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Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC-MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Proteínas Quinases Ativadas por AMP , Cromatografia Líquida , Proteômica , Proliferação de Células , Movimento Celular , Espectrometria de Massas em Tandem , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Modelos Animais de Doenças , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Stroke-caused synergies may result from the preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or abnormal synergies, and accordingly, the controllability of individual muscles decreases. However, it is not clear whether muscles involuntarily activated by abnormal synergy vary depending on the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from the merging and reweighting of synergies in individuals without neurological deficits. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment that could characterize the neuroanatomical architecture in individuals with a wide range of impairments. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% [8/57, 95% confidence interval (5.0%, 23.1%)] of the participants with severe impairment (total Fugl-Meyer score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants underwent a different course of neural reorganization, which enhanced abnormal synergies in comparison with individuals with mild impairment (P < 0.05). These results provide evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.NEW & NOTEWORTHY We demonstrate that abnormal synergies are still selectively excited depending on the context.
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Músculo Esquelético , Tratos Piramidais , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Músculo Esquelético/fisiologia , Músculo Esquelético/fisiopatologia , Tratos Piramidais/fisiopatologia , Tratos Piramidais/fisiologia , Idoso , Adulto , Cotovelo/fisiologia , Cotovelo/fisiopatologia , Ombro/fisiologia , Ombro/fisiopatologiaRESUMO
The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and the lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the interlimb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. We used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis after stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy after stroke. We found that, generally, strong interlimb correlations (r > 0.65 with all P values < 0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). However, the correlations of the lower-extremity extension synergy with the upper-extremity flexion synergy and extension synergy decreased (down to r = 0.38) 360 days after stroke (P < 0.05). These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances the interlimb correlations between the flexion synergy and extension synergy. At the same time, the results imply that the recovery of CST integrity or/and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase may contribute to diversity in neural pathways in motor execution, eventually leading to reduced interlimb correlations.NEW & NOTEWORTHY For the first time, this article addresses the asynchronous relationships in the strengths of flexion and extension synergy expressions between the paretic upper extremity and lower extremity across various phases of stroke.
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Extremidade Inferior , Paresia , Acidente Vascular Cerebral , Extremidade Superior , Humanos , Masculino , Acidente Vascular Cerebral/fisiopatologia , Feminino , Extremidade Superior/fisiopatologia , Pessoa de Meia-Idade , Idoso , Paresia/fisiopatologia , Paresia/etiologia , Extremidade Inferior/fisiopatologia , Tratos Piramidais/fisiopatologia , AdultoRESUMO
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in circulating tumor deoxyribonucleic acid (ctDNA) have been reported as representative noninvasive prognostic markers for pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to evaluate single KRAS mutations as prognostic and predictive biomarkers, with an emphasis on potential therapeutic approaches to PDAC. A total of 128 patients were analyzed for multiple or single KRAS mutations (G12A, G12C, G12D, G12R, G12S, G12V, and G13D) in their tumors and plasma using droplet digital polymerase chain reaction (ddPCR). Overall, KRAS mutations were detected by multiplex ddPCR in 119 (93%) of tumor DNA and 68 (53.1%) of ctDNA, with a concordance rate of 80% between plasma ctDNA and tumor DNA in the metastatic stage, which was higher than the 44% in the resectable stage. Moreover, the prognostic prediction of both overall survival (OS) and progression-free survival (PFS) was more relevant using plasma ctDNA than tumor DNA. Further, we evaluated the selective tumor-suppressive efficacy of the KRAS G12C inhibitor sotorasib in a patient-derived organoid (PDO) from a KRAS G12C-mutated patient using a patient-derived xenograft (PDX) model. Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , DNA de Neoplasias/genética , Mutação , Microambiente TumoralRESUMO
Pine, an evergreen conifer, is widely distributed worldwide. It is economically, scientifically, and ecologically important. However, pine wilt disease (PWD) induced by the pine wood nematode (PWN) adversely affects pine trees. Many studies have been conducted on the PWN and its beetle vectors to prevent the spread of PWD. However, studies providing a comprehensive understanding of the pine tree transcriptome in response to PWN infection are lacking. Here, we performed temporal profiling of the pine tree transcriptome using PWD-infected red pine trees, Pinus densiflora, inoculated with the PWN by RNA sequencing. Our analysis revealed that defense-responsive genes involved in cell wall modification, jasmonic acid signaling, and phenylpropanoid-related processes were significantly enriched 2 weeks after PWD infection. Furthermore, some WRKY-type and MYB-type transcription factors were upregulated 2 weeks after PWD infection, suggesting that these transcription factors might be responsible for the genome-wide reprogramming of defense-responsive genes in the early PWD stage. Our comprehensive transcriptome analysis will assist in developing PWD-resistant pine trees and identifying genes to diagnose PWD at the early stage of infection, during which large-scale phenotypic changes are absent in PWD-infected pine trees.
