body, the brain must maintain a coherent representation of the body. While the body and the brain are connected by dense ascending and descending sensory and motor pathways, representation of the body is not hardwired. This is demonstrated by the well-known rubber hand illusion in which a visible fake hand is erroneously felt as one's own hand when it is stroked in synchrony with the viewer's unseen actual hand. Thus, body representation in the brain is not mere maps of tactile and proprioceptive inputs, but a construct resulting from the interpretation and integration of inputs across sensory modalities.
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Mãos , Extremidade Superior , Encéfalo , Conscientização , EmoçõesRESUMO
Enterospora epinepheli is an intranuclear microsporidian parasite causing serious emaciative disease in hatchery-bred juvenile groupers (Epinephelus spp.). Rapid and sensitive detection is urgently needed as its chronic infection tends to cause emaciation as well as white faeces syndrome and results in fry mortality. This study established a TaqMan probe-based real-time quantitative PCR assays targeting the small subunit rRNA (SSU) gene of E. epinepheli. The relationship between the standard curve of cycle threshold (Ct) and the logarithmic starting quantity (SQ) was determined as Ct = -3.177 lg (SQ) + 38.397. The correlation coefficient (R2 ) was 0.999, and the amplification efficiency was 106.4%. The detection limit of the TaqMan probe-based qPCR assay was 1.0 × 101 copies/µL and that is 100 times sensitive than the traditional PCR method. There is no cross-reaction with other aquatic microsporidia such as Ecytonucleospora hepatopenaei, Nucleospora hippocampi, Potaspora sp., Ameson portunus. The intra-assay and inter-assay showed great repeatability and reproducibility. In addition, the test of clinical samples showed that this assay effectively detected E. epinepheli in the grouper's intestine tissue. The established TaqMan qPCR assays will be a valuable diagnostic tool for the epidemiological investigation as well as prevention and control of E. epinepheli.
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Apansporoblastina , Bass , Doenças dos Peixes , Microsporídios , Animais , Bass/genética , Reprodutibilidade dos Testes , Doenças dos Peixes/diagnóstico , Melhoramento Vegetal , Microsporídios/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Mounting evidence has demonstrated that high temperature was associated with adverse health outcomes, especially morbidity and mortality. Nonetheless, the impact of extreme high temperature on cognitive performance, which is the fundamental capacity for interpreting one's surroundings, decision-making, and acquiring new abilities, has not been thoroughly investigated. METHODS: We aimed to assess associations between extreme high temperature at different time scales and poor cognitive function. We used longitudinal survey data from the three waves of data from China Family Panel Study, providing an 8-year follow-up of 53,008 participants from China. We assessed temperature and extreme high temperature exposure for each participant based on the residential area and date of cognitive test. We defined the proportion of days/hours above 32 °C as the metric of the exposure to extreme high temperature. Then we used generalized additive model and difference-in-differences approach to explore the associations between extreme high temperature and cognitive function. RESULTS: Our results demonstrated that either acute exposure or long-term exposure to extreme high temperature was associated with cognitive decline. At hourly level, 0-1â¯hour acute exposure to extreme high temperature would induce -0.93 % (95 % CI: -1.46 %, -0.39 %) cognitive change. At annual level, 10 percentage point increase in the hours proportion exceeding 32 °C in the past two years induced -9.87 % (95 % CI: -13.99 %, -5.75 %) cognitive change. Furthermore, subgroup analyses indicated adaptation effect: for the same 10 percentage increase in hours proportion exceeding 32 °C, people in warmer areas had cognitive change of -6.41 % (-11.22 %, -1.61 %), compared with -15.30 % (-21.07 %, -9.53 %) for people in cool areas. CONCLUSION: Our results demonstrated that extreme high temperature was associated with reduced cognitive function at hourly, daily and annual levels, warning that people should take better measures to protect the cognitive function in the context of climate change.