Assuntos
Perfilação da Expressão Gênica , Pinus , Doenças das Plantas , Transcriptoma , Pinus/parasitologia , Pinus/genética , Animais , Doenças das Plantas/parasitologia , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Stroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics. METHODS: This cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl-Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment. RESULTS: The participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1. CONCLUSIONS: The results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.
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Espectroscopia de Luz Próxima ao Infravermelho , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior , Humanos , Masculino , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Feminino , Extremidade Superior/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Estudos Transversais , Pessoa de Meia-Idade , Hemodinâmica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagemRESUMO
Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers' characteristics and patients' clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients' disability (OR = 11.60; 95% CI 1.58-85.08; p = 0.016), caregivers' self-rated stress (OR = 0.03; 95% CI 0.00-0.47; p = 0.013), and caregivers' quality of life (OR = 0.76; 95% CI 0.59-0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients' disability (OR = 5.88; 95% CI 2.19-15.82; p < 0.001) and caregivers' psychosocial stress (OR = 1.26; 95% CI 1.10-1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients' disability and caregivers' stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.
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Sobrecarga do Cuidador , Cuidadores , Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/complicações , Estudos Retrospectivos , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Idoso , Inquéritos e Questionários , República da Coreia , Qualidade de Vida/psicologia , Sobrecarga do Cuidador/psicologia , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Adulto , Estresse Psicológico/psicologia , Estresse Psicológico/complicações , Estresse Psicológico/etiologia , Reabilitação do Acidente Vascular Cerebral/psicologia , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricosRESUMO
Nurses play a key role in providing integrated supportive care to cancer patients for their various needs. Efforts should be made to identify the competencies required for nurses providing integrated supportive care to cancer survivors, evaluate the competence level with reliable and reasonable tools, and continuously improve them. In Phase 1, the items of the scale were developed through a literature review and by conducting a focus group interview. In Phase 2, the validity and reliability of the scale were analyzed. A total of 504 nurses participated. Data were analyzed using item analysis, exploratory factor analysis, confirmatory factor analysis, Pearson's correlation with other scales, internal consistency, and split-half reliability. The developed scale consisted of 22 items. These items were grouped into five subscales and labeled as professionalism enhancement, care coordination, comprehensive nursing needs assessment, providing tailored information and education, and recurrence surveillance and secondary cancer prevention. Confirmatory factor analysis supported good convergent and discriminant validities. The criterion validity was verified. The internal consistency of the scale measured by Cronbach's α was 0.91. The developed scale is expected to be used as an instrument to identify cancer survivor integrated supportive care competencies of nurses in practice.
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This study investigates whether simultaneous high-definition transcranial direct current stimulation (HD-tDCS) enhances the effects of robot-assisted gait training in stroke patients. Twenty-four participants were randomly allocated to either the robot-assisted gait training with real HD-tDCS group (real HD-tDCS group) or robot-assisted gait training with sham HD-tDCS group (sham HD-tDCS group). Over four weeks, both groups completed 10 sessions. The 10 Meter Walk Test, Timed Up and Go, Functional Ambulation Category, Functional Reach Test, Berg Balance Scale, Dynamic Gait Index, Fugl-Meyer Assessment, and Korean version of the Modified Barthel Index were conducted before, immediately after, and one month after the intervention. The real HD-tDCS group showed significant improvements in the 10 Meter Walk Test, Timed Up and Go, Functional Reach Test, and Berg Balance Scale immediately and one month after the intervention, compared with before the intervention. Significant improvements in the Dynamic Gait Index and Fugl-Meyer Assessment were also observed immediately after the intervention. The sham HD-tDCS group showed no significant improvements in any of the tests. Application of HD-tDCS during robot-assisted gait training has a positive effect on gait and physical function in chronic stroke patients, ensuring long-term training effects. Our results suggest the effectiveness of HD-tDCS as a complementary tool to enhance robotic gait rehabilitation therapy in chronic stroke patients.
Assuntos
Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Robótica/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Marcha/fisiologia , Resultado do TratamentoRESUMO
This review aimed to determine the effectiveness of Intermittent Pneumatic Compression (IPC) intervention on Deep Vein Thrombosis (DVT) in surgical patients. An electronic database search was conducted with PubMed, OVID-MEDLINE, EMBASE, and CENTRAL, from September 22 to 28, 2023. Three researchers independently selected the studies, assessed their methodological quality, and extracted relevant data. We conducted a meta-analysis of the effect of IPC versus the control group and summarized the intervention results from the included studies. Of the 2,696 articles identified 16 randomized control trials met the inclusion criteria for review. IPC interventions significantly affected DVT prevention (OR = 0.81, 95% CI: 0.59-1.11). In the subgroup analysis, there was a significant pooled effect (OR = 0.41, 95% CI: 0.26-0.65]), when the comparison group was no prophylaxis group. However, when the comparison groups were the pharmacologic prophylaxis group ([OR = 1.32, 95% CI 0.78-2.21]) and IPC combined with the pharmacologic prophylaxis group (OR = 2.43, 95% CI: 0.99-5.96) did not affect DVT prevention. The pooled effects of Pulmonary Embolism (PE) (OR = 5.81, 95% CI: 1.25-26.91) were significant. IPC intervention showed a significant effect on bleeding prevention (OR = 0.17, 95% CI: 0.08-0.36) when compared to IPC combined with the pharmacologic groups. IPC intervention effectively prevented DVT, PE, and bleeding in surgical patients. Therefore, we propose that IPC intervention be applied to surgical patients to avoid DVT, pulmonary embolism, and bleeding in the surgical nursing field as scientific evidence suggests.
Assuntos
Dispositivos de Compressão Pneumática Intermitente , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose Venosa , Trombose Venosa/prevenção & controle , Trombose Venosa/etiologia , HumanosRESUMO
Inoculation of Chinese cabbage leaves with high titer (107 cfu/ml) of the non-adapted bacteria Xanthomonas campestris pv. vesicatoria (Xcv) strain Bv5-4a.1 triggered rapid leaf tissue collapses and hypersensitive cell death (HCD) at 24 h. Electrolyte leakage and lipid peroxidation markedly increased in the Xcv-inoculated leaves. Defence-related gene expressions (BrPR1, BrPR4, BrChi1, BrGST1 and BrAPX1) were preferentially activated in the Xcv-inoculated leaves. The Xcv-triggered HCD was attenuated by continuous light but accelerated by a dark environment, and the prolonged high relative humidity also alleviated the HCD. Constant dark and increased relative humidity provided favorable conditions for the Xcv bacterial growth in the leaves. Pretreated fluridone (biosynthetic inhibitor of endogenous abscisic acid [ABA]) increased the HCD in the Xcv-inoculated leaves, but exogenous ABA attenuated the HCD. The pretreated ABA also reduced the Xcv bacterial growth in the leaves. These results highlight that the onset of HCD in Chinese cabbage leaves initiated by non-adapted pathogen Xcv Bv5-4a.1 and in planta bacterial growth was differently modulated by internal and external conditional changes.