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Cognição , Temperatura Baixa , Humanos , Temperatura , China , Estações do Ano , Temperatura AltaRESUMO
Manure is one of the main sources of heavy metal (HM) pollution on farmlands. It has become the focus of global ecological research because of its potential threat to human health and the sustainability of food systems. Soil pH and organic matter are improved by manure and play pivotal roles in determining soil HM behavior. Geochemical modeling has been widely used to assess and predict the behavior of soil HMs; however, there remains a research gap in manure applications. In this study, a geochemical model (LeachXS) coupled with a pH-dependent leaching test with continuously simulations over a broad pH range was used to determine the effects and pollution risks of pig or cattle manure separate application on soil HMs distribution. Both pig and cattle manure applications led to soil pH reduction in alkaline soils and increased organic matter content. Pig manure application resulted in a potential 90.5-156.0â¯% increase in soil HM content. Cattle manure did not cause significant HM contamination. The leaching trend of soil HMs across treatments exhibited a V-shaped change, with the lowest concentration at pH = 7, gradually increasing toward strong acids and bases. The dissolved organic matter-bound HM content directly increased the HM availability, especially for Cu (up to 8.4â¯%) after pig manure application. However, more HMs (Cr, Cu, Zn, Ni) were in the particulate organic matter-bound state than in other solid phases (e.g., Fe-Al(hydr) oxides, clay minerals), which inhibited the HMs leaching by more than 19.3â¯% after cattle manure application. Despite these variations, high HM concentrations introduced by pig manure raised the soil contamination risk, potentially exceeding 40 times at pH ±1. When manure is returned to the field, reducing its HM content and mitigating possible pollution is necessary to realize the healthy and sustainable development of circular agriculture.
Assuntos
Esterco , Metais Pesados , Poluentes do Solo , Solo , Esterco/análise , Poluentes do Solo/análise , Metais Pesados/análise , Animais , Bovinos , Solo/química , Suínos , Concentração de Íons de Hidrogênio , Monitoramento AmbientalRESUMO
Current knowledge about public climate change perception mainly covers belief, concern, and attitudes. However, how this discourse is interpreted using individuals' own frame of reference remains largely unknown, particularly in many large emitters from non-Annex I countries such as China. This study, for the first time, performs a nationwide open-ended survey covering 4,037 respondents and collected 12,100 textual answers. Using a semiautomated coding method, we find seven mental images that exclusively represent the Chinese interpretation of the climate change issue, including global warming, distant icons, natural disasters, environmental degradation, cause, solution, and weather. Analysis of influencing factors shows that females, those with lower education levels, lower income, and older individuals tend to connect climate change with natural weather phenomena. Younger and well-educated residents in developed cities are more aware of various consequences and anthropogenic causes of climate change. People with stronger climate change beliefs, policy support, and personal experience of extreme weather are more likely to mention disastrous impacts, carbon emission as causes, and potential solutions. Employing the multilevel regression and post-stratification technique, we map the prevalence of mental images in China at the prefecture-city level. The results reveal significant geographical heterogeneity, with estimated national means ranging from a high of 55% (weather) to a low of 11% (solution). Our findings reveal diverse perspectives and a widespread misconception of climate change in China, suggesting the need for tailored clarification strategies to gain public consent.
RESUMO
The issues of state estimations based on distributed observers for linear time-invariant (LTI) systems with multiple sensors are discussed in this paper. We deal with the scenario when the information exchange has known time delays, and aim at designing a distributed observer for each subsystem such that each distributed observer can estimate the system state asymptotically by rejecting the time delay. To begin with, by rewriting the target system in a connecting form, a subsystem which is affected by the time-delay states of other nodes is established. And then, for this subsystem, a distributed observer with time delay is constructed. Moreover, an equivalent state transformation is made for the observer error dynamic system based on the observable canonic decomposition theorem. Further, in order to ensure that the distributed observer error dynamic system is asymptotically stable even if there exists a time delay, a linear matrix inequality (LMI) which is relative to the Laplace matrix is elaborately set up, and a special Lyapunov function candidate based on the LMI is considered. Next, based on the Lyapunov function and Lyapunov stability theory, we prove that the error dynamic system of the distributed observer is asymptotically stable, and the observer gain is determined by a feasible solution of the LMI. Finally, a simulation example is given to illustrate the effectiveness of the proposed method.