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Robot-assisted motor training is applied for neurorehabilitation in stroke patients, using motor imagery (MI) as a representative paradigm of brain-computer interfaces to offer real-life assistance to individuals facing movement challenges. However, the effectiveness of training with MI may vary depending on the location of the stroke lesion, which should be considered. This paper introduces a multi-task electroencephalogram-based heterogeneous ensemble learning (MEEG-HEL) specifically designed for cross-subject training. In the proposed framework, common spatial patterns were used for feature extraction, and the features according to stroke lesions are shared and selected through sequential forward floating selection. The heterogeneous ensembles were used as classifiers. Nine patients with chronic ischemic stroke participated, engaging in MI and motor execution (ME) paradigms involving finger tapping. The classification criteria for the multi-task were established in two ways, taking into account the characteristics of stroke patients. In the cross-subject session, the first involved a direction recognition task for two-handed classification, achieving a performance of 0.7419 (±0.0811) in MI and 0.7061 (±0.1270) in ME. The second task focused on motor assessment for lesion location, resulting in a performance of 0.7457 (±0.1317) in MI and 0.6791 (±0.1253) in ME. Comparing the specific-subject session, except for ME on the motor assessment task, performance on both tasks was significantly higher than the cross-subject session. Furthermore, classification performance was similar to or statistically higher in cross-subject sessions compared to baseline models. The proposed MEEG-HEL holds promise in improving the practicality of neurorehabilitation in clinical settings and facilitating the detection of lesions.
Assuntos
Algoritmos , Interfaces Cérebro-Computador , Eletroencefalografia , Aprendizado de Máquina , Reabilitação do Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Eletroencefalografia/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Imaginação/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Robótica , Adulto , Desempenho Psicomotor , AVC Isquêmico/fisiopatologia , AVC Isquêmico/reabilitação , Imagens, Psicoterapia/métodosRESUMO
BACKGROUND: Effects of Dictamnus dasycarpus Turcz. on allergic asthma and their underlying mechanisms remain unclarified. Thus, we investigated the effects of D. dasycarpus Turcz. water extract (DDW) on mucus hypersecretion in mice with ovalbumin (OVA)-induced asthma and human bronchial epithelial cells. METHODS: BALB/c mice were used to establish an OVA-induced allergic asthma model. Mice were grouped into the OVA sensitization/challenge, 100 and 300â¯mg/kg DDW treatment, and dexamethasone groups. In mice, cell counts in bronchoalveolar lavage fluid (BALF), serum and BALF analyses, and histopathological lung tissue analyses were performed. Furthermore, we confirmed the basic mechanism in interleukin (IL)-4/IL-13-treated human bronchial epithelial cells through western blotting. RESULTS: In OVA-induced asthma mice, DDW treatment reduced inflammatory cell number and airway hyperresponsiveness and ameliorated histological changes (immune cell infiltration, mucus secretion, and collagen deposition) in lung tissues and serum total immunoglobulin E levels. DDW treatment lowered BALF IL-4, IL-5, and IL-13 levels; reduced levels of inflammatory mediators, such as thymus- and activation-regulated chemokine, macrophage-derived chemokine, and interferon gamma-induced protein; decreased mucin 5AC (MUC5AC) production; decreased signal transducer and activator of transcription (STAT) 6 and STAT3 expression; and restored forkhead box protein A2 (FOXA2) expression. In IL-4/IL-13-treated human bronchial epithelial cells, DDW treatment inhibited MUC5AC production, suppressed STAT6 and STAT3 expression (related to mucus hypersecretion), and increased FOXA2 expression. CONCLUSIONS: DDW treatment modulates MUC5AC expression and mucus hypersecretion by downregulating STAT6 and STAT3 expression and upregulating FOXA2 expression. These findings provide a novel approach to manage mucus hypersecretion in asthma using DDW.
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Asma , Dictamnus , Fator 3-beta Nuclear de Hepatócito , Fator de Transcrição STAT3 , Camundongos , Humanos , Animais , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Ovalbumina , Modelos Animais de Doenças , Asma/induzido quimicamente , Asma/tratamento farmacológico , Pulmão , Inflamação/metabolismo , Muco/metabolismo , Líquido da Lavagem Broncoalveolar , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Fator de Transcrição STAT6/metabolismoRESUMO
The northeastern East China Sea is a highly dynamic marine ecosystem influenced by seasonally varying water mass properties. However, despite being among the world's fastest-warming ocean, there has been limited investigation into the impacts of warming on protistan communities. We collected seawater from two stations (E42 and E46) with different natural protist communities and environmental attributes to investigate the acclimation of the two communities to artificially elevated temperatures (ambient T, +2, and +4 °C). Nutrient and Chl-a conditions reflected oceanographic differences, providing insights into protistan community dynamics. Notably, small-sized autotrophic protists prevailed in the phosphate-deficient E42 community, with mid-incubation heterotrophic conversions. Higher temperatures exacerbated the effects of the P deficiency on the E42 community. While the proportions of Bacillariophyta increased only in the nutrient-balanced E46 communities, those of mixotrophic dinoflagellates increased with elevated temperature, regardless of P deficiency, suggesting that mixotrophy likely aids adaptation in changing marine environments. In summary, the findings of this microcosm study illuminate the potential modulation of spring protistan communities in the northeastern East China Sea under anticipated future warming.
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Diatomáceas , Dinoflagellida , Ecossistema , Água do Mar , Diatomáceas/fisiologia , China , Fitoplâncton/fisiologiaRESUMO
Objective: The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However less attention has been paid to the inter-limb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. Methods: In this study, we used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis post stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy post stroke. Results: We found that generally, strong inter-limb correlations (r>0.65 with all p-values<0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). But correlations of lower-extremity extension synergy with upper-extremity flexion synergy and extension synergy decreased (down to r=0.38) around 360 days after stroke (p<0.05). Interpretation: These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances inter-limb correlations between the flexion synergy and extension, however a recovery of the CST or/and the functional fragmentation (remodeling) of the alternative neural substrates in the chronic phase contribute to diversity in neural pathways in motor execution, eventually leading to reduced inter-limb correlations.
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BACKGROUND: Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes. METHODS: Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1. RESULTS: Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13-75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14-3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23-1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30-1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73-1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61-1.56, P = 0.93). CONCLUSIONS: It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336565.
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Precondicionamento Isquêmico , Transplante de Rim , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Rim/mortalidade , Humanos , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/mortalidade , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Função Retardada do EnxertoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer, and novel treatment regimens are direly needed. Epigenetic regulation contributes to the development of various cancer types, but its role in the development of and potential as a therapeutic target for PDAC remains underexplored. Here, we show that PRMT1 is highly expressed in murine and human pancreatic cancer and is essential for cancer cell proliferation and tumorigenesis. Deletion of PRMT1 delays pancreatic cancer development in a KRAS-dependent mouse model, and multi-omics analyses reveal that PRMT1 depletion leads to global changes in chromatin accessibility and transcription, resulting in reduced glycolysis and a decrease in tumorigenic capacity. Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Linhagem Celular Tumoral , Epigênese Genética , Gencitabina , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/uso terapêutico , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Although microalgae typically serve as prey for jellyfish ephyrae in marine food webs, this study investigated the potential of harmful microalgae to produce detrimental effects on the moon jellyfish Aurelia aurita. Understanding the biological interactions between Aurelia and microalgal species is crucial, particularly considering their common co-occurrence in coastal waters worldwide. We examined the effects of 11 protist strains, comprising seven species of harmful microalgae and two non-toxic microalgae, on A. aurita ephyrae. The rhythmic pulsation behavior of A. aurita was significantly suppressed when exposed to the raphidophytes Heterosigma akashiwo and Chattonella marina var. ovata and the dinoflagellates Amphidinium carterae, Coolia canariensis, and Pfiesteria piscicida. Notably, the media filtrates of all H. akashiwo strains and C. marina var. ovata killed ephyrae, implying a possible extracellular release of chemicals. This study discovered novel interactions between microalgae and jellyfish ephyrae, implying that harmful algal blooms may suppress mass occurrences of Aurelia medusae.
Assuntos
Proliferação Nociva de Algas , Microalgas , Cifozoários , Microalgas/fisiologia , Animais , Cifozoários/fisiologia , Dinoflagellida/fisiologia , Cadeia Alimentar , Estramenópilas/fisiologiaRESUMO
BACKGROUND: Information on the long-term prognosis in patients with isolated thalamic stroke is sparse. We report the functional outcomes of patients with thalamic stroke up to 24 months from the KOSCO (Korean Stroke Cohort for Functioning and Rehabilitation) study. METHODS AND RESULTS: Isolated thalamic stroke was defined as the presence of lesions solely in the thalamus, excluding cases with lesions in other brain parenchyma areas apart from the thalamus, as identified by brain magnetic resonance imaging or computed tomography scans. The Fugl-Meyer Assessment, the Functional Ambulatory Category, the Korean Mini-Mental State Examination, the American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and the short version of the Korean Frenchay Aphasia Screening Test were used to assess physical impairment. The Functional Independence Measure and modified Rankin Scale were used to assess functional outcomes. All measurements were conducted up to 24 months poststroke. A total of 297 patients were included, consisting of 235 with ischemic and 62 with hemorrhagic stroke. Except for the Functional Ambulatory Category and Functional Independence Measure, all physical impairments showed significant improvement up to 3 months poststroke (P<0.001) and reached a plateau. The Functional Ambulatory Category and Functional Independence Measure scores continued to improve up to 12 months poststroke (P<0.05) and reached a plateau. At 7 days poststroke, 47.5% of patients had no disability (modified Rankin Scale score<2), whereas at 24 months poststroke, 76.4% of patients had no significant disability. CONCLUSIONS: Patients showed rapid recovery from physical impairment up to 3 months poststroke, with additional improvements in ambulatory function and independence observed up to 12 months poststroke. Additionally, relatively favorable long-term functional prognosis at 24 months after onset was demonstrated. These results could provide insights into the proper management regarding functional outcomes of patients with isolated thalamic stroke.
Assuntos
Acidente Vascular Cerebral Hemorrágico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Prognóstico , Imageamento por Ressonância Magnética , Recuperação de Função FisiológicaRESUMO
Many physical factors influence post-stroke functional outcomes. However, few studies have examined the influence of height on these outcomes. Here, data from the Korean Stroke Cohort for Functioning and Rehabilitation were used and patients' height was categorized into three groups: short (lower 25%), middle (middle 50%), and tall (upper 25%). Differences in the modified Rankin scale (mRS), functional ambulatory category (FAC), and Korean-translated version of the Modified Barthel Index (K-MBI) scores were analyzed for each group at 6 months post-stroke. A subgroup analysis was conducted based on the initial Fugl-Meyer Assessment (FMA) score. We analyzed functional outcomes in 5296 patients at 6 months post-stroke, adjusting for age and body mass index. The short-height group exhibited higher mRS scores (1.88 ± 0.043), lower FAC scores (3.74 ± 0.045), and lower K-MBI scores (82.83 ± 0.748) than the other height groups (p < 0.05). In the subgroup analysis, except for the very severe FMA group, the short-height group also exhibited worse outcomes in terms of mRS, FAC, and K-MBI scores (p < 0.05). Taken together, the short-height group exhibited worse outcomes related to disability, gait function, and ADLs at 6 months post-stroke.